Original article
Sequential Histological and Immunohistochemical Assessment of Proliferation and Apoptotic Markers During Treatment of Psoriasis With Antitumor Necrosis Factor α (Infliximab)
Evaluación Histológica e Inmunohistoquímica Secuencial Demarcadores de Proliferación y Apoptosis Durante El Tratamiento de la Psoriasis con Anti-factor de Necrosis Tumoral α (Infliximab)
C. Gómez-Mateoa, S.P. Ávalos-Peraltab, J.J. Ríos-Martína,
, A.M. Carrizosa-Esquivelb, R. González-Cámporaa, F. Camacho-Martínezb
Corresponding author
jjrios@ono.com
Correspondence: Departamento de Anatomía Patológica, Hospital Universitario Virgen Macarena, Avda. Dr. Fedriani, s/n, 41009 Sevilla, Spain.
Correspondence: Departamento de Anatomía Patológica, Hospital Universitario Virgen Macarena, Avda. Dr. Fedriani, s/n, 41009 Sevilla, Spain.
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Marcoval" "autores" => array:3 [ 0 => array:2 [ "nombre" => "J.R." "apellidos" => "Ferreres" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Moreno" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Marcoval" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219009700873?idApp=UINPBA000044" "url" => "/15782190/0000010000000005/v1_201304241456/S1578219009700873/v1_201304241456/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Sequential Histological and Immunohistochemical Assessment of Proliferation and Apoptotic Markers During Treatment of Psoriasis With Antitumor Necrosis Factor α (Infliximab)" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "420" "paginaFinal" => "424" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "C. Gómez-Mateo, S.P. Ávalos-Peralta, J.J. Ríos-Martín, A.M. Carrizosa-Esquivel, R. González-Cámpora, F. Camacho-Martínez" "autores" => array:6 [ 0 => array:3 [ "nombre" => "C." "apellidos" => "Gómez-Mateo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] ] ] 1 => array:3 [ "nombre" => "S.P." "apellidos" => "Ávalos-Peralta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] 2 => array:4 [ "nombre" => "J.J." "apellidos" => "Ríos-Martín" "email" => array:1 [ 0 => "jjrios@ono.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor1" ] ] ] 3 => array:3 [ "nombre" => "A.M." "apellidos" => "Carrizosa-Esquivel" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] 4 => array:3 [ "nombre" => "R." "apellidos" => "González-Cámpora" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] ] ] 5 => array:3 [ "nombre" => "F." "apellidos" => "Camacho-Martínez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Anatomía Patológica, Hospital Universitario Virgen Macarena, Seville, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Universitario Virgen Macarena, Seville, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "⁎" "correspondencia" => "Correspondence: Departamento de Anatomía Patológica, Hospital Universitario Virgen Macarena, Avda. Dr. Fedriani, s/n, 41009 Sevilla, Spain." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evaluación Histológica e Inmunohistoquímica Secuencial Demarcadores de Proliferación y Apoptosis Durante El Tratamiento de la Psoriasis con Anti-factor de Necrosis Tumoral α (Infliximab)" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaAceptado" => "2008-10-06" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec84486" "palabras" => array:5 [ 0 => "psoriasis" 1 => "tumor necrosis factor a" 2 => "histology" 3 => "immunohistochemistry" 4 => "apoptosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec84485" "palabras" => array:5 [ 0 => "psoriasis" 1 => "tumor necrosis factor a" 2 => "histology" 3 => "immunohistochemistry" 4 => "apoptosis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Background and objectives</span><p class="elsevierStyleSimplePara elsevierViewall">Psoriasis is an inflammatory skin disease of immunologic nature that is mediated by T-helper-1 cytokines. Clinical response to treatment with antitumor necrosis factor (TNF) a antibodies (infliximab) has been significant; however, the mechanisms for clearance of lesions have not been elucidated. The aim of the present study was to assess variations in the histology and expression of proliferation and apoptotic markers in sequential skin biopsies of patients with psoriasis treated with infliximab.</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p class="elsevierStyleSimplePara elsevierViewall">We studied skin biopsies (of lesioned and healthy skin) from 3 patients with extensive moderate-to-severe psoriasis (mean psoriasis area and severity index [PASI] score, 35) treated with intravenous infliximab infusions (5 mg/kg) at weeks 0, 2, and 6. Biopsies were taken on days 0, 14, and 28, and were processed for conventional histological and immunohistochemical study. The apoptotic markers used were TP53, B-cell lymphoma 2 protein, anticaspase 3, and anticaspase 8. The cell proliferation marker used was Ki67.</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">Treatment with infliximab was associated with a significant clinical improvement in 3 patients (mean PASI score, 21.6 at 14 days and 13.9 at 6 weeks), which correlated with the progressive disappearance of histological lesions with a decrease in epidermal proliferation. However, apoptosis was not observed, and the samples tested negative for anticaspase antibodies. Expression of TP53 decreased 2 weeks after starting treatment, and was similar to that in normal skin at 28 days.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">Clinical and histological response of psoriasis to infliximab was not associated with a significant increase in the apoptotic markers assessed.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle">Introducción y objetivos</span><p class="elsevierStyleSimplePara elsevierViewall">La psoriasis es una enfermedad inflamatoria cutánea de naturaleza inmunológica mediada por citoquinas de tipo Th1. El tratamiento con anticuerpos anti-factor de necrosis tumoral a (TNF-a) (infliximab) ha proporcionado respuestas clínicas significativas; sin embargo, los mecanismos implicados en la curación no están bien aclarados. El objetivo del presente trabajo es evaluar las variaciones de la histología y en la expresión de marcadores de proliferación y apoptosis, en biopsias cutáneas secuenciales de pacientes con psoriasis tratados con in fliximab.</p> <span class="elsevierStyleSectionTitle">Material y métodos</span><p class="elsevierStyleSimplePara elsevierViewall">Se estudiaron biopsias de piel (sana y lesionada) de 3 pacientes afectados de psoriasis generalizada moderada-grave (índice de área y gravedad de la soriasis [PASI]: 35 de media) tratados con infusiones por vía intravenosa de infliximab (5 mg/kg) en las semanas 0, 2 y 6. Las biopsias se realizaron en los días 0, 14 y 28, y fueron procesadas para estudio histológico convencional e inmunohistoquímico con marcadores de apoptosis –TP53, BCL-2 y anticaspasas 3 y 8– y de proliferación celular –Ki67–.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">El tratamiento con infliximab se asoció con una significativa mejoría clínica en los 3 pacientes (PASI medio: 21,6 a los 14 días y 13,9 a las 6 semanas), que se correlacionó con la desaparición progresiva de las lesiones histológicas, con disminución de la proliferación epidérmica. Sin embargo, no observamos imágenes de apoptosis ni obtuvimos positividad con los anticuerpos anticaspasas. La expresión de TP53 disminuyó a las2 semanas del inicio del tratamiento, siendo similar a la piel normal a los 2 8 días.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">La respuesta clínica e histológica de la psoriasis con infliximab no se asoció a un incremento significativo en los marcadores de apoptosis evaluados.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunopathogenic mechanisms in psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.E. Gudjonsson" 1 => "A. Johnston" 2 => "H. Sigmundsdottur" 3 => "H. Valdmarsson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Exp Immunol" "fecha" => "2004" "volumen" => "135" "paginaInicial" => "1" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14678257" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The inflammatory response in mild and in severe psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P.R. Pereira" 1 => "A.S. Silva" 2 => "I. Rebelo" 3 => "A. Figueiredo" 4 => "A. Quintanilla" 5 => "F. Teixeira" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2004.05984.x" "Revista" => array:5 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2004" "volumen" => "150" "paginaInicial" => "917" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15149504" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biology of tumor necrosis factor-aimplications for psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.J. Schottelius" 1 => "L.L. Moldawer" 2 => "C.A. Dinarello" 3 => "K. Asadullah" 4 => "W. Sterry" 5 => "C.K. Edwards III" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.0906-6705.2004.00205.x" "Revista" => array:6 [ "tituloSerie" => "Exp Dermatol" "fecha" => "2004" "volumen" => "13" "paginaInicial" => "193" "paginaFinal" => "222" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15086336" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Terapia biológica y psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. Gamo" 1 => "J.L. López-Estebaranz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "2006" "volumen" => "97" "paginaInicial" => "1" "paginaFinal" => "17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16540046" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebocontrolled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.B. Gottlieb" 1 => "R. Evans" 2 => "S. Li" 3 => "L.T. Dooley" 4 => "C.A. Guzzo" 5 => "D. Baker" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2004.02.021" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2004" "volumen" => "51" "paginaInicial" => "534" "paginaFinal" => "542" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15389187" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of survivin and NFkappaB in psoriasis, an immunohistochemical study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.G. Abdou" 1 => "H.M. Hanout" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1600-0560.2007.00841.x" "Revista" => array:7 [ "tituloSerie" => "J Cutan Pathol" "fecha" => "2008" "volumen" => "35" "paginaInicial" => "445" "paginaFinal" => "451" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18005174" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1474442207700571" "estado" => "S300" "issn" => "14744422" ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apoptosis in stablised and healing psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Laporte" 1 => "P. Galand" 2 => "D. Fokan" 3 => "C. de Graef" 4 => "M. Heenen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "18394" "Revista" => array:6 [ "tituloSerie" => "Dermatology" "fecha" => "2000" "volumen" => "200" "paginaInicial" => "314" "paginaFinal" => "316" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10894962" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aberrant expression of apoptosis-related molecules in psoriatic epidermis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H. Takahashi" 1 => "A. Manabe" 2 => "A. Ishida-Yamamoto" 3 => "Y. Hashimoto" 4 => "H. Iizuka" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Dermatol Sci" "fecha" => "2002" "volumen" => "28" "paginaInicial" => "187" "paginaFinal" => "197" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11912006" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Examination of bcl-2 and p53 expressions and apoptotic index by TUNEL method in psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K. Gündüz" 1 => "P. Demireli" 2 => "S. Vatansever" 3 => "I. Inanir" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1600-0560.2006.00564.x" "Revista" => array:6 [ "tituloSerie" => "J Cutan Pathol" "fecha" => "2006" "volumen" => "33" "paginaInicial" => "788" "paginaFinal" => "792" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17177938" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of cell death and proliferation in psoriatic epidermis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Kawashima" 1 => "H. Doi" 2 => "Y. Ito" 3 => "M.A. Shibata" 4 => "R. Yoshinaka" 5 => "Y. Otsuki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jdermsci.2004.05.008" "Revista" => array:6 [ "tituloSerie" => "J Dermatol Sci" "fecha" => "2004" "volumen" => "35" "paginaInicial" => "207" "paginaFinal" => "214" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15381242" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "P53 and oncogenes expression in psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "G. Tadini" 1 => "A. Cerri" 2 => "L. Crosti" 3 => "G. Cattoretti" 4 => "E. Berti" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Acta Derm Venereol" "fecha" => "1989" "volumen" => "146" "paginaInicial" => "33" "paginaFinal" => "35" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expressions of p53 protein before and after PUVA treatment in psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Hannuksela-Svahn" 1 => "P. Paakko" 2 => "P. Autio" 3 => "T. Reunala" 4 => "J. Karvonen" 5 => "K. Vähäkangas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Acta Derm Venereol" "fecha" => "1999" "volumen" => "79" "paginaInicial" => "195" "paginaFinal" => "199" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10384915" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Programmed cell death of keratinocytes in infliximab-treated plaque-type psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Krüger-Krasagakis" 1 => "V.K. Galanapoulos" 2 => "L. Giannikaki" 3 => "M. Stefanidou" 4 => "A.D. Tosca" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2133.2005.07078.x" "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2006" "volumen" => "154" "paginaInicial" => "460" "paginaFinal" => "466" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16445776" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apoptosis, P53 and Bcl-2 expressions in response to topical calcipotriol therapy for psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. El-Domyati" 1 => "M. Barakat" 2 => "R. Abdel-Razek" 3 => "T. El-Din Anbar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-4632.2007.03099.x" "Revista" => array:6 [ "tituloSerie" => "Int J Dermatol" "fecha" => "2007" "volumen" => "46" "paginaInicial" => "468" "paginaFinal" => "474" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17472673" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Abnormal-Bcl-2 and “tissue” transglutaminase expression in psoriaticskin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L. Bianchi" 1 => "M.G. Faarace" 2 => "G. Mini" 3 => "M. Piacentini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Invest Dermatol" "fecha" => "1994" "volumen" => "103" "paginaInicial" => "829" "paginaFinal" => "833" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7798623" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Discordant expression of Bcl-xl and Bcl-2 by keratinocytes in vitro and psoriatic keratinocytes in vivo" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Wrone-Smith" 1 => "T. Johnson" 2 => "B. Nelson" 3 => "L.H. Boise" 4 => "C.B. Thompson" 5 => "G. Núñez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Pathol" "fecha" => "1995" "volumen" => "146" "paginaInicial" => "1079" "paginaFinal" => "1088" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7747803" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010000000005/v1_201304241456/S1578219009700885/v1_201304241456/en/main.assets" "Apartado" => array:4 [ "identificador" => "6155" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010000000005/v1_201304241456/S1578219009700885/v1_201304241456/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219009700885?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 55 | 52 | 107 |
| 2024 September | 59 | 31 | 90 |
| 2024 August | 93 | 67 | 160 |
| 2024 July | 64 | 36 | 100 |
| 2024 June | 68 | 39 | 107 |
| 2024 May | 49 | 35 | 84 |
| 2024 April | 58 | 42 | 100 |
| 2024 March | 53 | 37 | 90 |
| 2024 February | 49 | 39 | 88 |
| 2024 January | 34 | 47 | 81 |
| 2023 December | 35 | 39 | 74 |
| 2023 November | 35 | 45 | 80 |
| 2023 October | 35 | 30 | 65 |
| 2023 September | 34 | 39 | 73 |
| 2023 August | 30 | 20 | 50 |
| 2023 July | 36 | 41 | 77 |
| 2023 June | 28 | 32 | 60 |
| 2023 May | 34 | 23 | 57 |
| 2023 April | 28 | 22 | 50 |
| 2023 March | 19 | 29 | 48 |
| 2023 February | 19 | 26 | 45 |
| 2023 January | 24 | 35 | 59 |
| 2022 December | 23 | 52 | 75 |
| 2022 November | 17 | 28 | 45 |
| 2022 October | 13 | 26 | 39 |
| 2022 September | 15 | 36 | 51 |
| 2022 August | 17 | 37 | 54 |
| 2022 July | 18 | 40 | 58 |
| 2022 June | 15 | 30 | 45 |
| 2022 May | 43 | 42 | 85 |
| 2022 April | 26 | 40 | 66 |
| 2022 March | 31 | 58 | 89 |
| 2022 February | 34 | 28 | 62 |
| 2022 January | 54 | 49 | 103 |
| 2021 December | 38 | 39 | 77 |
| 2021 November | 25 | 46 | 71 |
| 2021 October | 34 | 50 | 84 |
| 2021 September | 15 | 43 | 58 |
| 2021 August | 13 | 41 | 54 |
| 2021 July | 20 | 45 | 65 |
| 2021 June | 18 | 38 | 56 |
| 2021 May | 23 | 29 | 52 |
| 2021 April | 43 | 84 | 127 |
| 2021 March | 44 | 26 | 70 |
| 2021 February | 53 | 31 | 84 |
| 2021 January | 31 | 13 | 44 |
| 2020 December | 27 | 18 | 45 |
| 2020 November | 23 | 19 | 42 |
| 2020 October | 28 | 8 | 36 |
| 2020 September | 29 | 14 | 43 |
| 2020 August | 24 | 27 | 51 |
| 2020 July | 15 | 5 | 20 |
| 2020 June | 19 | 28 | 47 |
| 2020 May | 18 | 18 | 36 |
| 2020 April | 25 | 18 | 43 |
| 2020 March | 19 | 21 | 40 |
| 2020 February | 1 | 3 | 4 |
| 2020 January | 0 | 7 | 7 |
| 2019 December | 0 | 8 | 8 |
| 2019 November | 0 | 5 | 5 |
| 2019 October | 0 | 2 | 2 |
| 2019 September | 0 | 1 | 1 |
| 2019 August | 0 | 1 | 1 |
| 2019 July | 0 | 9 | 9 |
| 2019 June | 0 | 6 | 6 |
| 2019 May | 1 | 59 | 60 |
| 2019 April | 1 | 12 | 13 |
| 2019 March | 0 | 5 | 5 |
| 2019 February | 0 | 3 | 3 |
| 2019 January | 0 | 4 | 4 |
| 2018 March | 0 | 6 | 6 |
| 2018 February | 10 | 9 | 19 |
| 2018 January | 16 | 18 | 34 |
| 2017 December | 16 | 15 | 31 |
| 2017 November | 16 | 16 | 32 |
| 2017 October | 14 | 18 | 32 |
| 2017 September | 22 | 10 | 32 |
| 2017 August | 25 | 21 | 46 |
| 2017 July | 30 | 9 | 39 |
| 2017 June | 45 | 25 | 70 |
| 2017 May | 41 | 38 | 79 |
| 2017 April | 43 | 26 | 69 |
| 2017 March | 22 | 20 | 42 |
| 2017 February | 13 | 18 | 31 |
| 2017 January | 13 | 17 | 30 |
| 2016 December | 26 | 5 | 31 |
| 2016 November | 22 | 11 | 33 |
| 2016 October | 25 | 25 | 50 |
| 2016 September | 32 | 20 | 52 |
| 2016 August | 27 | 15 | 42 |
| 2016 July | 36 | 8 | 44 |
| 2016 June | 8 | 5 | 13 |
| 2016 May | 12 | 22 | 34 |
| 2016 April | 5 | 6 | 11 |
| 2016 March | 4 | 14 | 18 |
| 2016 February | 6 | 8 | 14 |
| 2016 January | 5 | 12 | 17 |
| 2015 December | 9 | 8 | 17 |
| 2015 November | 10 | 9 | 19 |
| 2015 October | 6 | 12 | 18 |
| 2015 September | 17 | 4 | 21 |
| 2015 August | 20 | 6 | 26 |
| 2015 July | 27 | 13 | 40 |
| 2015 June | 30 | 14 | 44 |
| 2015 May | 60 | 21 | 81 |
| 2015 April | 50 | 15 | 65 |
| 2015 March | 27 | 14 | 41 |
| 2015 February | 22 | 19 | 41 |
| 2015 January | 19 | 20 | 39 |
| 2014 December | 22 | 22 | 44 |
| 2014 November | 15 | 26 | 41 |
| 2014 October | 30 | 26 | 56 |
| 2014 September | 29 | 28 | 57 |
| 2014 August | 32 | 18 | 50 |
| 2014 July | 34 | 23 | 57 |
| 2014 June | 33 | 13 | 46 |
| 2014 May | 44 | 12 | 56 |
| 2014 April | 43 | 12 | 55 |
| 2014 March | 38 | 21 | 59 |
| 2014 February | 24 | 24 | 48 |
| 2014 January | 33 | 21 | 54 |
| 2013 December | 36 | 17 | 53 |
| 2013 November | 31 | 23 | 54 |
| 2013 October | 36 | 22 | 58 |
| 2013 September | 29 | 19 | 48 |
| 2013 August | 16 | 32 | 48 |
| 2013 July | 41 | 37 | 78 |
| 2013 June | 31 | 39 | 70 |
| 2013 May | 32 | 18 | 50 |
| 2013 April | 31 | 36 | 67 |
| 2013 March | 34 | 26 | 60 |
| 2013 February | 38 | 15 | 53 |
| 2013 January | 8 | 6 | 14 |
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