Visceral adipose tissue visfatin in nonalcoholic fatty liver disease
Read
1692
Timeswas read the article
472
Total PDF
1220
Total HTML
Share statistics
array:24 [ "pii" => "S1665268119316357" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31635-7" "estado" => "S300" "fechaPublicacion" => "2010-07-01" "aid" => "71321" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2010" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2010;9:266-70" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 79 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 19 "PDF" => 50 ] ] "itemSiguiente" => array:19 [ "pii" => "S1665268119316369" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31636-9" "estado" => "S300" "fechaPublicacion" => "2010-07-01" "aid" => "71322" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2010;9:271-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 68 "formatos" => array:3 [ "EPUB" => 9 "HTML" => 32 "PDF" => 27 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Short and long term outcome of kidney transplanted patients with chronic viral hepatitis B and C" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "271" "paginaFinal" => "277" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1723 "Ancho" => 1000 "Tamanyo" => 95182 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Cumulative graft survival according to antiHCV status (A) and HBsAg status (B).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ezequiel Ridruejo, Carlos Díaz, Mario Dávalos Michel, Gervasio Soler Pujol, Alfredo Martínez, Sebastián Marciano, Oscar G. Mandó, Antonio Vilches" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Ezequiel" "apellidos" => "Ridruejo" ] 1 => array:2 [ "nombre" => "Carlos" "apellidos" => "Díaz" ] 2 => array:2 [ "nombre" => "Mario" "apellidos" => "Dávalos Michel" ] 3 => array:2 [ "nombre" => "Gervasio" "apellidos" => "Soler Pujol" ] 4 => array:2 [ "nombre" => "Alfredo" "apellidos" => "Martínez" ] 5 => array:2 [ "nombre" => "Sebastián" "apellidos" => "Marciano" ] 6 => array:2 [ "nombre" => "Oscar G." "apellidos" => "Mandó" ] 7 => array:2 [ "nombre" => "Antonio" "apellidos" => "Vilches" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119316369?idApp=UINPBA00004N" "url" => "/16652681/0000000900000003/v1_201906230902/S1665268119316369/v1_201906230902/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119316345" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31634-5" "estado" => "S300" "fechaPublicacion" => "2010-07-01" "aid" => "71320" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "rev" "cita" => "Ann Hepatol. 2010;9:251-65" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 83 "formatos" => array:3 [ "EPUB" => 8 "HTML" => 45 "PDF" => 30 ] ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "Kava hepatotoxicity. A clinical review" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "251" "paginaFinal" => "265" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rolf Teschke" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Rolf" "apellidos" => "Teschke" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119316345?idApp=UINPBA00004N" "url" => "/16652681/0000000900000003/v1_201906230902/S1665268119316345/v1_201906230902/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "titulo" => "Visceral adipose tissue visfatin in nonalcoholic fatty liver disease" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "266" "paginaFinal" => "270" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Radhika Gaddipati, Sasikala Mitnala, Nagarajarao Padaki, Rathindra Mohan Mukherjee, Anuradha Sekaran, Magnus Jayaraj-Mansard, Pradeep Rabella, Venkat Rao-Guduru, Nageshwar Reddy-Duwuru" "autores" => array:9 [ 0 => array:3 [ "nombre" => "Radhika" "apellidos" => "Gaddipati" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff1" ] ] ] 1 => array:5 [ "preGrado" => "PhD" "nombre" => "Sasikala" "apellidos" => "Mitnala" "email" => array:1 [ 0 => "aigres.mit@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] 2 => array:3 [ "nombre" => "Nagarajarao" "apellidos" => "Padaki" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">**</span>" "identificador" => "aff2" ] ] ] 3 => array:3 [ "nombre" => "Rathindra Mohan" "apellidos" => "Mukherjee" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "aff1" ] ] ] 4 => array:3 [ "nombre" => "Anuradha" "apellidos" => "Sekaran" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">**</span>" "identificador" => "aff2" ] ] ] 5 => array:3 [ "nombre" => "Magnus" "apellidos" => "Jayaraj-Mansard" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">**</span>" "identificador" => "aff2" ] ] ] 6 => array:3 [ "nombre" => "Pradeep" "apellidos" => "Rabella" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">**</span>" "identificador" => "aff2" ] ] ] 7 => array:3 [ "nombre" => "Venkat" "apellidos" => "Rao-Guduru" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">**</span>" "identificador" => "aff2" ] ] ] 8 => array:3 [ "nombre" => "Nageshwar" "apellidos" => "Reddy-Duwuru" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">**</span>" "identificador" => "aff2" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Institute of Basic Sciences and Translational Research, Asian Health Care Foundation" "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Asian Institute of Gastroenterology" "etiqueta" => "**" "identificador" => "aff2" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1466 "Ancho" => 1604 "Tamanyo" => 221675 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Levels of visceral adipose tissue visfatin, TNF-α, IL-6 and circulating NEFA in non NAFLD and NAFLD patients. <span class="elsevierStyleBold">A.</span> Visfatin. <span class="elsevierStyleBold">B.</span> TNFα. <span class="elsevierStyleBold">C.</span> IL-6. <span class="elsevierStyleBold">D.</span> NEFA. *P < 0.05. **P < 0.001</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Visfatin (PBEF/NAMPT/Visfatin), a novel adipo-kine predominantly expressed in visceral adipose tissue, has gained increasing importance not only in metabolism but also in inflammatory<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and immunological processes.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It was initially identified in lymphocytes as pre β-cell colony enhancing factor (PBEF) which, along with IL-7, acts synergistically to promote the differentiation of β cell precur-sors.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Its phosphoribosyl transferase activity (NAMPT) is the rate limiting step in NAD biosynthesis.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Thus, it regulates cellular energetics and NAD dependent enzymes such as silent information regulator proteins (SIRTUINS).<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Many investigators have demonstrated the role of adipose tissue derived adipokines in the pathogenesis and in the progression of NAFLD to NASH (Non alcoholic steatohepatitis).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Despite large number of reports on the role of proinflammatory cytokines including adiponectin in NAFLD studies on visceral adipose tissue visfatin in NAFLD are scanty. Visfatin was shown to be expressed in various tissues including liver<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and upregulated in visceral adipose tissue (VAT) of mice and humans<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">–</span><a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> under the conditions of obesity. VAT has been proposed to be a major contributor of steatosis in NAFLD.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Recently decrease in plasma visfatin was shown to be associated with NASH,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> while the incidence of portal inflammation increased with increase in circulating visfatin level.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Considering the importance of the portal delivery of visceral adipose tissue factors on liver, role of visceral visfatin in NAFLD needs to be elucidated.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In view of this, the present study was conducted to assess the level of visceral adipose tissue visfatin in NAFLD.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Subjects</span><p id="p0010" class="elsevierStylePara elsevierViewall">A total of 115 patients (non diabetic) referred to Asian Institute of Gastroenterology, Hyderabad, India for diagnostic laparoscopy were recruited in the study. Those with a history of diabetes mellitus (treated/untreated), chronic liver diseases, excessive consumption of alcohol (< 20 gm/day) and those on medication that influence glucose metabolism were excluded from the study. Patients who were radiologically diagnosed to have fatty liver and devoid of any history of alcohol consumption were considered as NAFLD group and patients without fatty liver were considered separately as non NAFLD group. The number of obese patients were fourteen in NAFLD and six in non NAFLD groups. Informed consent was obtained from all the patients and the study protocol was approved by the institutional ethical and scientific review committee.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Methods</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Samples</span><p id="p0015" class="elsevierStylePara elsevierViewall">Visceral adipose tissue from greater omentum was obtained at the time of laparoscopy in Dulbecco’s minimum essential medium (DMEM) containing 1000 mg/L glucose and 27 BSA for estimation of pro inflammatory cytokines and visfatin. Formalin preserved liver biopsy specimens taken from the patients were sub<span class="elsevierStyleBold">j</span>ected to histopathologi-cal examinations. Fasting blood samples (5 ml) were collected in heparin for the estimation of glucose, lipids, liver enzymes and non esterified fatty acids (NEFA).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Measurment of proinflammatory cytokines and visfatin</span><p id="p0020" class="elsevierStylePara elsevierViewall">The visceral adipose tissues were washed with PBS (pH 7.4) and extracted immediately using cell extraction buffer (Biosource, Camarillo, CA, USA) containing cocktail of protease inhibitors. The extracts were stored at-80° C until analysis. TNF-α (Tumor necrosis factor-α) and IL-6 (Interleukin-6) levels were estimated using ELISA kits (Sanquin reagents, AD Amsterdam, Netherlands) as per manufacturers’ instructions. Visfatin level was estimated by ELISA (Adipogen, Seoul, Korea) employing microplate wells pre-coated with monoclonal antibody specific for human visfatin. The bound visfatin in the adipose tissue extract was captured by HRP conjugated rabbit anti human visfatin. The extent of color developed with the addition of substrate was measured at 450nm using an ELISA plate reader (Bio-Rad, Tokyo, Japan). Lipid profiles, glucose and liver enzymes were estimated on autoanalyser (Daytona, Randox laboratories, Co. Antrim, UK) and non esterified fatty acids (NEFA) were measured on spectrophotometer (Bec-kman Coulter, Fullerton, CA, USA) using commercial kits (Randox).</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Histopathological examination of liver biopsy</span><p id="p0025" class="elsevierStylePara elsevierViewall">Formalin fixed liver biopsy specimens were routinely processed, sectioned and stained with haema-toxylin-eosin. Biopsies were evaluated by two independent pathologists. The degree of steatosis was graded as per Brunt’s classification.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Simple hepatocellular fat accumulation was considered as indicative of simple steatosis, moderate steatosis was diagnosed when predominant ballooning degeneration was observed while NASH was diagnosed by the presence of lobular inflammation and pericellu-lar fibrosis.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Statistical Analysis</span><p id="p0030" class="elsevierStylePara elsevierViewall">The data was analysed by ANOVA analysis of variance, Pearson’s correlation, and Kendell’s correlation as and when applicable using SPSS software, version 13.0 (SPSS, IL USA). A <span class="elsevierStyleItalic">P</span> value of < 0.05 was considered significant throughout the study.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Results</span><p id="p0035" class="elsevierStylePara elsevierViewall">Demographic and clinical details of the patients are given in <a class="elsevierStyleCrossRef" href="#t0005">table 1</a>. Grouping of the patients (n = 115; male: female ratio = 63:52) on the basis of histopathological grading resulted in two groups, NAFLD (n = 77), non NAFLD (n = 38).</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Histopathology of liver</span><p id="p0040" class="elsevierStylePara elsevierViewall">Histopathological examination of liver biopsies revealed varying degrees of steatosis in NAFLD group ranging from simple steatosis (457, n = 35), moderate steatosis (407, n = 30) to NASH (157, n = 12). Subjects from Non NAFLD group were devoid of any histological signs of steatosis (<a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>).</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Visceral adipose tissue visfatin</span><p id="p0045" class="elsevierStylePara elsevierViewall">Visceral adipose tissue visfatin levels were high in non NAFLD group (210 ± 93.16 ng /mg protein). Significant decline in visceral visfatin level was evident in all the groups of NAFLD which was more pronounced in simple steatosis (87.25 ± 75.22 ng/mg protein) as compared to non NAFLD group. This decline maintained the same waning trend in patients having moderate steatosis (61.36 ± 56.46 ng/mg protein) and reduced drastically in those diagnosed for NASH (31.83 ± 29.43 ng/mg protein) as depicted in <a class="elsevierStyleCrossRef" href="#f0005">figure 1A</a>. The decrease in simple steato-sis showed an inverse correlation between the level of visceral visfatin and occurrence of simple steato-sis in NAFLD (P < 0.001; r – 0.576).</p><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Visceral adipose tissue proinflammatory cytokines</span><p id="p0050" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#f0005">figure 1B</a>, TNF α levels in visceral adipose tissue was higher in all the groups of NA-FLD including patients with NASH, showing an increase of 13.27, 307 and 737 in simple steatosis, moderate steatosis and NASH patients respectively. Visceral adipose tissue IL 6 levels (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1C</a>) showed a considerable decrease in simple steatosis and an increase in NASH group of NAFLD as compared to non NAFLD group. Although there was an increasing trend in IL 6 levels in NASH, statistical significance could not be attained for such observed increase.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Circulating nonesterified fatty acids (NEFA)</span><p id="p0055" class="elsevierStylePara elsevierViewall">In comparison to non NAFLD group, circulating NEFA levels increased in NAFLD group as evidenced by an increase of 15.47, 25.27 and 27.97 in simple steatosis, moderate steatosis and NASH respectively. The elevated levels of NEFA in moderate steatosis and in NASH patients were found to be statistically significant (P < 0.02) (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1D</a>).</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="p0060" class="elsevierStylePara elsevierViewall">The present study was conducted to estimate visceral adipose tissue visfatin levels in NAFLD. This study demonstrated a significant decline in visceral visfatin levels i.e. 607 decline in simple steatosis 707 in moderate steatosis and 857 in NASH. This result corroborates with recent reports in which circulating visfatin was shown to be decreased in</p><p id="p0065" class="elsevierStylePara elsevierViewall">NASH patients<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> and with worsening of the clinical stage of liver disease in cirrhosis<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> as well as aetherogenesity of lipid profile.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> The observed decline in visceral visfatin levels in the present study was found to be independent of BMI as measured by standard methods (data not shown). Although association of insulin resistance measured by HOMA model with NASH was demonstrated,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> our study did not find any association of visceral visfatin with IR in NASH patients. Non association of visceral visfatin was also true with circulating glucose, cholesterol and triglycerides. Alagasham and Barakat also did not find any correlation between visfatin and BMI, insulin, HOMA IR (Homeostasis Model Assessment-Insulin Resistance).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="p0070" class="elsevierStylePara elsevierViewall">Our study reports increased levels of adipose tissue TNF-α in all the groups of NAFLD as compared to non NAFLD group emphasizing its role in the pathogenesis. Earlier studies also reported a potential role for TNF-α in NAFLD and NASH.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Since visceral adipose tissue is considered as an independent risk factor for NAFLD,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> increased visceral adipose TNF-α levels even in simple steatosis implicate its significant role in steatogenesis. While TNF-α levels increased, visceral visfatin levels decreased in all the groups of NAFLD in this study. These results corroborate with similar recent observations which showed that TNF-α down regulated the expression of adipose triglyceride lipase, adiponectin, visfatin and PPAR (Peroxisome proliferator activator receptor) gamma. <a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Decrease in IL-6 levels observed in simple steatosis in this study may indicate a hepato-protective role of IL-6 in steatotic livers.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Contrary to this finding, IL-6 levels increased in moderate steatosis to NASH, which is in agreement with a previous study which showed increase in both IL-6 and IL-6R levels in NASH patients. <a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Despite these reports, the role of IL-6 in pathogenesis of NAFLD is not clear.</p><p id="p0075" class="elsevierStylePara elsevierViewall">A significant increase in circulating NEFA level was observed in moderate steatosis and in NASH patients (P < 0.02) as compared to non NAFLD group in this study. Hepatic steatosis in NAFLD is attributed either to increased delivery of FFA (NEFA) to the liver from visceral adipose tissue through portal delivery or decreased FA degradation or impaired TG release from the liver. Although pro-inflammatory nature of visfatin has been demonstrated, its phosphoribosyl transferase activity in visceral adipose tissue may have an important central role in fatty acid metabolism and triacyl glycerol release from the visceral adipose tissue. Significant decrease of tissue visfatin level in NAFLD as</p><p id="p0080" class="elsevierStylePara elsevierViewall">observed in the present study might be indicative of a potential link between the NAD generating properties of visfatin and adipose tissue fatty acid metabolism.</p><p id="p0085" class="elsevierStylePara elsevierViewall">Limitation of our study is the small number of obese patients in both NAFLD and non NAFLD groups. In spite of the limitation, decline in visceral visfatin was evident in NAFLD group. Measurement of NEFA levels in the portal vein might throw more light on the autocrine effect of visfain on visceral adipose tissue lipid metabolism which need further study. To our knowledge, this is the first report involving visceral adipose tissue visfatin in NAFLD. In agreement with recent reports which indicate a protective role of visfatin in steatosis of liver,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> our data shows that there is strong association between increased TNF-α and decreased levels of adipose tissue visfatin in NAFLD patients.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Acknowledgements</span><p id="p0090" class="elsevierStylePara elsevierViewall">The authors wish to acknowledge Asian Health care Foundation for funding the project. Authors express their gratitude to Dr. B. Sadasivudu for the intellectual inputs and critical advise on the manuscript.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1211007" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1127291" "titulo" => "Key words" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and Methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Subjects" ] ] ] 4 => array:3 [ "identificador" => "sec0020" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Samples" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Measurment of proinflammatory cytokines and visfatin" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Histopathological examination of liver biopsy" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical Analysis" ] ] ] 5 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Histopathology of liver" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Visceral adipose tissue visfatin" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Visceral adipose tissue proinflammatory cytokines" ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "Circulating nonesterified fatty acids (NEFA)" ] ] ] 6 => array:2 [ "identificador" => "sec0070" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Acknowledgements" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2010-02-02" "fechaAceptado" => "2010-05-10" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec1127291" "palabras" => array:4 [ 0 => "NAFLD" 1 => "TNF α" 2 => "NEFA" 3 => "Visceral visfatin" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0005" class="elsevierStyleSection elsevierViewall"><p id="sp0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Background.</span> Visfatin is a novel adipocytokine predominantly expressed and secreted by visceral adipose tissue. It is realized for its multiple functions of central importance in NAD biosynthesis, innate immunity and inflammation. Its phosphoribosyl transferase activity regulates cellular energetics and NAD dependent enzymes such as SIRTUINS. Although its expression in various tissues and circulating levels are documented, visceral visfatin levels in Nonalcoholic fatty liver disease (NAFLD) patients have not been reported.</p><p id="sp0016" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Objective.</span> The aim of the present study was to assess visceral adipose tissue visfatin levels in NAFLD.</p><p id="sp0017" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Materials and methods.</span> A total of 115 patients undergoing diagnostic laparoscopy were recruited in the study and categorized into two groups based on standard criteria for NAFLD. Visceral adipose tissue TNF-α, IL-6 and visfatin levels were measured by ELISA. Blood glucose, lipids, liver enzymes and non esterified fatty acids (NEFA) were estimated using standard procedures. Formalin fixed, Hematoxylene Eosin stained liver biopsy specimens were examined for the presence of steatosis and the degree of steatosis was ascertained as per Brunt’s classification.</p><p id="sp0018" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Results.</span> The visceral visfatin level declined significantly (P < 0.001) in all groups of NAFLD as compared to non NAFLD group, while plasma NEFA level increased with progressive steatosis (P < 0.02). Significant increase in TNF a was observed in all groups of NAFLD, while IL-6 increased in NASH only.</p><p id="sp0019" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Conclusion.</span> A significant decline in visceral adipose tissue visfatin level was found to be associated with degree of steatosis in NAFLD patients.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="tnp0005">P < 0.05. **P < 0.001. HPE: Histopathological examination. RBS: Random blood sugar. TG:Tri glycerides.</p>" "identificador" => "t1_fn1" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1466 "Ancho" => 1604 "Tamanyo" => 221675 ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Levels of visceral adipose tissue visfatin, TNF-α, IL-6 and circulating NEFA in non NAFLD and NAFLD patients. <span class="elsevierStyleBold">A.</span> Visfatin. <span class="elsevierStyleBold">B.</span> TNFα. <span class="elsevierStyleBold">C.</span> IL-6. <span class="elsevierStyleBold">D.</span> NEFA. *P < 0.05. **P < 0.001</p>" ] ] 1 => array:7 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="npara0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleFootnote" id="t1_fn1"><span class="elsevierStyleLabel">*</span><p class="elsevierStyleNotepara" id="tnp0005">P < 0.05. **P < 0.001. HPE: Histopathological examination. RBS: Random blood sugar. TG:Tri glycerides.</p></span></p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="middle" 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="middle" scope="col" style="border-bottom: 2px solid black">Non NAFLD (n=38) \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="middle" scope="col" style="border-bottom: 2px solid black">Simple Steatosis \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="middle" scope="col" style="border-bottom: 2px solid black">NAFLD (n=77) Moderate Steatosis \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="middle" scope="col" style="border-bottom: 2px solid black">NASH \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="middle"><span class="elsevierStyleBold">Age</span> (yrs) \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="middle">46.5 ± 16.48 \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="middle">48.94 ± 13.12 \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="middle">46.2 ± 12.22 \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="middle">49 ± 13.19 \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="middle"><span class="elsevierStyleBold">RBS</span> (mg/mL) \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="middle">128.08 ± 60 \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="middle">150.6 ± 81.13 \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="middle">129.29 ± 53.58 \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="middle">136.12 ± 40 \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="middle"><span class="elsevierStyleBold">Cholesterol</span> (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="left" valign="middle">184.71 ± 70.24 \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="middle">214.37 ± 72.39 \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="middle">210.6± 54.93 \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="middle">222.8 ± 59 \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="middle"><span class="elsevierStyleBold">TG</span> (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="left" valign="middle">135.63 ± 77.73 \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="middle">175.14 ± 96.83 \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="middle">173.66 ± 69.47 \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="middle">184 ± 82.9 \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="middle"><span class="elsevierStyleBold">ALT</span> (U/L) \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="middle">22.75 ± 14.8 \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="middle">28.05 ± 21.69 \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="middle">66.89 ± 47.79 \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="middle">52.27 ± 33.8 \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="middle"><span class="elsevierStyleBold">Insulin</span> (mlU) \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="middle">75.6± 103 \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="middle">98.9 ± 147 \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="middle">89.8 ± 172 \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="middle">108.4 ± 130 \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="middle"><span class="elsevierStyleBold">Visfatin</span> (ng /mg pro) \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="middle">210.38 ± 93.16 \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="middle">87.25 ± 75.22<a class="elsevierStyleCrossRef" href="#t1_fn1">*</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="left" valign="middle">61.36 ± 56.46<a class="elsevierStyleCrossRef" href="#t1_fn1">**</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="left" valign="middle">31.83 ± 29.43<a class="elsevierStyleCrossRef" href="#t1_fn1">**</a> \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="middle"><span class="elsevierStyleBold">TNF a</span> (pg/mg pro) \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="middle">81.3 ± 56.23 \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="middle">92.1 ± 41.9 \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="middle">105.7 ± 65.9 \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="middle">141.2 ± 91.2<a class="elsevierStyleCrossRef" href="#t1_fn1">*</a> \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="middle"><span class="elsevierStyleBold">IL-6</span> (pg/mg pro) \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="middle">131.12 ± 96.91 \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="middle">58.39 ± 30.28 \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="middle">86.7 ± 82.1 \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="middle">152.23 ± 134.7 \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="middle"><span class="elsevierStyleBold">NEFA</span> (μmol/L) \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="middle">726.06 ± 248.75 \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="middle">838.23 ± 277.19 \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="middle">910 ± 359.3<a class="elsevierStyleCrossRef" href="#t1_fn1">*</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="left" valign="middle">929.09 ± 251.03<a class="elsevierStyleCrossRef" href="#t1_fn1">*</a> \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="middle">HPE of <span class="elsevierStyleBold">liver biopsy</span> \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="middle">No fat accumulation \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="middle">Up to 66% hepatocytes showed fat accumulation \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="middle">Steatosis with ballooning degeneration \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="middle">Above 66°% hepatocytes showed fat accumulation ballooning degeneration, lobular inflammation and peri cellular fibrosis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2067318.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Demographic and clinical details of the patients.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of adiponectin and PBEF/Visfatin as regulators of inflammation: involvement in obesity associated diseases." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Herbert T.I.L.G." 1 => "Alexander R.M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1042/CS20070196" "Revista" => array:6 [ "tituloSerie" => "Clin Sci" "fecha" => "2008" "volumen" => "114" "paginaInicial" => "275" "paginaFinal" => "288" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18194136" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pre Beta cell colony enhancing factor (PBEF) Visfatin: A novel mediator of innate immunity." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Luk T." 1 => "Malam Z." 2 => "Marshall J.C." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Leukoe Biol" "fecha" => "2008" "volumen" => "83" "numero" => "4" "paginaInicial" => "804" "paginaFinal" => "816" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cloning and characterization of the cDNA encoding a novel pre B cell colony enhancing factor." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Samal B." 1 => "Sun Y." 2 => "Stearms G." 3 => "Xie C." 4 => "Suggs S." 5 => "McNiece I." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/mcb.14.2.1431" "Revista" => array:6 [ "tituloSerie" => "Mol cell Biol" "fecha" => "1994" "volumen" => "14" "paginaInicial" => "1431" "paginaFinal" => "1437" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8289818" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/vis-fatin in mammals." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Revollo J.R." 1 => "Grimm A.A." 2 => "Imai S." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MOG.0b013e32801b3c8f" "Revista" => array:7 [ "tituloSerie" => "Curr Opin Gastroenterol" "fecha" => "2007" "volumen" => "23" "numero" => "2" "paginaInicial" => "164" "paginaFinal" => "170" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17268245" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human sirt 1." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Bitterman K.J." 1 => "Anderson R.M." 2 => "Cohen H.Y." 3 => "Latorre-Esteves M." 4 => "Sinclair D.A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1074/jbc.M205670200" "Revista" => array:7 [ "tituloSerie" => "J Biol Chem" "fecha" => "2002" "volumen" => "277" "numero" => "47" "paginaInicial" => "45099" "paginaFinal" => "45107" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12297502" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non alcoholic fatty liver disease: An overview." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Mulhall B.P." 1 => "Ong J.P." 2 => "Younossi Z.M." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Gastroenterol Hepatol" "fecha" => "2002" "volumen" => "17" "paginaInicial" => "1136" "paginaFinal" => "1143" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12453271" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gene expression of leptin, resistin and adiponectin in the white adipose tissue of obese patients with non alcoholic fatty liver disease and insulin resistance." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Baranova A." 1 => "Gowder S.J." 2 => "Schlauch K." 3 => "Elariny H." 4 => "Collantes R." 5 => "Afendy A." 6 => "Ong Janus P." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1381/096089206778392149" "Revista" => array:7 [ "tituloSerie" => "Obes Surg" "fecha" => "2006" "volumen" => "16" "paginaInicial" => "1118" "paginaFinal" => "1125" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16989692" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0165178115301463" "estado" => "S300" "issn" => "01651781" ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Visfatin: The missing link between intra-abdominal obesity and diabetes." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Sethi J.K." 1 => "Vidal - Puig A." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Trends in Mol Medieine" "fecha" => "2005" "volumen" => "11" "numero" => "8" "paginaInicial" => "344" "paginaFinal" => "347" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma visfatin concentrations and fat depot specific mRNA expression in humans." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Berndt J." 1 => "Kloting N." 2 => "Kralisch S." 3 => "Kovacs P." 4 => "Fasshauer M." 5 => "Sohan M.R." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/diabetes.54.10.2911" "Revista" => array:6 [ "tituloSerie" => "Diabetes" "fecha" => "2005" "volumen" => "54" "paginaInicial" => "2911" "paginaFinal" => "2916" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16186392" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased plasma visfatin levels in subjects with the metabolic syndrome." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "FiIippatos T.D." 1 => "Derdemezis C.S." 2 => "Gazi I.F." 3 => "Logos K." 4 => "Kiortsis D.N." 5 => "Tselepis A.D." 6 => "Elisaf M.S." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2362.2007.01904.x" "Revista" => array:6 [ "tituloSerie" => "Eur J Clin Invest" "fecha" => "2008" "volumen" => "38" "paginaInicial" => "71" "paginaFinal" => "72" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18173555" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "Chen M.P." 1 => "Chung F.M." 2 => "Chang D.M." 3 => "Jack CR Tsai" 4 => "Huang H.F." 5 => "Shin S.J." 6 => "Lee Y.J." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Endoerinol Metab" "fecha" => "2006" "volumen" => "91" "paginaInicial" => "295" "paginaFinal" => "299" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Visceral adipose tissue area is an independent risk factor for hepatic steatosis." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Park B.J." 1 => "Kim Y.J." 2 => "Kim D.H." 3 => "Kim W." 4 => "Jung Y.J." 5 => "Yoon J.H." 6 => "Kim C.Y." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1440-1746.2007.05212.x" "Revista" => array:7 [ "tituloSerie" => "J Gastroenterol Hepatol" "fecha" => "2008" "volumen" => "23" "numero" => "6" "paginaInicial" => "900" "paginaFinal" => "907" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17995942" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adipokines and cytokines in nonalcoholic fatty liver disease." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Jarrar M.H." 1 => "Baranova A." 2 => "Collantes R." 3 => "Ranard B." 4 => "Stepanova M." 5 => "Bennett C." 6 => "Fang Y." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2036.2007.03586.x" "Revista" => array:7 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2008" "volumen" => "27" "numero" => "5" "paginaInicial" => "412" "paginaFinal" => "421" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18081738" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of visfatin on histopa-thological changes of non-alcoholic fatty liver disease." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Aller R." 1 => "De Luis D.A." 2 => "Izaola O." 3 => "Sagrado M.G." 4 => "Conde R." 5 => "Velasco M.C." 6 => "Álvarez T." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10620-008-0539-9" "Revista" => array:6 [ "tituloSerie" => "Dig Dis Sci" "fecha" => "2009" "volumen" => "54" "paginaInicial" => "1772" "paginaFinal" => "1777" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19005759" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adipokines in nonalcoholic fatty liver disease." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Baranova A." 1 => "Younossi Z.M." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "editores" => "FantuzziG., MazzoneT." "titulo" => "Adipose tissue and adipokines in health and disease." "paginaInicial" => "291" "paginaFinal" => "305" "serieFecha" => "2007" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Brunt E.M." 1 => "Janney C.G." 2 => "Di Bisceglie A.M." 3 => "Neuschwander-Tetri B.A." 4 => "Bacon B.R." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Gastrol" "fecha" => "1999" "volumen" => "94" "paginaInicial" => "2467" "paginaFinal" => "2474" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma levels of PBEF/Nampt/visfatin are decreased in patients with liver cirrhosis." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "De Boer J.F." 1 => "Matthias J.B." 2 => "Klaus H.W." 3 => "Manns M.P." 4 => "Tietge U.J.F." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajpgi.00029.2008" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Gastrointest Liver Physiol" "fecha" => "2009" "volumen" => "296" "paginaInicial" => "G196" "paginaFinal" => "G201" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19074645" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of insulin resistance and adipokines in the grade of steatosis of nonalcoholic fatty liver disease." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Aller R." 1 => "De Luis D.A." 2 => "Fernández L." 3 => "Calle F." 4 => "Veloys B." 5 => "Olcoz J.L." 6 => "Izaola O." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10620-007-9981-3" "Revista" => array:7 [ "tituloSerie" => "Dig Dis Sci" "fecha" => "2008" "volumen" => "53" "numero" => "4" "paginaInicial" => "1088" "paginaFinal" => "1092" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17934820" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum visfatin and its relation to insulin resistance and inflammation in type 2 diabetic patients with and without macro angiopathy." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Alghasham A.A." 1 => "Barakat Y.A." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Saudi Med J" "fecha" => "2008" "volumen" => "29" "paginaInicial" => "185" "paginaFinal" => "192" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18246224" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Beyond insulin resistance in NASH: TNF-alpha or adiponectin?." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Hui J.M." 1 => "Hodge A." 2 => "Farrell G.C." 3 => "Kench J.G." 4 => "Kriketos A." 5 => "George J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.20280" "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "2004" "volumen" => "40" "numero" => "1" "paginaInicial" => "46" "paginaFinal" => "54" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15239085" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cytokines and NASH. A pilot study of the effects of lifestyle modification and vitamin E." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Kugelmas M." 1 => "Hill D.B." 2 => "Vivian B." 3 => "Marsano L." 4 => "McClain C.J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/jhep.2003.50316" "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "2003" "volumen" => "38" "numero" => "2" "paginaInicial" => "413" "paginaFinal" => "419" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12883485" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The adipose triglyceride lipase, adiponectin and visfatin are downregulated by tumor necrosis factor-alpha (TNF-alpha) in vivo." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Li L." 1 => "Yang G." 2 => "Shi S." 3 => "Yang M." 4 => "Liu H." 5 => "Boden G." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cyto.2008.10.006" "Revista" => array:7 [ "tituloSerie" => "Cytokine" "fecha" => "2009" "volumen" => "45" "numero" => "1" "paginaInicial" => "12" "paginaFinal" => "19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19026557" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis." "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Abiru S." 1 => "Migita K." 2 => "Maeda Y." 3 => "Daikoku M." 4 => "Ito M." 5 => "Ohata K." 6 => "Nagaoka S." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1478-3231.2005.01191.x" "Revista" => array:6 [ "tituloSerie" => "Liver Int" "fecha" => "2006" "volumen" => "26" "paginaInicial" => "39" "paginaFinal" => "45" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16420507" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apelin and visfatin: unique “beneficial” adipokines upregulated in obesity?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Beltowski J." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Sci Monit" "fecha" => "2006" "volumen" => "12" "paginaInicial" => "112" "paginaFinal" => "119" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/0000000900000003/v1_201906230902/S1665268119316357/v1_201906230902/en/main.assets" "Apartado" => array:4 [ "identificador" => "77721" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/0000000900000003/v1_201906230902/S1665268119316357/v1_201906230902/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119316357?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 0 | 3 |
| 2024 October | 29 | 3 | 32 |
| 2024 September | 44 | 5 | 49 |
| 2024 August | 31 | 5 | 36 |
| 2024 July | 22 | 3 | 25 |
| 2024 June | 39 | 7 | 46 |
| 2024 May | 29 | 1 | 30 |
| 2024 April | 21 | 3 | 24 |
| 2024 March | 23 | 6 | 29 |
| 2024 February | 28 | 9 | 37 |
| 2024 January | 42 | 6 | 48 |
| 2023 December | 45 | 10 | 55 |
| 2023 November | 40 | 7 | 47 |
| 2023 October | 77 | 3 | 80 |
| 2023 September | 24 | 3 | 27 |
| 2023 August | 16 | 5 | 21 |
| 2023 July | 7 | 4 | 11 |
| 2023 June | 19 | 7 | 26 |
| 2023 May | 44 | 3 | 47 |
| 2023 April | 23 | 0 | 23 |
| 2023 March | 14 | 2 | 16 |
| 2023 February | 6 | 7 | 13 |
| 2023 January | 7 | 2 | 9 |
| 2022 December | 4 | 4 | 8 |
| 2022 November | 11 | 5 | 16 |
| 2022 October | 17 | 9 | 26 |
| 2022 September | 7 | 6 | 13 |
| 2022 August | 7 | 6 | 13 |
| 2022 July | 17 | 10 | 27 |
| 2022 June | 17 | 6 | 23 |
| 2022 May | 18 | 8 | 26 |
| 2022 April | 24 | 15 | 39 |
| 2022 March | 24 | 29 | 53 |
| 2022 February | 22 | 9 | 31 |
| 2022 January | 47 | 13 | 60 |
| 2021 December | 22 | 9 | 31 |
| 2021 November | 16 | 11 | 27 |
| 2021 October | 30 | 17 | 47 |
| 2021 September | 12 | 10 | 22 |
| 2021 August | 10 | 10 | 20 |
| 2021 July | 14 | 11 | 25 |
| 2021 June | 9 | 6 | 15 |
| 2021 May | 23 | 6 | 29 |
| 2021 April | 68 | 38 | 106 |
| 2021 March | 31 | 5 | 36 |
| 2021 February | 14 | 5 | 19 |
| 2021 January | 6 | 8 | 14 |
| 2020 December | 15 | 7 | 22 |
| 2020 November | 10 | 10 | 20 |
| 2020 October | 11 | 5 | 16 |
| 2020 September | 21 | 8 | 29 |
| 2020 August | 12 | 8 | 20 |
| 2020 July | 10 | 3 | 13 |
| 2020 June | 3 | 1 | 4 |
| 2020 May | 8 | 12 | 20 |
| 2020 April | 4 | 7 | 11 |
| 2020 March | 4 | 4 | 8 |
| 2020 February | 1 | 2 | 3 |
| 2020 January | 5 | 12 | 17 |
| 2019 December | 4 | 7 | 11 |
| 2019 November | 3 | 11 | 14 |
| 2019 October | 2 | 2 | 4 |
| 2019 September | 1 | 4 | 5 |
| 2019 August | 1 | 1 | 2 |
| 2019 July | 1 | 7 | 8 |
| 2019 June | 1 | 4 | 5 |
Show all
