The proinflammatory mediator CD40 ligand is increased in the metabolic syndrome and modulated by adiponectin

OBJECTIVES: We hypothesized that the CD40/CD40 ligand (CD40L) system is up-regulated in the metabolic syndrome (MS) and modulated by adiponectin (AN). The objectives were: 1) to compare plasma and monocyte CD40L in patients with MS and controls and its association with clinical and biochemical parameters, 2) to investigate platelets as a source of soluble CD40L (sCD40L), and 3) to analyze the effects of AN on CD40/CD40L. METHODS: Plasma sCD40L and AN were measured in 246 controls and 128 patients with MS by ELISA. Monocyte CD40/CD40L expression and platelet CD40L content and release were compared in patients with MS and controls. Monocytes and endothelial cells were cultured with AN and CD40/CD40L expression determined by real-time RT-PCR and Western blotting. RESULTS: Patients with MS had higher sCD40L and lower AN levels than controls (0.89 +/- 0.1 vs. 0.76 +/- 0.07 ng/ml and 10.10 +/- 0.65 vs. 12.99 +/- 0.80 microg /ml, P < 0.05). Monocyte CD40/CD40L expression was higher (P < 0.05) in patients than controls (CD40: 1.31 +/- 0.31 vs. 0.80 +/- 0.14 arbitrary units; CD40L: 1.24 +/- 0.85 vs. 0.43 +/- 0.14 pg/microg protein). No differences were observed on CD40L content between resting platelets from patients with MS and controls (7.7 +/- 3.5 vs. 7.2 +/- 2.2 pg/microg protein). Stimulated platelets from patients with the MS released more (P < 0.05) sCD40L than controls (582 +/- 141 vs. 334 +/- 60% change vs. nonstimulated platelets). AN reduced CD40L mRNA and protein expression in monocytes from MS patients and endothelial cells. CONCLUSIONS: The enhanced sCD40L and cellular CD40L expression in the MS suggests that CD40L is of pathophysiological relevance in MS. Also, a new antiinflammatory effect of AN is described through the modulation of the CD40/CD40L system

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

The proinflammatory mediator CD40 ligand is increased in the metabolic syndrome and modulated by adiponectin

OBJECTIVES: We hypothesized that the CD40/CD40 ligand (CD40L) system is up-regulated in the metabolic syndrome (MS) and modulated by adiponectin (AN). The objectives were: 1) to compare plasma and monocyte CD40L in patients with MS and controls and its association with clinical and biochemical parameters, 2) to investigate platelets as a source of soluble CD40L (sCD40L), and 3) to analyze the effects of AN on CD40/CD40L. METHODS: Plasma sCD40L and AN were measured in 246 controls and 128 patients with MS by ELISA. Monocyte CD40/CD40L expression and platelet CD40L content and release were compared in patients with MS and controls. Monocytes and endothelial cells were cultured with AN and CD40/CD40L expression determined by real-time RT-PCR and Western blotting. RESULTS: Patients with MS had higher sCD40L and lower AN levels than controls (0.89 +/- 0.1 vs. 0.76 +/- 0.07 ng/ml and 10.10 +/- 0.65 vs. 12.99 +/- 0.80 microg /ml, P < 0.05). Monocyte CD40/CD40L expression was higher (P < 0.05) in patients than controls (CD40: 1.31 +/- 0.31 vs. 0.80 +/- 0.14 arbitrary units; CD40L: 1.24 +/- 0.85 vs. 0.43 +/- 0.14 pg/microg protein). No differences were observed on CD40L content between resting platelets from patients with MS and controls (7.7 +/- 3.5 vs. 7.2 +/- 2.2 pg/microg protein). Stimulated platelets from patients with the MS released more (P < 0.05) sCD40L than controls (582 +/- 141 vs. 334 +/- 60% change vs. nonstimulated platelets). AN reduced CD40L mRNA and protein expression in monocytes from MS patients and endothelial cells. CONCLUSIONS: The enhanced sCD40L and cellular CD40L expression in the MS suggests that CD40L is of pathophysiological relevance in MS. Also, a new antiinflammatory effect of AN is described through the modulation of the CD40/CD40L system

Pemphigus vulgaris autoantibodies induce apoptosis in HaCaT keratinocytes

Pemphigus vulgaris (PV) is an autoimmune disease characterized by binding of IgG autoantibodies to epidermal keratinocyte desmosomes. IgG autoantibodies obtained from a patient with mucocutaneous PV reacted with plakoglobin (Plkg) in addition to desmoglein-3 (Dsg3) and Dsg1. Immunofluorescence analysis confirmed that IgG autoantibodies, unlike antibodies from a healthy volunteer, caused disruption of cell-cell contacts in HaCaT keratinocytes. Moreover, apoptosis was enhanced in cells treated with autoantibodies compared to those treated with normal antibodies. The apoptotic process induced by IgG autoantibodies was characterized by caspase-3 activation, Bcl-2 depletion and Bax expression. The present report demonstrates that PV IgG autoantibodies promote apoptosis in HaCaT keratinocytes

Cardiotrophin-1 is expressed in adipose tissue and upregulated in the metabolic syndrome

Adipose tissue is a target for cardiotrophin-1 (CT-1), a cytokine member of the IL-6 family of cytokines that is involved in cardiac growth and dysfunction. However, it is unknown whether adipocytes are a source of CT-1 and whether CT-1 is overexpressed in diseases characterized by increased fat depots [i.e., the metabolic syndrome (MS)]. Thus this work aimed 1) to test whether adipose tissue expresses CT-1 and whether CT-1 expression can be modulated and 2) to compare serum CT-1 levels in subjects with and without MS diagnosed by National Cholesterol Education Program Adult Treatment Panel III criteria. Gene and protein expression of CT-1 was determined by real-time RT-PCR, ELISA, and Western blotting. CT-1 expression progressively increased, along with differentiation time from preadipocyte to mature adipocyte in 3T3-L1 cells. CT-1 expression was enhanced by glucose in a dose-dependent manner in these cells. mRNA and protein CT-1 expression was also demonstrated in human adipose biopsies. Immunostaining showed positive staining in adipocytes. Finally, increased CT-1 serum levels were observed in patients with MS compared with control subjects (127 +/- 9 vs. 106 +/- 4 ng/ml, P < 0.05). Circulating levels of CT-1 were associated with glucose levels (r = 0.2, P < 0.05). Taken together, our data suggest that adipose tissue can be recognized as a source of CT-1, which could account for the high circulating levels of CT-1 in patients with MS

Desempenho de serviços de saúde no tratamento diretamente observado no domicílio para controle da tuberculose Desempeño de los servicios de salud para el control de la tuberculosis a través del tratamiento domiciliar directamente observado The performance of health services in providing dots in households to control tuberculosis

Este é um estudo exploratório de natureza quantitativa e qualitativa, que avalia o desempenho dos serviços de saúde na execução do DOT no domicílio em um município de grande porte. Para a análise quantitativa foram construídos indicadores que avaliaram a otimização dos recursos materiais/humanos e a efetivação da observação da ingestão da medicação. Identificou-se que o desempenho dos serviços é influenciado pela disponibilidade de recursos humanos/materiais, organização interna dos serviços e ausência do doente no domicílio. Para a análise qualitativa, utilizou-se a técnica de análise de conteúdo, modalidade temática. A Debilidade de recursos materiais e humanos dos serviços de saúde e o Contexto sócio-cultural e econômico do doente foram identificados como os principais fatores que influenciam no desempenho dos serviços de saúde. Considera-se necessário uma permanente qualificação gerencial, organizativa e técnico-assistencial dos profissionais no controle da TB.<br>Estudio exploratorio de tipo cuantitativo y cualitativo, que evalúa el desempeño de los servicios de salud al realizar el DOT en el domicilio en una ciudad grande. Para el análisis cuantitativo fueron construidos indicadores que evalúan la optimización de los recursos materiales/humanos y la observación de la ingestión de los medicamentos. Se identificó que el desempeño es influenciado por la disponibilidad de recursos humanos/materiales, organización interna de los servicios y la ausencia del enfermo en el domicilio. Para el análisis cualitativo, se utilizó la técnica de análisis de contenido por temática. La Debilidad en cuanto a recursos materiales y humanos en los servicios de salud y el Contexto socio-cultural y económico del enfermo fueron identificados como principales factores que influyen en el desempeño de los servicios de salud. Es importante una permanente calificación gerencial, organizativa y técnico-asistencial de los profesionales para el control de la TBC.<br>Exploratory study of qualitative and quantitative nature that evaluates the performance of the health services in providing DOT in households of a big city in Brazil. For the quantitative analysis, indexes were created to evaluate the optimization of material/human resources and the observation of the medicine ingestion. It was observed that performance of services is influenced by the availability of human/material resources, the internal organization of services and the absence of the ill person in the household. For the qualitative analysis it was used the content analysis, thematic modality. The main factors influencing the performance of the health service were found to be its insufficiency ofmaterial and human resources and the ill person's social-cultural and economic context. Concluding, it is necessary permanent managerial, organizational and techno-assistance qualification of the health professionals in the TB control