Original Article
Decreased Plasma Levels of Clusterin in Patients With Psoriasis
Disminución de los niveles plasmáticos de clusterina en pacientes con psoriasis
S. García-Rodríguezb,1, S. Arias-Santiagoa,1, R. Perandrés-Lópezb, J. Orgaz-Molinaa, L. Castellotec, A. Buendía-Eismana, J.C. Ruiza, R. Naranjoa, P. Navarrob, J. Sanchob, M. Zubiaurb,
Autor para correspondencia
a Departamento de Dermatología, Hospital Universitario San Cecilio (HCUSC), Granada, Spain
b Departamento de Biología Celular e Inmunología, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain
c Departamento de Radiología, Hospital Universitario San Cecilio (HCUSC), Granada, Spain
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Los resultados se presentan como media<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>DE. La determinación de la concentración plasmática se realizó mediante ELISA, según se describe en el apartado <span class="elsevierStyleItalic">Material y métodos</span>. a). Concentración plasmática de clusterina. b). Concentración plasmática de MIF. Para el análisis de los resultados de los niveles plasmáticos de clusterina y de MIF entre los grupos se utilizó el test no paramétrico Mann-Whitney. Para el análisis de los resultados se utilizó el software Graph-Pad Prism versión 5.01.</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">AtP: placa de ateroma carotídea; MIF: factor inhibitorio de la migración del macrófago; P: pacientes; SMt: síndrome metabólico.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "S. García-Rodríguez, S. Arias-Santiago, R. Perandrés-López, J. Orgaz-Molina, L. Castellote, A. 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"apellidos" => "Zubiaur" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219013001194" "doi" => "10.1016/j.adengl.2012.11.018" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013001194?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731013000033?idApp=UINPBA000044" "url" => "/00017310/0000010400000006/v2_202210080525/S0001731013000033/v2_202210080525/es/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S1578219013001200" "issn" => "15782190" "doi" => "10.1016/j.adengl.2012.12.004" "estado" => "S300" "fechaPublicacion" => "2013-07-01" "aid" => "709" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2013;104:504-11" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5711 "formatos" => array:3 [ "EPUB" => 49 "HTML" => 5086 "PDF" => 576 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Infantile Hemangiomas Treated by Sequential Application of Pulsed Dye Laser and Nd:YAG Laser Radiation: A Retrospective Study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "504" "paginaFinal" => "511" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hemangiomas infantiles tratados con aplicación secuencial de láser de colorante pulsado y Nd:YAG: estudio retrospectivo" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2028 "Ancho" => 1333 "Tamanyo" => 298611 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A, Patient number 4 with an involuting infantile hemangioma on the upper lip before treatment. B, Marked improvement without residual scarring, despite ulceration of the labial mucosa, after 1 treatment session.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Alcántara-González, P. Boixeda, M.T. Truchuelo-Díez, B. Pérez-García, L. Alonso-Castro, P. Jaén Olasolo" "autores" => array:6 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Alcántara-González" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Boixeda" ] 2 => array:2 [ "nombre" => "M.T." "apellidos" => "Truchuelo-Díez" ] 3 => array:2 [ "nombre" => "B." "apellidos" => "Pérez-García" ] 4 => array:2 [ "nombre" => "L." "apellidos" => "Alonso-Castro" ] 5 => array:2 [ "nombre" => "P." "apellidos" => "Jaén Olasolo" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S000173101300015X" "doi" => "10.1016/j.ad.2012.12.010" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S000173101300015X?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013001200?idApp=UINPBA000044" "url" => "/15782190/0000010400000006/v2_202210010908/S1578219013001200/v2_202210010908/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S1578219013001182" "issn" => "15782190" "doi" => "10.1016/j.adengl.2012.12.003" "estado" => "S300" "fechaPublicacion" => "2013-07-01" "aid" => "787" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Actas Dermosifiliogr. 2013;104:488-96" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3090 "formatos" => array:3 [ "EPUB" => 46 "HTML" => 2336 "PDF" => 708 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Adherence and Patient Satisfaction With Topical Treatment in Psoriasis, and the Use, and Organoleptic Properties of Such Treatments: A Delphi Study With an Expert Panel and Members of the Psoriasis Group of the Spanish Academy of Dermatology and Venereology" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "488" "paginaFinal" => "496" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Adherencia y satisfacción del paciente y características organolépticas y de uso de los tratamientos tópicos utilizados para la psoriasis: Consenso Delphi del panel de expertos y miembros del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2372 "Ancho" => 3087 "Tamanyo" => 430357 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Expert panel's Delphi consensus on factors that affect adherence to topical therapy and patient satisfaction, showing the medians, interquartile ranges (IQR), and actual ranges (minimum [Min] and maximum [Max] scores on a scale of 1 to 7). The 9 panelists did not reach a consensus on the following items:</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">- Attempting to use topical therapy to manage large areas of affected skin, with multiple lesions, is doomed to failure.</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">- Loss of response after long-term use of topical corticosteroids is a real problem in clinical practice</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">- Adherence to therapy is partly dependent on age and sex.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Puig, J.M. Carrascosa, I. Belinchón, V. Fernández-Redondo, G. Carretero, J.C. Ruiz-Carrascosa, J.M. Careaga, P. de la Cueva, M.T. Gárate, M. Ribera" "autores" => array:11 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Puig" ] 1 => array:2 [ "nombre" => "J.M." "apellidos" => "Carrascosa" ] 2 => array:2 [ "nombre" => "I." "apellidos" => "Belinchón" ] 3 => array:2 [ "nombre" => "V." "apellidos" => "Fernández-Redondo" ] 4 => array:2 [ "nombre" => "G." "apellidos" => "Carretero" ] 5 => array:2 [ "nombre" => "J.C." "apellidos" => "Ruiz-Carrascosa" ] 6 => array:2 [ "nombre" => "J.M." "apellidos" => "Careaga" ] 7 => array:2 [ "nombre" => "P." "apellidos" => "de la Cueva" ] 8 => array:2 [ "nombre" => "M.T." "apellidos" => "Gárate" ] 9 => array:2 [ "nombre" => "M." "apellidos" => "Ribera" ] 10 => array:1 [ "colaborador" => "Panel de Expertos del Consenso Delphi sobre Tratamiento tópico de la psoriasis y miembros del Grupo de Psoriasis de la Academia Española de Dermatología y Venereología" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731013000021" "doi" => "10.1016/j.ad.2012.12.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731013000021?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219013001182?idApp=UINPBA000044" "url" => "/15782190/0000010400000006/v2_202210010908/S1578219013001182/v2_202210010908/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Decreased Plasma Levels of Clusterin in Patients With Psoriasis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "497" "paginaFinal" => "503" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "S. García-Rodríguez, S. Arias-Santiago, R. Perandrés-López, J. Orgaz-Molina, L. Castellote, A. Buendía-Eisman, J.C. Ruiz, R. Naranjo, P. Navarro, J. Sancho, M. Zubiaur" "autores" => array:11 [ 0 => array:3 [ "nombre" => "S." "apellidos" => "García-Rodríguez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn1" ] ] ] 1 => array:3 [ "nombre" => "S." "apellidos" => "Arias-Santiago" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn1" ] ] ] 2 => array:3 [ "nombre" => "R." "apellidos" => "Perandrés-López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "J." "apellidos" => "Orgaz-Molina" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "L." "apellidos" => "Castellote" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "A." "apellidos" => "Buendía-Eisman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "J.C." "apellidos" => "Ruiz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 7 => array:3 [ "nombre" => "R." "apellidos" => "Naranjo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "P." "apellidos" => "Navarro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 9 => array:3 [ "nombre" => "J." "apellidos" => "Sancho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 10 => array:4 [ "nombre" => "M." "apellidos" => "Zubiaur" "email" => array:1 [ 0 => "mzubiaur@ipb.csic.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Universitario San Cecilio (HCUSC), Granada, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Biología Celular e Inmunología, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Granada, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Radiología, Hospital Universitario San Cecilio (HCUSC), Granada, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding Author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Disminución de los niveles plasmáticos de clusterina en pacientes con psoriasis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2380 "Ancho" => 1628 "Tamanyo" => 197889 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Plasma levels of clusterin and macrophage migration inhibitory factor (MIF). Results are expressed as means (SD). Levels were measured by enzyme-linked immunosorbent assay, as described in the Material and Methods section. A, Plasma clusterin levels. B, Plasma MIF levels. Between-group differences were analyzed using the nonparametric Mann-Whitney U test Results were analyzed using GraphPad Prism, version 5.01. Pt indicates patients; MetSyn, metabolic syndrome; CAP, carotid atheromatous plaque.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Psoriasis is a chronic inflammatory disease of the skin that can also affect joints. Current evidence indicates that patients with psoriasis have an increased frequency of cardiovascular risk factors, metabolic syndrome, obesity, dyslipidemia, diabetes, and hypertension.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> Carotid intima-media thickness (CIMT) is considered a useful, sensitive marker of atherosclerosis, even when this is not clinically evident.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Several studies have shown higher CIMT values in patients with psoriasis compared with controls.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Clusterin, also known as apolipoprotein J, is a heterodimeric glycoprotein with a molecular weight of approximately 70 to 80 kDa. It is encoded by a single gene. It has several isoforms, which are referred to as nuclear or secreted, depending on their location. Secreted clusterin is the most common isoform. Clusterin is constitutively expressed in many mammalian tissues.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a> It has been implicated in a wide range of biological processes, including regulation of apoptosis, attenuation of complement activation, response to damage and stress, autoimmune damage, elimination of toxic substrates, and interaction with lipids.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> More recently, it has been proposed as a possible biomarker of senescence and oxidative stress in erythrocytes<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and it has also been linked to diabetes and metabolic syndrome.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> Clusterin, like apolipoprotein A-I, is a component of high-density lipoproteins (HDLs). Evidence that it can bind lipids has led to the suggestion that it may have a protective role against atherosclerosis through its involvement in the transport of cholesterol to the liver. Low levels of circulating HDL-clusterin may also be significantly associated with metabolic syndrome. Yu et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> also recently reported that low plasma levels of clusterin in patients with Kawasaki disease appeared to be significantly associated with the presence of coronary artery lesions and suggested that this protein could be a useful biomarker for Kawasaki disease. Kujiraoka et al.,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> in turn, described significantly higher serum levels of clusterin in healthy individuals than in patients with diabetes, myocardial infarction, or coronary artery disease. Furthermore, underexpression of the clusterin gene in synovial tissue has been observed in patients with rheumatoid arthritis (an autoimmune chronic inflammatory disease) compared with patients with osteoarthritis and healthy individuals.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Migration inhibitory factor (MIF) is a proinflammatory cytokine, identified in activated T cells, that inhibits the migration of macrophages in vitro. The monomeric form of MIF has a molecular weight of approximately 12.5 kDa and its active form is homotrimeric. MIF is produced by a wide variety of cells, including monocytes and macrophages, T and B cells, and endocrine, endothelial, and epithelial cells.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> It has been implicated in innate and acquired immune responses, immune regulation, and inflammation.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17–19</span></a> MIF regulates macrophage function by suppressing the anti-inflammatory effects of corticosteroids,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and has been reported to favor the development and progression of autoimmune diseases such as rheumatoid arthritis.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> It has also been implicated in the clonal expansion and increased survival of inflammatory cells, promoting migration and stimulating the production of inflammatory mediators such as interleukin (IL) 1, tumor necrosis factor α, IL-6, IL-17, and nitric oxide.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a> Increased levels of MIF have been described in patients with systemic lupus erythematosus,<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,21</span></a> systemic scleroderma, Wegener granulomatosis, atopic dermatitis, psoriasis,<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,23</span></a> and inflammatory diseases in general.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> This cytokine has also been associated with cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome, and atherosclerosis.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> It has also been postulated that MIF might have a role in various skin disorders and in wound healing time.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Clusterin levels have not been analyzed in patients with psoriasis. The aim of this study was to evaluate plasma levels of clusterin and MIF in patients with severe psoriasis and to compare results in patients with different levels of cardiovascular risk.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0025" class="elsevierStylePara elsevierViewall">We studied 21 patients with severe psoriasis diagnosed on the basis of clinical criteria.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> The inclusion criteria were age of over 18 years and the presence of severe plaque psoriasis (Psoriasis Area Severity Index [PASI] and body surface area [BSA] scores of <span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span> 10). The patients were consecutively enrolled at the dermatology office of Hospital Clínico Universitario San Cecilio in Granada, Spain. During the same period, 11 unmatched healthy volunteers, with no skin disorders, were enrolled as controls. The exclusion criteria for both patients and controls were the presence of cutaneous lymphomas or other cancers and established cardiovascular disease (myocardial infarction or stroke). The study protocol was approved by the research commissions and ethics committees of Hospital Clínico Universitario San Cecilio and Instituto de Parasitología y Biomedicina “López-Neyra”, which belongs to the Spanish National Research Council (CSIC). All the patients and controls signed an informed consent form in accordance with the principles of the Declaration of Helsinki.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clinical and Laboratory Variables</span><p id="par0030" class="elsevierStylePara elsevierViewall">Psoriasis severity was determined by PASI and BSA scores. The following variables were recorded for each patient: weight, height, abdominal circumference, body mass index (kg/m<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>), and systolic and diastolic blood pressures (mean of 3 readings taken after 10<span class="elsevierStyleHsp" style=""></span>minutes of rest). Serum levels of HDL cholesterol (HDL-C) and triglycerides were measured in patients and controls. A diagnosis of metabolic syndrome was established using the Adult Treatment Panel III (ATP-III) criteria, whereby patients are considered to have metabolic syndrome if they have 3 or more of the following: abdominal circumference ><span class="elsevierStyleHsp" style=""></span>102<span class="elsevierStyleHsp" style=""></span>cm in men and ><span class="elsevierStyleHsp" style=""></span>80<span class="elsevierStyleHsp" style=""></span>cm in women, serum triglycerides ><span class="elsevierStyleHsp" style=""></span>150<span class="elsevierStyleHsp" style=""></span>mg/dL, HDL-C <<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>mg/dL in men and <<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>mg/dL in women, blood pressure ><span class="elsevierStyleHsp" style=""></span>130/85<span class="elsevierStyleHsp" style=""></span>mm Hg, and fasting glucose ><span class="elsevierStyleHsp" style=""></span>110<span class="elsevierStyleHsp" style=""></span>mg/dL.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Blood and Plasma Samples</span><p id="par0035" class="elsevierStylePara elsevierViewall">Blood samples were collected following standard procedures (K<span class="elsevierStyleInf">2</span> EDTA tubes, Vacutainer BD system; BD Diagnostics) in the hospital laboratory. Plasma was obtained by Ficoll gradient centrifugation,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> and the aliquots were stored at –80<span class="elsevierStyleHsp" style=""></span>°C until their analysis.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Plasma Clusterin and MIF Levels</span><p id="par0040" class="elsevierStylePara elsevierViewall">Plasma levels of clusterin and MIF were measured in patients and controls by enzyme-linked immunosorbent assay (ELISA), which was performed in duplicate using the corresponding ELISA kits (No. RD194034200R, BioVendor and No. DMF00B; R&D Systems, respectively), in accordance with the manufacturers’ instructions.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ultrasound</span><p id="par0045" class="elsevierStylePara elsevierViewall">Patients underwent color Doppler ultrasound examination of the carotid artery (10-5<span class="elsevierStyleHsp" style=""></span>MHz transducer with imaging software to visualize the supra-aortic vessels), with evaluation of flow (mL/s) and CIMT (mm). CIMT was measured by calculating the distance from the inner hyperechogenic line of the vessel (intima) to the outer hypoechogenic line (media). Carotid atheromatous plaque was considered to be present when the CIMT was greater than 1.5<span class="elsevierStyleHsp" style=""></span>cm. CIMT was measured on the posterior wall of the common carotid artery, 1<span class="elsevierStyleHsp" style=""></span>cm proximal to the bifurcation.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistic Analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Data were expressed as means (SD). The nonparametric Mann-Whitney U test was used to analyze between-group differences, while the Fisher test was used to analyze qualitative variables. Correlations were calculated using the nonparametric Spearman rank correlation coefficient. Results were considered to be statistically different at a <span class="elsevierStyleItalic">P</span> value of less than .05 and to be close to significance up to <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>.1 (GraphPad Prism version 5.01; GraphPad Software, Inc).</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Clinical Data and Lipid Profiles</span><p id="par0055" class="elsevierStylePara elsevierViewall">Of the 21 patients studied, 9 (43%) were men (age, 44.2 [7.4] years) and 12 (57%) were women (age, 43.3 [19.1] years).<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> In the control group, there were 5 men (45%) and 6 women (age, 56.2 [15.5] and 52.0 [13.9] years, respectively). No significant differences were observed between patients and controls for sex (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.0, Fisher test) or age (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.059 [men] and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.303 [women], Mann-Whitney U test).<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> All the patients and controls were white. The mean PASI and BSA scores in the patient group were 17.24 (10.42) and 14.33 (6.06), respectively, and the mean CIMT was 0.743 (0.21).<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Ten patients (47.62%) met the ATP-III criteria for metabolic syndrome and 7 (33.3%) had carotid plaque. CIMT values were significantly higher in patients with plaque (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7) than in those without (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>14) (0.97 [0.17]<span class="elsevierStyleHsp" style=""></span>mm vs 0.63 [0.11<span class="elsevierStyleHsp" style=""></span>] mm], <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">=</span><span class="elsevierStyleHsp" style=""></span>.001).<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> At the time of blood collection, only 12 of the 21 patients were receiving treatment (methotrexate in 10 cases and acitretin in 2). None of the patients were on ciclosporin, corticosteroids, or biologic therapy.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">HDL-C levels were significantly lower in patients with metabolic syndrome or carotid plaque than in controls (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). There were no significant differences between patients (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21) and controls (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7) for triglycerides, (144.4 [98.7] vs 123.7<span class="elsevierStyleMonospace">[</span>7.04]; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.791) or for HDL-C (45.8 [13.5] vs 54 [4.3]; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.124).<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> It should be noted that our results might have been influenced by the dispersion of data and by our small sample size.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Reduction in Plasma Clusterin Levels</span><p id="par0065" class="elsevierStylePara elsevierViewall">Plasma clusterin levels were significantly lower in patients (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21) than in controls (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11) (81.39 [27.30] μg/mL vs 117 [21.6] μg/mL, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.002) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). The difference remained significant when the results were analyzed according to the concomitant presence of metabolic syndrome or carotid plaque (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). However, no significant differences were observed between patients with metabolic syndrome (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10) and those without (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11) (85.45 [24.39] μg/mL vs 80.43 [30.88] μg/mL, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.751). Similar results were seen when the patients were analyzed according to the presence (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7) or absence of carotid plaque (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>14) (85.03 [26.1] μg/mL vs 79.58 [28.66] μg/mL, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.628), and according to whether the patients were receiving treatment (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>12) or not (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9) (85.84 [28.48] μg/mL vs 75.47 [26.05] μg/mL, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">.</span>414). Finally, no significant correlations were observed between plasma clusterin levels and the different variables analyzed (age, blood glucose, PASI, BSA, HDL-C, and triglycerides).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Increased Plasma Levels of Clusterin and MIF</span><p id="par0070" class="elsevierStylePara elsevierViewall">Plasma MIF concentrations were higher in patients (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20 because 1 out-of-range result was excluded from the analysis) than in controls (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11), but the differences were not significant (42.19 [22.39] vs 34.21 [9.654], <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.171) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). MIF concentrations were, however, significantly higher in controls than in patients with carotid plaque (57.30 [32.11], <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">.</span>039) and showed a tendency towards significance in patients with metabolic syndrome (53.22 [29.02]) compared with controls (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">.</span>058). No significant correlations were observed between plasma MIF levels and age, blood glucose, PASI, BSA, HDL-C, or triglycerides.</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">The main finding of the present study is that plasma clusterin levels were decreased in patients with psoriasis compared with controls. It has been postulated that clusterin, like other components of HDL, may have a protective role against atherosclerosis in humans through its involvement in the transport of circulating cholesterol to the liver. Yuet al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> recently reported that low plasma clusterin levels were significantly associated with the presence of coronary artery lesions in patients with Kawasaki disease. Clusterin is a heterodimeric glycoprotein and may be sequestered by HDL, of which it is a component. In our series, patients with psoriasis and either metabolic syndrome or carotid plaque had significantly lower levels of HDL-C than controls (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Low HDL-C levels, which are one of the hallmarks of metabolic syndrome, have also been described in patients with coronary aneurysms.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29,30</span></a> Furthermore, we observed no differences in clusterin levels between patients with metabolic syndrome and those with carotid plaque, or any correlation between clusterin and HDL-C levels in patients with psoriasis.</p><p id="par0080" class="elsevierStylePara elsevierViewall">MIF plays a key role in various serious chronic inflammatory diseases (e.g., autoimmune and metabolic disorders) and other disease states,<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,19,24</span></a> and significantly increased serum levels have been described in patients with psoriasis compared with controls.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> In our series, plasma MIF levels were significantly increased in patients with psoriasis and carotid plaque (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Recent findings reported by our group indicate that there may be an association between psoriasis, carotid plaque, and metabolic syndrome.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In another study by our group, we observed that patients with severe psoriasis had significantly increased expression of the toll-like receptor (TLR) genes <span class="elsevierStyleItalic">TLR4</span> and <span class="elsevierStyleItalic">TLR2</span> in peripheral blood mononuclear cells.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> The detection of correlations between <span class="elsevierStyleItalic">TLR4</span> and <span class="elsevierStyleItalic">TLR2</span> overexpression and regulatory and proinflammatory cytokines and acute phase proteins such as S100A9 highlights the role played by the innate immune response in psoriasis. We also observed significantly elevated gene expression of helper T (T<span class="elsevierStyleInf">h</span>) cells with elevated T<span class="elsevierStyleInf">h</span>1/T<span class="elsevierStyleInf">h</span>2 and T<span class="elsevierStyleInf">h</span>17/T<span class="elsevierStyleInf">h</span>2, ratios, indicating activation of T<span class="elsevierStyleInf">h</span>1 and T<span class="elsevierStyleInf">h</span>17 cells. Furthermore, systemic inflammation in patients with psoriasis may give rise to or aggravate other associated inflammatory diseases such as atherosclerosis.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3,28</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Despite the limitations of the present study, we obtained significant results that suggest that there are certain biologic functions and associations of clusterin and MIF that warrant further study. Our patient and control groups were small and we did not perform a prior sample size calculation as our aim was to conduct a pilot study and there are no published data on clusterin and MIF levels in psoriasis patients. The preliminary results reported in this article should be validated in studies with larger samples.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion, our observation of decreased plasma levels of clusterin in patients with severe psoriasis suggests that clusterin is associated with psoriasis and also possibly with a systemic inflammatory state. Furthermore, increased plasma levels of MIF in psoriasis patients appear to be associated with the presence of cardiovascular risk factors (carotid plaques). Plasma measurements of both clusterin and MIF could contribute to a better understanding of systemic inflammation in psoriasis.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Ethical Disclosures</span><p id="par0100" class="elsevierStylePara elsevierViewall">Protection of humans and animals, The authors declare that no tests were carried out in humans or animals for the purpose of this study.</p><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Confidentiality of data</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that they have followed their hospital's protocol on the publication of data concerning patients and that all patients included in the study have received sufficient information and have given their written informed consent to participate in the study.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Right to privacy and informed consent</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data are disclosed in this article.</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Funding</span><p id="par0115" class="elsevierStylePara elsevierViewall">European Social Fund (European-Commission–European Regional Development Fund [ERDF]); Instituto de Carlos III Health Research Fund (ISCIII-FIS06/1502) (MZ); Spanish National Research Council (CSIC-PI 200820I216) (MZ); Junta de Andalucía, Departments of Innovation-Science-Business and Education-Science (CVI 226, CVI 908/2006 y PC08-CTS-04046) (JS and MZ); Ministry of Education-Ministry of Science and Education (SAF-2008-03685) (JS and MZ) and SAF-2011- 27261 (JS); and CSIC JAE-Doc program-CSIC-ERDF (contract SGR).</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicts of Interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1777508" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1560672" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1777509" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1560673" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and Methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinical and Laboratory Variables" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Blood and Plasma Samples" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Plasma Clusterin and MIF Levels" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Ultrasound" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistic Analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Clinical Data and Lipid Profiles" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Reduction in Plasma Clusterin Levels" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Increased Plasma Levels of Clusterin and MIF" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0070" "titulo" => "Ethical Disclosures" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0080" "titulo" => "Confidentiality of data" ] 1 => array:2 [ "identificador" => "sec0085" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0090" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0095" "titulo" => "Conflicts of Interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-06-26" "fechaAceptado" => "2012-11-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1560672" "palabras" => array:4 [ 0 => "Clusterin" 1 => "Carotid intima-media thickness" 2 => "Macrophage migration inhibitory factor" 3 => "Psoriasis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1560673" "palabras" => array:4 [ 0 => "Clusterina" 1 => "Grosor íntima-media carotídeo" 2 => "Factor inhibitorio de la migración del macrófago" 3 => "Psoriasis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Psoriasis is a chronic inflammatory disease that has been linked to increased cardiovascular risk. The glycoprotein clusterin (apolipoprotein J) is a component of high-density lipoproteins and has a protective role in atherosclerosis. The aim of the present study was to evaluate the plasma levels of clusterin and the proinflammatory cytokine macrophage migration inhibitory factor (MIF) in patients with severe psoriasis, comparing groups of patients with different risks of cardiovascular disease.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Twenty-one patients with severe psoriasis (psoriasis area severity index and body surface area<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>10) and 11 healthy controls with no dermatologic disease were studied. Cardiovascular risk factors were assessed according to the Adult Treatment Panel (ATP) <span class="elsevierStyleSmallCaps">III</span> criteria. Subclinical carotid atheromatosis was assessed by Doppler ultrasonography of the carotid arteries. Plasma clusterin and MIF levels were measured by enzyme-linked immunosorbent assay.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">ATP-<span class="elsevierStyleSmallCaps">III</span> criteria for metabolic syndrome were met by 47% of the patients, and 33% had carotid atheromatous plaque. Mean (SD) clusterin plasma levels were significantly lower in patients with psoriasis compared with controls (81.39 [27.30] μg/mL for the 21 patients vs 117 [21.6] μg/mL for the 11 controls; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0017). MIF plasma levels (ng/ml) were significantly higher in patients with atheromatous plaque compared with controls (53.22 [29.02] for the 6 patients with plaque vs 34.21 [9.65] for the 11 controls; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0394).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The decreased plasma levels of clusterin in psoriatic patients suggested an association with the disease and might be an indicator of systemic inflammatory activity. Increased levels of MIF appear to be associated with cardiovascular risk factors and carotid atheromatous plaque.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La psoriasis es una enfermedad inflamatoria crónica que se ha asociado a un incremento del riesgo cardiovascular. La clusterina (apolipoproteína J) es un componente de las lipoproteínas de alta densidad (HDL) y tiene un papel protector de la ateroesclerosis. El objetivo del estudio ha sido evaluar la clusterina y el factor inhibitorio de la migración del macrófago (MIF) plasmáticos en pacientes con psoriasis grave comparando grupos de pacientes con distintos riesgos cardiovasculares asociados.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron 21 pacientes con psoriasis grave (<span class="elsevierStyleItalic">Psoriasis Area Severity Index</span> [PASI] y <span class="elsevierStyleItalic">Body Surface Area</span> [BSA]<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>10) y 11 controles sin enfermedad dermatológica. Se evaluaron los factores de riesgo cardiovascular según criterios del síndrome metabólico del <span class="elsevierStyleItalic">Adult Treatment Panel <span class="elsevierStyleSmallCaps">III</span></span> (ATP-<span class="elsevierStyleSmallCaps">III</span>) y la ateromatosis carotídea subclínica mediante ecografía doppler de carótidas. La clusterina y MIF plasmáticos se midieron mediante <span class="elsevierStyleItalic">Enzyme-Linked ImmunoSorbent Assay</span> (ELISA).</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El 47% de los pacientes con psoriasis presentaba criterios de síndrome metabólico y el 33% presentó placa de ateroma carotídea. Se observó una disminución significativa de la clusterina plasmática (μg/ml) en pacientes con psoriasis respecto a controles (81,39<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>27,30; n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21, versus 117<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>21,6, n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,0017). El MIF plasmático (ng/ml) estaba aumentado significativamente en los pacientes con psoriasis y placa de ateroma carotídea respecto a los controles (53,22<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>29,02; n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6, versus 34,21<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9,65; n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,0394).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La disminución de clusterina en pacientes con psoriasis sugiere una relación con la enfermedad y con la situación inflamatoria sistémica. El aumento de MIF en pacientes parece relacionarse con la presencia de factores de riesgo cardiovascular asociados y placa de ateroma carotídea.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as: García-Rodríguez S, et al. Disminución de los niveles plasmáticos de clusterina en pacientes con psoriasis. Actas Dermosifiliogr. 2013;104:497–503.</p>" ] 1 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">The two authors contributed equally.</p>" "identificador" => "fn1" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2380 "Ancho" => 1628 "Tamanyo" => 197889 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Plasma levels of clusterin and macrophage migration inhibitory factor (MIF). Results are expressed as means (SD). Levels were measured by enzyme-linked immunosorbent assay, as described in the Material and Methods section. A, Plasma clusterin levels. B, Plasma MIF levels. Between-group differences were analyzed using the nonparametric Mann-Whitney U test Results were analyzed using GraphPad Prism, version 5.01. Pt indicates patients; MetSyn, metabolic syndrome; CAP, carotid atheromatous plaque.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: CAP, carotid atheromatous plaque; MetSyn, metabolic syndrome.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \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="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients</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">Controls \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"> \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">MetSyn (+) (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10) \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">MetSyn (–) (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11) \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">CAP (+) (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">7)</span> \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">CAP (–) (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>14) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">(n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triglycerides,<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> mean (SD), mg/dL \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">182,9 (13.02) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">109.5 (37.51) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">197.7 (152.6) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">117.8 (44.23) \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">123.7 (7.04) \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"><span class="elsevierStyleItalic">P</span> value<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.187 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.469 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.201 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.737 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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">HDL-C, mean (SD), mg/dL \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.5 (10.88) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53.27 (11.23) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39.14 (10.88) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.07 (13.75) \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">53.86 (4.26) \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"><span class="elsevierStyleItalic">P</span> value<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.001 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.751 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.004 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.654 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Data available for 7 of 11 controls studied.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Measured using standard methodology in hospital laboratory.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Results for patients and controls compared using the Mann-Whitney U test.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Serum Triglyceride 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 8 | 8 | 16 |
| 2024 Octubre | 65 | 227 | 292 |
| 2024 Septiembre | 70 | 33 | 103 |
| 2024 Agosto | 106 | 63 | 169 |
| 2024 Julio | 60 | 27 | 87 |
| 2024 Junio | 76 | 20 | 96 |
| 2024 Mayo | 78 | 35 | 113 |
| 2024 Abril | 74 | 28 | 102 |
| 2024 Marzo | 59 | 23 | 82 |
| 2024 Febrero | 48 | 35 | 83 |
| 2024 Enero | 62 | 34 | 96 |
| 2023 Diciembre | 61 | 23 | 84 |
| 2023 Noviembre | 69 | 24 | 93 |
| 2023 Octubre | 84 | 26 | 110 |
| 2023 Septiembre | 67 | 28 | 95 |
| 2023 Agosto | 49 | 24 | 73 |
| 2023 Julio | 60 | 38 | 98 |
| 2023 Junio | 61 | 28 | 89 |
| 2023 Mayo | 71 | 31 | 102 |
| 2023 Abril | 69 | 22 | 91 |
| 2023 Marzo | 70 | 28 | 98 |
| 2023 Febrero | 56 | 24 | 80 |
| 2023 Enero | 34 | 31 | 65 |
| 2022 Diciembre | 71 | 51 | 122 |
| 2022 Noviembre | 47 | 23 | 70 |
| 2022 Octubre | 33 | 31 | 64 |
| 2022 Septiembre | 26 | 31 | 57 |
| 2022 Agosto | 15 | 34 | 49 |
| 2022 Julio | 19 | 39 | 58 |
| 2022 Junio | 20 | 24 | 44 |
| 2022 Mayo | 51 | 48 | 99 |
| 2022 Abril | 36 | 43 | 79 |
| 2022 Marzo | 31 | 57 | 88 |
| 2022 Febrero | 36 | 38 | 74 |
| 2022 Enero | 35 | 38 | 73 |
| 2021 Diciembre | 37 | 47 | 84 |
| 2021 Noviembre | 43 | 44 | 87 |
| 2021 Octubre | 51 | 58 | 109 |
| 2021 Septiembre | 37 | 48 | 85 |
| 2021 Agosto | 38 | 38 | 76 |
| 2021 Julio | 29 | 51 | 80 |
| 2021 Junio | 38 | 42 | 80 |
| 2021 Mayo | 34 | 44 | 78 |
| 2021 Abril | 92 | 57 | 149 |
| 2021 Marzo | 60 | 37 | 97 |
| 2021 Febrero | 55 | 28 | 83 |
| 2021 Enero | 29 | 26 | 55 |
| 2020 Diciembre | 31 | 26 | 57 |
| 2020 Noviembre | 17 | 27 | 44 |
| 2020 Octubre | 29 | 23 | 52 |
| 2020 Septiembre | 36 | 15 | 51 |
| 2020 Agosto | 27 | 25 | 52 |
| 2020 Julio | 19 | 20 | 39 |
| 2020 Junio | 35 | 29 | 64 |
| 2020 Mayo | 35 | 16 | 51 |
| 2020 Abril | 28 | 20 | 48 |
| 2020 Marzo | 36 | 20 | 56 |
| 2020 Febrero | 3 | 3 | 6 |
| 2019 Diciembre | 4 | 4 | 8 |
| 2019 Noviembre | 0 | 3 | 3 |
| 2019 Octubre | 0 | 0 | 0 |
| 2019 Septiembre | 6 | 1 | 7 |
| 2019 Junio | 0 | 12 | 12 |
| 2019 Mayo | 3 | 40 | 43 |
| 2019 Abril | 0 | 8 | 8 |
| 2019 Marzo | 0 | 10 | 10 |
| 2019 Febrero | 4 | 0 | 4 |
| 2018 Diciembre | 1 | 0 | 1 |
| 2018 Noviembre | 10 | 0 | 10 |
| 2018 Octubre | 61 | 2 | 63 |
| 2018 Septiembre | 4 | 0 | 4 |
| 2018 Mayo | 0 | 13 | 13 |
| 2018 Abril | 0 | 4 | 4 |
| 2018 Marzo | 8 | 10 | 18 |
| 2018 Febrero | 21 | 8 | 29 |
| 2018 Enero | 35 | 11 | 46 |
| 2017 Diciembre | 36 | 11 | 47 |
| 2017 Noviembre | 36 | 8 | 44 |
| 2017 Octubre | 43 | 14 | 57 |
| 2017 Septiembre | 36 | 10 | 46 |
| 2017 Agosto | 27 | 19 | 46 |
| 2017 Julio | 37 | 10 | 47 |
| 2017 Junio | 58 | 14 | 72 |
| 2017 Mayo | 32 | 16 | 48 |
| 2017 Abril | 23 | 9 | 32 |
| 2017 Marzo | 30 | 34 | 64 |
| 2017 Febrero | 26 | 16 | 42 |
| 2017 Enero | 20 | 6 | 26 |
| 2016 Diciembre | 43 | 3 | 46 |
| 2016 Noviembre | 47 | 8 | 55 |
| 2016 Octubre | 44 | 17 | 61 |
| 2016 Septiembre | 36 | 10 | 46 |
| 2016 Agosto | 46 | 6 | 52 |
| 2016 Julio | 45 | 6 | 51 |
| 2016 Junio | 5 | 6 | 11 |
| 2016 Mayo | 6 | 8 | 14 |
| 2016 Abril | 4 | 2 | 6 |
| 2016 Marzo | 4 | 1 | 5 |
| 2016 Febrero | 6 | 1 | 7 |
| 2016 Enero | 6 | 1 | 7 |
| 2015 Diciembre | 9 | 7 | 16 |
| 2015 Noviembre | 8 | 11 | 19 |
| 2015 Octubre | 20 | 1 | 21 |
| 2015 Septiembre | 9 | 1 | 10 |
| 2015 Agosto | 15 | 3 | 18 |
| 2015 Julio | 66 | 13 | 79 |
| 2015 Junio | 29 | 12 | 41 |
| 2015 Mayo | 40 | 8 | 48 |
| 2015 Abril | 42 | 6 | 48 |
| 2015 Marzo | 22 | 7 | 29 |
| 2015 Febrero | 16 | 1 | 17 |
| 2015 Enero | 84 | 3 | 87 |
| 2014 Diciembre | 36 | 4 | 40 |
| 2014 Noviembre | 49 | 7 | 56 |
| 2014 Octubre | 62 | 2 | 64 |
| 2014 Septiembre | 33 | 1 | 34 |
| 2014 Agosto | 54 | 2 | 56 |
| 2014 Julio | 166 | 1 | 167 |
| 2014 Junio | 60 | 3 | 63 |
| 2014 Mayo | 36 | 13 | 49 |
| 2014 Abril | 42 | 6 | 48 |
| 2014 Marzo | 59 | 16 | 75 |
| 2014 Febrero | 40 | 9 | 49 |
| 2014 Enero | 34 | 13 | 47 |
| 2013 Diciembre | 26 | 8 | 34 |
| 2013 Noviembre | 24 | 4 | 28 |
| 2013 Octubre | 16 | 5 | 21 |
| 2013 Septiembre | 4 | 3 | 7 |
| 2013 Agosto | 1 | 4 | 5 |
| 2013 Julio | 5 | 7 | 12 |
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