array:24 [
  "pii" => "S2666275220301521"
  "issn" => "26662752"
  "doi" => "10.1016/j.abdp.2019.11.002"
  "estado" => "S300"
  "fechaPublicacion" => "2020-05-01"
  "aid" => "171"
  "copyright" => "Sociedade Brasileira de Dermatologia"
  "copyrightAnyo" => "2020"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by/4.0/"
  "subdocumento" => "fla"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "en" => array:19 [
      "pii" => "S0365059620300829"
      "issn" => "03650596"
      "doi" => "10.1016/j.abd.2019.11.003"
      "estado" => "S300"
      "fechaPublicacion" => "2020-05-01"
      "aid" => "171"
      "copyright" => "Sociedade Brasileira de Dermatologia"
      "documento" => "article"
      "crossmark" => 1
      "licencia" => "http://creativecommons.org/licenses/by/4.0/"
      "subdocumento" => "fla"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:1 [
        "total" => 0
      ]
      "en" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Investigation</span>"
        "titulo" => "Quantification of mitochondrial DNA damage and copy number in circulating blood of patients with systemic sclerosis by a qPCR-based assay"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "tieneResumen" => "en"
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "314"
            "paginaFinal" => "319"
          ]
        ]
        "contieneResumen" => array:1 [
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "en" => true
        ]
        "contienePdf" => array:1 [
          "en" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0010"
            "etiqueta" => "Figure 2"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr2.jpeg"
                "Alto" => 934
                "Ancho" => 1651
                "Tamanyo" => 61673
              ]
            ]
            "descripcion" => array:1 [
              "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Increased mtDNA damage in patients with systemic sclerosis as compared to normal controls&#46; The &#916;Ct is the difference between Ct value from DNA sample treated with FPG and Ct value from DNA sample without FPG treatment&#46; Please note that a higher &#916;Ct value corresponds to a comparably higher levels of oxidative these damage&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Shafieh Movassaghi, Sara Jafari, Kowsar Falahati, Mitra Ataei, Mohammad Hossein Sanati, Zohreh Jadali"
            "autores" => array:6 [
              0 => array:2 [
                "nombre" => "Shafieh"
                "apellidos" => "Movassaghi"
              ]
              1 => array:2 [
                "nombre" => "Sara"
                "apellidos" => "Jafari"
              ]
              2 => array:2 [
                "nombre" => "Kowsar"
                "apellidos" => "Falahati"
              ]
              3 => array:2 [
                "nombre" => "Mitra"
                "apellidos" => "Ataei"
              ]
              4 => array:2 [
                "nombre" => "Mohammad Hossein"
                "apellidos" => "Sanati"
              ]
              5 => array:2 [
                "nombre" => "Zohreh"
                "apellidos" => "Jadali"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "pt" => array:9 [
          "pii" => "S2666275220301521"
          "doi" => "10.1016/j.abdp.2019.11.002"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "pt"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275220301521?idApp=UINPBA00008Z"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059620300829?idApp=UINPBA00008Z"
      "url" => "/03650596/0000009500000003/v4_202007210853/S0365059620300829/v4_202007210853/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2666275220301624"
    "issn" => "26662752"
    "doi" => "10.1016/j.abdp.2019.11.006"
    "estado" => "S300"
    "fechaPublicacion" => "2020-05-01"
    "aid" => "180"
    "copyright" => "Sociedade Brasileira de Dermatologia"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "fla"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "pt" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Investiga&#231;&#227;o</span>"
      "titulo" => "Um ensaio cl&#237;nico hemicorporal&#44; randomizado&#44; duplo&#8208;cego&#44; controlado&#44; sobre os efeitos de um hidratante com pH modificado <span class="elsevierStyleItalic">vs</span>&#46; hidratante convencional na dermatite at&#243;pica leve a moderada"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "tieneResumen" => "pt"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "320"
          "paginaFinal" => "325"
        ]
      ]
      "contieneResumen" => array:1 [
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Siew Wen Goh, Adawiyah Jamil, Nazarudin Safian, Norazirah Md Nor, Norliza Muhammad, Nur Liyana Saharudin"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Siew Wen"
              "apellidos" => "Goh"
            ]
            1 => array:2 [
              "nombre" => "Adawiyah"
              "apellidos" => "Jamil"
            ]
            2 => array:2 [
              "nombre" => "Nazarudin"
              "apellidos" => "Safian"
            ]
            3 => array:2 [
              "nombre" => "Norazirah"
              "apellidos" => "Md Nor"
            ]
            4 => array:2 [
              "nombre" => "Norliza"
              "apellidos" => "Muhammad"
            ]
            5 => array:2 [
              "nombre" => "Nur Liyana"
              "apellidos" => "Saharudin"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S036505962030091X"
        "doi" => "10.1016/j.abd.2019.11.007"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S036505962030091X?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275220301624?idApp=UINPBA00008Z"
    "url" => "/26662752/0000009500000003/v1_202006250813/S2666275220301624/v1_202006250813/pt/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2666275220301582"
    "issn" => "26662752"
    "doi" => "10.1016/j.abdp.2019.11.004"
    "estado" => "S300"
    "fechaPublicacion" => "2020-05-01"
    "aid" => "176"
    "copyright" => "Sociedade Brasileira de Dermatologia"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "fla"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "pt" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Investiga&#231;&#227;o</span>"
      "titulo" => "Diferentes padr&#245;es de distribui&#231;&#227;o das c&#233;lulas dendr&#237;ticas plasmocitoides no l&#250;pus eritematoso discoide e no l&#237;quen plano pilar demonstrados pela imunomarca&#231;&#227;o com CD123"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "tieneResumen" => "pt"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "307"
          "paginaFinal" => "313"
        ]
      ]
      "contieneResumen" => array:1 [
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0015"
          "etiqueta" => "Figura 3"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr3.jpeg"
              "Alto" => 1256
              "Ancho" => 2108
              "Tamanyo" => 151166
            ]
          ]
          "descripcion" => array:1 [
            "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Padr&#245;es de distribui&#231;&#227;o de c&#233;lulas dendr&#237;ticas plasmocitoides &#40;CPD&#41; no l&#237;quen plano pilar &#40;LPP&#41; e l&#250;pus eritematoso discoide &#40;LED&#41;&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Azadeh Rakhshan, Parviz Toossi, Maliheh Amani, Sahar Dadkhahfar, Arash Bagheri Hamidi"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "Azadeh"
              "apellidos" => "Rakhshan"
            ]
            1 => array:2 [
              "nombre" => "Parviz"
              "apellidos" => "Toossi"
            ]
            2 => array:2 [
              "nombre" => "Maliheh"
              "apellidos" => "Amani"
            ]
            3 => array:2 [
              "nombre" => "Sahar"
              "apellidos" => "Dadkhahfar"
            ]
            4 => array:2 [
              "nombre" => "Arash Bagheri"
              "apellidos" => "Hamidi"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0365059620300878"
        "doi" => "10.1016/j.abd.2019.11.005"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059620300878?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275220301582?idApp=UINPBA00008Z"
    "url" => "/26662752/0000009500000003/v1_202006250813/S2666275220301582/v1_202006250813/pt/main.assets"
  ]
  "pt" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Investiga&#231;&#227;o</span>"
    "titulo" => "Quantifica&#231;&#227;o do dano ao DNA mitocondrial e n&#250;mero de c&#243;pias no sangue circulante de pacientes com esclerose sist&#234;mica em um ensaio baseado em qPCR"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "314"
        "paginaFinal" => "319"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Shafieh Movassaghi, Sara Jafari, Kowsar Falahati, Mitra Ataei, Mohammad Hossein Sanati, Zohreh Jadali"
        "autores" => array:6 [
          0 => array:3 [
            "nombre" => "Shafieh"
            "apellidos" => "Movassaghi"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Sara"
            "apellidos" => "Jafari"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Kowsar"
            "apellidos" => "Falahati"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Mitra"
            "apellidos" => "Ataei"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Mohammad Hossein"
            "apellidos" => "Sanati"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          5 => array:4 [
            "nombre" => "Zohreh"
            "apellidos" => "Jadali"
            "email" => array:1 [
              0 => "zjadali@yahoo.co.uk"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Departamento de Reumatologia&#44; Hospital Imam Khomeini&#44; Tehran University of Medical Sciences&#44; Teer&#227;&#44; Ir&#227;"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Departamento de Gen&#233;tica Cl&#237;nica&#44; National Institute of Genetic Engineering and Biotechnology&#44; Teer&#227;&#44; Ir&#227;"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Faculdade de Sa&#250;de P&#250;blica&#44; Tehran University of Medical Sciences&#44; Teer&#227;&#44; Ir&#227;"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Autor para correspond&#234;ncia&#46;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 868
            "Ancho" => 1667
            "Tamanyo" => 66452
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">N&#250;mero m&#233;dio de c&#243;pias mitocondriais no sangue perif&#233;rico de pacientes com esclerose sist&#234;mica e indiv&#237;duos saud&#225;veis&#46; O n&#250;mero de c&#243;pias do DNAmt foi quantificado com o delta Ct &#40;Ct&#41; da Ct m&#233;dia do DNAmt e o DNA nuclear &#40;Ct<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>CtmtDNA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Ctactin&#41;&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A esclerose sist&#234;mica &#40;ES&#41; &#233; doen&#231;a cr&#244;nica rara do tecido conjuntivo caracterizada por vasculopatia e fibrose na pele e em v&#225;rios &#243;rg&#227;os internos&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1&#44;2</span></a> Sua causa exata &#233; desconhecida&#44; mas sua ocorr&#234;ncia pode ser influenciada por uma intera&#231;&#227;o complexa de fatores gen&#233;ticos&#44; epigen&#233;ticos e ambientais&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">3</span></a> Recentemente&#44; grande aten&#231;&#227;o tem sido dedicada ao papel do estresse oxidativo na patog&#234;nese da ES&#46; Acredita&#8208;se que ele esteja envolvido nos processos fisiopatol&#243;gicos de aumento da s&#237;ntese e ac&#250;mulo de matriz extracelular&#44; ativa&#231;&#227;o imune anormal e dano endotelial vascular&#44; as tr&#234;s principais caracter&#237;sticas da ES&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">O aumento do estresse oxidativo reflete um desequil&#237;brio entre a homeostase pr&#243;&#8208;oxidante&#47;antioxidante e leva a n&#237;veis aumentados de esp&#233;cies reativas de oxig&#234;nio &#40;ERO&#41; t&#243;xicas&#46; Existem duas vias principais de gera&#231;&#227;o de ERO&#58; end&#243;gena e ex&#243;gena&#46; As mitoc&#244;ndrias s&#227;o a principal fonte end&#243;gena de ERO&#46; Elas t&#234;m seu pr&#243;prio genoma &#40;DNA mitocondrial &#91;mtDNA&#93;&#41; e s&#227;o organelas indispens&#225;veis para a fisiologia celular normal&#46; O mtDNA &#233; multic&#243;pias e sua abund&#226;ncia &#233; regulada de forma espec&#237;fica em cada tipo de tecido&#46; O mtDNAcn flutua em resposta ao ambiente fisiol&#243;gico ao redor da c&#233;lula&#59; em condi&#231;&#245;es fisiol&#243;gicas&#44; permanece relativamente est&#225;vel dentro das c&#233;lulas&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a> Em circunst&#226;ncias patol&#243;gicas&#44; o mtDNAcn pode variar&#44; depende de diferentes fatores&#44; inclusive o equil&#237;brio redox celular alterado&#46; O mtDNA tamb&#233;m &#233; propenso a danos por estresse oxidativo devido &#224; sua alta exposi&#231;&#227;o aos EROs produzidos pelas mitoc&#244;ndrias&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Os produtos de oxida&#231;&#227;o da guanina s&#227;o importantes indicadores de dano oxidativo ao DNA&#46; Esses marcadores qu&#237;micos podem ser removidos por Fpg &#40;DNA&#8208;formamidopirimidina glicosilase&#41;&#44; uma enzima de reparo por excis&#227;o de base que libera les&#245;es de purina&#44; tanto do DNA nuclear quanto do mtDNA&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">7&#44;8</span></a> A clivagem por Fpg do DNA oxidativamente danificado pode reduzir a amplifica&#231;&#227;o do DNA alvo digerido pela enzima Taq DNA polimerase&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a> Portanto&#44; esse m&#233;todo tem sido amplamente usado como uma medida de dano oxidativo ao DNA&#46; Os objetivos do presente estudo foram determinar se a varia&#231;&#227;o do mtDNAcn e seu &#237;ndice de dano oxidativo &#40;mtDNA &#91;&#916;CT&#93;&#41; podem ser detectados em pacientes com ES&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">O estudo foi aprovado pelo Comit&#234; de &#201;tica da Universidade de Ci&#234;ncias M&#233;dicas e foi feito de acordo com os princ&#237;pios de &#233;tica da Declara&#231;&#227;o de Helsinque&#46; Todos os participantes concordaram voluntariamente em participar do estudo e assinaram o termo de consentimento livre e esclarecido&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Popula&#231;&#227;o do estudo</span><p id="par0025" class="elsevierStylePara elsevierViewall">O estudo incluiu 46 pacientes com ES e 49 indiv&#237;duos saud&#225;veis pareados por idade e sexo&#44; sem hist&#243;rico de esclerodermia ou outras doen&#231;as cr&#244;nicas e autoimunes&#46; Os pacientes com ES foram diagnosticados de acordo com os crit&#233;rios do Col&#233;gio Americano de Reumatologia &#40;ACR&#41;&#47;Liga Europeia Contra Reumatismo &#40;EULAR&#41; de 2013&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">10&#44;11</span></a> Entre os pacientes inclu&#237;dos&#44; seis &#40;13&#44;04&#37;&#41; apresentavam forma limitada de ES e 40 &#40;86&#44;96&#37;&#41; ES difusa&#46; Doze &#40;26&#44;09&#37;&#41; apresentavam doen&#231;a pulmonar intersticial &#40;DPI&#41;&#44; tr&#234;s &#40;6&#44;52&#37;&#41; hipertens&#227;o arterial pulmonar &#40;HAP&#41; e tr&#234;s &#40;6&#44;52&#37;&#41; DPI e HAP&#46; A idade m&#233;dia dos pacientes com ES &#40;seis homens&#44; 40 mulheres&#41; e os controles &#40;cinco homens&#44; 44 mulheres&#41; foi de 46&#44;09 e 41&#44;90 anos&#44; respectivamente&#46; A dura&#231;&#227;o m&#233;dia da doen&#231;a foi de 7&#44;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;13 anos&#44; com varia&#231;&#227;o de um a 40 anos&#46; Trinta e oito pacientes com ES difusa e seis pacientes com ES cut&#226;nea limitada haviam recebido tratamento com esteroides e&#47;ou imunossupressores antes da amostragem&#46; A dose e a dura&#231;&#227;o do tratamento foram diferentes&#44; dependeram da gravidade das les&#245;es e dos &#243;rg&#227;os afetados&#46; Nenhum dos pacientes apresentava doen&#231;as inflamat&#243;rias&#47;autoimunes al&#233;m da ES e todos estavam inativos no momento da visita&#46; A <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a> apresenta as caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas dos pacientes com ES e controles&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Extra&#231;&#227;o de DNA</span><p id="par0030" class="elsevierStylePara elsevierViewall">As amostras de sangue foram coletadas em tubos de 5<span class="elsevierStyleHsp" style=""></span>mL com &#225;cido etileno diamino tetraac&#233;tico &#40;EDTA&#41;&#46; O DNA do sangue total foi extra&#237;do com o kit de isolamento de DNA &#40;GeneAll &#8211; Seul&#44; Coreia&#41;&#44; de acordo com as instru&#231;&#245;es do fabricante&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A concentra&#231;&#227;o e purifica&#231;&#227;o do DNA extra&#237;do foram medidas com eletroforese em gel de agarose &#40;1&#44;5&#37;&#41; e espectrofotometria com NanoDrop 2000c &#40;Thermo Fisher Scientific&#44; EUA&#41;&#46; Todas as amostras de DNA foram armazenadas a &#8208;20<span class="elsevierStyleHsp" style=""></span>&#176;C at&#233; o uso&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Prepara&#231;&#227;o do modelo de DNA</span><p id="par0040" class="elsevierStylePara elsevierViewall">Para a detec&#231;&#227;o de dano oxidativo&#44; 100 ng de DNA da amostra &#40;2<span class="elsevierStyleHsp" style=""></span>&#956;L de solu&#231;&#227;o&#8208;padr&#227;o&#41; foram incubados por 1<span class="elsevierStyleHsp" style=""></span>h a 37<span class="elsevierStyleHsp" style=""></span>&#176;C em 10<span class="elsevierStyleHsp" style=""></span>&#956;L de mistura de reagente com uma unidade de enzima FPG &#40;New England BioLabs &#8211; Massachusetts&#44; EUA&#41;&#44; 10<span class="elsevierStyleHsp" style=""></span>mM Bis Tris Propano&#8208;HCl&#44; 10<span class="elsevierStyleHsp" style=""></span>mM MgCl<span class="elsevierStyleInf">2</span>&#44; 1<span class="elsevierStyleHsp" style=""></span>mM DTT e 0&#44;1<span class="elsevierStyleHsp" style=""></span>mg&#47;mL de albumina de soro bovino&#46; Para a detec&#231;&#227;o do mtDNAcn&#44; o DNA da amostra foi preparado de maneira semelhante&#44; mas sem FPG&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Determina&#231;&#227;o quantitativa do n&#250;mero de c&#243;pias do mtDNA</span><p id="par0045" class="elsevierStylePara elsevierViewall">As rea&#231;&#245;es para o ensaio quantitativo de rea&#231;&#227;o em cadeia de polimerase em tempo real &#40;qPCR&#41; foram feitas com o kit SYBR Premix EX Taq II &#40;Takara &#8211; Jap&#227;o&#41; e com um aparelho Rotor&#8208;Gene 6000 &#40;Corbett Life Science &#8211; Austr&#225;lia&#41;&#46; A PCR foi feita em 42 ciclos&#44; com uma desnatura&#231;&#227;o inicial de 1<span class="elsevierStyleHsp" style=""></span>min a 95<span class="elsevierStyleHsp" style=""></span>&#176;C no primeiro ciclo&#46; Todos os ciclos subsequentes consistiram em desnatura&#231;&#227;o a 95<span class="elsevierStyleHsp" style=""></span>&#176;C por 4s&#44; emparelhamento a 62<span class="elsevierStyleHsp" style=""></span>&#176;C por 30s e extens&#227;o a 72<span class="elsevierStyleHsp" style=""></span>&#176;C por 15s&#44; bem como uma etapa final de extens&#227;o a 72<span class="elsevierStyleHsp" style=""></span>&#176;C por 15s&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">As rea&#231;&#245;es de PCR foram feitas em um volume total de 10<span class="elsevierStyleHsp" style=""></span>&#956;L com 1<span class="elsevierStyleHsp" style=""></span>&#956;L de DNA gen&#244;mico&#44; 0&#44;5<span class="elsevierStyleHsp" style=""></span>&#956;L de cada iniciador&#44; 5<span class="elsevierStyleHsp" style=""></span>&#956;L de SYBR Premix e 3<span class="elsevierStyleHsp" style=""></span>&#956;L de &#225;gua destilada&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Para quantifica&#231;&#227;o de mtDNA&#44; foi usado um conjunto de iniciadores direcionados &#224; subunidade NADH desidrogenase tipo 2 codificada mitocondrialmente &#40;ND2&#41;&#46; Para quantifica&#231;&#227;o nuclear de DNA&#44; um conjunto de iniciadores direcionados ao gene da &#946;&#8208;actina foi selecionado&#46; Todos os iniciadores foram comprados na Gene Fanavaran Company &#40;Teer&#227;&#44; Ir&#227;&#41; e suas sequ&#234;ncias exatas foram descritas anteriormente&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a> A propor&#231;&#227;o de mtDNA para DNA nuclear em cada amostra foi calculada como uma estimativa para o n&#250;mero de mtDNA&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Determina&#231;&#227;o quantitativa do dano ao mtDNA</span><p id="par0060" class="elsevierStylePara elsevierViewall">O conte&#250;do de produtos de oxida&#231;&#227;o de guanina foi determinado pela t&#233;cnica baseada em qPCR&#46; O n&#237;vel de dano oxidativo no DNA mitocondrial &#233; indicado por um aumento dos nucleot&#237;deos de purina oxidados&#44; inclusive 8&#8208;OHdG&#46; A digest&#227;o com FPG foi usada para a detec&#231;&#227;o de produtos do dano oxidativo no DNA&#46; Os n&#237;veis de dano oxidativo ao mtDNA foram apresentados como &#916;Ct&#44; que &#233; a diferen&#231;a entre os valores do ciclo limiar &#40;Ct&#41; entre as amostras tratadas com enzima e as n&#227;o tratadas com enzima &#40;Ct&#8208;T e Ct&#8208;N&#44; respectivamente&#41;&#46; Valores mais elevados de &#916;Ct indicam n&#237;veis mais altos de estresse oxidativo nas mitoc&#244;ndrias&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lise estat&#237;stica</span><p id="par0065" class="elsevierStylePara elsevierViewall">Os dados distribu&#237;dos normalmente e n&#227;o normalmente foram analisados pelo teste <span class="elsevierStyleItalic">t</span> para amostras independentes e pelo teste U de Mann&#8208;Whitney&#44; respectivamente&#46; Os n&#237;veis de depend&#234;ncia linear entre duas vari&#225;veis foram calculados pelo coeficiente de correla&#231;&#227;o de Pearson&#46; Esse teste &#233; adequado para vari&#225;veis cont&#237;nuas normais&#59; valores&#8208;p inferiores a 0&#44;05 foram considerados estatisticamente significativos&#46; Os resultados experimentais foram apresentados como m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desvio&#8208;padr&#227;o&#46; O <span class="elsevierStyleItalic">software</span> SPSS &#40;v11&#46;0&#59; SPSS&#44; Inc&#46; Chicago&#44; IL&#44; EUA&#41; foi usado para as opera&#231;&#245;es estat&#237;sticas e interpreta&#231;&#227;o dos resultados do estudo&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Diminui&#231;&#227;o do mtDNAcn no sangue perif&#233;rico em pacientes com ES</span><p id="par0070" class="elsevierStylePara elsevierViewall">Como mostrado na <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#44; o mtDNAcn do sangue perif&#233;rico diminuiu significativamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; no grupo de pacientes &#40;0&#44;49<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41; em compara&#231;&#227;o com o grupo controle &#40;0&#44;52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41;&#46; N&#227;o foi observada associa&#231;&#227;o entre mtDNAcn e idade&#44; sexo e dura&#231;&#227;o da doen&#231;a&#46; Al&#233;m disso&#44; n&#227;o houve diferen&#231;a significativa no mtDNAcn entre os pacientes com doen&#231;a limitada e difusa &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Aumento do dano oxidativo ao DNA em pacientes com ES</span><p id="par0075" class="elsevierStylePara elsevierViewall">Para avaliar a exist&#234;ncia de dano oxidativo&#44; a presen&#231;a de bases de purinas oxidadas &#40;principalmente 8&#8208;oxodGuo&#41;&#44; que s&#227;o locais sens&#237;veis &#224; FPG&#44; foi determinada no DNA de amostras de sangue perif&#233;rico de pacientes com ES e controles normais&#46; Os resultados indicaram &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41; que o valor m&#233;dio do dano oxidativo ao DNA em pacientes &#40;0&#44;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;40&#41; aumentou significativamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;045&#41; em compara&#231;&#227;o ao grupo controle &#40;0&#44;42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;37&#41;&#46; Al&#233;m disso&#44; n&#227;o foi observada associa&#231;&#227;o entre dano oxidativo ao DNA e idade&#44; sexo e dura&#231;&#227;o da doen&#231;a&#46; A an&#225;lise estat&#237;stica tamb&#233;m n&#227;o indicou diferen&#231;as significativas entre os pacientes com ES limitada e difusa em termos de dano oxidativo ao DNA &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Curiosamente&#44; observou&#8208;se uma correla&#231;&#227;o negativa entre o mtDNAcn e o dano oxidativo ao DNA &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8208;0&#44;392&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discuss&#227;o</span><p id="par0080" class="elsevierStylePara elsevierViewall">H&#225; um consenso geral de que a ES &#233; doen&#231;a autoimune e que a complexidade de sua imunopatog&#234;nese &#233; similar &#224; de outras doen&#231;as autoimunes&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">13</span></a> Sua etiologia exata n&#227;o &#233; clara&#46; No entanto&#44; estudos recentes apontam a import&#226;ncia da influ&#234;ncia do estresse oxidativo nos processos da doen&#231;a&#46; Por exemplo&#44; Bourji et al&#46; mostraram que peles fibr&#243;ticas e n&#227;o fibr&#243;ticas de pacientes com ES apresentam n&#237;veis mais altos de ERO do que as de controles saud&#225;veis&#46; Eles tamb&#233;m observaram que pacientes com ES apresentavam n&#237;veis mais baixos de vitamina C &#40;que tem poderosa atividade antioxidante&#41; do que os controles saud&#225;veis&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a> O aumento da produ&#231;&#227;o de ERO por fibroblastos&#44; c&#233;lulas endoteliais e c&#233;lulas T&#44; os principais agentes celulares na patog&#234;nese da ES&#44; &#233; outra evid&#234;ncia que associa o estresse oxidativo aos principais eventos da doen&#231;a&#44; como fibrose e dano vascular&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Existem muitas vias distintas para a gera&#231;&#227;o de ERO&#46; As mitoc&#244;ndrias s&#227;o as principais fontes de ERO e&#44; ao mesmo tempo&#44; os principais alvos de seus efeitos desfavor&#225;veis&#46; A maior parte das ERO mitocondriais decorre da cadeia de transporte de el&#233;trons&#44; como subproduto do processo de respira&#231;&#227;o aer&#243;bica&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">16</span></a> As ERO agem como uma faca de dois gumes&#44; porque sua gera&#231;&#227;o descontrolada promove estresse oxidativo que causa les&#245;es graves em tipos b&#225;sicos de macromol&#233;culas biol&#243;gicas&#44; inclusive DNA&#44; prote&#237;nas&#44; carboidratos e lip&#237;dios&#46; Por outro lado&#44; a ERO pode participar de v&#225;rios processos biol&#243;gicos em c&#233;lulas normais&#44; inclusive vias de sinaliza&#231;&#227;o celular e respostas imunes contra pat&#243;genos ou subst&#226;ncias estranhas&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Nos &#250;ltimos anos&#44; v&#225;rios estudos examinaram o impacto da varia&#231;&#227;o quantitativa e qualitativa do mtDNAcn em doen&#231;as humanas e demonstraram altera&#231;&#245;es not&#225;veis no mtDNAcn em v&#225;rias doen&#231;as&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">12&#44;18</span></a> O mtDNAcn pode ser modificado pelo estresse oxidativo&#46; Al&#233;m disso&#44; o aumento da produ&#231;&#227;o de ERO pode causar danos oxidativos aos componentes celulares&#44; inclusive o DNA&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a> Portanto&#44; a avalia&#231;&#227;o do mtDNAcn e de seu &#237;ndice de dano oxidativo melhorar&#225; o entendimento sobre a patog&#234;nese de doen&#231;as relacionadas ao estresse oxidativo&#44; como a ES&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Os resultados do presente estudo indicaram que o valor m&#233;dio do mtDNAcn foi significativamente menor do que o observado em controles normais&#46; Tanto quanto &#233; do conhecimento dos autores&#44; este &#233; o primeiro relato que mediu as altera&#231;&#245;es do mtDNAcn no sangue perif&#233;rico de pacientes com ES&#46; Atualmente&#44; existem poucas informa&#231;&#245;es sobre a rela&#231;&#227;o entre altera&#231;&#245;es bioqu&#237;micas&#44; estruturais e funcionais nas mitoc&#244;ndrias e ES&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Um relato de Feldmann et al&#46; indicou a presen&#231;a de mitoc&#244;ndrias gigantes nos hepat&#243;citos de pacientes com esclerodermia sist&#234;mica&#46; Entretanto&#44; esses autores n&#227;o forneceram explica&#231;&#227;o sobre o&#40;s&#41; mecanismo&#40;s&#41; por tr&#225;s desse evento celular&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> Alguns pesquisadores tamb&#233;m relataram a presen&#231;a de anticorpos antimitoc&#244;ndrias &#40;AMAs&#41; nos soros de pacientes com ES&#46; Esses anticorpos s&#227;o encontrados em at&#233; 25&#37; dos pacientes<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a> e atuam contra componentes da multienzima piruvato desidrogenase complexa &#40;PDHC&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> que est&#225; localizada na matriz mitocondrial interna e produz substratos reduzidos para a cadeia de transporte de el&#233;trons&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a> Os AMAs s&#227;o considerados um marcador s&#233;rico de doen&#231;as autoimunes&#44; como a cirrose biliar prim&#225;ria &#40;CBP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">23</span></a> A motiva&#231;&#227;o cl&#237;nica por tr&#225;s da avalia&#231;&#227;o dos AMAs em pacientes com ES foi a observa&#231;&#227;o de que uma grande propor&#231;&#227;o desses pacientes apresentava uma condi&#231;&#227;o autoimune coexistente&#44; inclusive CBP&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">V&#225;rios outros autoanticorpos&#44; inclusive anticorpos anticentr&#244;mero &#40;ACA&#41;&#44; anti&#8208;topoisomerase &#40;ATA&#41; e anti&#8208;RNA polimerase III &#40;anti&#8208;RNAP&#41;&#44; foram descritos em pacientes com ES como poss&#237;veis bons biomarcadores para v&#225;rias manifesta&#231;&#245;es cl&#237;nicas e progn&#243;sticas em subconjuntos de ES&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Existem tamb&#233;m algumas evid&#234;ncias de associa&#231;&#227;o positiva entre esses anticorpos e AMA&#46; Por exemplo&#44; Wielose et al&#46; conclu&#237;ram que a preval&#234;ncia de ACAs &#233; significativamente maior em pacientes com ES que apresentam t&#237;tulos positivos de AMA do que naqueles com t&#237;tulos negativos de AMA&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a> Este estudo tamb&#233;m apontou uma forte associa&#231;&#227;o entre AMAs e ACAs em pacientes com ES cut&#226;nea limitada&#44; o que &#233; consistente com relatos anteriores&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Esses achados sugerem indiretamente que as mitoc&#244;ndrias podem estar envolvidas na ES&#44; al&#233;m de sugerir um poss&#237;vel papel para o estresse oxidativo&#46; Essa hip&#243;tese &#233; refor&#231;ada por outras observa&#231;&#245;es&#46; Por exemplo&#44; a an&#225;lise do fluido obtido na lavagem broncoalveolar &#40;LBA&#41; de pacientes com ES e fibrose pulmonar &#40;SSc<span class="elsevierStyleInf">Fib&#43;</span>&#41; indicou significativa suprarregula&#231;&#227;o da topoisomerase 1 do DNA mitocondrial &#40;mtDNA TOP1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a> uma enzima que tem papel funcional na manuten&#231;&#227;o e na topologia do mtDNA&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">29</span></a> Al&#233;m disso&#44; foi observada infrarregula&#231;&#227;o da glutationa S&#8208;transferase P &#40;GSTP&#41; e super&#243;xido dismutase &#40;SOD&#41; no LBA de pacientes com SSc<span class="elsevierStyleInf">Fib&#43;</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a> &#201; importante mencionar que SOD e GSTP s&#227;o dois componentes do sistema de defesa antioxidante que protege as c&#233;lulas e os tecidos contra oxidantes&#44; especialmente no pulm&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">30&#44;31</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Os produtos de danos oxidativos em bases de DNA tamb&#233;m servem como marcadores de estresse oxidativo&#59; entre as quatro bases nitrogenadas no DNA&#44; a guanina &#233; a base de &#225;cido nucleico mais facilmente oxid&#225;vel&#46; Portanto&#44; a guanina &#233; alvo prim&#225;rio de modifica&#231;&#227;o oxidativa<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a> e a medi&#231;&#227;o de esp&#233;cies de guanina oxidada pode ser uma ferramenta &#250;til para avaliar os danos ao DNA induzidos pelo estresse oxidativo nos compartimentos nuclear e mitocondrial&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">No presente estudo&#44; o teste qPCR foi usado para avaliar a oxida&#231;&#227;o da base de DNA nas c&#233;lulas sangu&#237;neas perif&#233;ricas de pacientes com ES e controles saud&#225;veis&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Os resultados indicaram diferen&#231;a estatisticamente significativa entre os grupos analisados em rela&#231;&#227;o ao dano oxidativo do mtDNA&#46; Al&#233;m disso&#44; uma correla&#231;&#227;o negativa significativa foi observada entre o mtDNAcn e o grau de mtDNA oxidativo &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8208;0&#44;392&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Esses resultados s&#227;o similares aos de estudos anteriores que relataram aumento do estresse oxidativo e danos ao DNA em fibroblastos obtidos de pacientes com ES &#40;esclerodermia&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">33&#44;34</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Embora o mecanismo molecular exato do dano ao DNA ainda n&#227;o tenha sido elucidado&#44; aparentemente os autoanticorpos derivados de pacientes com ES podem estimular v&#225;rias vias de sinaliza&#231;&#227;o intracelular &#40;como as vias Wnt e Ras&#41; que podem ser influenciadas pelos ERO e tamb&#233;m podem ter impacto na produ&#231;&#227;o de ERO&#46; Nesse cen&#225;rio&#44; altera&#231;&#245;es descontroladas na produ&#231;&#227;o de ERO e na transdu&#231;&#227;o de sinal podem resultar em ac&#250;mulo de danos ao DNA&#44; ativa&#231;&#227;o de genes dependentes de ERO e alta suscetibilidade &#224; apoptose&#46; Acredita&#8208;se que esses eventos participem da forma&#231;&#227;o de fibrose tecidual como consequ&#234;ncia da apoptose e da deposi&#231;&#227;o de col&#225;geno&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclus&#227;o</span><p id="par0145" class="elsevierStylePara elsevierViewall">O presente estudo avaliou os danos ao mtDNAcn e ao mtDNA com um ensaio quantitativo baseado em PCR&#46; Os presentes resultados indicam que pacientes com ES apresentavam redu&#231;&#227;o no mtDNAcn e aumento no dano mitocondrial&#44; o que &#233; consistente com a disfun&#231;&#227;o mitocondrial&#46; Al&#233;m de experimentos tradicionais para desvendar a fisiopatologia da ES&#44; estudos futuros s&#227;o necess&#225;rios para confirmar os presentes achados&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Suporte financeiro</span><p id="par0150" class="elsevierStylePara elsevierViewall">Universidade de Ci&#234;ncias M&#233;dicas de Teer&#227; &#40;contrato n&#176; 24&#46;743&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Contribui&#231;&#227;o dos autores</span><p id="par0155" class="elsevierStylePara elsevierViewall">Shafieh Movassaghi&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Sara Jafari&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Kowsar Falahati&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Mitra Ataei&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Mohammad Hossein Sanati&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Zohreh Jadali&#58; An&#225;lise estat&#237;stica&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflitos de interesse</span><p id="par0185" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:11 [
        0 => array:3 [
          "identificador" => "xres1354622"
          "titulo" => "Resumo"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Fundamentos"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Objetivo"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "M&#233;todos"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Resultados"
            ]
            4 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Limita&#231;&#245;es do estudo"
            ]
            5 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Conclus&#227;o"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1245560"
          "titulo" => "Palavras&#8208;chave"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introdu&#231;&#227;o"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "M&#233;todos"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Popula&#231;&#227;o do estudo"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Extra&#231;&#227;o de DNA"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Prepara&#231;&#227;o do modelo de DNA"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Determina&#231;&#227;o quantitativa do n&#250;mero de c&#243;pias do mtDNA"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Determina&#231;&#227;o quantitativa do dano ao mtDNA"
            ]
            5 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "An&#225;lise estat&#237;stica"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "sec0045"
          "titulo" => "Resultados"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Diminui&#231;&#227;o do mtDNAcn no sangue perif&#233;rico em pacientes com ES"
            ]
            1 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Aumento do dano oxidativo ao DNA em pacientes com ES"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Discuss&#227;o"
        ]
        6 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Conclus&#227;o"
        ]
        7 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Suporte financeiro"
        ]
        8 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Contribui&#231;&#227;o dos autores"
        ]
        9 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Conflitos de interesse"
        ]
        10 => array:1 [
          "titulo" => "Refer&#234;ncias"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-04-24"
    "fechaAceptado" => "2019-11-12"
    "PalabrasClave" => array:1 [
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras&#8208;chave"
          "identificador" => "xpalclavsec1245560"
          "palabras" => array:5 [
            0 => "Autoimunidade"
            1 => "DNA mitocondrial"
            2 => "Esclerodermia sist&#234;mica"
            3 => "Estresse oxidativo"
            4 => "Rea&#231;&#227;o em cadeia da polimerase em tempo real"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Embora n&#227;o totalmente compreendido&#44; o estresse oxidativo tem sido associado &#224; patog&#234;nese de diferentes doen&#231;as autoimunes&#44; como a esclerose sist&#234;mica&#46; A evid&#234;ncia acumulada indica que o estresse oxidativo pode induzir danos no DNA mitocondrial &#40;mtDNA&#41; e varia&#231;&#245;es no n&#250;mero de c&#243;pias do mtDNA &#40;mtDNAcn&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Explorar o mtDNAcn e subprodutos de danos oxidativos ao DNA no sangue perif&#233;rico de pacientes com esclerose sist&#234;mica e em controles saud&#225;veis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">O estudo incluiu 46 pacientes com esclerose sist&#234;mica e 49 indiv&#237;duos saud&#225;veis&#46; PCR quantitativa em tempo real foi usada para mensurar o mtDNAcn relativo e o dano oxidativo &#40;purinas oxidadas&#41; de cada amostra&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">O mtDNAcn m&#233;dio foi menor em pacientes com esclerose sist&#234;mica do que nos controles&#44; enquanto o grau de dano ao mtDNA foi significativamente maior nos doentes em compara&#231;&#227;o com os controles&#46; Al&#233;m disso&#44; observou&#8208;se correla&#231;&#227;o negativa entre o mtDNAcn e o dano oxidativo ao DNA&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A falta de an&#225;lise e quantifica&#231;&#227;o simult&#226;nea de marcadores de dano oxidativo ao DNA no soro ou na urina de pacientes com esclerose sist&#234;mica e em controles saud&#225;veis&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Esses dados sugerem que a altera&#231;&#227;o no mtDNAcn e o aumento do dano oxidativo ao DNA podem estar envolvidos na patog&#234;nese da esclerose sist&#234;mica&#46;</p></span>"
        "secciones" => array:6 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Fundamentos"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objetivo"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "M&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Limita&#231;&#245;es do estudo"
          ]
          5 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Conclus&#227;o"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Como citar este artigo&#58; Movassaghi S&#44; Jafari S&#44; Falahati K&#44; Ataei M&#44; Sanati MH&#44; Jadali Z&#46; Quantification of mitochondrial DNA damage and copy number in circulating blood of patients with systemic sclerosis by a qPCR&#8208;based assay&#46; An Bras Dermatol&#46; 2020&#59;95&#58;314&#8211;9&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Trabalho realizado no Tehran University of Medical Sciences&#44; Teer&#227;&#44; Ir&#227;&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 868
            "Ancho" => 1667
            "Tamanyo" => 66452
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">N&#250;mero m&#233;dio de c&#243;pias mitocondriais no sangue perif&#233;rico de pacientes com esclerose sist&#234;mica e indiv&#237;duos saud&#225;veis&#46; O n&#250;mero de c&#243;pias do DNAmt foi quantificado com o delta Ct &#40;Ct&#41; da Ct m&#233;dia do DNAmt e o DNA nuclear &#40;Ct<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>CtmtDNA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Ctactin&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 935
            "Ancho" => 1652
            "Tamanyo" => 62126
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Aumento do dano ao DNAmt em pacientes com esclerose sist&#234;mica em compara&#231;&#227;o aos controles normais&#46; O Ct &#233; a diferen&#231;a entre o valor de Ct da amostra de DNA tratada com FPG e o valor de Ct da amostra de DNA sem tratamento com FPG&#46; Observe que um valor mais alto de Ct corresponde a n&#237;veis comparativamente mais altos desses danos oxidativos&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabela 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Caracter&#237;sticas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pacientes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N&#250;mero</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade &#40;anos&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#44;09&#177;12&#44;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#44;90&#177;12&#44;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dura&#231;&#227;o da doen&#231;a &#40;anos&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;61&#177;6&#44;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo &#40;Feminino&#47;Masculino&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IcSSc&#47;dcSSc&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;13&#44;04&#37;&#41;&#47;40 &#40;86&#44;96&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">&#211;rg&#227;os afetados</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pulm&#227;o &#40;DPI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cora&#231;&#227;o &#40;HAP&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rim &#40;Hist&#243;rico de crise renal&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gastrointestinal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Articula&#231;&#245;es&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2326229.png"
              ]
            ]
            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tratamento</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tipo de doen&#231;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#250;mero de pacientes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Esclerose sist&#234;mica cut&#226;nea limitada</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Metotrexato&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Azatioprina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Micofenolato&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Esclerose sist&#234;mica difusa</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Metotrexato&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Azatioprina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Micofenolato&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisolona&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Azatioprina<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolona&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nenhum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2326230.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas de pacientes com esclerose sist&#234;mica e controles saud&#225;veis</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:35 [
            0 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and epidemiological differences between men and women with systemic sclerosis&#58; a study in a Spanish systemic sclerosis cohort and literature review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Freire"
                            1 => "A&#46; Rivera"
                            2 => "B&#46; Sope&#241;a"
                            3 => "C&#46; Tolosa Vilella"
                            4 => "A&#46; Guill&#233;n-Del Castillo"
                            5 => "D&#46; Colunga Arg&#252;elles"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Rheumatol&#46;"
                        "fecha" => "2017"
                        "volumen" => "35"
                        "paginaInicial" => "89"
                        "paginaFinal" => "97"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28980905"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "One year in review 2017&#58; systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Barsotti"
                            1 => "C&#46; Bruni"
                            2 => "M&#46; Orlandi"
                            3 => "A&#46; Della Rossa"
                            4 => "E&#46; Marasco"
                            5 => "V&#46; Codullo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Exp Rheumatol&#46;"
                        "fecha" => "2017"
                        "volumen" => "35"
                        "numero" => "Suppl 106"
                        "paginaInicial" => "3"
                        "paginaFinal" => "20"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29035173"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epigenetics&#58; The Future Direction in Systemic Sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Walczyk"
                            1 => "A&#46; Paradowska-Gorycka"
                            2 => "M&#46; Olesinska"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/sji.12595"
                      "Revista" => array:6 [
                        "tituloSerie" => "Scand J Immunol&#46;"
                        "fecha" => "2017"
                        "volumen" => "86"
                        "paginaInicial" => "427"
                        "paginaFinal" => "435"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28930377"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative damage and antioxidative therapy in systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46; Grygiel-G&#243;rniak"
                            1 => "M&#46; Puszczewicz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2014/389582"
                      "Revista" => array:5 [
                        "tituloSerie" => "Mediators Inflamm&#46;"
                        "fecha" => "2014"
                        "volumen" => "2014"
                        "paginaInicial" => "389582"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25313270"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative stress in the pathogenesis of systemic scleroderma&#58; An overview"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Vona"
                            1 => "A&#46; Giovannetti"
                            2 => "L&#46; Gambardella"
                            3 => "W&#46; Malorni"
                            4 => "D&#46; Pietraforte"
                            5 => "E&#46; Straface"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jcmm.13630"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cell Mol Med&#46;"
                        "fecha" => "2018"
                        "volumen" => "22"
                        "paginaInicial" => "3308"
                        "paginaFinal" => "3314"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29664231"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mitochondrial Nucleoid&#58; Shield and Switch of the Mitochondrial Genome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;R&#46; Lee"
                            1 => "J&#46; Han"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2017/8060949"
                      "Revista" => array:5 [
                        "tituloSerie" => "Oxid Med Cell Longev&#46;"
                        "fecha" => "2017"
                        "volumen" => "2017"
                        "paginaInicial" => "8060949"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28680532"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The maintenance of mitochondrial DNA integrity &#8211; critical analysis and update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Alexeyev"
                            1 => "I&#46; Shokolenko"
                            2 => "G&#46; Wilson"
                            3 => "S&#46; LeDoux"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cold Spring Harb Perspect Biol&#46;"
                        "fecha" => "2013"
                        "volumen" => "5"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Physical association of the 2&#44;6&#8208;diamino&#8208;4&#8208;hydroxy&#8208;5N&#8208;formamidopyrimidine&#8208;DNA glycosylase of Escherichia coli and an activity nicking DNA at apurinic&#47;apyrimidinic sites"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46;R&#46; O&#8217;Connor"
                            1 => "J&#46; Laval"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.86.14.5222"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci U S A&#46;"
                        "fecha" => "1989"
                        "volumen" => "86"
                        "paginaInicial" => "5222"
                        "paginaFinal" => "5226"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2664776"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biological consequences of free radical&#8208;damaged DNA bases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46;S&#46; Wallace"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0891-5849(02)00827-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Free Radic Biol Med&#46;"
                        "fecha" => "2002"
                        "volumen" => "33"
                        "paginaInicial" => "1"
                        "paginaFinal" => "14"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12086677"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2013 classification criteria for systemic sclerosis&#58; an American college of rheumatology&#47;European league against rheumatism collaborative initiative"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; van den Hoogen"
                            1 => "D&#46; Khanna"
                            2 => "J&#46; Fransen"
                            3 => "S&#46;R&#46; Johnson"
                            4 => "M&#46; Baron"
                            5 => "A&#46; Tyndall"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Rheum Dis&#46;"
                        "fecha" => "2013"
                        "volumen" => "72"
                        "paginaInicial" => "1747"
                        "paginaFinal" => "1755"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnostic criteria of systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Hudson"
                            1 => "M&#46;J&#46; Fritzler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaut.2020.102419"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Autoimmun&#46;"
                        "fecha" => "2014"
                        "volumen" => "48&#8211;49"
                        "paginaInicial" => "38"
                        "paginaFinal" => "41"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32035747"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased levels of mitochondrial DNA copy number in patients with vitiligo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H&#46; Vaseghi"
                            1 => "M&#46; Houshmand"
                            2 => "Z&#46; Jadali"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/ced.13185"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Dermatol&#46;"
                        "fecha" => "2017"
                        "volumen" => "42"
                        "paginaInicial" => "749"
                        "paginaFinal" => "754"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28866865"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current perspectives on the immunopathogenesis of systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46; Fuschiotti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2147/ITT.S82037"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunotargets Ther&#46;"
                        "fecha" => "2016"
                        "volumen" => "5"
                        "paginaInicial" => "21"
                        "paginaFinal" => "35"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27529059"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High reactive oxygen species in fibrotic and nonfibrotic skin of patients with diffuse cutaneous systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Bourji"
                            1 => "A&#46; Meyer"
                            2 => "E&#46; Chatelus"
                            3 => "J&#46; Pincemail"
                            4 => "E&#46; Pigatto"
                            5 => "J&#46;O&#46; Defraigne"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.freeradbiomed.2015.07.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Free Radic Biol Med&#46;"
                        "fecha" => "2015"
                        "volumen" => "87"
                        "paginaInicial" => "282"
                        "paginaFinal" => "289"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26143738"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intracellular free radical production by peripheral blood T lymphocytes from patients with systemic sclerosis&#58; role of NADPH oxidase and ERK1&#47;2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Amico"
                            1 => "T&#46; Spadoni"
                            2 => "M&#46; Rovinelli"
                            3 => "M&#46; Serafini"
                            4 => "G&#46; D&#8217;Amico"
                            5 => "N&#46; Campelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13075-015-0591-8"
                      "Revista" => array:5 [
                        "tituloSerie" => "Arthritis Res Ther&#46;"
                        "fecha" => "2015"
                        "volumen" => "17"
                        "paginaInicial" => "68"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25889655"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mitochondrial Dysfunction and Redox Imbalance as a Diagnostic Marker of &#8220;Free Radical Diseases&#8221;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E&#46; Georgieva"
                            1 => "D&#46; Ivanova"
                            2 => "Z&#46; Zhelev"
                            3 => "R&#46; Bakalova"
                            4 => "M&#46; Gulubova"
                            5 => "I&#46; Aoki"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.21873/anticanres.11963"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anticancer Res&#46;"
                        "fecha" => "2017"
                        "volumen" => "37"
                        "paginaInicial" => "5373"
                        "paginaFinal" => "5381"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28982845"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Activation of apoptosis signalling pathways by reactive oxygen species"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Redza-Dutordoir"
                            1 => "D&#46;A&#46; Averill-Bates"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbamcr.2016.09.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochim Biophys Acta&#46;"
                        "fecha" => "2016"
                        "volumen" => "1863"
                        "paginaInicial" => "2977"
                        "paginaFinal" => "2992"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27646922"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High mitochondrial DNA copy number was associated with an increased gastric cancer risk in a Chinese population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "X&#46; Zhu"
                            1 => "Y&#46; Mao"
                            2 => "T&#46; Huang"
                            3 => "C&#46; Yan"
                            4 => "F&#46; Yu"
                            5 => "J&#46; Du"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/mc.22703"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Carcinog&#46;"
                        "fecha" => "2017"
                        "volumen" => "56"
                        "paginaInicial" => "2593"
                        "paginaFinal" => "2600"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28688194"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatocyte giant mitochondria&#58; an almost constant lesion in systemic scleroderma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Feldmann"
                            1 => "M&#46; Maurice"
                            2 => "J&#46;M&#46; Husson"
                            3 => "J&#46;N&#46; Fiessinger"
                            4 => "J&#46;P&#46; Camilleri"
                            5 => "J&#46;P&#46; Benhamou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/BF00427116"
                      "Revista" => array:6 [
                        "tituloSerie" => "Virchows Arch A Pathol Anat Histol&#46;"
                        "fecha" => "1977"
                        "volumen" => "374"
                        "paginaInicial" => "215"
                        "paginaFinal" => "227"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/142348"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Precipitating autoantibodies to mitochondrial proteins in progressive systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46;C&#46; Gupta"
                            1 => "J&#46;R&#46; Seibold"
                            2 => "M&#46;R&#46; Krishnan"
                            3 => "J&#46;C&#46; Steigerwald"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Immunol&#46;"
                        "fecha" => "1984"
                        "volumen" => "58"
                        "paginaInicial" => "68"
                        "paginaFinal" => "76"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6434213"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detection of anti&#8208;mitochondrial antibodies by immunoprecipitation in patients with systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Ceribelli"
                            1 => "N&#46; Isailovic"
                            2 => "M&#46; De Santis"
                            3 => "E&#46; Generali"
                            4 => "M&#46; Satoh"
                            5 => "C&#46; Selmi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jim.2017.10.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol Methods&#46;"
                        "fecha" => "2018"
                        "volumen" => "452"
                        "paginaInicial" => "1"
                        "paginaFinal" => "5"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28986201"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The pyruvate dehydrogenase complexes&#58; structure&#8208;based function and regulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;S&#46; Patel"
                            1 => "N&#46;S&#46; Nemeria"
                            2 => "W&#46; Furey"
                            3 => "F&#46; Jordan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.R114.563148"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem&#46;"
                        "fecha" => "2014"
                        "volumen" => "289"
                        "paginaInicial" => "16615"
                        "paginaFinal" => "16623"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24798336"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Importance of Autoantibody Detection in Primary Biliary Cirrhosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46;L&#46;R&#46; Cancado"
                            1 => "M&#46; Harriz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fimmu.2015.00309"
                      "Revista" => array:5 [
                        "tituloSerie" => "Front Immunol&#46;"
                        "fecha" => "2015"
                        "volumen" => "6"
                        "paginaInicial" => "309"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26157439"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High prevalence of primary biliary cirrhosis and disease&#8208;associated autoantibodies in Japanese patients with systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Imura-Kumada"
                            1 => "M&#46; Hasegawa"
                            2 => "T&#46; Matsushita"
                            3 => "Y&#46; Hamaguchi"
                            4 => "S&#46; Encabo"
                            5 => "Z&#46; Shums"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10165-012-0607-z"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mod Rheumatol&#46;"
                        "fecha" => "2012"
                        "volumen" => "22"
                        "paginaInicial" => "892"
                        "paginaFinal" => "898"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22327744"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The concept of early systemic sclerosis following 2013 ACR&#47;EULAR criteria for the classification of systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "G&#46; Valentini"
                            1 => "A&#46; Marcoccia"
                            2 => "G&#46; Cuomo"
                            3 => "M&#46; Iudici"
                            4 => "S&#46; Vettori"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2174/1573397110666140404001756"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Rheumatol Rev&#46;"
                        "fecha" => "2014"
                        "volumen" => "10"
                        "paginaInicial" => "38"
                        "paginaFinal" => "44"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24720644"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Presence of organ specific antibodies in patients with systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Wielosz"
                            1 => "M&#46; Majdan"
                            2 => "A&#46; Koszarny"
                            3 => "M&#46; Dryglewska"
                            4 => "J&#46; Tabarkiewicz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.20452/pamw.3583"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pol Arch Med Wewn&#46;"
                        "fecha" => "2016"
                        "volumen" => "126"
                        "paginaInicial" => "862"
                        "paginaFinal" => "869"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27906879"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Primary biliary cirrhosis&#8208;related autoantibodies in a large cohort of italian patients with systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Cavazzana"
                            1 => "A&#46; Ceribelli"
                            2 => "M&#46; Taraborelli"
                            3 => "M&#46; Fredi"
                            4 => "G&#46; Norman"
                            5 => "A&#46; Tincani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3899/jrheum.110167"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol&#46;"
                        "fecha" => "2011"
                        "volumen" => "38"
                        "paginaInicial" => "2180"
                        "paginaFinal" => "2185"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21921093"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional&#44; clinical and radiological signs of lung fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Fietta"
                            1 => "A&#46; Bardoni"
                            2 => "R&#46; Salvini"
                            3 => "I&#46; Passadore"
                            4 => "M&#46; Morosini"
                            5 => "L&#46; Cavagna"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/ar2067"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Res Ther&#46;"
                        "fecha" => "2006"
                        "volumen" => "8"
                        "paginaInicial" => "R160"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17044913"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1529943012009977"
                          "estado" => "S300"
                          "issn" => "15299430"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mitochondrial topoisomerase I sites in the regulatory D&#8208;loop region of mitochondrial DNA"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46; Zhang"
                            1 => "Y&#46; Pommier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1021/bi800774b"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochemistry&#46;"
                        "fecha" => "2008"
                        "volumen" => "47"
                        "paginaInicial" => "11196"
                        "paginaFinal" => "11203"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18826252"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glutathione S&#8208;transferase P1 &#40;GSTP1&#41; polymorphism in patients with chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Ishii"
                            1 => "T&#46; Matsuse"
                            2 => "S&#46; Teramoto"
                            3 => "H&#46; Matsui"
                            4 => "M&#46; Miyao"
                            5 => "T&#46; Hosoi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.54.8.693"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax&#46;"
                        "fecha" => "1999"
                        "volumen" => "54"
                        "paginaInicial" => "693"
                        "paginaFinal" => "696"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10413721"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The pathophysiological role of mitochondrial oxidative stress in lung diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "X&#46; Liu"
                            1 => "Z&#46; Chen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12967-017-1306-5"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Transl Med&#46;"
                        "fecha" => "2017"
                        "volumen" => "15"
                        "paginaInicial" => "207"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29029603"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recent aspects of oxidative DNA damage&#58; guanine lesions&#44; measurement and substrate specificity of DNA repair glycosylases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Cadet"
                            1 => "S&#46; Bellon"
                            2 => "M&#46; Berger"
                            3 => "A&#46;G&#46; Bourdat"
                            4 => "T&#46; Douki"
                            5 => "V&#46; Duarte"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1515/BC.2002.100"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Chem&#46;"
                        "fecha" => "2002"
                        "volumen" => "383"
                        "paginaInicial" => "933"
                        "paginaFinal" => "943"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12222683"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Platelet&#8208;derived growth factor and Reactive Oxygen Species &#40;ROS&#41; regulate Ras protein levels in primary human fibroblasts via ERK1&#47;2 Amplification of ROS and Ras in systemic sclerosis fibroblasts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Svegliati"
                            1 => "R&#46; Cancello"
                            2 => "P&#46; Sambo"
                            3 => "M&#46; Luchetti"
                            4 => "P&#46; Paroncini"
                            5 => "G&#46; Orlandini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.M502851200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem&#46;"
                        "fecha" => "2005"
                        "volumen" => "280"
                        "paginaInicial" => "36474"
                        "paginaFinal" => "36482"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16081426"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative DNA damage induces the ATM&#8208;mediated transcriptional suppression of the Wnt inhibitor WIF&#8208;1 in systemic sclerosis and fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Svegliati"
                            1 => "G&#46; Marrone"
                            2 => "A&#46; Pezone"
                            3 => "T&#46; Spadoni"
                            4 => "A&#46; Grieco"
                            5 => "G&#46; Moroncini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/scisignal.2005633"
                      "Revista" => array:4 [
                        "tituloSerie" => "Sci Signal&#46;"
                        "fecha" => "2014"
                        "volumen" => "7"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25351248"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Scleroderma &#8211; pathophysiology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "T&#46; Yamamoto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1684/ejd.2008.0570"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Dermatol&#46;"
                        "fecha" => "2009"
                        "volumen" => "19"
                        "paginaInicial" => "14"
                        "paginaFinal" => "24"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19059831"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "pt"
  "url" => "/26662752/0000009500000003/v1_202006250813/S2666275220301521/v1_202006250813/pt/main.assets"
  "Apartado" => array:4 [
    "identificador" => "81728"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Investiga&#231;&#227;o"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/26662752/0000009500000003/v1_202006250813/S2666275220301521/v1_202006250813/pt/main.pdf?idApp=UINPBA00008Z&text.app=https://clinics.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275220301521?idApp=UINPBA00008Z"
]
Share
Journal Information

Statistics

Follow this link to access the full text of the article

Investigação
Quantificação do dano ao DNA mitocondrial e número de cópias no sangue circulante de pacientes com esclerose sistêmica em um ensaio baseado em qPCR
Shafieh Movassaghia, Sara Jafaria, Kowsar Falahatib, Mitra Ataeib, Mohammad Hossein Sanatib, Zohreh Jadalic,
Corresponding author
zjadali@yahoo.co.uk

Autor para correspondência.
a Departamento de Reumatologia, Hospital Imam Khomeini, Tehran University of Medical Sciences, Teerã, Irã
b Departamento de Genética Clínica, National Institute of Genetic Engineering and Biotechnology, Teerã, Irã
c Faculdade de Saúde Pública, Tehran University of Medical Sciences, Teerã, Irã
Read
7151
Times
was read the article
3133
Total PDF
4018
Total HTML
Share statistics
 array:24 [
  "pii" => "S2666275220301521"
  "issn" => "26662752"
  "doi" => "10.1016/j.abdp.2019.11.002"
  "estado" => "S300"
  "fechaPublicacion" => "2020-05-01"
  "aid" => "171"
  "copyright" => "Sociedade Brasileira de Dermatologia"
  "copyrightAnyo" => "2020"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by/4.0/"
  "subdocumento" => "fla"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "en" => array:19 [
      "pii" => "S0365059620300829"
      "issn" => "03650596"
      "doi" => "10.1016/j.abd.2019.11.003"
      "estado" => "S300"
      "fechaPublicacion" => "2020-05-01"
      "aid" => "171"
      "copyright" => "Sociedade Brasileira de Dermatologia"
      "documento" => "article"
      "crossmark" => 1
      "licencia" => "http://creativecommons.org/licenses/by/4.0/"
      "subdocumento" => "fla"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:1 [
        "total" => 0
      ]
      "en" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Investigation</span>"
        "titulo" => "Quantification of mitochondrial DNA damage and copy number in circulating blood of patients with systemic sclerosis by a qPCR-based assay"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "tieneResumen" => "en"
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "314"
            "paginaFinal" => "319"
          ]
        ]
        "contieneResumen" => array:1 [
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "en" => true
        ]
        "contienePdf" => array:1 [
          "en" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0010"
            "etiqueta" => "Figure 2"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr2.jpeg"
                "Alto" => 934
                "Ancho" => 1651
                "Tamanyo" => 61673
              ]
            ]
            "descripcion" => array:1 [
              "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Increased mtDNA damage in patients with systemic sclerosis as compared to normal controls&#46; The &#916;Ct is the difference between Ct value from DNA sample treated with FPG and Ct value from DNA sample without FPG treatment&#46; Please note that a higher &#916;Ct value corresponds to a comparably higher levels of oxidative these damage&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Shafieh Movassaghi, Sara Jafari, Kowsar Falahati, Mitra Ataei, Mohammad Hossein Sanati, Zohreh Jadali"
            "autores" => array:6 [
              0 => array:2 [
                "nombre" => "Shafieh"
                "apellidos" => "Movassaghi"
              ]
              1 => array:2 [
                "nombre" => "Sara"
                "apellidos" => "Jafari"
              ]
              2 => array:2 [
                "nombre" => "Kowsar"
                "apellidos" => "Falahati"
              ]
              3 => array:2 [
                "nombre" => "Mitra"
                "apellidos" => "Ataei"
              ]
              4 => array:2 [
                "nombre" => "Mohammad Hossein"
                "apellidos" => "Sanati"
              ]
              5 => array:2 [
                "nombre" => "Zohreh"
                "apellidos" => "Jadali"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "pt" => array:9 [
          "pii" => "S2666275220301521"
          "doi" => "10.1016/j.abdp.2019.11.002"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "pt"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275220301521?idApp=UINPBA00008Z"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059620300829?idApp=UINPBA00008Z"
      "url" => "/03650596/0000009500000003/v4_202007210853/S0365059620300829/v4_202007210853/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2666275220301624"
    "issn" => "26662752"
    "doi" => "10.1016/j.abdp.2019.11.006"
    "estado" => "S300"
    "fechaPublicacion" => "2020-05-01"
    "aid" => "180"
    "copyright" => "Sociedade Brasileira de Dermatologia"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "fla"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "pt" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Investiga&#231;&#227;o</span>"
      "titulo" => "Um ensaio cl&#237;nico hemicorporal&#44; randomizado&#44; duplo&#8208;cego&#44; controlado&#44; sobre os efeitos de um hidratante com pH modificado <span class="elsevierStyleItalic">vs</span>&#46; hidratante convencional na dermatite at&#243;pica leve a moderada"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "tieneResumen" => "pt"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "320"
          "paginaFinal" => "325"
        ]
      ]
      "contieneResumen" => array:1 [
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Siew Wen Goh, Adawiyah Jamil, Nazarudin Safian, Norazirah Md Nor, Norliza Muhammad, Nur Liyana Saharudin"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Siew Wen"
              "apellidos" => "Goh"
            ]
            1 => array:2 [
              "nombre" => "Adawiyah"
              "apellidos" => "Jamil"
            ]
            2 => array:2 [
              "nombre" => "Nazarudin"
              "apellidos" => "Safian"
            ]
            3 => array:2 [
              "nombre" => "Norazirah"
              "apellidos" => "Md Nor"
            ]
            4 => array:2 [
              "nombre" => "Norliza"
              "apellidos" => "Muhammad"
            ]
            5 => array:2 [
              "nombre" => "Nur Liyana"
              "apellidos" => "Saharudin"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S036505962030091X"
        "doi" => "10.1016/j.abd.2019.11.007"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S036505962030091X?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275220301624?idApp=UINPBA00008Z"
    "url" => "/26662752/0000009500000003/v1_202006250813/S2666275220301624/v1_202006250813/pt/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2666275220301582"
    "issn" => "26662752"
    "doi" => "10.1016/j.abdp.2019.11.004"
    "estado" => "S300"
    "fechaPublicacion" => "2020-05-01"
    "aid" => "176"
    "copyright" => "Sociedade Brasileira de Dermatologia"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by/4.0/"
    "subdocumento" => "fla"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "pt" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Investiga&#231;&#227;o</span>"
      "titulo" => "Diferentes padr&#245;es de distribui&#231;&#227;o das c&#233;lulas dendr&#237;ticas plasmocitoides no l&#250;pus eritematoso discoide e no l&#237;quen plano pilar demonstrados pela imunomarca&#231;&#227;o com CD123"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => "pt"
      "tieneResumen" => "pt"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "307"
          "paginaFinal" => "313"
        ]
      ]
      "contieneResumen" => array:1 [
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "pt" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0015"
          "etiqueta" => "Figura 3"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr3.jpeg"
              "Alto" => 1256
              "Ancho" => 2108
              "Tamanyo" => 151166
            ]
          ]
          "descripcion" => array:1 [
            "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Padr&#245;es de distribui&#231;&#227;o de c&#233;lulas dendr&#237;ticas plasmocitoides &#40;CPD&#41; no l&#237;quen plano pilar &#40;LPP&#41; e l&#250;pus eritematoso discoide &#40;LED&#41;&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Azadeh Rakhshan, Parviz Toossi, Maliheh Amani, Sahar Dadkhahfar, Arash Bagheri Hamidi"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "Azadeh"
              "apellidos" => "Rakhshan"
            ]
            1 => array:2 [
              "nombre" => "Parviz"
              "apellidos" => "Toossi"
            ]
            2 => array:2 [
              "nombre" => "Maliheh"
              "apellidos" => "Amani"
            ]
            3 => array:2 [
              "nombre" => "Sahar"
              "apellidos" => "Dadkhahfar"
            ]
            4 => array:2 [
              "nombre" => "Arash Bagheri"
              "apellidos" => "Hamidi"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0365059620300878"
        "doi" => "10.1016/j.abd.2019.11.005"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059620300878?idApp=UINPBA00008Z"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275220301582?idApp=UINPBA00008Z"
    "url" => "/26662752/0000009500000003/v1_202006250813/S2666275220301582/v1_202006250813/pt/main.assets"
  ]
  "pt" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Investiga&#231;&#227;o</span>"
    "titulo" => "Quantifica&#231;&#227;o do dano ao DNA mitocondrial e n&#250;mero de c&#243;pias no sangue circulante de pacientes com esclerose sist&#234;mica em um ensaio baseado em qPCR"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "314"
        "paginaFinal" => "319"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Shafieh Movassaghi, Sara Jafari, Kowsar Falahati, Mitra Ataei, Mohammad Hossein Sanati, Zohreh Jadali"
        "autores" => array:6 [
          0 => array:3 [
            "nombre" => "Shafieh"
            "apellidos" => "Movassaghi"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Sara"
            "apellidos" => "Jafari"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Kowsar"
            "apellidos" => "Falahati"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Mitra"
            "apellidos" => "Ataei"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Mohammad Hossein"
            "apellidos" => "Sanati"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          5 => array:4 [
            "nombre" => "Zohreh"
            "apellidos" => "Jadali"
            "email" => array:1 [
              0 => "zjadali@yahoo.co.uk"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Departamento de Reumatologia&#44; Hospital Imam Khomeini&#44; Tehran University of Medical Sciences&#44; Teer&#227;&#44; Ir&#227;"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Departamento de Gen&#233;tica Cl&#237;nica&#44; National Institute of Genetic Engineering and Biotechnology&#44; Teer&#227;&#44; Ir&#227;"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Faculdade de Sa&#250;de P&#250;blica&#44; Tehran University of Medical Sciences&#44; Teer&#227;&#44; Ir&#227;"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Autor para correspond&#234;ncia&#46;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 868
            "Ancho" => 1667
            "Tamanyo" => 66452
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">N&#250;mero m&#233;dio de c&#243;pias mitocondriais no sangue perif&#233;rico de pacientes com esclerose sist&#234;mica e indiv&#237;duos saud&#225;veis&#46; O n&#250;mero de c&#243;pias do DNAmt foi quantificado com o delta Ct &#40;Ct&#41; da Ct m&#233;dia do DNAmt e o DNA nuclear &#40;Ct<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>CtmtDNA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Ctactin&#41;&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A esclerose sist&#234;mica &#40;ES&#41; &#233; doen&#231;a cr&#244;nica rara do tecido conjuntivo caracterizada por vasculopatia e fibrose na pele e em v&#225;rios &#243;rg&#227;os internos&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">1&#44;2</span></a> Sua causa exata &#233; desconhecida&#44; mas sua ocorr&#234;ncia pode ser influenciada por uma intera&#231;&#227;o complexa de fatores gen&#233;ticos&#44; epigen&#233;ticos e ambientais&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">3</span></a> Recentemente&#44; grande aten&#231;&#227;o tem sido dedicada ao papel do estresse oxidativo na patog&#234;nese da ES&#46; Acredita&#8208;se que ele esteja envolvido nos processos fisiopatol&#243;gicos de aumento da s&#237;ntese e ac&#250;mulo de matriz extracelular&#44; ativa&#231;&#227;o imune anormal e dano endotelial vascular&#44; as tr&#234;s principais caracter&#237;sticas da ES&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">O aumento do estresse oxidativo reflete um desequil&#237;brio entre a homeostase pr&#243;&#8208;oxidante&#47;antioxidante e leva a n&#237;veis aumentados de esp&#233;cies reativas de oxig&#234;nio &#40;ERO&#41; t&#243;xicas&#46; Existem duas vias principais de gera&#231;&#227;o de ERO&#58; end&#243;gena e ex&#243;gena&#46; As mitoc&#244;ndrias s&#227;o a principal fonte end&#243;gena de ERO&#46; Elas t&#234;m seu pr&#243;prio genoma &#40;DNA mitocondrial &#91;mtDNA&#93;&#41; e s&#227;o organelas indispens&#225;veis para a fisiologia celular normal&#46; O mtDNA &#233; multic&#243;pias e sua abund&#226;ncia &#233; regulada de forma espec&#237;fica em cada tipo de tecido&#46; O mtDNAcn flutua em resposta ao ambiente fisiol&#243;gico ao redor da c&#233;lula&#59; em condi&#231;&#245;es fisiol&#243;gicas&#44; permanece relativamente est&#225;vel dentro das c&#233;lulas&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a> Em circunst&#226;ncias patol&#243;gicas&#44; o mtDNAcn pode variar&#44; depende de diferentes fatores&#44; inclusive o equil&#237;brio redox celular alterado&#46; O mtDNA tamb&#233;m &#233; propenso a danos por estresse oxidativo devido &#224; sua alta exposi&#231;&#227;o aos EROs produzidos pelas mitoc&#244;ndrias&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Os produtos de oxida&#231;&#227;o da guanina s&#227;o importantes indicadores de dano oxidativo ao DNA&#46; Esses marcadores qu&#237;micos podem ser removidos por Fpg &#40;DNA&#8208;formamidopirimidina glicosilase&#41;&#44; uma enzima de reparo por excis&#227;o de base que libera les&#245;es de purina&#44; tanto do DNA nuclear quanto do mtDNA&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">7&#44;8</span></a> A clivagem por Fpg do DNA oxidativamente danificado pode reduzir a amplifica&#231;&#227;o do DNA alvo digerido pela enzima Taq DNA polimerase&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a> Portanto&#44; esse m&#233;todo tem sido amplamente usado como uma medida de dano oxidativo ao DNA&#46; Os objetivos do presente estudo foram determinar se a varia&#231;&#227;o do mtDNAcn e seu &#237;ndice de dano oxidativo &#40;mtDNA &#91;&#916;CT&#93;&#41; podem ser detectados em pacientes com ES&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">O estudo foi aprovado pelo Comit&#234; de &#201;tica da Universidade de Ci&#234;ncias M&#233;dicas e foi feito de acordo com os princ&#237;pios de &#233;tica da Declara&#231;&#227;o de Helsinque&#46; Todos os participantes concordaram voluntariamente em participar do estudo e assinaram o termo de consentimento livre e esclarecido&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Popula&#231;&#227;o do estudo</span><p id="par0025" class="elsevierStylePara elsevierViewall">O estudo incluiu 46 pacientes com ES e 49 indiv&#237;duos saud&#225;veis pareados por idade e sexo&#44; sem hist&#243;rico de esclerodermia ou outras doen&#231;as cr&#244;nicas e autoimunes&#46; Os pacientes com ES foram diagnosticados de acordo com os crit&#233;rios do Col&#233;gio Americano de Reumatologia &#40;ACR&#41;&#47;Liga Europeia Contra Reumatismo &#40;EULAR&#41; de 2013&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">10&#44;11</span></a> Entre os pacientes inclu&#237;dos&#44; seis &#40;13&#44;04&#37;&#41; apresentavam forma limitada de ES e 40 &#40;86&#44;96&#37;&#41; ES difusa&#46; Doze &#40;26&#44;09&#37;&#41; apresentavam doen&#231;a pulmonar intersticial &#40;DPI&#41;&#44; tr&#234;s &#40;6&#44;52&#37;&#41; hipertens&#227;o arterial pulmonar &#40;HAP&#41; e tr&#234;s &#40;6&#44;52&#37;&#41; DPI e HAP&#46; A idade m&#233;dia dos pacientes com ES &#40;seis homens&#44; 40 mulheres&#41; e os controles &#40;cinco homens&#44; 44 mulheres&#41; foi de 46&#44;09 e 41&#44;90 anos&#44; respectivamente&#46; A dura&#231;&#227;o m&#233;dia da doen&#231;a foi de 7&#44;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;13 anos&#44; com varia&#231;&#227;o de um a 40 anos&#46; Trinta e oito pacientes com ES difusa e seis pacientes com ES cut&#226;nea limitada haviam recebido tratamento com esteroides e&#47;ou imunossupressores antes da amostragem&#46; A dose e a dura&#231;&#227;o do tratamento foram diferentes&#44; dependeram da gravidade das les&#245;es e dos &#243;rg&#227;os afetados&#46; Nenhum dos pacientes apresentava doen&#231;as inflamat&#243;rias&#47;autoimunes al&#233;m da ES e todos estavam inativos no momento da visita&#46; A <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a> apresenta as caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas dos pacientes com ES e controles&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Extra&#231;&#227;o de DNA</span><p id="par0030" class="elsevierStylePara elsevierViewall">As amostras de sangue foram coletadas em tubos de 5<span class="elsevierStyleHsp" style=""></span>mL com &#225;cido etileno diamino tetraac&#233;tico &#40;EDTA&#41;&#46; O DNA do sangue total foi extra&#237;do com o kit de isolamento de DNA &#40;GeneAll &#8211; Seul&#44; Coreia&#41;&#44; de acordo com as instru&#231;&#245;es do fabricante&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A concentra&#231;&#227;o e purifica&#231;&#227;o do DNA extra&#237;do foram medidas com eletroforese em gel de agarose &#40;1&#44;5&#37;&#41; e espectrofotometria com NanoDrop 2000c &#40;Thermo Fisher Scientific&#44; EUA&#41;&#46; Todas as amostras de DNA foram armazenadas a &#8208;20<span class="elsevierStyleHsp" style=""></span>&#176;C at&#233; o uso&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Prepara&#231;&#227;o do modelo de DNA</span><p id="par0040" class="elsevierStylePara elsevierViewall">Para a detec&#231;&#227;o de dano oxidativo&#44; 100 ng de DNA da amostra &#40;2<span class="elsevierStyleHsp" style=""></span>&#956;L de solu&#231;&#227;o&#8208;padr&#227;o&#41; foram incubados por 1<span class="elsevierStyleHsp" style=""></span>h a 37<span class="elsevierStyleHsp" style=""></span>&#176;C em 10<span class="elsevierStyleHsp" style=""></span>&#956;L de mistura de reagente com uma unidade de enzima FPG &#40;New England BioLabs &#8211; Massachusetts&#44; EUA&#41;&#44; 10<span class="elsevierStyleHsp" style=""></span>mM Bis Tris Propano&#8208;HCl&#44; 10<span class="elsevierStyleHsp" style=""></span>mM MgCl<span class="elsevierStyleInf">2</span>&#44; 1<span class="elsevierStyleHsp" style=""></span>mM DTT e 0&#44;1<span class="elsevierStyleHsp" style=""></span>mg&#47;mL de albumina de soro bovino&#46; Para a detec&#231;&#227;o do mtDNAcn&#44; o DNA da amostra foi preparado de maneira semelhante&#44; mas sem FPG&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Determina&#231;&#227;o quantitativa do n&#250;mero de c&#243;pias do mtDNA</span><p id="par0045" class="elsevierStylePara elsevierViewall">As rea&#231;&#245;es para o ensaio quantitativo de rea&#231;&#227;o em cadeia de polimerase em tempo real &#40;qPCR&#41; foram feitas com o kit SYBR Premix EX Taq II &#40;Takara &#8211; Jap&#227;o&#41; e com um aparelho Rotor&#8208;Gene 6000 &#40;Corbett Life Science &#8211; Austr&#225;lia&#41;&#46; A PCR foi feita em 42 ciclos&#44; com uma desnatura&#231;&#227;o inicial de 1<span class="elsevierStyleHsp" style=""></span>min a 95<span class="elsevierStyleHsp" style=""></span>&#176;C no primeiro ciclo&#46; Todos os ciclos subsequentes consistiram em desnatura&#231;&#227;o a 95<span class="elsevierStyleHsp" style=""></span>&#176;C por 4s&#44; emparelhamento a 62<span class="elsevierStyleHsp" style=""></span>&#176;C por 30s e extens&#227;o a 72<span class="elsevierStyleHsp" style=""></span>&#176;C por 15s&#44; bem como uma etapa final de extens&#227;o a 72<span class="elsevierStyleHsp" style=""></span>&#176;C por 15s&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">As rea&#231;&#245;es de PCR foram feitas em um volume total de 10<span class="elsevierStyleHsp" style=""></span>&#956;L com 1<span class="elsevierStyleHsp" style=""></span>&#956;L de DNA gen&#244;mico&#44; 0&#44;5<span class="elsevierStyleHsp" style=""></span>&#956;L de cada iniciador&#44; 5<span class="elsevierStyleHsp" style=""></span>&#956;L de SYBR Premix e 3<span class="elsevierStyleHsp" style=""></span>&#956;L de &#225;gua destilada&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Para quantifica&#231;&#227;o de mtDNA&#44; foi usado um conjunto de iniciadores direcionados &#224; subunidade NADH desidrogenase tipo 2 codificada mitocondrialmente &#40;ND2&#41;&#46; Para quantifica&#231;&#227;o nuclear de DNA&#44; um conjunto de iniciadores direcionados ao gene da &#946;&#8208;actina foi selecionado&#46; Todos os iniciadores foram comprados na Gene Fanavaran Company &#40;Teer&#227;&#44; Ir&#227;&#41; e suas sequ&#234;ncias exatas foram descritas anteriormente&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a> A propor&#231;&#227;o de mtDNA para DNA nuclear em cada amostra foi calculada como uma estimativa para o n&#250;mero de mtDNA&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Determina&#231;&#227;o quantitativa do dano ao mtDNA</span><p id="par0060" class="elsevierStylePara elsevierViewall">O conte&#250;do de produtos de oxida&#231;&#227;o de guanina foi determinado pela t&#233;cnica baseada em qPCR&#46; O n&#237;vel de dano oxidativo no DNA mitocondrial &#233; indicado por um aumento dos nucleot&#237;deos de purina oxidados&#44; inclusive 8&#8208;OHdG&#46; A digest&#227;o com FPG foi usada para a detec&#231;&#227;o de produtos do dano oxidativo no DNA&#46; Os n&#237;veis de dano oxidativo ao mtDNA foram apresentados como &#916;Ct&#44; que &#233; a diferen&#231;a entre os valores do ciclo limiar &#40;Ct&#41; entre as amostras tratadas com enzima e as n&#227;o tratadas com enzima &#40;Ct&#8208;T e Ct&#8208;N&#44; respectivamente&#41;&#46; Valores mais elevados de &#916;Ct indicam n&#237;veis mais altos de estresse oxidativo nas mitoc&#244;ndrias&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lise estat&#237;stica</span><p id="par0065" class="elsevierStylePara elsevierViewall">Os dados distribu&#237;dos normalmente e n&#227;o normalmente foram analisados pelo teste <span class="elsevierStyleItalic">t</span> para amostras independentes e pelo teste U de Mann&#8208;Whitney&#44; respectivamente&#46; Os n&#237;veis de depend&#234;ncia linear entre duas vari&#225;veis foram calculados pelo coeficiente de correla&#231;&#227;o de Pearson&#46; Esse teste &#233; adequado para vari&#225;veis cont&#237;nuas normais&#59; valores&#8208;p inferiores a 0&#44;05 foram considerados estatisticamente significativos&#46; Os resultados experimentais foram apresentados como m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desvio&#8208;padr&#227;o&#46; O <span class="elsevierStyleItalic">software</span> SPSS &#40;v11&#46;0&#59; SPSS&#44; Inc&#46; Chicago&#44; IL&#44; EUA&#41; foi usado para as opera&#231;&#245;es estat&#237;sticas e interpreta&#231;&#227;o dos resultados do estudo&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Diminui&#231;&#227;o do mtDNAcn no sangue perif&#233;rico em pacientes com ES</span><p id="par0070" class="elsevierStylePara elsevierViewall">Como mostrado na <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a>&#44; o mtDNAcn do sangue perif&#233;rico diminuiu significativamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; no grupo de pacientes &#40;0&#44;49<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41; em compara&#231;&#227;o com o grupo controle &#40;0&#44;52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41;&#46; N&#227;o foi observada associa&#231;&#227;o entre mtDNAcn e idade&#44; sexo e dura&#231;&#227;o da doen&#231;a&#46; Al&#233;m disso&#44; n&#227;o houve diferen&#231;a significativa no mtDNAcn entre os pacientes com doen&#231;a limitada e difusa &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Aumento do dano oxidativo ao DNA em pacientes com ES</span><p id="par0075" class="elsevierStylePara elsevierViewall">Para avaliar a exist&#234;ncia de dano oxidativo&#44; a presen&#231;a de bases de purinas oxidadas &#40;principalmente 8&#8208;oxodGuo&#41;&#44; que s&#227;o locais sens&#237;veis &#224; FPG&#44; foi determinada no DNA de amostras de sangue perif&#233;rico de pacientes com ES e controles normais&#46; Os resultados indicaram &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41; que o valor m&#233;dio do dano oxidativo ao DNA em pacientes &#40;0&#44;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;40&#41; aumentou significativamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;045&#41; em compara&#231;&#227;o ao grupo controle &#40;0&#44;42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;37&#41;&#46; Al&#233;m disso&#44; n&#227;o foi observada associa&#231;&#227;o entre dano oxidativo ao DNA e idade&#44; sexo e dura&#231;&#227;o da doen&#231;a&#46; A an&#225;lise estat&#237;stica tamb&#233;m n&#227;o indicou diferen&#231;as significativas entre os pacientes com ES limitada e difusa em termos de dano oxidativo ao DNA &#40;p<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41;&#46; Curiosamente&#44; observou&#8208;se uma correla&#231;&#227;o negativa entre o mtDNAcn e o dano oxidativo ao DNA &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8208;0&#44;392&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discuss&#227;o</span><p id="par0080" class="elsevierStylePara elsevierViewall">H&#225; um consenso geral de que a ES &#233; doen&#231;a autoimune e que a complexidade de sua imunopatog&#234;nese &#233; similar &#224; de outras doen&#231;as autoimunes&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">13</span></a> Sua etiologia exata n&#227;o &#233; clara&#46; No entanto&#44; estudos recentes apontam a import&#226;ncia da influ&#234;ncia do estresse oxidativo nos processos da doen&#231;a&#46; Por exemplo&#44; Bourji et al&#46; mostraram que peles fibr&#243;ticas e n&#227;o fibr&#243;ticas de pacientes com ES apresentam n&#237;veis mais altos de ERO do que as de controles saud&#225;veis&#46; Eles tamb&#233;m observaram que pacientes com ES apresentavam n&#237;veis mais baixos de vitamina C &#40;que tem poderosa atividade antioxidante&#41; do que os controles saud&#225;veis&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a> O aumento da produ&#231;&#227;o de ERO por fibroblastos&#44; c&#233;lulas endoteliais e c&#233;lulas T&#44; os principais agentes celulares na patog&#234;nese da ES&#44; &#233; outra evid&#234;ncia que associa o estresse oxidativo aos principais eventos da doen&#231;a&#44; como fibrose e dano vascular&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Existem muitas vias distintas para a gera&#231;&#227;o de ERO&#46; As mitoc&#244;ndrias s&#227;o as principais fontes de ERO e&#44; ao mesmo tempo&#44; os principais alvos de seus efeitos desfavor&#225;veis&#46; A maior parte das ERO mitocondriais decorre da cadeia de transporte de el&#233;trons&#44; como subproduto do processo de respira&#231;&#227;o aer&#243;bica&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">16</span></a> As ERO agem como uma faca de dois gumes&#44; porque sua gera&#231;&#227;o descontrolada promove estresse oxidativo que causa les&#245;es graves em tipos b&#225;sicos de macromol&#233;culas biol&#243;gicas&#44; inclusive DNA&#44; prote&#237;nas&#44; carboidratos e lip&#237;dios&#46; Por outro lado&#44; a ERO pode participar de v&#225;rios processos biol&#243;gicos em c&#233;lulas normais&#44; inclusive vias de sinaliza&#231;&#227;o celular e respostas imunes contra pat&#243;genos ou subst&#226;ncias estranhas&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Nos &#250;ltimos anos&#44; v&#225;rios estudos examinaram o impacto da varia&#231;&#227;o quantitativa e qualitativa do mtDNAcn em doen&#231;as humanas e demonstraram altera&#231;&#245;es not&#225;veis no mtDNAcn em v&#225;rias doen&#231;as&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">12&#44;18</span></a> O mtDNAcn pode ser modificado pelo estresse oxidativo&#46; Al&#233;m disso&#44; o aumento da produ&#231;&#227;o de ERO pode causar danos oxidativos aos componentes celulares&#44; inclusive o DNA&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a> Portanto&#44; a avalia&#231;&#227;o do mtDNAcn e de seu &#237;ndice de dano oxidativo melhorar&#225; o entendimento sobre a patog&#234;nese de doen&#231;as relacionadas ao estresse oxidativo&#44; como a ES&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Os resultados do presente estudo indicaram que o valor m&#233;dio do mtDNAcn foi significativamente menor do que o observado em controles normais&#46; Tanto quanto &#233; do conhecimento dos autores&#44; este &#233; o primeiro relato que mediu as altera&#231;&#245;es do mtDNAcn no sangue perif&#233;rico de pacientes com ES&#46; Atualmente&#44; existem poucas informa&#231;&#245;es sobre a rela&#231;&#227;o entre altera&#231;&#245;es bioqu&#237;micas&#44; estruturais e funcionais nas mitoc&#244;ndrias e ES&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Um relato de Feldmann et al&#46; indicou a presen&#231;a de mitoc&#244;ndrias gigantes nos hepat&#243;citos de pacientes com esclerodermia sist&#234;mica&#46; Entretanto&#44; esses autores n&#227;o forneceram explica&#231;&#227;o sobre o&#40;s&#41; mecanismo&#40;s&#41; por tr&#225;s desse evento celular&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> Alguns pesquisadores tamb&#233;m relataram a presen&#231;a de anticorpos antimitoc&#244;ndrias &#40;AMAs&#41; nos soros de pacientes com ES&#46; Esses anticorpos s&#227;o encontrados em at&#233; 25&#37; dos pacientes<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a> e atuam contra componentes da multienzima piruvato desidrogenase complexa &#40;PDHC&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> que est&#225; localizada na matriz mitocondrial interna e produz substratos reduzidos para a cadeia de transporte de el&#233;trons&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a> Os AMAs s&#227;o considerados um marcador s&#233;rico de doen&#231;as autoimunes&#44; como a cirrose biliar prim&#225;ria &#40;CBP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">23</span></a> A motiva&#231;&#227;o cl&#237;nica por tr&#225;s da avalia&#231;&#227;o dos AMAs em pacientes com ES foi a observa&#231;&#227;o de que uma grande propor&#231;&#227;o desses pacientes apresentava uma condi&#231;&#227;o autoimune coexistente&#44; inclusive CBP&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">V&#225;rios outros autoanticorpos&#44; inclusive anticorpos anticentr&#244;mero &#40;ACA&#41;&#44; anti&#8208;topoisomerase &#40;ATA&#41; e anti&#8208;RNA polimerase III &#40;anti&#8208;RNAP&#41;&#44; foram descritos em pacientes com ES como poss&#237;veis bons biomarcadores para v&#225;rias manifesta&#231;&#245;es cl&#237;nicas e progn&#243;sticas em subconjuntos de ES&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Existem tamb&#233;m algumas evid&#234;ncias de associa&#231;&#227;o positiva entre esses anticorpos e AMA&#46; Por exemplo&#44; Wielose et al&#46; conclu&#237;ram que a preval&#234;ncia de ACAs &#233; significativamente maior em pacientes com ES que apresentam t&#237;tulos positivos de AMA do que naqueles com t&#237;tulos negativos de AMA&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a> Este estudo tamb&#233;m apontou uma forte associa&#231;&#227;o entre AMAs e ACAs em pacientes com ES cut&#226;nea limitada&#44; o que &#233; consistente com relatos anteriores&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Esses achados sugerem indiretamente que as mitoc&#244;ndrias podem estar envolvidas na ES&#44; al&#233;m de sugerir um poss&#237;vel papel para o estresse oxidativo&#46; Essa hip&#243;tese &#233; refor&#231;ada por outras observa&#231;&#245;es&#46; Por exemplo&#44; a an&#225;lise do fluido obtido na lavagem broncoalveolar &#40;LBA&#41; de pacientes com ES e fibrose pulmonar &#40;SSc<span class="elsevierStyleInf">Fib&#43;</span>&#41; indicou significativa suprarregula&#231;&#227;o da topoisomerase 1 do DNA mitocondrial &#40;mtDNA TOP1&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a> uma enzima que tem papel funcional na manuten&#231;&#227;o e na topologia do mtDNA&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">29</span></a> Al&#233;m disso&#44; foi observada infrarregula&#231;&#227;o da glutationa S&#8208;transferase P &#40;GSTP&#41; e super&#243;xido dismutase &#40;SOD&#41; no LBA de pacientes com SSc<span class="elsevierStyleInf">Fib&#43;</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a> &#201; importante mencionar que SOD e GSTP s&#227;o dois componentes do sistema de defesa antioxidante que protege as c&#233;lulas e os tecidos contra oxidantes&#44; especialmente no pulm&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">30&#44;31</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Os produtos de danos oxidativos em bases de DNA tamb&#233;m servem como marcadores de estresse oxidativo&#59; entre as quatro bases nitrogenadas no DNA&#44; a guanina &#233; a base de &#225;cido nucleico mais facilmente oxid&#225;vel&#46; Portanto&#44; a guanina &#233; alvo prim&#225;rio de modifica&#231;&#227;o oxidativa<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a> e a medi&#231;&#227;o de esp&#233;cies de guanina oxidada pode ser uma ferramenta &#250;til para avaliar os danos ao DNA induzidos pelo estresse oxidativo nos compartimentos nuclear e mitocondrial&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">No presente estudo&#44; o teste qPCR foi usado para avaliar a oxida&#231;&#227;o da base de DNA nas c&#233;lulas sangu&#237;neas perif&#233;ricas de pacientes com ES e controles saud&#225;veis&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Os resultados indicaram diferen&#231;a estatisticamente significativa entre os grupos analisados em rela&#231;&#227;o ao dano oxidativo do mtDNA&#46; Al&#233;m disso&#44; uma correla&#231;&#227;o negativa significativa foi observada entre o mtDNAcn e o grau de mtDNA oxidativo &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8208;0&#44;392&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Esses resultados s&#227;o similares aos de estudos anteriores que relataram aumento do estresse oxidativo e danos ao DNA em fibroblastos obtidos de pacientes com ES &#40;esclerodermia&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">33&#44;34</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Embora o mecanismo molecular exato do dano ao DNA ainda n&#227;o tenha sido elucidado&#44; aparentemente os autoanticorpos derivados de pacientes com ES podem estimular v&#225;rias vias de sinaliza&#231;&#227;o intracelular &#40;como as vias Wnt e Ras&#41; que podem ser influenciadas pelos ERO e tamb&#233;m podem ter impacto na produ&#231;&#227;o de ERO&#46; Nesse cen&#225;rio&#44; altera&#231;&#245;es descontroladas na produ&#231;&#227;o de ERO e na transdu&#231;&#227;o de sinal podem resultar em ac&#250;mulo de danos ao DNA&#44; ativa&#231;&#227;o de genes dependentes de ERO e alta suscetibilidade &#224; apoptose&#46; Acredita&#8208;se que esses eventos participem da forma&#231;&#227;o de fibrose tecidual como consequ&#234;ncia da apoptose e da deposi&#231;&#227;o de col&#225;geno&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclus&#227;o</span><p id="par0145" class="elsevierStylePara elsevierViewall">O presente estudo avaliou os danos ao mtDNAcn e ao mtDNA com um ensaio quantitativo baseado em PCR&#46; Os presentes resultados indicam que pacientes com ES apresentavam redu&#231;&#227;o no mtDNAcn e aumento no dano mitocondrial&#44; o que &#233; consistente com a disfun&#231;&#227;o mitocondrial&#46; Al&#233;m de experimentos tradicionais para desvendar a fisiopatologia da ES&#44; estudos futuros s&#227;o necess&#225;rios para confirmar os presentes achados&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Suporte financeiro</span><p id="par0150" class="elsevierStylePara elsevierViewall">Universidade de Ci&#234;ncias M&#233;dicas de Teer&#227; &#40;contrato n&#176; 24&#46;743&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Contribui&#231;&#227;o dos autores</span><p id="par0155" class="elsevierStylePara elsevierViewall">Shafieh Movassaghi&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Sara Jafari&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Kowsar Falahati&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Mitra Ataei&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Mohammad Hossein Sanati&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Zohreh Jadali&#58; An&#225;lise estat&#237;stica&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflitos de interesse</span><p id="par0185" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:11 [
        0 => array:3 [
          "identificador" => "xres1354622"
          "titulo" => "Resumo"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Fundamentos"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Objetivo"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "M&#233;todos"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Resultados"
            ]
            4 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Limita&#231;&#245;es do estudo"
            ]
            5 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Conclus&#227;o"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1245560"
          "titulo" => "Palavras&#8208;chave"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introdu&#231;&#227;o"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "M&#233;todos"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Popula&#231;&#227;o do estudo"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Extra&#231;&#227;o de DNA"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Prepara&#231;&#227;o do modelo de DNA"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Determina&#231;&#227;o quantitativa do n&#250;mero de c&#243;pias do mtDNA"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Determina&#231;&#227;o quantitativa do dano ao mtDNA"
            ]
            5 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "An&#225;lise estat&#237;stica"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "sec0045"
          "titulo" => "Resultados"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Diminui&#231;&#227;o do mtDNAcn no sangue perif&#233;rico em pacientes com ES"
            ]
            1 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Aumento do dano oxidativo ao DNA em pacientes com ES"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Discuss&#227;o"
        ]
        6 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Conclus&#227;o"
        ]
        7 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Suporte financeiro"
        ]
        8 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Contribui&#231;&#227;o dos autores"
        ]
        9 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Conflitos de interesse"
        ]
        10 => array:1 [
          "titulo" => "Refer&#234;ncias"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-04-24"
    "fechaAceptado" => "2019-11-12"
    "PalabrasClave" => array:1 [
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras&#8208;chave"
          "identificador" => "xpalclavsec1245560"
          "palabras" => array:5 [
            0 => "Autoimunidade"
            1 => "DNA mitocondrial"
            2 => "Esclerodermia sist&#234;mica"
            3 => "Estresse oxidativo"
            4 => "Rea&#231;&#227;o em cadeia da polimerase em tempo real"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Embora n&#227;o totalmente compreendido&#44; o estresse oxidativo tem sido associado &#224; patog&#234;nese de diferentes doen&#231;as autoimunes&#44; como a esclerose sist&#234;mica&#46; A evid&#234;ncia acumulada indica que o estresse oxidativo pode induzir danos no DNA mitocondrial &#40;mtDNA&#41; e varia&#231;&#245;es no n&#250;mero de c&#243;pias do mtDNA &#40;mtDNAcn&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Explorar o mtDNAcn e subprodutos de danos oxidativos ao DNA no sangue perif&#233;rico de pacientes com esclerose sist&#234;mica e em controles saud&#225;veis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">O estudo incluiu 46 pacientes com esclerose sist&#234;mica e 49 indiv&#237;duos saud&#225;veis&#46; PCR quantitativa em tempo real foi usada para mensurar o mtDNAcn relativo e o dano oxidativo &#40;purinas oxidadas&#41; de cada amostra&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">O mtDNAcn m&#233;dio foi menor em pacientes com esclerose sist&#234;mica do que nos controles&#44; enquanto o grau de dano ao mtDNA foi significativamente maior nos doentes em compara&#231;&#227;o com os controles&#46; Al&#233;m disso&#44; observou&#8208;se correla&#231;&#227;o negativa entre o mtDNAcn e o dano oxidativo ao DNA&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A falta de an&#225;lise e quantifica&#231;&#227;o simult&#226;nea de marcadores de dano oxidativo ao DNA no soro ou na urina de pacientes com esclerose sist&#234;mica e em controles saud&#225;veis&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#227;o</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Esses dados sugerem que a altera&#231;&#227;o no mtDNAcn e o aumento do dano oxidativo ao DNA podem estar envolvidos na patog&#234;nese da esclerose sist&#234;mica&#46;</p></span>"
        "secciones" => array:6 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Fundamentos"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objetivo"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "M&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Limita&#231;&#245;es do estudo"
          ]
          5 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Conclus&#227;o"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Como citar este artigo&#58; Movassaghi S&#44; Jafari S&#44; Falahati K&#44; Ataei M&#44; Sanati MH&#44; Jadali Z&#46; Quantification of mitochondrial DNA damage and copy number in circulating blood of patients with systemic sclerosis by a qPCR&#8208;based assay&#46; An Bras Dermatol&#46; 2020&#59;95&#58;314&#8211;9&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Trabalho realizado no Tehran University of Medical Sciences&#44; Teer&#227;&#44; Ir&#227;&#46;</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 868
            "Ancho" => 1667
            "Tamanyo" => 66452
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">N&#250;mero m&#233;dio de c&#243;pias mitocondriais no sangue perif&#233;rico de pacientes com esclerose sist&#234;mica e indiv&#237;duos saud&#225;veis&#46; O n&#250;mero de c&#243;pias do DNAmt foi quantificado com o delta Ct &#40;Ct&#41; da Ct m&#233;dia do DNAmt e o DNA nuclear &#40;Ct<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>CtmtDNA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Ctactin&#41;&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 935
            "Ancho" => 1652
            "Tamanyo" => 62126
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Aumento do dano ao DNAmt em pacientes com esclerose sist&#234;mica em compara&#231;&#227;o aos controles normais&#46; O Ct &#233; a diferen&#231;a entre o valor de Ct da amostra de DNA tratada com FPG e o valor de Ct da amostra de DNA sem tratamento com FPG&#46; Observe que um valor mais alto de Ct corresponde a n&#237;veis comparativamente mais altos desses danos oxidativos&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabela 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Caracter&#237;sticas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pacientes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Controles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N&#250;mero</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade &#40;anos&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#44;09&#177;12&#44;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#44;90&#177;12&#44;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Dura&#231;&#227;o da doen&#231;a &#40;anos&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;61&#177;6&#44;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo &#40;Feminino&#47;Masculino&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">IcSSc&#47;dcSSc&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;13&#44;04&#37;&#41;&#47;40 &#40;86&#44;96&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">&#211;rg&#227;os afetados</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pulm&#227;o &#40;DPI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cora&#231;&#227;o &#40;HAP&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rim &#40;Hist&#243;rico de crise renal&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gastrointestinal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Articula&#231;&#245;es&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2326229.png"
              ]
            ]
            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tratamento</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Tipo de doen&#231;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#250;mero de pacientes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Esclerose sist&#234;mica cut&#226;nea limitada</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Metotrexato&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Azatioprina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Micofenolato&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Esclerose sist&#234;mica difusa</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Metotrexato&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Azatioprina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Micofenolato&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prednisolona&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Azatioprina<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>prednisolona&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nenhum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2326230.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas demogr&#225;ficas e cl&#237;nicas de pacientes com esclerose sist&#234;mica e controles saud&#225;veis</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:35 [
            0 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and epidemiological differences between men and women with systemic sclerosis&#58; a study in a Spanish systemic sclerosis cohort and literature review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Freire"
                            1 => "A&#46; Rivera"
                            2 => "B&#46; Sope&#241;a"
                            3 => "C&#46; Tolosa Vilella"
                            4 => "A&#46; Guill&#233;n-Del Castillo"
                            5 => "D&#46; Colunga Arg&#252;elles"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Rheumatol&#46;"
                        "fecha" => "2017"
                        "volumen" => "35"
                        "paginaInicial" => "89"
                        "paginaFinal" => "97"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28980905"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "One year in review 2017&#58; systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Barsotti"
                            1 => "C&#46; Bruni"
                            2 => "M&#46; Orlandi"
                            3 => "A&#46; Della Rossa"
                            4 => "E&#46; Marasco"
                            5 => "V&#46; Codullo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Exp Rheumatol&#46;"
                        "fecha" => "2017"
                        "volumen" => "35"
                        "numero" => "Suppl 106"
                        "paginaInicial" => "3"
                        "paginaFinal" => "20"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29035173"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epigenetics&#58; The Future Direction in Systemic Sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46; Walczyk"
                            1 => "A&#46; Paradowska-Gorycka"
                            2 => "M&#46; Olesinska"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/sji.12595"
                      "Revista" => array:6 [
                        "tituloSerie" => "Scand J Immunol&#46;"
                        "fecha" => "2017"
                        "volumen" => "86"
                        "paginaInicial" => "427"
                        "paginaFinal" => "435"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28930377"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative damage and antioxidative therapy in systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46; Grygiel-G&#243;rniak"
                            1 => "M&#46; Puszczewicz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2014/389582"
                      "Revista" => array:5 [
                        "tituloSerie" => "Mediators Inflamm&#46;"
                        "fecha" => "2014"
                        "volumen" => "2014"
                        "paginaInicial" => "389582"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25313270"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative stress in the pathogenesis of systemic scleroderma&#58; An overview"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Vona"
                            1 => "A&#46; Giovannetti"
                            2 => "L&#46; Gambardella"
                            3 => "W&#46; Malorni"
                            4 => "D&#46; Pietraforte"
                            5 => "E&#46; Straface"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jcmm.13630"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cell Mol Med&#46;"
                        "fecha" => "2018"
                        "volumen" => "22"
                        "paginaInicial" => "3308"
                        "paginaFinal" => "3314"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29664231"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mitochondrial Nucleoid&#58; Shield and Switch of the Mitochondrial Genome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "S&#46;R&#46; Lee"
                            1 => "J&#46; Han"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1155/2017/8060949"
                      "Revista" => array:5 [
                        "tituloSerie" => "Oxid Med Cell Longev&#46;"
                        "fecha" => "2017"
                        "volumen" => "2017"
                        "paginaInicial" => "8060949"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28680532"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The maintenance of mitochondrial DNA integrity &#8211; critical analysis and update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Alexeyev"
                            1 => "I&#46; Shokolenko"
                            2 => "G&#46; Wilson"
                            3 => "S&#46; LeDoux"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cold Spring Harb Perspect Biol&#46;"
                        "fecha" => "2013"
                        "volumen" => "5"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Physical association of the 2&#44;6&#8208;diamino&#8208;4&#8208;hydroxy&#8208;5N&#8208;formamidopyrimidine&#8208;DNA glycosylase of Escherichia coli and an activity nicking DNA at apurinic&#47;apyrimidinic sites"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46;R&#46; O&#8217;Connor"
                            1 => "J&#46; Laval"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.86.14.5222"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci U S A&#46;"
                        "fecha" => "1989"
                        "volumen" => "86"
                        "paginaInicial" => "5222"
                        "paginaFinal" => "5226"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2664776"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biological consequences of free radical&#8208;damaged DNA bases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46;S&#46; Wallace"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0891-5849(02)00827-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Free Radic Biol Med&#46;"
                        "fecha" => "2002"
                        "volumen" => "33"
                        "paginaInicial" => "1"
                        "paginaFinal" => "14"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12086677"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2013 classification criteria for systemic sclerosis&#58; an American college of rheumatology&#47;European league against rheumatism collaborative initiative"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; van den Hoogen"
                            1 => "D&#46; Khanna"
                            2 => "J&#46; Fransen"
                            3 => "S&#46;R&#46; Johnson"
                            4 => "M&#46; Baron"
                            5 => "A&#46; Tyndall"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Rheum Dis&#46;"
                        "fecha" => "2013"
                        "volumen" => "72"
                        "paginaInicial" => "1747"
                        "paginaFinal" => "1755"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnostic criteria of systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Hudson"
                            1 => "M&#46;J&#46; Fritzler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaut.2020.102419"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Autoimmun&#46;"
                        "fecha" => "2014"
                        "volumen" => "48&#8211;49"
                        "paginaInicial" => "38"
                        "paginaFinal" => "41"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32035747"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased levels of mitochondrial DNA copy number in patients with vitiligo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H&#46; Vaseghi"
                            1 => "M&#46; Houshmand"
                            2 => "Z&#46; Jadali"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/ced.13185"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Dermatol&#46;"
                        "fecha" => "2017"
                        "volumen" => "42"
                        "paginaInicial" => "749"
                        "paginaFinal" => "754"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28866865"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current perspectives on the immunopathogenesis of systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46; Fuschiotti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2147/ITT.S82037"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunotargets Ther&#46;"
                        "fecha" => "2016"
                        "volumen" => "5"
                        "paginaInicial" => "21"
                        "paginaFinal" => "35"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27529059"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High reactive oxygen species in fibrotic and nonfibrotic skin of patients with diffuse cutaneous systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Bourji"
                            1 => "A&#46; Meyer"
                            2 => "E&#46; Chatelus"
                            3 => "J&#46; Pincemail"
                            4 => "E&#46; Pigatto"
                            5 => "J&#46;O&#46; Defraigne"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.freeradbiomed.2015.07.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Free Radic Biol Med&#46;"
                        "fecha" => "2015"
                        "volumen" => "87"
                        "paginaInicial" => "282"
                        "paginaFinal" => "289"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26143738"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intracellular free radical production by peripheral blood T lymphocytes from patients with systemic sclerosis&#58; role of NADPH oxidase and ERK1&#47;2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Amico"
                            1 => "T&#46; Spadoni"
                            2 => "M&#46; Rovinelli"
                            3 => "M&#46; Serafini"
                            4 => "G&#46; D&#8217;Amico"
                            5 => "N&#46; Campelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13075-015-0591-8"
                      "Revista" => array:5 [
                        "tituloSerie" => "Arthritis Res Ther&#46;"
                        "fecha" => "2015"
                        "volumen" => "17"
                        "paginaInicial" => "68"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25889655"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mitochondrial Dysfunction and Redox Imbalance as a Diagnostic Marker of &#8220;Free Radical Diseases&#8221;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E&#46; Georgieva"
                            1 => "D&#46; Ivanova"
                            2 => "Z&#46; Zhelev"
                            3 => "R&#46; Bakalova"
                            4 => "M&#46; Gulubova"
                            5 => "I&#46; Aoki"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.21873/anticanres.11963"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anticancer Res&#46;"
                        "fecha" => "2017"
                        "volumen" => "37"
                        "paginaInicial" => "5373"
                        "paginaFinal" => "5381"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28982845"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Activation of apoptosis signalling pathways by reactive oxygen species"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Redza-Dutordoir"
                            1 => "D&#46;A&#46; Averill-Bates"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbamcr.2016.09.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochim Biophys Acta&#46;"
                        "fecha" => "2016"
                        "volumen" => "1863"
                        "paginaInicial" => "2977"
                        "paginaFinal" => "2992"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27646922"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High mitochondrial DNA copy number was associated with an increased gastric cancer risk in a Chinese population"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "X&#46; Zhu"
                            1 => "Y&#46; Mao"
                            2 => "T&#46; Huang"
                            3 => "C&#46; Yan"
                            4 => "F&#46; Yu"
                            5 => "J&#46; Du"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/mc.22703"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Carcinog&#46;"
                        "fecha" => "2017"
                        "volumen" => "56"
                        "paginaInicial" => "2593"
                        "paginaFinal" => "2600"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28688194"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatocyte giant mitochondria&#58; an almost constant lesion in systemic scleroderma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Feldmann"
                            1 => "M&#46; Maurice"
                            2 => "J&#46;M&#46; Husson"
                            3 => "J&#46;N&#46; Fiessinger"
                            4 => "J&#46;P&#46; Camilleri"
                            5 => "J&#46;P&#46; Benhamou"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/BF00427116"
                      "Revista" => array:6 [
                        "tituloSerie" => "Virchows Arch A Pathol Anat Histol&#46;"
                        "fecha" => "1977"
                        "volumen" => "374"
                        "paginaInicial" => "215"
                        "paginaFinal" => "227"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/142348"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Precipitating autoantibodies to mitochondrial proteins in progressive systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46;C&#46; Gupta"
                            1 => "J&#46;R&#46; Seibold"
                            2 => "M&#46;R&#46; Krishnan"
                            3 => "J&#46;C&#46; Steigerwald"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Immunol&#46;"
                        "fecha" => "1984"
                        "volumen" => "58"
                        "paginaInicial" => "68"
                        "paginaFinal" => "76"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6434213"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detection of anti&#8208;mitochondrial antibodies by immunoprecipitation in patients with systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Ceribelli"
                            1 => "N&#46; Isailovic"
                            2 => "M&#46; De Santis"
                            3 => "E&#46; Generali"
                            4 => "M&#46; Satoh"
                            5 => "C&#46; Selmi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jim.2017.10.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol Methods&#46;"
                        "fecha" => "2018"
                        "volumen" => "452"
                        "paginaInicial" => "1"
                        "paginaFinal" => "5"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28986201"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The pyruvate dehydrogenase complexes&#58; structure&#8208;based function and regulation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;S&#46; Patel"
                            1 => "N&#46;S&#46; Nemeria"
                            2 => "W&#46; Furey"
                            3 => "F&#46; Jordan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.R114.563148"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem&#46;"
                        "fecha" => "2014"
                        "volumen" => "289"
                        "paginaInicial" => "16615"
                        "paginaFinal" => "16623"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24798336"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The Importance of Autoantibody Detection in Primary Biliary Cirrhosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46;L&#46;R&#46; Cancado"
                            1 => "M&#46; Harriz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fimmu.2015.00309"
                      "Revista" => array:5 [
                        "tituloSerie" => "Front Immunol&#46;"
                        "fecha" => "2015"
                        "volumen" => "6"
                        "paginaInicial" => "309"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26157439"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High prevalence of primary biliary cirrhosis and disease&#8208;associated autoantibodies in Japanese patients with systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Imura-Kumada"
                            1 => "M&#46; Hasegawa"
                            2 => "T&#46; Matsushita"
                            3 => "Y&#46; Hamaguchi"
                            4 => "S&#46; Encabo"
                            5 => "Z&#46; Shums"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10165-012-0607-z"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mod Rheumatol&#46;"
                        "fecha" => "2012"
                        "volumen" => "22"
                        "paginaInicial" => "892"
                        "paginaFinal" => "898"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22327744"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The concept of early systemic sclerosis following 2013 ACR&#47;EULAR criteria for the classification of systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "G&#46; Valentini"
                            1 => "A&#46; Marcoccia"
                            2 => "G&#46; Cuomo"
                            3 => "M&#46; Iudici"
                            4 => "S&#46; Vettori"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2174/1573397110666140404001756"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Rheumatol Rev&#46;"
                        "fecha" => "2014"
                        "volumen" => "10"
                        "paginaInicial" => "38"
                        "paginaFinal" => "44"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24720644"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Presence of organ specific antibodies in patients with systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Wielosz"
                            1 => "M&#46; Majdan"
                            2 => "A&#46; Koszarny"
                            3 => "M&#46; Dryglewska"
                            4 => "J&#46; Tabarkiewicz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.20452/pamw.3583"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pol Arch Med Wewn&#46;"
                        "fecha" => "2016"
                        "volumen" => "126"
                        "paginaInicial" => "862"
                        "paginaFinal" => "869"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27906879"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Primary biliary cirrhosis&#8208;related autoantibodies in a large cohort of italian patients with systemic sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46; Cavazzana"
                            1 => "A&#46; Ceribelli"
                            2 => "M&#46; Taraborelli"
                            3 => "M&#46; Fredi"
                            4 => "G&#46; Norman"
                            5 => "A&#46; Tincani"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3899/jrheum.110167"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Rheumatol&#46;"
                        "fecha" => "2011"
                        "volumen" => "38"
                        "paginaInicial" => "2180"
                        "paginaFinal" => "2185"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21921093"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional&#44; clinical and radiological signs of lung fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Fietta"
                            1 => "A&#46; Bardoni"
                            2 => "R&#46; Salvini"
                            3 => "I&#46; Passadore"
                            4 => "M&#46; Morosini"
                            5 => "L&#46; Cavagna"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/ar2067"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Res Ther&#46;"
                        "fecha" => "2006"
                        "volumen" => "8"
                        "paginaInicial" => "R160"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17044913"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1529943012009977"
                          "estado" => "S300"
                          "issn" => "15299430"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mitochondrial topoisomerase I sites in the regulatory D&#8208;loop region of mitochondrial DNA"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46; Zhang"
                            1 => "Y&#46; Pommier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1021/bi800774b"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochemistry&#46;"
                        "fecha" => "2008"
                        "volumen" => "47"
                        "paginaInicial" => "11196"
                        "paginaFinal" => "11203"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18826252"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glutathione S&#8208;transferase P1 &#40;GSTP1&#41; polymorphism in patients with chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Ishii"
                            1 => "T&#46; Matsuse"
                            2 => "S&#46; Teramoto"
                            3 => "H&#46; Matsui"
                            4 => "M&#46; Miyao"
                            5 => "T&#46; Hosoi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.54.8.693"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax&#46;"
                        "fecha" => "1999"
                        "volumen" => "54"
                        "paginaInicial" => "693"
                        "paginaFinal" => "696"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10413721"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The pathophysiological role of mitochondrial oxidative stress in lung diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "X&#46; Liu"
                            1 => "Z&#46; Chen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12967-017-1306-5"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Transl Med&#46;"
                        "fecha" => "2017"
                        "volumen" => "15"
                        "paginaInicial" => "207"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29029603"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recent aspects of oxidative DNA damage&#58; guanine lesions&#44; measurement and substrate specificity of DNA repair glycosylases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Cadet"
                            1 => "S&#46; Bellon"
                            2 => "M&#46; Berger"
                            3 => "A&#46;G&#46; Bourdat"
                            4 => "T&#46; Douki"
                            5 => "V&#46; Duarte"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1515/BC.2002.100"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biol Chem&#46;"
                        "fecha" => "2002"
                        "volumen" => "383"
                        "paginaInicial" => "933"
                        "paginaFinal" => "943"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12222683"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Platelet&#8208;derived growth factor and Reactive Oxygen Species &#40;ROS&#41; regulate Ras protein levels in primary human fibroblasts via ERK1&#47;2 Amplification of ROS and Ras in systemic sclerosis fibroblasts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Svegliati"
                            1 => "R&#46; Cancello"
                            2 => "P&#46; Sambo"
                            3 => "M&#46; Luchetti"
                            4 => "P&#46; Paroncini"
                            5 => "G&#46; Orlandini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.M502851200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem&#46;"
                        "fecha" => "2005"
                        "volumen" => "280"
                        "paginaInicial" => "36474"
                        "paginaFinal" => "36482"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16081426"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative DNA damage induces the ATM&#8208;mediated transcriptional suppression of the Wnt inhibitor WIF&#8208;1 in systemic sclerosis and fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Svegliati"
                            1 => "G&#46; Marrone"
                            2 => "A&#46; Pezone"
                            3 => "T&#46; Spadoni"
                            4 => "A&#46; Grieco"
                            5 => "G&#46; Moroncini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/scisignal.2005633"
                      "Revista" => array:4 [
                        "tituloSerie" => "Sci Signal&#46;"
                        "fecha" => "2014"
                        "volumen" => "7"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25351248"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Scleroderma &#8211; pathophysiology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "T&#46; Yamamoto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1684/ejd.2008.0570"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Dermatol&#46;"
                        "fecha" => "2009"
                        "volumen" => "19"
                        "paginaInicial" => "14"
                        "paginaFinal" => "24"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19059831"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "pt"
  "url" => "/26662752/0000009500000003/v1_202006250813/S2666275220301521/v1_202006250813/pt/main.assets"
  "Apartado" => array:4 [
    "identificador" => "81728"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Investiga&#231;&#227;o"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/26662752/0000009500000003/v1_202006250813/S2666275220301521/v1_202006250813/pt/main.pdf?idApp=UINPBA00008Z&text.app=https://clinics.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275220301521?idApp=UINPBA00008Z"
]
Article information
ISSN: 26662752
Original language: Portuguese
The statistics are updated each day
Year/Month Html Pdf Total
2024 November 19 9 28
2024 October 137 103 240
2024 September 197 94 291
2024 August 198 97 295
2024 July 178 123 301
2024 June 154 75 229
2024 May 110 55 165
2024 April 120 93 213
2024 March 114 71 185
2024 February 129 73 202
2024 January 94 55 149
2023 December 83 73 156
2023 November 91 93 184
2023 October 83 74 157
2023 September 88 80 168
2023 August 81 43 124
2023 July 102 47 149
2023 June 80 57 137
2023 May 88 29 117
2023 April 93 20 113
2023 March 102 44 146
2023 February 65 44 109
2023 January 55 55 110
2022 December 63 31 94
2022 November 90 48 138
2022 October 194 49 243
2022 September 48 67 115
2022 August 47 51 98
2022 July 41 49 90
2022 June 46 60 106
2022 May 41 53 94
2022 April 68 77 145
2022 March 57 56 113
2022 February 36 42 78
2022 January 53 75 128
2021 December 35 54 89
2021 November 49 65 114
2021 October 54 73 127
2021 September 33 56 89
2021 August 44 61 105
2021 July 38 50 88
2021 June 40 53 93
2021 May 48 86 134
2021 April 102 239 341
2021 March 63 82 145
2021 February 31 18 49
2021 January 51 14 65
2020 December 30 18 48
2020 November 38 12 50
2020 October 18 19 37
2020 September 29 13 42
2020 August 17 13 30
2020 July 38 20 58
2020 June 11 15 26
2020 May 4 7 11
Show all

Follow this link to access the full text of the article

Idiomas
Anais Brasileiros de Dermatologia
en pt
Cookies policy Política de cookies
To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.