Study of endothelial dysfunction and vascular inflammation in sleep apnea, obesity and aged humans

Obstructive sleep apnea [OSA] has been associated with cardiovascular complications. The overnight repetitive hypoxia represents a form of oxidative stress in the vasculature which may activate the oxidant-sensitive, proinflammatory transcription factor nuclear factor kjB [NF-kjB], affecting endothelial function and atherosclerosis. We investigated whether the endothelial alterations attributed to OSA rather than to other confounding factors. Also, the production of inflammatory cytokine nuclear factor-kappa beta [NFKbeta] was investigated as the molecular mechanism involved in vascular endothelial dysfunction with OSA. Sixty subjects underwent attended nocturnal polysomnography were grouped by apnea hypopnea index: control [AHI<5/h] and OSA cases [AHI>5/h] the cases were further classified according to age and BMI into subgroup IIA: OSA, non-obese, middle age [35-52 y], subgroup IIB: OSA, non-obese, older age group [55-68 y], subgroup IIIA: OSA, obese, middle age group [35-52 y] and subgroup IIIB: OSA, obese, older age group [55-68 y]. A morning venous blood sample was obtained. Neutrophils were isolated, and NF-kjB activity was determined. Plasma sVCAM-1 was assayed by enzyme-linked immunosorbent assay and flow-mediated dilation [FMD] was performed. NF-jB activation and plasma level of sVCAM-1 were significantly increased in OSA patients as compared to the control group and there was no significant difference between the obese and non-obese cases also no significant difference between the middle and old age cases. The degree of NF-kjB activation was positively correlated with indices of apnea severity[r = 0.938; p< 0.001]. FMD was significantly decreased in OSA patients as compared to the control group. These findings suggested that OSA is an independent risk factor for cardiovascular morbidity also that OSA leads to NF-kjB activation, which may constitute an important pathway linking OSA with systemic inflammation and cardiovascular disease

Plasma and ascitic fluid level of calprotectin in chronic liver disease: malignant and non malignant

Calprotectin was widely investigated in alcoholic liver disease and proved to be a new prognostic marker of survival independent of the severity of liver disease as well as marker of malignancy. However it was not widely investigated in other causes of liver cirrhosis. Of the present work was to study the level of calprotectin both in plasma and ascitic fluid in patients with hepatitis C [HCV] related chronic liver disease with and without malignancy, and to find out whether one or both of them correlate with the severity of liver damage and presence of malignancy. This study was conducted at the Faculty of Medicine, Alexandria University and the National Liver Institute, Menoufiya University. Thirty patients with Hepatitis C related liver cirrhosis were recruited. Fifteen of these patients suffered from concomitant hepatocellular carcinoma [HCC] diagnosed by elevated alpha foeto-protein [AFP] and one imaging technique OR by two imaging techniques in the case of normal AFP. Calprotectin was significantly elevated in patients with cirrhosis and cirrhosis/HCC than in controls [p=<0.01]. However there was no significant difference in the levels of plasma or ascitic calprotectin between the cirrhotic group and the group with HCC. There was no correlation between plasma and ascitic calprotectin levels. Ascitic calprotectin correlated significantly with bilirubin, and markers of synthetic liver function [p=<0.05], but plasma calprotectin correlated only with prothombin activity [p=<0.05]. In patients with spontaneous bacterial peritonitis, ascitic calprotectin was significantly higher in patients having this complication [879.8 +/- 67.5] than patients without SBP [534.2 +/- 59.3 [p<0.01] and a highly significant correlation was found between ascitic calprotectin and total leucocytic count in ascitic fluid [p=<0.01]. Calprotectin is elevated in HCV-related cirrhosis but not further elevation with the occurrence of hepatocellular carcinoma. Ascitic calprotectin correlated with the degree of hepatocellular injury and was significantly higher in patients with SBP. Further studies are warranted to establish a role of plasma calprotectin for the risk assessment of infectious complications secondary to bacterial translocation in patients with HCV- related liver cirrhosis