Case and Research Letters
CD25+CD8+, CLA+CD4+, CD11a+ CD4+, and CD11a+ CD8+ T Cell Counts Are Elevated in the Blood of Brazilian Patients With Chronic Plaque Psoriasis
Los linfocitos T CD25+CD8+, CD4+CLA+, CD11a+CD4+ y CD11a+ CD8+ están elevados en la sangre de los pacientes brasileños con psoriasis en placas crónica
C. Porto Ferreiraa,b,
, A. Gomes da Silvaa, C.J. Martinsc, A.M. Da-Cruza,d
Autor para correspondencia
a Laboratório de Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz/FIOCRUZ, Brazil
b Instituto de Pesquisa Clínica Evandro Chagas/FIOCRUZ, Brazil
c Serviço de Dermatologia, Hospital Universitário Gaffré e Guinle, Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Brazil
d Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Brazil
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Porto Ferreira, A. Gomes da Silva, C.J. Martins, A.M. Da-Cruz" "autores" => array:4 [ 0 => array:4 [ "nombre" => "C." "apellidos" => "Porto Ferreira" "email" => array:1 [ 0 => "drcassioferreira@yahoo.com.br" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Gomes da Silva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "C.J." "apellidos" => "Martins" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "A.M." "apellidos" => "Da-Cruz" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Laboratório de Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz/FIOCRUZ, Brazil" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto de Pesquisa Clínica Evandro Chagas/FIOCRUZ, Brazil" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Serviço de Dermatologia, Hospital Universitário Gaffré e Guinle, Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Brazil" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Brazil" "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Autor para correspondencia." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Los linfocitos T CD25+CD8+, CD4+CLA+, CD11a+CD4+ y CD11a+ CD8+ están elevados en la sangre de los pacientes brasileños con psoriasis en placas crónica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1403 "Ancho" => 3312 "Tamanyo" => 174098 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A and B: Assessment of the degree of activation of CD4<span class="elsevierStyleSup">+</span> and CD8<span class="elsevierStyleSup">+</span> T cells in psoriasis patients and controls. Each point represents an individual. The horizontal bar represent the median.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Psoriasis is a recurrent, chronic inflammatory disorder that mainly affects the skin and joints<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>. In view of the scarcity of studies on peripheral lymphocyte subpopulations in Brazilian psoriasis patients, we performed cytofluorometric analysis of peripheral blood mononuclear cells (PBMC) in psoriatic patients and healthy controls in order to characterize the lymphocyte subpopulations and certain molecules involved in cell activation and migration.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The study was approved by the Ethics Committee of Escola de Medicina e Cirurgia (UNIRIO, MEC, Brazil) and all patients signed an informed consent.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Twenty-five individuals were recruited from the Dermatology Department of HUGG/UNIRIO/MEC-Brazil. Seventeen had chronic plaque psoriasis and there were 8 healthy controls. None of the psoriasis patients was receiving systemic treatment. The physician's global assessment score<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4</span></a> was 4 in 6 cases, 5 in 6 cases, and 6 in 5 cases.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A 20-ml blood sample was drawn from each patient and PBMCs were separated using the Ficoll-Hypaque gradient (Sigma Chemical Co, St.Louis, USA). Five microliters of each monoclonal antibody—anti-CD3, anti-CD4, anti-CD8, anti-CD11a (Immunotech, Beckman Coulter, France), anti-CD25, anti-CD69, and anti-CLA (BD Biosciences, California, USA)—were added according to the combinations listed in the <a class="elsevierStyleCrossRef" href="#tbl0005">table 1</a> table 1. Laboratory procedures were performed according to the manufacturer's instructions<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>. The nonparametric Mann-Whitney and Kruskal-Wallis tests were used for the statistical analysis, which was performed using GraphPad Prism version 4.00 for Windows (GraphPad Software, San Diego, California, USA).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Analysis of the lymphocyte subpopulations (CD3<span class="elsevierStyleSup">+</span> or total T cells, CD4<span class="elsevierStyleSup">+</span> or helper T cells, and CD8<span class="elsevierStyleSup">+</span> or cytotoxic T cells) revealed no significant differences between patients with psoriasis and healthy controls. The relative percentages of each lymphocyte subpopulation in patients and controls are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>. Lymphocyte activation was determined through analysis of CD25 and CD69 expression (<a class="elsevierStyleCrossRef" href="#fig0010">figs. 2 A and B</a>). Higher percentages of activated (CD25<span class="elsevierStyleSup">+</span> and CD69<span class="elsevierStyleSup">+</span>) cells were detected in the 2 lymphocyte subpopulations (CD4<span class="elsevierStyleSup">+</span> and CD8<span class="elsevierStyleSup">+</span>) in psoriatic patients; the difference compared to controls was significant for the percentage of CD25<span class="elsevierStyleSup">+</span> cells in the CD8<span class="elsevierStyleSup">+</span> T-cell subpopulation (mean [SD], 39.2% (26.9); median, 35.1%; <span class="elsevierStyleItalic">P</span> <.05), and there was a trend to elevation of the CD25<span class="elsevierStyleSup">+</span> CD4<span class="elsevierStyleSup">+</span> subpopulation. There was also a trend to elevation in the percentage of CD69<span class="elsevierStyleSup">+</span> cells in both T-cell subpopulations (CD4<span class="elsevierStyleSup">+</span>: mean, 16.0% [19.6]; median, 7.8%; CD8<span class="elsevierStyleSup">+</span>: mean, 2.0% [1.47]; median, 2.23%) in psoriatic patients when compared to controls (<a class="elsevierStyleCrossRef" href="#fig0010">fig. 2</a>B). Migration of circulating T lymphocytes to the skin was studied through an analysis of CLA and CD11a expression. Compared to control subjects, patients with psoriasis presented an increase in the percentage of CD4<span class="elsevierStyleSup">+</span> T cells expressing CLA (control group: mean, 19.30% [13.13]; median, 14.67%; psoriasis group: mean, 38.86% [20.67]; median, 39.76%; <span class="elsevierStyleItalic">P</span><.05). However, this was not observed in the CD8<span class="elsevierStyleSup">+</span> T cells, although increased CLA expression was detected in 4 of the 10 patients with high levels of CD8<span class="elsevierStyleSup">+</span> lymphocytes (<a class="elsevierStyleCrossRef" href="#fig0015">fig. 3</a>A). A significant increase in the percentage of cells with CD11a expression was observed in psoriasis patients compared to controls in both CD4<span class="elsevierStyleSup">+</span> (mean, 82.17% [29.91]; median, 99.45%; <span class="elsevierStyleItalic">P</span> < .01) and CD8<span class="elsevierStyleSup">+</span> T cells (mean, 84.96 [29.77]; median, 99.75; <span class="elsevierStyleItalic">P</span> < .05) (<a class="elsevierStyleCrossRef" href="#fig0015">fig. 3</a>B).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Although our study is somewhat limited by the small sample size, the results showed that there was no change in the proportion of CD4<span class="elsevierStyleSup">+</span> and CD8<span class="elsevierStyleSup">+</span> T cells in the PBMC population in psoriatic patients when compared with general population, as has been reported in previous studies<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>. However, we observed qualitative differences between the 2 groups in the expression of activation molecules CD25 and CD69. Although the results were significant only for CD25 expression in CD8<span class="elsevierStyleSup">+</span> T cells, there was a trend to increased expression of CD25 and CD69 in both CD4<span class="elsevierStyleSup">+</span> and CD8<span class="elsevierStyleSup">+</span> T cells, findings not reported by other authors<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>. The presence of activation molecules has been detected in the initial stages of psoriasis, even prior to the onset of clinically apparent lesions; these molecules are therefore presumably involved in lymphocyte recruitment and migration<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a>.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Our data indicate that, although there is no significant increase or variation in the relative percentages of circulating mononuclear cells in psoriatic patients, these cells are qualitatively different because they express activation molecules that are involved in the initiation and progression of psoriasis lesions.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1403 "Ancho" => 1639 "Tamanyo" => 98700 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Quantification of T lymphocyte subpopulations (CD4<span class="elsevierStyleSup">+</span> and CD8<span class="elsevierStyleSup">+</span> T cells) in the peripheral blood of patients with chronic plaque psoriasis. The results are expressed as percentage of positive cells. The horizontal bars represent the median values of the results. Each point represents an individual.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1403 "Ancho" => 3312 "Tamanyo" => 174098 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A and B: Assessment of the degree of activation of CD4<span class="elsevierStyleSup">+</span> and CD8<span class="elsevierStyleSup">+</span> T cells in psoriasis patients and controls. Each point represents an individual. The horizontal bar represent the median.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1271 "Ancho" => 3375 "Tamanyo" => 192480 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A. Elevated expression of molecules related to cutaneous cell migration (cutaneous lymphocyte associated antigen [CLA]) B. Endothelial tissue inflammation (CD11a) in CD4<span class="elsevierStyleSup">+</span> and CD8<span class="elsevierStyleSup">+</span> T cells in psoriasis patients and controls. Each point represents an individual. The horizontal bars represent the median values.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td 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" style="border-bottom: 2px solid black">Monoclonal markers \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Analysis</td><td 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" style="border-bottom: 2px solid black">Source \t\t\t\t\t\t\n \t\t\t\t</td></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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD3-PC5/CD4-PE/CD8-FITC \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">CD3 in total lymphocytes \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">CD4 into CD3 \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">CD8 into CD3 \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">Immunotech, Beckman Coulter, France \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD4-PC5/CD8-FITC/CD25-PE \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">CD25 in total lymphocytes \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">CD25 into CD4 \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">CD25 into CD8 \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">BD Biosciences, CA, USA \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD4-PC5/CD8-PE/CD69-FITC \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">CD69 in total lymphocytes \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">CD69 into CD4 \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">CD69 into CD8 \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">BD Biosciences, CA, USA \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD4-PC5/CD8-PE/CLA-FITC \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">CLA in total lymphocytes \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">CLA into CD4 \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">CLA into CD8 \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">BD Biosciences, CA, USA \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CD4-PC5/CD8-PE/CD11a-FITC \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">CD11a in total lymphocytes \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">CD11a into CD4 \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">CD11a into CD8 \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">Immunotech, Beckman Coulter, France \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab182362.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Set of monoclonal markers</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Psoriasis–epidemiology and clinical spectrum" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E. 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"fecha" => "2004" "volumen" => "29" "paginaInicial" => "658" "paginaFinal" => "663" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15550147" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:3 [ "identificador" => "xack35246" "titulo" => "Acknowledgments" "texto" => "<p id="par0040" class="elsevierStylePara elsevierViewall">We are grateful to Ana Cristina de Almeida for her valuable suggestions, to Gustavo Estef Lino da Silveira for the linguistic revision, and to the medical staff of Serviço de Dermatologia-HUGG/UNIRIO, Rio de Janeiro, Brazil. C Porto-Ferreira is a graduate student at Programa de Pós-Graduação em Ciências Médicas, FCM-UERJ, Rio de Janeiro, Brazil. AM Da-Cruz is a research fellow from FAPERJ, Rio de Janeiro, Brazil.</p>" ] ] ] "idiomaDefecto" => "en" "url" => "/00017310/0000010200000005/v1_201304241325/S000173101100041X/v1_201304241325/en/main.assets" "Apartado" => array:4 [ "identificador" => "6143" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Cartas científico-clínicas" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/00017310/0000010200000005/v1_201304241325/S000173101100041X/v1_201304241325/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S000173101100041X?idApp=UINPBA000044" "pdfAlternativo" => array:1 [ 0 => array:3 [ "idioma" => "es" "documentoPdf" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/file/00017310/addon/S000173101100041X/S300/es/103v102n05a90014935pdf001_2.pdf" "portada" => "103v102n05a90014935pdf001_2.png" ] ] ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 8 | 8 | 16 |
| 2024 Octubre | 36 | 46 | 82 |
| 2024 Septiembre | 37 | 27 | 64 |
| 2024 Agosto | 56 | 53 | 109 |
| 2024 Julio | 49 | 22 | 71 |
| 2024 Junio | 53 | 24 | 77 |
| 2024 Mayo | 45 | 30 | 75 |
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| 2024 Marzo | 48 | 32 | 80 |
| 2024 Febrero | 46 | 27 | 73 |
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| 2023 Diciembre | 45 | 13 | 58 |
| 2023 Noviembre | 47 | 30 | 77 |
| 2023 Octubre | 45 | 15 | 60 |
| 2023 Septiembre | 40 | 28 | 68 |
| 2023 Agosto | 32 | 18 | 50 |
| 2023 Julio | 53 | 35 | 88 |
| 2023 Junio | 37 | 17 | 54 |
| 2023 Mayo | 26 | 19 | 45 |
| 2023 Abril | 23 | 23 | 46 |
| 2023 Marzo | 37 | 30 | 67 |
| 2023 Febrero | 38 | 23 | 61 |
| 2023 Enero | 23 | 32 | 55 |
| 2022 Diciembre | 38 | 27 | 65 |
| 2022 Noviembre | 46 | 28 | 74 |
| 2022 Octubre | 31 | 26 | 57 |
| 2022 Septiembre | 42 | 50 | 92 |
| 2022 Agosto | 37 | 48 | 85 |
| 2022 Julio | 48 | 51 | 99 |
| 2022 Junio | 57 | 31 | 88 |
| 2022 Mayo | 71 | 47 | 118 |
| 2022 Abril | 31 | 31 | 62 |
| 2022 Marzo | 45 | 65 | 110 |
| 2022 Febrero | 27 | 30 | 57 |
| 2022 Enero | 26 | 49 | 75 |
| 2021 Diciembre | 36 | 37 | 73 |
| 2021 Noviembre | 44 | 47 | 91 |
| 2021 Octubre | 38 | 54 | 92 |
| 2021 Septiembre | 30 | 39 | 69 |
| 2021 Agosto | 29 | 18 | 47 |
| 2021 Julio | 30 | 36 | 66 |
| 2021 Junio | 36 | 44 | 80 |
| 2021 Mayo | 30 | 32 | 62 |
| 2021 Abril | 59 | 69 | 128 |
| 2021 Marzo | 49 | 13 | 62 |
| 2021 Febrero | 27 | 23 | 50 |
| 2021 Enero | 33 | 22 | 55 |
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| 2020 Noviembre | 26 | 17 | 43 |
| 2020 Octubre | 23 | 8 | 31 |
| 2020 Septiembre | 49 | 5 | 54 |
| 2020 Agosto | 30 | 19 | 49 |
| 2020 Julio | 25 | 9 | 34 |
| 2020 Junio | 34 | 22 | 56 |
| 2020 Mayo | 30 | 12 | 42 |
| 2020 Abril | 39 | 12 | 51 |
| 2020 Marzo | 40 | 18 | 58 |
| 2020 Febrero | 5 | 2 | 7 |
| 2019 Diciembre | 4 | 2 | 6 |
| 2019 Noviembre | 0 | 3 | 3 |
| 2019 Octubre | 0 | 6 | 6 |
| 2019 Septiembre | 5 | 6 | 11 |
| 2019 Julio | 0 | 5 | 5 |
| 2019 Junio | 0 | 7 | 7 |
| 2019 Mayo | 4 | 11 | 15 |
| 2019 Abril | 3 | 7 | 10 |
| 2019 Marzo | 0 | 5 | 5 |
| 2019 Febrero | 2 | 1 | 3 |
| 2019 Enero | 0 | 1 | 1 |
| 2018 Diciembre | 1 | 2 | 3 |
| 2018 Noviembre | 1 | 0 | 1 |
| 2018 Octubre | 2 | 2 | 4 |
| 2018 Septiembre | 0 | 2 | 2 |
| 2018 Febrero | 80 | 4 | 84 |
| 2018 Enero | 40 | 0 | 40 |
| 2017 Diciembre | 95 | 8 | 103 |
| 2017 Noviembre | 31 | 6 | 37 |
| 2017 Octubre | 30 | 0 | 30 |
| 2017 Septiembre | 33 | 6 | 39 |
| 2017 Agosto | 32 | 5 | 37 |
| 2017 Julio | 29 | 5 | 34 |
| 2017 Junio | 33 | 15 | 48 |
| 2017 Mayo | 32 | 8 | 40 |
| 2017 Abril | 24 | 5 | 29 |
| 2017 Marzo | 30 | 5 | 35 |
| 2017 Febrero | 17 | 2 | 19 |
| 2017 Enero | 14 | 5 | 19 |
| 2016 Diciembre | 41 | 6 | 47 |
| 2016 Noviembre | 41 | 7 | 48 |
| 2016 Octubre | 54 | 6 | 60 |
| 2016 Septiembre | 56 | 17 | 73 |
| 2016 Agosto | 40 | 6 | 46 |
| 2016 Julio | 36 | 15 | 51 |
| 2016 Junio | 21 | 11 | 32 |
| 2016 Mayo | 15 | 12 | 27 |
| 2016 Abril | 15 | 2 | 17 |
| 2016 Marzo | 22 | 3 | 25 |
| 2016 Febrero | 17 | 8 | 25 |
| 2016 Enero | 14 | 39 | 53 |
| 2015 Diciembre | 21 | 14 | 35 |
| 2015 Noviembre | 20 | 20 | 40 |
| 2015 Octubre | 18 | 12 | 30 |
| 2015 Septiembre | 15 | 10 | 25 |
| 2015 Agosto | 19 | 6 | 25 |
| 2015 Julio | 95 | 1 | 96 |
| 2015 Junio | 70 | 13 | 83 |
| 2015 Mayo | 87 | 8 | 95 |
| 2015 Abril | 69 | 9 | 78 |
| 2015 Marzo | 82 | 2 | 84 |
| 2015 Febrero | 57 | 1 | 58 |
| 2015 Enero | 90 | 0 | 90 |
| 2014 Diciembre | 70 | 0 | 70 |
| 2014 Noviembre | 60 | 0 | 60 |
| 2014 Octubre | 99 | 0 | 99 |
| 2014 Septiembre | 67 | 0 | 67 |
| 2014 Agosto | 81 | 0 | 81 |
| 2014 Julio | 86 | 0 | 86 |
| 2014 Junio | 99 | 0 | 99 |
| 2014 Mayo | 114 | 0 | 114 |
| 2014 Abril | 97 | 0 | 97 |
| 2014 Marzo | 127 | 26 | 153 |
| 2014 Febrero | 101 | 24 | 125 |
| 2014 Enero | 96 | 27 | 123 |
| 2013 Diciembre | 93 | 29 | 122 |
| 2013 Noviembre | 70 | 29 | 99 |
| 2013 Octubre | 78 | 34 | 112 |
| 2013 Septiembre | 78 | 30 | 108 |
| 2013 Agosto | 67 | 36 | 103 |
| 2013 Julio | 97 | 42 | 139 |
| 2013 Junio | 84 | 42 | 126 |
| 2013 Mayo | 37 | 17 | 54 |
| 2013 Abril | 19 | 24 | 43 |
| 2013 Marzo | 27 | 14 | 41 |
| 2013 Febrero | 26 | 14 | 40 |
| 2013 Enero | 22 | 8 | 30 |
| 2012 Diciembre | 13 | 7 | 20 |
| 2012 Noviembre | 1 | 2 | 3 |
| 2012 Octubre | 1 | 3 | 4 |
| 2012 Septiembre | 0 | 3 | 3 |
| 2012 Agosto | 0 | 1 | 1 |
| 2011 Mayo | 4 | 0 | 4 |
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