Absence of peripheral blood mononuclear cells priming in hemodialysis patients

As a consequence of the proinflammatory environment occurring in dialytic patients, cytokine overproduction has been implicated in hemodialysis co-morbidity. However, there are discrepancies among the various studies that have analyzed TNF-alpha synthesis and the presence of peripheral blood mononuclear cell (PBMC) priming in this clinical setting. We measured bioactive cytokine by the L929 cell bioassay, and evaluated PBMC TNF-alpha production by 32 hemodialysis patients (HP) and 51 controls. No difference in TNF-alpha secretion was observed between controls and HP (859 ± 141 vs 697 ± 130 U/10(6) cells). Lipopolysaccharide (5 µg/ml) did not induce any further TNF-alpha release, showing no PBMC priming. Paraformaldehyde-fixed HP PBMC were not cytotoxic to L929 cells, suggesting the absence of membrane-anchored TNF-alpha. Cycloheximide inhibited PBMC cytotoxicity in HP and controls, indicating lack of a PBMC TNF-alpha pool, and dependence on de novo cytokine synthesis. Actinomycin D reduced TNF-alpha production in HP, but had no effect on controls. Therefore, our data imply that TNF-alpha production is an intrinsic activity of normal PBMC and is not altered in HP. Moreover, TNF-alpha is a product of de novo synthesis by PBMC and is not constitutively expressed on HP cell membranes. The effect of actinomycin D suggests a putative tighter control of TNF-alpha mRNA turnover in HP. This increased dependence on TNF-alpha RNA transcription in HP may reflect an adaptive response to hemodialysis stimuli.Universidade de São Paulo Instituto de Ciências Biomédicas Departamento de ImunologiaInstituto Butantan Laboratório de ImunogenéticaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUNIFESP, EPM, Depto. de MedicinaSciEL

Relationship between vascularity, age and survival in non-small-cell lung cancer.

Lung tumours in the elderly show reduced growth potential; impaired angiogenesis may contribute to this phenomenon. Recent studies have suggested that the angiogenic potential of a tumour may be inferred by the vascularity measured in histological sections. The purpose of this study has been to determine whether vascularity is related to age, survival or other clinical parameters in resected non-small-cell lung cancer (NSCLC). A group of 88 consecutive patients with a follow-up period of at least 5 years was selected. The group exhibited a wide age range (37-78 years) and similar survival characteristics to those of the general NSCLC population. Tumour sections were stained with a pan-endothelial antibody (vWF) and vascularity was quantitated, without knowledge of the clinical details, by three methods: highest microvascular density; average microvascular density; and average microvascular volume. The results were analysed by non-parametric statistical tests. A correlation was found between all three methods of quantitation. Vascularity was not associated with age, sex, tumour type, stage, volume, size (TNM-T) nodal status (TNM-N) or survival. However, survival time was generally longer for patients with higher vascularity, reaching borderline significance (P = 0.06) for the average microvascular density values. Higher tumour volume (P = 0.02) and stage (P = 0.05) were associated with lower survival times. Using multivariate survival analysis, tumour volume was the only factor related to survival. We conclude that vascularity is not associated with age and has no significant prognostic value in NSCLC

The circadian syndrome predicts cardiovascular disease better than metabolic syndrome in Chinese adults

Background To compare the predictive value of the circadian syndrome (CircS) and Metabolic syndrome (MetS) for cardiovascular disease. Method We used the data of 9360 Chinese adults aged >= 40 years from the 2011 China Health and Retirement Longitudinal Study (CHARLS). Of the participants, 8253 people were followed in the 2015 survey. MetS was defined using the harmonized criteria. CircS was based on the components of the International Diabetes Federation (IDF) MetS plus short sleep and depression. The cut-off for CircS was set as >= 4. Multivariable logistic regression analysis was used to examine the associations. Results The prevalence of CircS and MetS was 39.0% and 44.7%. Both MetS and CircS were directly associated with prevalent CVD. The odds ratios for prevalent CVD comparing CircS with MetS, respectively, were 2.83 (95%CI 2.33-3.43) and 2.34 (1.93-2.83) in men, and 2.33 (1.98-2.73) and 1.79 (1.53-2.10) in women. Similar associations were found for incident CVD. The five-year incidence of CVD was 15.1% in CircS and 14.0% in MetS. The number of CircS components has a better predictive power for both prevalent and incident CVD than those of Mets components as indicated by the area under the ROC (AUC). AUC values for CVD in 2011 were higher for CircS than MetS in both men (0.659 (95%CI 0.634-0.684) vs 0.635 (95%CI 0.610-0.661)) and women (0.652 (95%CI 0.632-0.672) vs 0.619 (95%CI 0.599-0.640)). Conclusion The circadian syndrome is a strong and better predictor for CVD than the metabolic syndrome in Chinese adults.Peer reviewe

Collagen XVIII/endostatin expression in experimental endotoxemic acute renal failure

Acute renal failure (ARF) is a frequent complication of Gram-negative sepsis, with a high risk of mortality. Lipopolysaccharide (LPS)-induced ARF is associated with hemodynamic changes that are strongly influenced by the overproduction of nitric oxide (NO) through the cytokine-mediated up-regulation of inducible NO synthase. LPS-induced reductions in systemic vascular resistance paradoxically culminate in renal vasoconstriction. Collagen XVIII is an important component of the extracellular matrix expressed in basement membranes. Its degradation by matrix metalloproteases, cathepsins and elastases results in the formation of endostatin, claimed to have antiangiogenic activity and to be a prominent vasorelaxing agent. We evaluated the expression of endostatin/collagen XVIII in an endotoxemic ARF model. ARF was induced in C57BL/6 mice by intraperitoneal injection of LPS (10 mg/kg) followed by sacrifice 4 and 12 h later. Kidney tissue was the source of RNA and protein and the subject of histological analysis. As early as 4 h after LPS administration, blood urea, creatinine and NO levels were significantly increased compared to control. Endostatin/collagen XVIII mRNA levels were 0.71 times lower than sham-inoculated mice 4 h after LPS inoculation, returning to normal levels 12 h after LPS inoculation. Immunohistological examination revealed that acute injury caused by LPS leads to an increase of endostatin basement membrane staining in association with the decrease of CD31 endothelial basement membrane staining. These results indicate that in the early phase of endotoxemic ARF the endostatin levels were not regulated by gene expression, but by the metabolism of collagen XVIII

Laser-UV-microirradiation of interphase nuclei and posttreatment with caffeine: a new approach to establish the arrangement of interphase chromosomes

Laser UV microirradiation of Chinese hamster interphase cells combined with caffeine post-treatment produced different patterns of chromosome damage in mitosis following irradiation of a small area of the nucleus that may be classified in three categories: I) intact metaphase figures, II) chromosome damage confined to a small area of the metaphase spread, III) mitotic figures with damage on all chromosomes. Category III might be the consequence of a non-localized distortion of nuclear metabolism. By contrast, category II may reflect localized DNA damage induced by microirradiation, which could not be efficiently repaired due to the effect of caffeine. If this interpretation is right, in metaphase figures of category II chromosome damage should occur only at the irradiation site. The effect might then be used to investigate neighbourhood relationships of individual chromosomes in the interphase nucleus