Matrix metalloproteinases and soluble Fas/FasL system as novel regulators of apoptosis in children and young adults on chronic dialysis

The system of membrane receptor Fas and its ligand FasL compose one of the main pathways triggering apoptosis. However, the role of their soluble forms has not been clarified yet. Although sFasL can be converted from the membrane-bound form by matrix metalloproteinases (MMPs), there are no data on relations between sFas/sFasL, MMPs and their tissue inhibitors (TIMPs) in patients on chronic dialysis—neither children nor adults. The aim of our study was to evaluate serum concentrations of sFas, sFasL, and their potential regulators (MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2), in children and young adults chronically dialyzed. Twenty-two children on automated peritoneal dialysis (APD), 19 patients on hemodialysis (HD) and 30 controls were examined. Serum concentrations of sFas, sFasL, MMPs and TIMPs were assessed by ELISA. Median values of sFas, sFasL, sFas/sFasL ratio, MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 were significantly elevated in all dialyzed patients vs. controls, the highest values being observed in subjects on HD. A single HD session caused the decrease in values of all parameters to the levels below those seen in children on APD. Regression analysis revealed that MMP-7 and TIMP-1 were the best predictors of sFas and sFasL concentrations. Children and young adults on chronic dialysis are prone to sFas/sFasL system dysfunction, more pronounced in patients on hemodialysis. The correlations between sFas/sFasL and examined enzymes suggest that MMPs and TIMPs take part in the regulation of cell death in the pediatric population on chronic dialysis, triggering both anti- (sFas) and pro-apoptotic (sFasL) mechanisms

Impact of Excess Weight On the Relationship Between Blood Pressure and Cardiovascular Disease: the Asia Pacific Cohort Studies Collaboration

Poster session 2: Chronic disease: P2-309 IEA World Congress of Epidemiology, Edinburgh, Scotland, United Kingdom, 7-11 August 2011. In Journal of Epidemiology & Community Health, 2011, v. 65 n. Suppl. 1, p. A307-A308, abstract no. P2-30

Does Body Mass Index Impact on the Relationship Between Systolic Blood Pressure and Cardiovascular Disease? Meta-Analysis of 419 488 Individuals From the Asia Pacific Cohort Studies Collaboration

BACKGROUND AND PURPOSE: Elevated blood pressure and excess body mass index (BMI) are established risk factors for cardiovascular disease (CVD) but controversy exists as to whether, and how, they interact. METHODS: The interactions between systolic blood pressure and BMI on coronary heart disease, ischemic and hemorrhagic stroke and CVD were examined using data from 419 448 participants (>/= 30 years) in the Asia-Pacific region. BMI was categorized into 5 groups, using standard criteria, and systolic blood pressure was analyzed both as a categorical and continuous variable. Cox proportional hazard models, stratified by sex and study, were used to estimate hazard ratios, adjusting for age and smoking and the interaction was assessed by likelihood ratio tests. RESULTS: During 2.6 million person-years of follow-up, there were 10 877 CVD events. Risks of CVD and subtypes increased monotonically with increasing systolic blood pressure in all BMI subgroups. There was some evidence of a decreasing hazard ratio, per additional 10 mm Hg systolic blood pressure, with increasing BMI, but the differences, although significant, are unlikely to be of clinical relevance. The hazard ratio for CVD was 1.34 (95% CI, 1.32-1.36) overall with individual hazard ratios ranging between 1.28 and 1.36 across all BMI groups. For coronary heart disease, ischemic stroke, and hemorrhagic stroke, the overall hazard ratios per 10 mm Hg systolic blood pressure were 1.24, 1.46, and 1.65, respectively. CONCLUSIONS: Increased blood pressure is an important determinant of CVD risk irrespective of BMI. Although its effect tends to be weaker in people with relatively high BMI, the difference is not sufficiently great to warrant alterations to existing guidelines.link_to_subscribed_fulltex

Expression of hepatocyte growth factor and the proto-oncogenic receptor c-Met in canine osteosarcoma

Hepatocyte growth factor (HGF) and the proto-oncogenic receptor c-Met are implicated in growth, invasion, and metastasis in human cancer. Little information is available on the expression and role of both gene products in canine osteosarcoma. We hypothesized that the expression of c-Met is associated with malignant histologic characteristics, a short survival time, and a reduced disease-free interval in canine osteosarcoma. Quantitative real-time polymerase chain reaction was used to analyze the messenger RNA (mRNA) expression of both HGF and c-Met in 59 canine osteosarcoma samples. The relationship between HGF and c-Met expression, patient outcome, and histologic characteristics of the tumor were studied. Western blot analysis was performed to investigate the presence of active HGF protein. The expression pattern of c-Met in 16 slides of canine osteosarcoma was identified by immunohistochemistry. Coexpression of HGF and c-Met mRNA in all canine osteosarcoma samples suggested autocrine or paracrine receptor activation. A significant, moderately positive correlation was found between c-Met and HGF mRNA expression. c-Met mRNA expression was not associated with survival time or disease-free interval. Expression of c-Met was significantly associated with metastasis via the lymphogenic route. Immunolabeling with c-Met revealed a cytoplasmic staining pattern in all osteosarcoma cell types. In this study, c-Met mRNA expression in canine osteosarcoma was found to be of no influence on survival time and disease-free interval. Further studies are necessary to confirm the involvement of the c-Met pathway in the lymphogenic route of metastasis