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decorrentes da intera&#231;&#227;o complexa entre queratin&#243;citos&#44; melan&#243;citos e componentes da derme superior&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">H&#225; clara rela&#231;&#227;o entre a exposi&#231;&#227;o solar e a pioria do melasma&#44; desde ocorr&#234;ncia exclusiva em &#225;reas fotoexpostas at&#233; preval&#234;ncia em profissionais que se exp&#245;em ao sol e melhor resposta terap&#234;utica associada &#224; fotoprote&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;10</span></a> Mesmo com evid&#234;ncias do papel da radia&#231;&#227;o solar na hist&#243;ria cl&#237;nica da doen&#231;a&#44; n&#227;o se conhece o padr&#227;o de resposta individualizada do melasma em compara&#231;&#227;o com a pele normal adjacente &#224;s diferentes faixas de radia&#231;&#227;o solar &#40;UVB&#44; UVA e luz vis&#237;vel &#8211; LV&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">O conhecimento das diferentes influ&#234;ncias da radia&#231;&#227;o solar na melanog&#234;nese do melasma pode levar a melhor compreens&#227;o da fisiopatologia da doen&#231;a&#44; assim como &#224; elabora&#231;&#227;o de novas op&#231;&#245;es de tratamento&#44; al&#233;m de aprimorar as estrat&#233;gias de fotoprote&#231;&#227;o&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Este estudo objetivou determinar a resposta melanog&#234;nica do melasma facial em compara&#231;&#227;o com a pele normal adjacente ap&#243;s irradia&#231;&#227;o com UVA&#44; UVB ou LV em modelo <span class="elsevierStyleItalic">ex vivo&#46;</span></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material e m&#233;todos</span><p id="par0030" class="elsevierStylePara elsevierViewall">Estudo <span class="elsevierStyleItalic">quasi</span>&#8208;experimental <span class="elsevierStyleItalic">ex vivo</span> que envolveu fragmentos de pele de 22 portadores de melasma facial diagnosticados por dermatologista experiente&#46; Os participantes foram selecionados entre os pacientes do servi&#231;o de dermatologia do Hospital das Cl&#237;nicas da Faculdade de Medicina de Botucatu &#40;SP&#41; entre setembro de 2018 e janeiro de 2019&#46; O projeto foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa &#40;n&#176; 2&#46;700&#46;889&#41; e todos os participantes assinaram o termo de consentimento antes da inclus&#227;o&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Foram eleg&#237;veis para o estudo pacientes adultos &#40;&#62; 18 anos&#41;&#44; de ambos os sexos&#44; entre os fototipos III&#8208;V&#44; com melasma facial e sem tratamento&#44; exceto filtro solar por&#44; no m&#237;nimo&#44; 30 dias&#46; A restri&#231;&#227;o aos fototipos baseou&#8208;se no fato de que os fototipos I e II representam menos de 10&#37; dos casos de melasma e n&#227;o apresentam melanog&#234;nese satisfat&#243;ria ap&#243;s irradia&#231;&#227;o experimental&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">3&#44;11</span></a> N&#227;o h&#225; descri&#231;&#227;o de melasma em fototipo VI&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">N&#227;o foram inclu&#237;dos no estudo os portadores de outras dermatoses faciais&#44; dermatoses com fotossensibilidade&#44; colagenoses&#44; discrasias sangu&#237;neas&#44; usu&#225;rios de medica&#231;&#227;o anticoagulante&#44; imunossuprimidos&#44; gestantes ou lactantes&#46; A amostragem foi feita por conveni&#234;ncia&#44; usaram&#8208;se pacientes consecutivos&#44; concordantes em participar do estudo&#44; durante consultas m&#233;dicas na institui&#231;&#227;o&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">A coleta de material ocorreu de maneira padronizada e sob procedimento est&#233;ril&#46; Duas amostras de cada participante foram coletadas&#58; pele com melasma e pele normal adjacente&#44; distantes at&#233; 2<span class="elsevierStyleHsp" style=""></span>cm entre si&#44; sob anestesia local infiltrativa com lidoca&#237;na 2&#37; com vasoconstritor&#46; A remo&#231;&#227;o contemplou at&#233; a derme reticular&#44; com <span class="elsevierStyleItalic">punch</span> 3<span class="elsevierStyleHsp" style=""></span>mm e sutura com fio <span class="elsevierStyleItalic">mononylon</span> 6&#44;0&#46; Foram privilegiadas &#225;reas perif&#233;ricas da face a fim de minimizar cicatrizes inest&#233;ticas&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">As amostras foram seccionadas longitudinalmente em duas partes e armazenadas em 10<span class="elsevierStyleHsp" style=""></span>mL do meio DMEM &#40;<span class="elsevierStyleItalic">Dulbecco&#39;s Modified Eagle&#39;s Medium&#44; high glicose</span> &#8211; D5796&#44; Sigma Inc&#44; UK&#41; em frasco pl&#225;stico transparente est&#233;ril e mantido em temperatura ambiente&#44; segundo protocolo estabelecido por Olivatti&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> Uma parte do fragmento foi acondicionada imediatamente ao abrigo da luz&#44; enquanto a outra foi exposta a uma das radia&#231;&#245;es&#44; com uma dose total &#40;efetiva no tecido&#41; UVB&#44; UVA e LV de 166<span class="elsevierStyleHsp" style=""></span>mJ&#47;cm<span class="elsevierStyleSup">2</span>&#44; 1&#44;524<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span> e 40<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span> &#40;componente luz azul&#8208;violeta&#41;&#46; Os fragmentos foram irradiados a partir de fontes artificiais de UVB &#40;230<span class="elsevierStyleHsp" style=""></span>&#956;W&#47;cm<span class="elsevierStyleSup">2</span>&#59; fonte FS72T12&#47;UVB&#47;HO&#41; &#8211; 12<span class="elsevierStyleHsp" style=""></span>min&#44; UVA &#40;1270<span class="elsevierStyleHsp" style=""></span>&#956;W&#47;cm<span class="elsevierStyleSup">2</span>&#59; fonte Phillips TL 100W&#47;10R&#41; &#8211; 6<span class="elsevierStyleHsp" style=""></span>min e luz LED &#40;110 mW&#47;cm<span class="elsevierStyleSup">2</span> na faixa azul&#8208;violeta&#59; fonte GBRLUX 200W&#41; &#8211; 20<span class="elsevierStyleHsp" style=""></span>min&#44; com dist&#226;ncia padronizada de 10<span class="elsevierStyleHsp" style=""></span>cm&#46; A absorb&#226;ncia dos frascos pl&#225;sticos foi de cerca de 50&#37; para todas as radia&#231;&#245;es&#46; A aloca&#231;&#227;o dos participantes em cada tipo de irradia&#231;&#227;o foi consecutiva &#40;n&#227;o randomizada&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Ap&#243;s a irradia&#231;&#227;o&#44; ambos os fragmentos &#40;irradiados e n&#227;o irradiados&#41; foram cultivados ao abrigo da luz&#46; Passadas 72 horas&#44; as amostras foram retiradas do meio de cultura e mantidas em formol 10&#37; tamponado por 36 horas&#46; Posteriormente&#44; foram desidratadas em &#225;lcool 70&#37; por no m&#237;nimo 12 horas antes de ser emblocadas em parafina e da colora&#231;&#227;o dos cortes pelo Fontana&#8208;Masson &#40;FM&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Para estimar a melaniza&#231;&#227;o dos fragmentos&#44; capturaram&#8208;se quatro fotografias de &#225;reas centrais e interfoliculares das amostras coradas pelo FM&#44; privilegiaram&#8208;se &#225;reas <span class="elsevierStyleItalic">hotspot</span>&#46; As imagens foram salvas em formato JPG &#40;1264 &#215; 681 pixels&#41;&#46; Todo o processo de captura e an&#225;lise ocorreu de maneira cega quanto &#224; topografia ou ao tipo e regime de irradia&#231;&#227;o&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">As imagens selecionadas foram analisadas no programa ImageJ 1&#46;43&#44; a partir da sele&#231;&#227;o manual da camada basal&#44; seguida pela limiariza&#231;&#227;o a partir do canal <span class="elsevierStyleItalic">red</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">13</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">O principal desfecho do estudo foi o percentual de melaniza&#231;&#227;o da camada basal&#44; comparado entre os grupos &#40;melasma <span class="elsevierStyleItalic">vs</span>&#46; pele normal adjacente&#41; para cada radia&#231;&#227;o &#40;UVB&#44; UVA ou LV&#41;&#46; Tamb&#233;m foram avaliados o percentual de melanina na derme superficial&#44; a contagem de dendritos e as granula&#231;&#245;es dos melanossomas &#40;Escore&#58; 1&#43;&#44; granula&#231;&#227;o fina&#59; 2&#43;&#44; granula&#231;&#227;o moderada&#59; 3&#43;&#44; granula&#231;&#227;o grosseira&#41; nas &#225;reas amostradas&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">O valor m&#233;dio do percentual de melanina da camada basal&#44; da derme superior&#44; a contagem de dendritos e os escores de granula&#231;&#227;o foram tabulados para cada esp&#233;cime&#46; Os grupos de compara&#231;&#227;o foram avaliados segundo modelo linear generalizado de efeitos mistos&#44; ajustados pelo fototipo&#44; an&#225;lise robusta&#44; com matriz de covari&#226;ncia n&#227;o estruturada e corre&#231;&#227;o <span class="elsevierStyleItalic">post hoc</span> de Sidak&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">14</span></a> As distribui&#231;&#245;es de probabilidade variaram para o tipo de vari&#225;vel analisada &#40;ordinal e gama&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">A amostra foi dimensionada ap&#243;s pr&#233;&#8208;teste com a dosimetria de radia&#231;&#227;o que levava &#224; expectativa de aumento de 10&#37; no percentual de melaniza&#231;&#227;o na camada basal avaliada por an&#225;lise de imagem digital das l&#226;minas coradas pelo FM&#44; consideraram&#8208;se alfa 5&#37; e poder de 20&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Os dados foram tabulados em MsExcel 2013&#44; analisados no IBM SPSS 25&#46; Considerou&#8208;se significativo p&#8208;valor &#8804; 0&#44;05 bicaudal&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0090" class="elsevierStylePara elsevierViewall">Foram avaliados 89 fragmentos de pele de 22 portadores de melasma facial &#40;um participante voluntariou&#8208;se para a coleta de quatro amostras com o intuito de testar todas as irradia&#231;&#245;es&#41;&#46; A idade m&#233;dia &#40;desvio&#8208;padr&#227;o&#41; dos participantes foi de 42&#44;1 &#40;10&#44;4&#41; anos &#8211; 21 do sexo feminino &#8211; e quanto aos fototipos&#44; III &#40;46&#37;&#41;&#44; IV &#40;27&#37;&#41; e V &#40;27&#37;&#41;&#46; Houve contamina&#231;&#227;o em tr&#234;s fragmentos de cultura &#40;UVA pele normal adjacente pr&#233;&#8208;irradia&#231;&#227;o&#59; UVB pele do melasma p&#243;s&#8208;irradia&#231;&#227;o&#44; UVB pele normal adjacente p&#243;s&#8208;irradia&#231;&#227;o&#41;&#44; que n&#227;o foram inclu&#237;dos na an&#225;lise dos resultados&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Os pacientes cujas amostras foram submetidas &#224; irradia&#231;&#227;o UVB&#44; UVA e LV apresentavam&#44; respectivamente&#44; fototipos&#58; III &#40;33&#37; <span class="elsevierStyleItalic">vs</span>&#46; 37&#37; <span class="elsevierStyleItalic">vs</span>&#46; 0&#37;&#41;&#44; IV &#40;44&#37; <span class="elsevierStyleItalic">vs</span>&#46; 37&#37; <span class="elsevierStyleItalic">vs</span>&#46; 71&#37;&#41; e V &#40;22&#37; <span class="elsevierStyleItalic">vs</span>&#46; 25&#37; <span class="elsevierStyleItalic">vs</span>&#46; 28&#37;&#41; &#40;p &#61; 0&#44;35&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Houve melanog&#234;nese no melasma e na pele normal adjacente &#40;p &#60; 0&#44;01&#41; ap&#243;s todas as irradia&#231;&#245;es &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1&#8208;3</a>&#44; <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#58; mediana de incremento UVB &#40;4&#44;7&#37; <span class="elsevierStyleItalic">vs</span>&#46; 8&#44;5&#37;&#41;&#44; UVA &#40;9&#44;5&#37; <span class="elsevierStyleItalic">vs</span>&#46; 9&#44;9&#37;&#41; e LV &#40;6&#44;8&#37; <span class="elsevierStyleItalic">vs</span>&#46; 11&#44;7&#37;&#41;&#44; sem diferen&#231;a significativa na compara&#231;&#227;o entre as topografias&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Quando ajustado para o fototipo&#44; a contagem de dendritos aumentou &#40;68&#44;8&#37;&#41; apenas ap&#243;s irradia&#231;&#227;o com UVB em ambas as topografias &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; Houve aumento no escore de granula&#231;&#227;o da melanina &#40;melanossomas mais grosseiros&#41; apenas ap&#243;s a irradia&#231;&#227;o com UVA e apenas na pele com melasma &#40;p &#61; 0&#44;05&#41;&#46; Houve tamb&#233;m aumento do percentual de melanina na derme superior na pele adjacente ap&#243;s irradia&#231;&#227;o com UVB e no melasma ap&#243;s irradia&#231;&#227;o com UVA &#40;p &#8804; 0&#44;05&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0110" class="elsevierStylePara elsevierViewall">Houve efetiva melanog&#234;nese epid&#233;rmica nos modelos de pele &#40;<span class="elsevierStyleItalic">ex vivo</span>&#41; submetidos &#224; UVB&#44; UVA e LV&#44; sem diferen&#231;a quantitativa entre as topografias &#40;melasma facial e pele normal adjacente&#41;&#44; subsidiou a import&#226;ncia da fotoprote&#231;&#227;o de amplo espectro no tratamento de dermatoses pigmentares&#44; como o melasma&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">As doses de radia&#231;&#227;o testadas&#44; apesar de independentes&#44; equivaleram a 6&#8208;12 minutos de exposi&#231;&#227;o solar ao meio&#8208;dia&#44; no ver&#227;o&#44; no interior do Brasil &#40;latitude&#58; 22&#176;53&#8217;09&#8221;S&#59; longitude&#58; 48&#176;26&#8217;42&#8221;W&#59; altitude&#58; 804 m&#41;&#44; em dia sem nuvens&#44; medida em 9&#47;12&#47;2018 pelos pesquisadores&#46; Entretanto&#44; os n&#237;veis de UVA e LV solares alcan&#231;am um plat&#244; de energia com dura&#231;&#227;o entre 9 horas at&#233; as 18 horas&#44; enquanto o UVB apresenta seu pico entre as 11 horas e as 15 horas&#44; tanto no ver&#227;o quanto no inverno&#46; Isso pode justificar o relato de pioria do melasma ap&#243;s breves exposi&#231;&#245;es desprotegidas fora do hor&#225;rio de pico de UVB&#44; ou mesmo ap&#243;s longas exposi&#231;&#245;es com fotoprotetor &#40;p&#46;ex&#46;&#44; congestionamento no tr&#226;nsito&#41;&#44; visto que n&#227;o h&#225; completo bloqueio das radia&#231;&#245;es solares pelos filtros solares&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a> Em tempo&#44; as radia&#231;&#245;es UVB&#44; UVA e LV medidas em ambientes fechados &#40;p&#46;ex&#46;&#44; telas de celular e computadores&#44; l&#226;mpadas fluorescentes&#41; s&#227;o desprez&#237;veis para efeitos de melanog&#234;nese &#40;dados n&#227;o mostrados&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">A LV tem amplo espectro de comprimentos de onda &#40;400&#8208;700<span class="elsevierStyleHsp" style=""></span>nm&#41; que n&#227;o atuam de maneira homog&#234;nea na pigmenta&#231;&#227;o&#46; Um estudo feito na Fran&#231;a testou o espectro da luz azul&#8208;violeta &#40;400&#8208;500<span class="elsevierStyleHsp" style=""></span>nm&#41; em compara&#231;&#227;o com o espectro da luz vermelha &#40;620&#8208;750<span class="elsevierStyleHsp" style=""></span>nm&#41; e n&#227;o houve pigmenta&#231;&#227;o induzida pela segunda&#44; o que justificou a escolha da faixa azul violeta para este estudo&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Apenas filtros solares com cor apresentam prote&#231;&#227;o efetiva contra LV e&#44; em sua maioria&#44; apresentam tamb&#233;m melhor desempenho na prote&#231;&#227;o UVA&#46; Em levantamento brasileiro com 41 filtros solares opacos&#44; 63&#37; bloquearam &#62; 99&#44;9&#37; de UVA e 63&#37; bloquearam &#62; 99&#44;9&#37; da transmit&#226;ncia da luz azul&#8208;violeta&#46; Entretanto&#44; tal bloqueio n&#227;o foi coincidente&#44; j&#225; que 31&#37; dos filtros opacos que bloquearam &#62; 99&#44;9&#37; da LV n&#227;o tiveram o mesmo desempenho quanto ao UVA&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a> Em tempo&#44; este estudo &#233; o primeiro a evidenciar o papel da LV na melanog&#234;nese de pacientes com melasma facial&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">N&#227;o ocorreu melanog&#234;nese diferencial entre a pele com melasma e normal adjacente nas doses testadas&#44; o que n&#227;o exclui a possibilidade de que a pele com melasma seja sens&#237;vel a doses mais baixas de irradia&#231;&#227;o ou responda diferentemente a exposi&#231;&#245;es repetidas&#46; A pr&#243;pria maior pigmenta&#231;&#227;o basal do melasma tamb&#233;m pode significar um <span class="elsevierStyleItalic">status</span> de resist&#234;ncia &#224; melanog&#234;nese induzida pela exposi&#231;&#227;o cr&#244;nica &#224; radia&#231;&#227;o UV e LV&#46; Al&#233;m disso&#44; h&#225; maior reten&#231;&#227;o epid&#233;rmica da melanina no melasma e sua melanog&#234;nese depende de diversas outras altera&#231;&#245;es d&#233;rmicas que favorecem a manuten&#231;&#227;o da pigmenta&#231;&#227;o&#44; em detrimento da indu&#231;&#227;o melanog&#234;nica pela radia&#231;&#227;o UV e LV&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">A melanog&#234;nese ocorre de maneira desigual&#44; depende do tipo e da dose de radia&#231;&#227;o&#46; O UVB causa eritema que persiste por dias a semanas &#40;depende do fototipo&#41; e pigmenta&#231;&#227;o que evolui para bronzeamento&#46; O UVA provoca eritema em 4 horas e pigmenta&#231;&#227;o imediata que evolui com bronzeamento duradouro&#46; Na LV&#44; o eritema &#233; menos proeminente&#44; pode ocorrer precocemente &#40;2 horas&#41; e a pigmenta&#231;&#227;o &#233; sustentada com evolu&#231;&#227;o para bronzeamento&#44; por&#233;m apenas nos fototipos altos&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">19&#8211;21</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Toda resposta melanog&#234;nica acontece de maneira dose&#8208;dependente&#46; No entanto&#44; &#233; indispens&#225;vel considerar os fototipos na an&#225;lise da atua&#231;&#227;o das diferentes radia&#231;&#245;es&#44; j&#225; que a melanog&#234;nese atua de modo diferente nos fototipos mais altos &#40;III&#8208;V&#41;&#44; provoca maior pigmenta&#231;&#227;o com evolu&#231;&#227;o para bronzeamento de modo dose&#8208;dependente&#44; diferentemente dos fototipos mais baixos &#40;I&#8208;II&#41;&#44; em que a irradia&#231;&#227;o promove menor est&#237;mulo&#46; Em estudo experimental&#44; UVA e LV n&#227;o induziram melanog&#234;nese em pacientes com fototipo II&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">11&#44;22</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">A melan&#244;genese humana &#233; um processo complexo em que diferentes intera&#231;&#245;es ocorrem de maneira organizada para a prote&#231;&#227;o das estruturas cut&#226;neas&#44; al&#233;m de regula&#231;&#227;o de ciclos essenciais para a sobreviv&#234;ncia do indiv&#237;duo&#44; como o ciclo circadiano&#46; Os melan&#243;citos comp&#245;em uma rede com uma leitura pr&#243;pria da luz ambiental que responde de acordo com os objetivos supracitados&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">23</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Houve diferentes caracter&#237;sticas na resposta melanog&#234;nica entre as topografias e entre as radia&#231;&#245;es&#46; A forma&#231;&#227;o de dendritos ocorre na fase G2 do crescimento dos melan&#243;citos e representa um importante sinal de resposta melanog&#234;nica&#44; em nosso caso induzida principalmente pela irradia&#231;&#227;o de maior potencial mutag&#234;nico &#40;UVB&#41;&#46; Apesar de a melanog&#234;nese ser percebida de modo semelhante em ambas as topografias&#44; a forma&#231;&#227;o de dendritos pode significar maior persist&#234;ncia do fen&#244;meno e maior efici&#234;ncia na transfer&#234;ncia de melanossomas na epiderme&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">A pele com melasma tamb&#233;m se caracteriza pela presen&#231;a de melanossomas mais maduros&#44; equivalentes ao que ocorre em popula&#231;&#245;es mais pigmentadas&#46; Neste experimento&#44; a irradia&#231;&#227;o UVA promoveu granula&#231;&#227;o mais evidente do que as demais radia&#231;&#245;es testadas&#44; exclusivamente na pele com melasma&#44; evidenciou que a melanog&#234;nese do melasma ocorra de modo mais intenso e assemelhe&#8208;se aos fen&#243;tipos mais pigmentados&#46; De fato&#44; a miscigena&#231;&#227;o africana foi associada ao maior risco de melasma em nossa popula&#231;&#227;o e genes ancestrais relacionados &#224; melanog&#234;nese podem justificar a resposta pigmentar diferenciada entre as topografias&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">7</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">O papel da melanina d&#233;rmica permanece sem defini&#231;&#227;o clara no melasma&#59; uma das hip&#243;teses &#233; que a disfun&#231;&#227;o arquitetural da membrana basal e a autofagia dos melan&#243;citos da derme possam ocasionar a presen&#231;a dos melan&#243;fagos d&#233;rmicos&#44; semelhantemente ao ocorrido no fotoenvelhecimento&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">24&#44;25</span></a> Neste estudo&#44; UVA e UVB promoveram maior taxa de melanina na derme superior&#59; entretanto&#44; tal densidade &#233; cerca de 100 vezes menor do que a epid&#233;rmica em ambas as topografias&#44; o que deve contribuir pouco para o fen&#243;tipo cl&#237;nico&#44; mas pode sinalizar altera&#231;&#245;es subjacentes na derme superior&#44; zona de membrana basal e camada basal&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Finalmente&#44; apesar do papel fundamental da radia&#231;&#227;o solar no agravamento do melasma&#44; n&#227;o foram evidenciadas express&#245;es diferenciais de p53 entre a pele com melasma e normal adjacente&#44; sugeriu&#8208;se que a manuten&#231;&#227;o da melanog&#234;nese possa se dever a altera&#231;&#245;es subjacentes da derme superior e da epiderme&#44; que induzem a hiperfun&#231;&#227;o melanoc&#237;tica&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> Ademais&#44; o uso exclusivo de filtro solar&#44; apesar de efeito preventivo&#44; n&#227;o &#233; suficiente para a completa remiss&#227;o do quadro&#44; o que significa a necessidade de cont&#237;nuo estudo fisiopatol&#243;gico em busca de tratamentos que levem &#224; revers&#227;o de todo o processo&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;26</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">O presente estudo promoveu uma an&#225;lise preliminar dos efeitos independentes das radia&#231;&#245;es UVB&#44; UVA e LV&#46; Novas investiga&#231;&#245;es devem ser conduzidas a fim de elucidar o efeito de combina&#231;&#245;es e dosagens de irradia&#231;&#245;es que espelhem as condi&#231;&#245;es ambientais&#46; A intera&#231;&#227;o entre UVA e LV ainda &#233; desconhecida&#59; acredita&#8208;se que interajam no mesmo precursor de melanina durante a melanog&#234;nese&#46; Essa associa&#231;&#227;o provavelmente resulta em um comportamento mais evidente da melanog&#234;nese em situa&#231;&#245;es naturais&#44; nas quais LV e UVA expressam&#8208;se conjuntamente&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">20</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Este estudo apresenta limita&#231;&#245;es inerentes &#224; t&#233;cnica com modelo <span class="elsevierStyleItalic">ex vivo</span>&#44; pode sofrer altera&#231;&#245;es quanto &#224;s diferentes condi&#231;&#245;es de coleta e armazenamento&#46; Entretanto&#44; n&#227;o impediu a identifica&#231;&#227;o de resposta melanog&#234;nica&#46; Outra limita&#231;&#227;o pode ser apontada pelo fato de as irradia&#231;&#245;es nos modelos de pele <span class="elsevierStyleItalic">ex vivo</span> ocorrerem com comprimentos de onda independentes &#40;UVB&#44; UVA e LV&#41;&#44; o que n&#227;o acontece na exposi&#231;&#227;o ambiental&#46; Al&#233;m dos fatores apresentados&#44; os modelos <span class="elsevierStyleItalic">ex vivo</span> est&#227;o dissociados do organismo&#44; limitam a intera&#231;&#227;o entre os sistemas hormonal&#44; neural e vasomotor&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Novas experimenta&#231;&#245;es devem considerar modelos de irradia&#231;&#245;es repetidas de baixa intensidade&#44; assim como associadas entre si&#44; a fim de reproduzir a exposi&#231;&#227;o cotidiana dos pacientes&#46; Al&#233;m disso&#44; pode&#8208;se testar a inclus&#227;o de ativos como &#225;cido tranex&#226;mico e antioxidantes na preven&#231;&#227;o da melanog&#234;nese no melasma&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0185" class="elsevierStylePara elsevierViewall">Houve resposta melanog&#234;nica epid&#233;rmica tanto na pele com melasma quanto na pele normal adjacente induzida por UVB&#44; UVA ou LV&#46; Os padr&#245;es morfol&#243;gicos relacionados &#224; fotobiologia da melanog&#234;nese sugerem que diferentes radia&#231;&#245;es promovam respostas individualizadas na pele com melasma&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Suporte financeiro</span><p id="par0190" class="elsevierStylePara elsevierViewall">CNPq &#40;Pibic n<span class="elsevierStyleSup">o</span>&#46;148501&#47;2018&#8208;4&#41;&#59; Funaderm &#40;001&#47;2019&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Contribui&#231;&#227;o dos autores</span><p id="par0195" class="elsevierStylePara elsevierViewall">Giovana Piteri Alc&#226;ntara&#58; 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; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Ana Cl&#225;udia Cavalcante Esp&#243;sito&#58; 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; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Thain&#225; Oliveira Felicio Olivatti&#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&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Melissa Mari Yoshida&#58; 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; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">H&#233;lio Amante Miot&#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="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflitos de interesse</span><p id="par0220" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">N&#227;o se conhece o papel independente das radia&#231;&#245;es solares na melanog&#234;nese diferencial entre melasma e a pele adjacente&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar respostas melanog&#234;nicas da pele com melasma facial e pele adjacente &#224;s irradia&#231;&#245;es UVB&#44; UVA e luz vis&#237;vel&#44; em modelo <span class="elsevierStyleItalic">ex vivo</span>&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudo <span class="elsevierStyleItalic">quasi</span>&#8208;experimental que envolveu 22 portadores de melasma&#46; Coletaram&#8208;se amostras de pele facial &#40;melasma e adjacente&#41;&#44; armazenadas em meio DMEM&#44; em temperatura ambiente&#46; Um fragmento foi acondicionado sob abrigo da luz&#44; enquanto outro foi exposto a uma das radia&#231;&#245;es UVB&#44; UVA e luz vis&#237;vel &#40;componente azul&#8208;violeta&#41;&#58; 166<span class="elsevierStyleHsp" style=""></span>mJ&#47;cm<span class="elsevierStyleSup">2</span>&#44; 1&#44;524<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span> e 40<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span>&#46; Em seguida&#44; todas as amostras foram mantidas por 72 horas ao abrigo da luz e coradas pelo Fontana&#8208;Masson para avaliar pigmenta&#231;&#227;o da camada basal&#44; dendritos e granula&#231;&#227;o da melanina&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Houve efetiva melanog&#234;nese na camada basal no melasma e na pele normal adjacente ap&#243;s todas as irradia&#231;&#245;es &#40;p &#60; 0&#44;01&#41;&#46; A mediana de incremento foi&#58; UVB 4&#44;7&#37; <span class="elsevierStyleItalic">vs</span>&#46; 8&#44;5&#37;&#59; UVA 9&#44;5&#37; <span class="elsevierStyleItalic">vs</span>&#46; 9&#44;9&#37;&#59; e luz vis&#237;vel 6&#44;8&#37; <span class="elsevierStyleItalic">vs</span>&#46; 11&#44;7&#37;&#44; sem diferen&#231;a significativa entre as topografias&#46; Houve aumento na granula&#231;&#227;o da melanina &#40;melanossomas mais grosseiros&#41; somente ap&#243;s a irradia&#231;&#227;o com UVA e apenas na pele com melasma &#40;p &#61; 0&#44;05&#41;&#46; Houve aumento da contagem de dendritos dos melan&#243;citos induzidos pela radia&#231;&#227;o UVB em ambas as topografias &#40;p &#8804; 0&#44;05&#41;&#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">Emprego de modelo <span class="elsevierStyleItalic">ex vivo</span>&#44; com regimes de irradia&#231;&#245;es independentes para UVB&#44; UVA e luz vis&#237;vel&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Houve melanog&#234;nese tanto no melasma quanto na pele adjacente induzida por UVB&#44; UVA e luz vis&#237;vel&#46; Os padr&#245;es morfol&#243;gicos sugerem que diferentes radia&#231;&#245;es promovam respostas individualizadas na pele com melasma&#46;</p></span>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Irradia&#231;&#227;o&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">Vari&#225;vel&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  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Melasma facial</th><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">Pele normal adjacente</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">p &#40;tempo&#42;grupo&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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">PRE&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">POS&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">p<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></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">PRE&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">POS&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">p<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UVB</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">MelBasal&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">64 &#40;60&#8208;65&#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">65 &#40;65&#8208;68&#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">&#60; 0&#44;01&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">54 &#40;53&#8208;56&#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">56 &#40;55&#8208;62&#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">&#60; 0&#44;01&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&#44;09&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">MelDS&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 &#40;30&#8208;77&#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">45 &#40;38&#8208;97&#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&#44;24&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 &#40;32&#8208;71&#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">67 &#40;41&#8208;87&#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&#44;04&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&#44;84&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">Dendritos&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;2&#8208;8&#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 &#40;8&#8208;18&#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">&#60; 0&#44;01&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;3&#8208;14&#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">11 &#40;7&#8208;16&#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&#44;05&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&#44;59&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">GranMelanos&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&#44;0 &#40;1&#44;5&#8208;2&#44;1&#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&#44;6 &#40;1&#44;3&#8208;2&#44;0&#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&#44;11&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&#44;9 &#40;1&#44;4&#8208;2&#44;0&#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&#44;9 &#40;1&#44;6&#8208;2&#44;0&#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&#44;80&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&#44;98&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="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UVA</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">MelBasal&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">62 &#40;54&#8208;66&#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">70 &#40;57&#8208;72&#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">&#60; 0&#44;01&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">56 &#40;49&#8208;61&#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">57 &#40;50&#8208;63&#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">&#60; 0&#44;01&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&#44;06&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">MelDS&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 &#40;18&#8208;88&#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">86 &#40;36&#8208;144&#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&#44;05&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">45 &#40;27&#8208;90&#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">74 &#40;34&#8208;204&#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&#44;50&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&#44;88&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">Dendritos&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">8 &#40;4&#8208;11&#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">8 &#40;2&#8208;22&#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&#44;92&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">3 &#40;2&#8208;5&#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
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          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Mediana e quartis &#40;p25&#8208;p75&#41; do percentual de melanina da camada basal&#44; da derme superior&#44; contagem de dendritos e granula&#231;&#227;o da melanina nos fragmentos de pele de melasma e pele n&#227;o afetada adjacente&#44; antes e ap&#243;s &#40;PRE e POS&#41; irradia&#231;&#227;o com UVB&#44; UVA e luz vis&#237;vel &#40;LV&#41;&#46; An&#225;lise dos dados ajustada por fototipo</p>"
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Investigação
Avaliação da resposta melanogênica ex vivo às radiações UVB, UVA e luz visível no melasma facial e na pele adjacente não afetada
Giovana Piteri Alcantaraa, Ana Cláudia Cavalcante Espositob, Thainá Oliveira Felicio Olivattic, Melissa Mari Yoshidac, Hélio Amante Miota,
Autor para correspondência
heliomiot@gmail.com

Autor para correspondência.
a Departamento de Dermatologia e Radioterapia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP, Brasil
b Programa de Pós‐Graduação da Patologia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP, Brasil
c Curso de Graduação em Medicina, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP, Brasil
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    "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">Melasma &#233; hipermelanose cr&#244;nica e adquirida resultante de uma disfun&#231;&#227;o da melanog&#234;nese&#58; aumento da produ&#231;&#227;o&#44; transfer&#234;ncia e maior maturidade dos melanossomos&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">1</span></a> &#201; uma condi&#231;&#227;o frequente na rotina dermatol&#243;gica&#44; totaliza 3&#44;6&#37; das consultas dermatol&#243;gicas segundo estudo da Sociedade Brasileira de Dermatologia&#44; em 2018&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a> Acomete principalmente mulheres na idade f&#233;rtil &#40;25&#8208;50 anos&#41; e fototipos intermedi&#225;rios &#40;III&#8208;V&#41;&#46; As les&#245;es cl&#237;nicas do melasma s&#227;o m&#225;culas comumente sim&#233;tricas&#44; hipercr&#244;micas&#44; bem delimitadas&#44; situadas nas topografias expostas ao sol&#44; especialmente a face&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a> A fisiopatologia ainda n&#227;o est&#225; completamente esclarecida&#44; mas h&#225; intera&#231;&#227;o entre gen&#233;tica &#40;heran&#231;a autoss&#244;mica dominante&#41;&#44; fatores hormonais e exposi&#231;&#227;o &#224; radia&#231;&#227;o solar&#44; o que leva &#224; maior melanog&#234;nese focal&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">3&#8211;7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">As altera&#231;&#245;es fenot&#237;picas na pele com melasma decorrem de modifica&#231;&#245;es epid&#233;rmicas tanto morfol&#243;gicas &#8211; melan&#243;citos aumentados de tamanho e dendritos proeminentes &#8722; quanto disfuncionais&#44; decorrentes da intera&#231;&#227;o complexa entre queratin&#243;citos&#44; melan&#243;citos e componentes da derme superior&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">H&#225; clara rela&#231;&#227;o entre a exposi&#231;&#227;o solar e a pioria do melasma&#44; desde ocorr&#234;ncia exclusiva em &#225;reas fotoexpostas at&#233; preval&#234;ncia em profissionais que se exp&#245;em ao sol e melhor resposta terap&#234;utica associada &#224; fotoprote&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;10</span></a> Mesmo com evid&#234;ncias do papel da radia&#231;&#227;o solar na hist&#243;ria cl&#237;nica da doen&#231;a&#44; n&#227;o se conhece o padr&#227;o de resposta individualizada do melasma em compara&#231;&#227;o com a pele normal adjacente &#224;s diferentes faixas de radia&#231;&#227;o solar &#40;UVB&#44; UVA e luz vis&#237;vel &#8211; LV&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">O conhecimento das diferentes influ&#234;ncias da radia&#231;&#227;o solar na melanog&#234;nese do melasma pode levar a melhor compreens&#227;o da fisiopatologia da doen&#231;a&#44; assim como &#224; elabora&#231;&#227;o de novas op&#231;&#245;es de tratamento&#44; al&#233;m de aprimorar as estrat&#233;gias de fotoprote&#231;&#227;o&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Este estudo objetivou determinar a resposta melanog&#234;nica do melasma facial em compara&#231;&#227;o com a pele normal adjacente ap&#243;s irradia&#231;&#227;o com UVA&#44; UVB ou LV em modelo <span class="elsevierStyleItalic">ex vivo&#46;</span></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material e m&#233;todos</span><p id="par0030" class="elsevierStylePara elsevierViewall">Estudo <span class="elsevierStyleItalic">quasi</span>&#8208;experimental <span class="elsevierStyleItalic">ex vivo</span> que envolveu fragmentos de pele de 22 portadores de melasma facial diagnosticados por dermatologista experiente&#46; Os participantes foram selecionados entre os pacientes do servi&#231;o de dermatologia do Hospital das Cl&#237;nicas da Faculdade de Medicina de Botucatu &#40;SP&#41; entre setembro de 2018 e janeiro de 2019&#46; O projeto foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa &#40;n&#176; 2&#46;700&#46;889&#41; e todos os participantes assinaram o termo de consentimento antes da inclus&#227;o&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Foram eleg&#237;veis para o estudo pacientes adultos &#40;&#62; 18 anos&#41;&#44; de ambos os sexos&#44; entre os fototipos III&#8208;V&#44; com melasma facial e sem tratamento&#44; exceto filtro solar por&#44; no m&#237;nimo&#44; 30 dias&#46; A restri&#231;&#227;o aos fototipos baseou&#8208;se no fato de que os fototipos I e II representam menos de 10&#37; dos casos de melasma e n&#227;o apresentam melanog&#234;nese satisfat&#243;ria ap&#243;s irradia&#231;&#227;o experimental&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">3&#44;11</span></a> N&#227;o h&#225; descri&#231;&#227;o de melasma em fototipo VI&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">N&#227;o foram inclu&#237;dos no estudo os portadores de outras dermatoses faciais&#44; dermatoses com fotossensibilidade&#44; colagenoses&#44; discrasias sangu&#237;neas&#44; usu&#225;rios de medica&#231;&#227;o anticoagulante&#44; imunossuprimidos&#44; gestantes ou lactantes&#46; A amostragem foi feita por conveni&#234;ncia&#44; usaram&#8208;se pacientes consecutivos&#44; concordantes em participar do estudo&#44; durante consultas m&#233;dicas na institui&#231;&#227;o&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">A coleta de material ocorreu de maneira padronizada e sob procedimento est&#233;ril&#46; Duas amostras de cada participante foram coletadas&#58; pele com melasma e pele normal adjacente&#44; distantes at&#233; 2<span class="elsevierStyleHsp" style=""></span>cm entre si&#44; sob anestesia local infiltrativa com lidoca&#237;na 2&#37; com vasoconstritor&#46; A remo&#231;&#227;o contemplou at&#233; a derme reticular&#44; com <span class="elsevierStyleItalic">punch</span> 3<span class="elsevierStyleHsp" style=""></span>mm e sutura com fio <span class="elsevierStyleItalic">mononylon</span> 6&#44;0&#46; Foram privilegiadas &#225;reas perif&#233;ricas da face a fim de minimizar cicatrizes inest&#233;ticas&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">As amostras foram seccionadas longitudinalmente em duas partes e armazenadas em 10<span class="elsevierStyleHsp" style=""></span>mL do meio DMEM &#40;<span class="elsevierStyleItalic">Dulbecco&#39;s Modified Eagle&#39;s Medium&#44; high glicose</span> &#8211; D5796&#44; Sigma Inc&#44; UK&#41; em frasco pl&#225;stico transparente est&#233;ril e mantido em temperatura ambiente&#44; segundo protocolo estabelecido por Olivatti&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> Uma parte do fragmento foi acondicionada imediatamente ao abrigo da luz&#44; enquanto a outra foi exposta a uma das radia&#231;&#245;es&#44; com uma dose total &#40;efetiva no tecido&#41; UVB&#44; UVA e LV de 166<span class="elsevierStyleHsp" style=""></span>mJ&#47;cm<span class="elsevierStyleSup">2</span>&#44; 1&#44;524<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span> e 40<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span> &#40;componente luz azul&#8208;violeta&#41;&#46; Os fragmentos foram irradiados a partir de fontes artificiais de UVB &#40;230<span class="elsevierStyleHsp" style=""></span>&#956;W&#47;cm<span class="elsevierStyleSup">2</span>&#59; fonte FS72T12&#47;UVB&#47;HO&#41; &#8211; 12<span class="elsevierStyleHsp" style=""></span>min&#44; UVA &#40;1270<span class="elsevierStyleHsp" style=""></span>&#956;W&#47;cm<span class="elsevierStyleSup">2</span>&#59; fonte Phillips TL 100W&#47;10R&#41; &#8211; 6<span class="elsevierStyleHsp" style=""></span>min e luz LED &#40;110 mW&#47;cm<span class="elsevierStyleSup">2</span> na faixa azul&#8208;violeta&#59; fonte GBRLUX 200W&#41; &#8211; 20<span class="elsevierStyleHsp" style=""></span>min&#44; com dist&#226;ncia padronizada de 10<span class="elsevierStyleHsp" style=""></span>cm&#46; A absorb&#226;ncia dos frascos pl&#225;sticos foi de cerca de 50&#37; para todas as radia&#231;&#245;es&#46; A aloca&#231;&#227;o dos participantes em cada tipo de irradia&#231;&#227;o foi consecutiva &#40;n&#227;o randomizada&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Ap&#243;s a irradia&#231;&#227;o&#44; ambos os fragmentos &#40;irradiados e n&#227;o irradiados&#41; foram cultivados ao abrigo da luz&#46; Passadas 72 horas&#44; as amostras foram retiradas do meio de cultura e mantidas em formol 10&#37; tamponado por 36 horas&#46; Posteriormente&#44; foram desidratadas em &#225;lcool 70&#37; por no m&#237;nimo 12 horas antes de ser emblocadas em parafina e da colora&#231;&#227;o dos cortes pelo Fontana&#8208;Masson &#40;FM&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Para estimar a melaniza&#231;&#227;o dos fragmentos&#44; capturaram&#8208;se quatro fotografias de &#225;reas centrais e interfoliculares das amostras coradas pelo FM&#44; privilegiaram&#8208;se &#225;reas <span class="elsevierStyleItalic">hotspot</span>&#46; As imagens foram salvas em formato JPG &#40;1264 &#215; 681 pixels&#41;&#46; Todo o processo de captura e an&#225;lise ocorreu de maneira cega quanto &#224; topografia ou ao tipo e regime de irradia&#231;&#227;o&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">As imagens selecionadas foram analisadas no programa ImageJ 1&#46;43&#44; a partir da sele&#231;&#227;o manual da camada basal&#44; seguida pela limiariza&#231;&#227;o a partir do canal <span class="elsevierStyleItalic">red</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">13</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">O principal desfecho do estudo foi o percentual de melaniza&#231;&#227;o da camada basal&#44; comparado entre os grupos &#40;melasma <span class="elsevierStyleItalic">vs</span>&#46; pele normal adjacente&#41; para cada radia&#231;&#227;o &#40;UVB&#44; UVA ou LV&#41;&#46; Tamb&#233;m foram avaliados o percentual de melanina na derme superficial&#44; a contagem de dendritos e as granula&#231;&#245;es dos melanossomas &#40;Escore&#58; 1&#43;&#44; granula&#231;&#227;o fina&#59; 2&#43;&#44; granula&#231;&#227;o moderada&#59; 3&#43;&#44; granula&#231;&#227;o grosseira&#41; nas &#225;reas amostradas&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">O valor m&#233;dio do percentual de melanina da camada basal&#44; da derme superior&#44; a contagem de dendritos e os escores de granula&#231;&#227;o foram tabulados para cada esp&#233;cime&#46; Os grupos de compara&#231;&#227;o foram avaliados segundo modelo linear generalizado de efeitos mistos&#44; ajustados pelo fototipo&#44; an&#225;lise robusta&#44; com matriz de covari&#226;ncia n&#227;o estruturada e corre&#231;&#227;o <span class="elsevierStyleItalic">post hoc</span> de Sidak&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">14</span></a> As distribui&#231;&#245;es de probabilidade variaram para o tipo de vari&#225;vel analisada &#40;ordinal e gama&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">A amostra foi dimensionada ap&#243;s pr&#233;&#8208;teste com a dosimetria de radia&#231;&#227;o que levava &#224; expectativa de aumento de 10&#37; no percentual de melaniza&#231;&#227;o na camada basal avaliada por an&#225;lise de imagem digital das l&#226;minas coradas pelo FM&#44; consideraram&#8208;se alfa 5&#37; e poder de 20&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Os dados foram tabulados em MsExcel 2013&#44; analisados no IBM SPSS 25&#46; Considerou&#8208;se significativo p&#8208;valor &#8804; 0&#44;05 bicaudal&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0090" class="elsevierStylePara elsevierViewall">Foram avaliados 89 fragmentos de pele de 22 portadores de melasma facial &#40;um participante voluntariou&#8208;se para a coleta de quatro amostras com o intuito de testar todas as irradia&#231;&#245;es&#41;&#46; A idade m&#233;dia &#40;desvio&#8208;padr&#227;o&#41; dos participantes foi de 42&#44;1 &#40;10&#44;4&#41; anos &#8211; 21 do sexo feminino &#8211; e quanto aos fototipos&#44; III &#40;46&#37;&#41;&#44; IV &#40;27&#37;&#41; e V &#40;27&#37;&#41;&#46; Houve contamina&#231;&#227;o em tr&#234;s fragmentos de cultura &#40;UVA pele normal adjacente pr&#233;&#8208;irradia&#231;&#227;o&#59; UVB pele do melasma p&#243;s&#8208;irradia&#231;&#227;o&#44; UVB pele normal adjacente p&#243;s&#8208;irradia&#231;&#227;o&#41;&#44; que n&#227;o foram inclu&#237;dos na an&#225;lise dos resultados&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Os pacientes cujas amostras foram submetidas &#224; irradia&#231;&#227;o UVB&#44; UVA e LV apresentavam&#44; respectivamente&#44; fototipos&#58; III &#40;33&#37; <span class="elsevierStyleItalic">vs</span>&#46; 37&#37; <span class="elsevierStyleItalic">vs</span>&#46; 0&#37;&#41;&#44; IV &#40;44&#37; <span class="elsevierStyleItalic">vs</span>&#46; 37&#37; <span class="elsevierStyleItalic">vs</span>&#46; 71&#37;&#41; e V &#40;22&#37; <span class="elsevierStyleItalic">vs</span>&#46; 25&#37; <span class="elsevierStyleItalic">vs</span>&#46; 28&#37;&#41; &#40;p &#61; 0&#44;35&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Houve melanog&#234;nese no melasma e na pele normal adjacente &#40;p &#60; 0&#44;01&#41; ap&#243;s todas as irradia&#231;&#245;es &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1&#8208;3</a>&#44; <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#58; mediana de incremento UVB &#40;4&#44;7&#37; <span class="elsevierStyleItalic">vs</span>&#46; 8&#44;5&#37;&#41;&#44; UVA &#40;9&#44;5&#37; <span class="elsevierStyleItalic">vs</span>&#46; 9&#44;9&#37;&#41; e LV &#40;6&#44;8&#37; <span class="elsevierStyleItalic">vs</span>&#46; 11&#44;7&#37;&#41;&#44; sem diferen&#231;a significativa na compara&#231;&#227;o entre as topografias&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Quando ajustado para o fototipo&#44; a contagem de dendritos aumentou &#40;68&#44;8&#37;&#41; apenas ap&#243;s irradia&#231;&#227;o com UVB em ambas as topografias &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; Houve aumento no escore de granula&#231;&#227;o da melanina &#40;melanossomas mais grosseiros&#41; apenas ap&#243;s a irradia&#231;&#227;o com UVA e apenas na pele com melasma &#40;p &#61; 0&#44;05&#41;&#46; Houve tamb&#233;m aumento do percentual de melanina na derme superior na pele adjacente ap&#243;s irradia&#231;&#227;o com UVB e no melasma ap&#243;s irradia&#231;&#227;o com UVA &#40;p &#8804; 0&#44;05&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0110" class="elsevierStylePara elsevierViewall">Houve efetiva melanog&#234;nese epid&#233;rmica nos modelos de pele &#40;<span class="elsevierStyleItalic">ex vivo</span>&#41; submetidos &#224; UVB&#44; UVA e LV&#44; sem diferen&#231;a quantitativa entre as topografias &#40;melasma facial e pele normal adjacente&#41;&#44; subsidiou a import&#226;ncia da fotoprote&#231;&#227;o de amplo espectro no tratamento de dermatoses pigmentares&#44; como o melasma&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">As doses de radia&#231;&#227;o testadas&#44; apesar de independentes&#44; equivaleram a 6&#8208;12 minutos de exposi&#231;&#227;o solar ao meio&#8208;dia&#44; no ver&#227;o&#44; no interior do Brasil &#40;latitude&#58; 22&#176;53&#8217;09&#8221;S&#59; longitude&#58; 48&#176;26&#8217;42&#8221;W&#59; altitude&#58; 804 m&#41;&#44; em dia sem nuvens&#44; medida em 9&#47;12&#47;2018 pelos pesquisadores&#46; Entretanto&#44; os n&#237;veis de UVA e LV solares alcan&#231;am um plat&#244; de energia com dura&#231;&#227;o entre 9 horas at&#233; as 18 horas&#44; enquanto o UVB apresenta seu pico entre as 11 horas e as 15 horas&#44; tanto no ver&#227;o quanto no inverno&#46; Isso pode justificar o relato de pioria do melasma ap&#243;s breves exposi&#231;&#245;es desprotegidas fora do hor&#225;rio de pico de UVB&#44; ou mesmo ap&#243;s longas exposi&#231;&#245;es com fotoprotetor &#40;p&#46;ex&#46;&#44; congestionamento no tr&#226;nsito&#41;&#44; visto que n&#227;o h&#225; completo bloqueio das radia&#231;&#245;es solares pelos filtros solares&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a> Em tempo&#44; as radia&#231;&#245;es UVB&#44; UVA e LV medidas em ambientes fechados &#40;p&#46;ex&#46;&#44; telas de celular e computadores&#44; l&#226;mpadas fluorescentes&#41; s&#227;o desprez&#237;veis para efeitos de melanog&#234;nese &#40;dados n&#227;o mostrados&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">A LV tem amplo espectro de comprimentos de onda &#40;400&#8208;700<span class="elsevierStyleHsp" style=""></span>nm&#41; que n&#227;o atuam de maneira homog&#234;nea na pigmenta&#231;&#227;o&#46; Um estudo feito na Fran&#231;a testou o espectro da luz azul&#8208;violeta &#40;400&#8208;500<span class="elsevierStyleHsp" style=""></span>nm&#41; em compara&#231;&#227;o com o espectro da luz vermelha &#40;620&#8208;750<span class="elsevierStyleHsp" style=""></span>nm&#41; e n&#227;o houve pigmenta&#231;&#227;o induzida pela segunda&#44; o que justificou a escolha da faixa azul violeta para este estudo&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Apenas filtros solares com cor apresentam prote&#231;&#227;o efetiva contra LV e&#44; em sua maioria&#44; apresentam tamb&#233;m melhor desempenho na prote&#231;&#227;o UVA&#46; Em levantamento brasileiro com 41 filtros solares opacos&#44; 63&#37; bloquearam &#62; 99&#44;9&#37; de UVA e 63&#37; bloquearam &#62; 99&#44;9&#37; da transmit&#226;ncia da luz azul&#8208;violeta&#46; Entretanto&#44; tal bloqueio n&#227;o foi coincidente&#44; j&#225; que 31&#37; dos filtros opacos que bloquearam &#62; 99&#44;9&#37; da LV n&#227;o tiveram o mesmo desempenho quanto ao UVA&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a> Em tempo&#44; este estudo &#233; o primeiro a evidenciar o papel da LV na melanog&#234;nese de pacientes com melasma facial&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">N&#227;o ocorreu melanog&#234;nese diferencial entre a pele com melasma e normal adjacente nas doses testadas&#44; o que n&#227;o exclui a possibilidade de que a pele com melasma seja sens&#237;vel a doses mais baixas de irradia&#231;&#227;o ou responda diferentemente a exposi&#231;&#245;es repetidas&#46; A pr&#243;pria maior pigmenta&#231;&#227;o basal do melasma tamb&#233;m pode significar um <span class="elsevierStyleItalic">status</span> de resist&#234;ncia &#224; melanog&#234;nese induzida pela exposi&#231;&#227;o cr&#244;nica &#224; radia&#231;&#227;o UV e LV&#46; Al&#233;m disso&#44; h&#225; maior reten&#231;&#227;o epid&#233;rmica da melanina no melasma e sua melanog&#234;nese depende de diversas outras altera&#231;&#245;es d&#233;rmicas que favorecem a manuten&#231;&#227;o da pigmenta&#231;&#227;o&#44; em detrimento da indu&#231;&#227;o melanog&#234;nica pela radia&#231;&#227;o UV e LV&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">A melanog&#234;nese ocorre de maneira desigual&#44; depende do tipo e da dose de radia&#231;&#227;o&#46; O UVB causa eritema que persiste por dias a semanas &#40;depende do fototipo&#41; e pigmenta&#231;&#227;o que evolui para bronzeamento&#46; O UVA provoca eritema em 4 horas e pigmenta&#231;&#227;o imediata que evolui com bronzeamento duradouro&#46; Na LV&#44; o eritema &#233; menos proeminente&#44; pode ocorrer precocemente &#40;2 horas&#41; e a pigmenta&#231;&#227;o &#233; sustentada com evolu&#231;&#227;o para bronzeamento&#44; por&#233;m apenas nos fototipos altos&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">19&#8211;21</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Toda resposta melanog&#234;nica acontece de maneira dose&#8208;dependente&#46; No entanto&#44; &#233; indispens&#225;vel considerar os fototipos na an&#225;lise da atua&#231;&#227;o das diferentes radia&#231;&#245;es&#44; j&#225; que a melanog&#234;nese atua de modo diferente nos fototipos mais altos &#40;III&#8208;V&#41;&#44; provoca maior pigmenta&#231;&#227;o com evolu&#231;&#227;o para bronzeamento de modo dose&#8208;dependente&#44; diferentemente dos fototipos mais baixos &#40;I&#8208;II&#41;&#44; em que a irradia&#231;&#227;o promove menor est&#237;mulo&#46; Em estudo experimental&#44; UVA e LV n&#227;o induziram melanog&#234;nese em pacientes com fototipo II&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">11&#44;22</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">A melan&#244;genese humana &#233; um processo complexo em que diferentes intera&#231;&#245;es ocorrem de maneira organizada para a prote&#231;&#227;o das estruturas cut&#226;neas&#44; al&#233;m de regula&#231;&#227;o de ciclos essenciais para a sobreviv&#234;ncia do indiv&#237;duo&#44; como o ciclo circadiano&#46; Os melan&#243;citos comp&#245;em uma rede com uma leitura pr&#243;pria da luz ambiental que responde de acordo com os objetivos supracitados&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">23</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Houve diferentes caracter&#237;sticas na resposta melanog&#234;nica entre as topografias e entre as radia&#231;&#245;es&#46; A forma&#231;&#227;o de dendritos ocorre na fase G2 do crescimento dos melan&#243;citos e representa um importante sinal de resposta melanog&#234;nica&#44; em nosso caso induzida principalmente pela irradia&#231;&#227;o de maior potencial mutag&#234;nico &#40;UVB&#41;&#46; Apesar de a melanog&#234;nese ser percebida de modo semelhante em ambas as topografias&#44; a forma&#231;&#227;o de dendritos pode significar maior persist&#234;ncia do fen&#244;meno e maior efici&#234;ncia na transfer&#234;ncia de melanossomas na epiderme&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">A pele com melasma tamb&#233;m se caracteriza pela presen&#231;a de melanossomas mais maduros&#44; equivalentes ao que ocorre em popula&#231;&#245;es mais pigmentadas&#46; Neste experimento&#44; a irradia&#231;&#227;o UVA promoveu granula&#231;&#227;o mais evidente do que as demais radia&#231;&#245;es testadas&#44; exclusivamente na pele com melasma&#44; evidenciou que a melanog&#234;nese do melasma ocorra de modo mais intenso e assemelhe&#8208;se aos fen&#243;tipos mais pigmentados&#46; De fato&#44; a miscigena&#231;&#227;o africana foi associada ao maior risco de melasma em nossa popula&#231;&#227;o e genes ancestrais relacionados &#224; melanog&#234;nese podem justificar a resposta pigmentar diferenciada entre as topografias&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">7</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">O papel da melanina d&#233;rmica permanece sem defini&#231;&#227;o clara no melasma&#59; uma das hip&#243;teses &#233; que a disfun&#231;&#227;o arquitetural da membrana basal e a autofagia dos melan&#243;citos da derme possam ocasionar a presen&#231;a dos melan&#243;fagos d&#233;rmicos&#44; semelhantemente ao ocorrido no fotoenvelhecimento&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">24&#44;25</span></a> Neste estudo&#44; UVA e UVB promoveram maior taxa de melanina na derme superior&#59; entretanto&#44; tal densidade &#233; cerca de 100 vezes menor do que a epid&#233;rmica em ambas as topografias&#44; o que deve contribuir pouco para o fen&#243;tipo cl&#237;nico&#44; mas pode sinalizar altera&#231;&#245;es subjacentes na derme superior&#44; zona de membrana basal e camada basal&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Finalmente&#44; apesar do papel fundamental da radia&#231;&#227;o solar no agravamento do melasma&#44; n&#227;o foram evidenciadas express&#245;es diferenciais de p53 entre a pele com melasma e normal adjacente&#44; sugeriu&#8208;se que a manuten&#231;&#227;o da melanog&#234;nese possa se dever a altera&#231;&#245;es subjacentes da derme superior e da epiderme&#44; que induzem a hiperfun&#231;&#227;o melanoc&#237;tica&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">4</span></a> Ademais&#44; o uso exclusivo de filtro solar&#44; apesar de efeito preventivo&#44; n&#227;o &#233; suficiente para a completa remiss&#227;o do quadro&#44; o que significa a necessidade de cont&#237;nuo estudo fisiopatol&#243;gico em busca de tratamentos que levem &#224; revers&#227;o de todo o processo&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;26</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">O presente estudo promoveu uma an&#225;lise preliminar dos efeitos independentes das radia&#231;&#245;es UVB&#44; UVA e LV&#46; Novas investiga&#231;&#245;es devem ser conduzidas a fim de elucidar o efeito de combina&#231;&#245;es e dosagens de irradia&#231;&#245;es que espelhem as condi&#231;&#245;es ambientais&#46; A intera&#231;&#227;o entre UVA e LV ainda &#233; desconhecida&#59; acredita&#8208;se que interajam no mesmo precursor de melanina durante a melanog&#234;nese&#46; Essa associa&#231;&#227;o provavelmente resulta em um comportamento mais evidente da melanog&#234;nese em situa&#231;&#245;es naturais&#44; nas quais LV e UVA expressam&#8208;se conjuntamente&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">20</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Este estudo apresenta limita&#231;&#245;es inerentes &#224; t&#233;cnica com modelo <span class="elsevierStyleItalic">ex vivo</span>&#44; pode sofrer altera&#231;&#245;es quanto &#224;s diferentes condi&#231;&#245;es de coleta e armazenamento&#46; Entretanto&#44; n&#227;o impediu a identifica&#231;&#227;o de resposta melanog&#234;nica&#46; Outra limita&#231;&#227;o pode ser apontada pelo fato de as irradia&#231;&#245;es nos modelos de pele <span class="elsevierStyleItalic">ex vivo</span> ocorrerem com comprimentos de onda independentes &#40;UVB&#44; UVA e LV&#41;&#44; o que n&#227;o acontece na exposi&#231;&#227;o ambiental&#46; Al&#233;m dos fatores apresentados&#44; os modelos <span class="elsevierStyleItalic">ex vivo</span> est&#227;o dissociados do organismo&#44; limitam a intera&#231;&#227;o entre os sistemas hormonal&#44; neural e vasomotor&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Novas experimenta&#231;&#245;es devem considerar modelos de irradia&#231;&#245;es repetidas de baixa intensidade&#44; assim como associadas entre si&#44; a fim de reproduzir a exposi&#231;&#227;o cotidiana dos pacientes&#46; Al&#233;m disso&#44; pode&#8208;se testar a inclus&#227;o de ativos como &#225;cido tranex&#226;mico e antioxidantes na preven&#231;&#227;o da melanog&#234;nese no melasma&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0185" class="elsevierStylePara elsevierViewall">Houve resposta melanog&#234;nica epid&#233;rmica tanto na pele com melasma quanto na pele normal adjacente induzida por UVB&#44; UVA ou LV&#46; Os padr&#245;es morfol&#243;gicos relacionados &#224; fotobiologia da melanog&#234;nese sugerem que diferentes radia&#231;&#245;es promovam respostas individualizadas na pele com melasma&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Suporte financeiro</span><p id="par0190" class="elsevierStylePara elsevierViewall">CNPq &#40;Pibic n<span class="elsevierStyleSup">o</span>&#46;148501&#47;2018&#8208;4&#41;&#59; Funaderm &#40;001&#47;2019&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Contribui&#231;&#227;o dos autores</span><p id="par0195" class="elsevierStylePara elsevierViewall">Giovana Piteri Alc&#226;ntara&#58; 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; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Ana Cl&#225;udia Cavalcante Esp&#243;sito&#58; 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; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica da literatura&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Thain&#225; Oliveira Felicio Olivatti&#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&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Melissa Mari Yoshida&#58; 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; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">H&#233;lio Amante Miot&#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="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflitos de interesse</span><p id="par0220" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">N&#227;o se conhece o papel independente das radia&#231;&#245;es solares na melanog&#234;nese diferencial entre melasma e a pele adjacente&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Avaliar respostas melanog&#234;nicas da pele com melasma facial e pele adjacente &#224;s irradia&#231;&#245;es UVB&#44; UVA e luz vis&#237;vel&#44; em modelo <span class="elsevierStyleItalic">ex vivo</span>&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudo <span class="elsevierStyleItalic">quasi</span>&#8208;experimental que envolveu 22 portadores de melasma&#46; Coletaram&#8208;se amostras de pele facial &#40;melasma e adjacente&#41;&#44; armazenadas em meio DMEM&#44; em temperatura ambiente&#46; Um fragmento foi acondicionado sob abrigo da luz&#44; enquanto outro foi exposto a uma das radia&#231;&#245;es UVB&#44; UVA e luz vis&#237;vel &#40;componente azul&#8208;violeta&#41;&#58; 166<span class="elsevierStyleHsp" style=""></span>mJ&#47;cm<span class="elsevierStyleSup">2</span>&#44; 1&#44;524<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span> e 40<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span>&#46; Em seguida&#44; todas as amostras foram mantidas por 72 horas ao abrigo da luz e coradas pelo Fontana&#8208;Masson para avaliar pigmenta&#231;&#227;o da camada basal&#44; dendritos e granula&#231;&#227;o da melanina&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Houve efetiva melanog&#234;nese na camada basal no melasma e na pele normal adjacente ap&#243;s todas as irradia&#231;&#245;es &#40;p &#60; 0&#44;01&#41;&#46; A mediana de incremento foi&#58; UVB 4&#44;7&#37; <span class="elsevierStyleItalic">vs</span>&#46; 8&#44;5&#37;&#59; UVA 9&#44;5&#37; <span class="elsevierStyleItalic">vs</span>&#46; 9&#44;9&#37;&#59; e luz vis&#237;vel 6&#44;8&#37; <span class="elsevierStyleItalic">vs</span>&#46; 11&#44;7&#37;&#44; sem diferen&#231;a significativa entre as topografias&#46; Houve aumento na granula&#231;&#227;o da melanina &#40;melanossomas mais grosseiros&#41; somente ap&#243;s a irradia&#231;&#227;o com UVA e apenas na pele com melasma &#40;p &#61; 0&#44;05&#41;&#46; Houve aumento da contagem de dendritos dos melan&#243;citos induzidos pela radia&#231;&#227;o UVB em ambas as topografias &#40;p &#8804; 0&#44;05&#41;&#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">Emprego de modelo <span class="elsevierStyleItalic">ex vivo</span>&#44; com regimes de irradia&#231;&#245;es independentes para UVB&#44; UVA e luz vis&#237;vel&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Houve melanog&#234;nese tanto no melasma quanto na pele adjacente induzida por UVB&#44; UVA e luz vis&#237;vel&#46; Os padr&#245;es morfol&#243;gicos sugerem que diferentes radia&#231;&#245;es promovam respostas individualizadas na pele com melasma&#46;</p></span>"
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Fragmentos histol&#243;gicos de pele corados pelo Fontana&#8208;Masson de melasma facial e pele normal adjacente antes e ap&#243;s irradia&#231;&#227;o com 40<span class="elsevierStyleHsp" style=""></span>J&#47;cm<span class="elsevierStyleSup">2</span> luz vis&#237;vel&#44; revelam aumento da densidade de melanina basal entre as amostras&#46; &#40;A&#41;&#44; pele normal adjacente pr&#233; irradia&#231;&#227;o LV&#59; &#40;B&#41;&#44; pele normal adjacente p&#243;s&#8208;irradia&#231;&#227;o LV&#59; &#40;C&#41;&#44; pele com melasma pr&#233;&#8208;irradia&#231;&#227;o LV&#59; &#40;D&#41;&#44; pele com melasma p&#243;s&#8208;irradia&#231;&#227;o com LV&#46;</p>"
        ]
      ]
      3 => 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:3 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">MelBasal</span>&#44; percentual de melanina na camada basal da epiderme&#59; <span class="elsevierStyleItalic">MelDS</span>&#44; percentual de melanina na derme superior &#40;&#215;100&#41;&#59; <span class="elsevierStyleItalic">GranMelanoss</span>&#44; escore de granula&#231;&#227;o dos melanossomas da epiderme &#40;1&#43;&#44; granula&#231;&#227;o fina&#59; 2&#43;&#44; granula&#231;&#227;o moderada&#59; 3&#43;&#44; granula&#231;&#227;o grosseira&#41; &#8211; m&#233;dia de 4 campos&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t" scope="col">Irradia&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">Vari&#225;vel&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">p &#40;tempo&#42;grupo&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PRE&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">POS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PRE&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">POS&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">p<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">MelBasal&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">64 &#40;60&#8208;65&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">65 &#40;65&#8208;68&#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
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                  \t\t\t\t">&#60; 0&#44;01&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">54 &#40;53&#8208;56&#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">56 &#40;55&#8208;62&#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">&#60; 0&#44;01&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&#44;09&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">MelDS&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
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                  \t\t\t\t">44 &#40;30&#8208;77&#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">45 &#40;38&#8208;97&#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
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                  \t\t\t\t">0&#44;24&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
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                  \t\t\t\t">44 &#40;32&#8208;71&#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
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                  \t\t\t\t">67 &#40;41&#8208;87&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;04&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;84&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Dendritos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6 &#40;2&#8208;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">10 &#40;8&#8208;18&#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
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                  \t\t\t\t">&#60; 0&#44;01&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;3&#8208;14&#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">11 &#40;7&#8208;16&#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
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                  \t\t\t\t">0&#44;05&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&#44;59&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">GranMelanos&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&#44;0 &#40;1&#44;5&#8208;2&#44;1&#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&#44;6 &#40;1&#44;3&#8208;2&#44;0&#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&#44;11&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&#44;9 &#40;1&#44;4&#8208;2&#44;0&#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&#44;9 &#40;1&#44;6&#8208;2&#44;0&#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&#44;80&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&#44;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " rowspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">UVA</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">MelBasal&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">62 &#40;54&#8208;66&#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">70 &#40;57&#8208;72&#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">&#60; 0&#44;01&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">56 &#40;49&#8208;61&#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">57 &#40;50&#8208;63&#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">&#60; 0&#44;01&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&#44;06&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">MelDS&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 &#40;18&#8208;88&#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">86 &#40;36&#8208;144&#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&#44;05&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">45 &#40;27&#8208;90&#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">74 &#40;34&#8208;204&#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
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                  """
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            1 => array:3 [
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">p&#44; melasma <span class="elsevierStyleItalic">vs</span>&#46; pele normal adjacente em fun&#231;&#227;o da resposta &#224; irradia&#231;&#227;o &#40;ajustado por fototipo&#41;&#46;</p>"
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          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Mediana e quartis &#40;p25&#8208;p75&#41; do percentual de melanina da camada basal&#44; da derme superior&#44; contagem de dendritos e granula&#231;&#227;o da melanina nos fragmentos de pele de melasma e pele n&#227;o afetada adjacente&#44; antes e ap&#243;s &#40;PRE e POS&#41; irradia&#231;&#227;o com UVB&#44; UVA e luz vis&#237;vel &#40;LV&#41;&#46; An&#225;lise dos dados ajustada por fototipo</p>"
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                      "titulo" => "Morphological and functional comparative study of melanocytes in melasma lesions"
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                          "etal" => false
                          "autores" => array:4 [
                            0 => "L&#46;D&#46;B&#46; Miot"
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                  "referenciaCompleta" => "Sociedade Brasileira de Dermatologia&#44; Miot HA&#44; Penna GO&#44; Ramos AMC&#44; Penna MLF&#44; Schmidt SM&#44; et al&#46; Profile of dermatological consultations in Brazil &#40;2018&#41;&#46; An Bras Dermatol&#46; 2018&#59;93&#58;916&#8208;28&#46;"
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                      "titulo" => "Clinical patterns and epidemiological characteristics of facial melasma in Brazilian women"
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                            0 => "A&#46;A&#46; Tamega"
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                            3 => "T&#46;C&#46; Gige"
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                            5 => "H&#46;A&#46; Miot"
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                      "Revista" => array:5 [
                        "tituloSerie" => "J Eur Acad Dermatology Venereol&#46;"
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                        "paginaFinal" => "1566"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Exploring pathways for sustained melanogenesis in facial melasma&#58; an immunofluorescence study"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46;C&#46;C&#46; Esp&#243;sito"
                            1 => "G&#46; Brianezi"
                            2 => "N&#46;P&#46; de Souza"
                            3 => "L&#46;D&#46;B&#46; Miot"
                            4 => "M&#46;E&#46;A&#46; Marques"
                            5 => "H&#46;A&#46; Miot"
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                    0 => array:2 [
                      "doi" => "10.1111/ics.12468"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Cosmet Sci&#46;"
                        "fecha" => "2018"
                        "volumen" => "40"
                        "paginaInicial" => "420"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29846953"
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ISSN: 26662752
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