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

Sex-specific p38 MAP kinase activation in myocardial ischemia reperfusion injury in dogs

Very little information exists concerning the influence of sex on the response of the myocardium itself to an acute insult such as ischemia-reperfusion [I/R]. It was suggested that differences in the activation of p38 may mediate the sex-related difference in myocardial signaling after I-R which may contribute to the lower incidence of cardiac complications in females after myocardial ischemia. To evaluate the effect of sex hormones on the activation of p38 MAP kinase in a canine model of ischemia reperfusion injury. This study was conducted on 42 adult dogs of both sexes, they were classified into three groups. The first group [group I] contained 14 male dogs, the second group [group II] included 14 cycling female dogs and the third one [group III] consisted of 14 female dogs which were ovariectomized 3 weeks prior to experiment. Each group was subdivided randomly into 2 equal subgroups, I/R group [n=7] and control group [n=7]. The myocardial I/R model included anesthesized open-chest dogs after 25 minutes occlusion of the left anterior descending coronary artery [LAD] and subsequent reperfusion. Myocardial p38 MAPK and TNF-alpha and serum estrogen as well as testosterone were measured. The present study revealed decreased levels of p38 and TNF- alpha levels in the hearts of female dogs compared to male dogs and ovariectomized females subjected to the same I/R injury, suggesting that sex differences may exist in the p38 MAPK signaling pathway and cytokine response. Our findings indicate that sex difference exists in the myocardial response to acute I/R, where females dogs showed some degree of myocardial protection than males and ovariectomized females. Endogenous estrogen may be partly responsible for this cardioprotective effect by lowering p38 MAPK activation and subsequent decrease in TNF-alpha production and this benificial effect is lost in ovariectomized females. In addition, the study confirmed the deleterious effects of testosterone on myocardium through activation ofp38 MAPK and the resulting increase in TNF- alpha production

Changes in urinary deoxypyridinoline [DPD] and serum osteocalcin levels in cadmium chloride induced liver damage in rats before and after vitamin D therapy

Chronic liver diseases have an increased prevalence of metabolic bone diseases in the form of osteopenia and osteoporosis, however, there is little information about the mechanisms of these effects. The present study was aimed to investigate the importance of changes of urinary deoxypyridinoline [Dpd] and serum osteocalcin levels in experimentally induced hepatocellular injury in rats by cadmium chloride [CdCl[2]] as well as to clarify the effect of l,25 [OH][2] D[3] administration. Thirty adult male albino rats were used. The study included 3 groups each of 10 rats, group 1 was normal rats used as a control group, group 2 consisted of rats with induced hepatic damage by CdCl[2] [0.1 mg/kg subcutaneously for 4 weeks] and group 3 consisted of rats with CdCl[2]induced damage and treated with 1,25 [OH][2] D[3] administration [0.1 micro g/kg orally once daily for one week]. Blood and urine samples were collected from all rats at the end of the experiment to measure the levels of the following parameters: serum alanine and aspartate aminotransferases [ALT and AST], urinary Dpd levels as well as serum osteocalcin levels. The results of the present study showed that CdCl[2] induced a significant elevation in the mean values of ALT and AST. Urinary Dpd levels were significantly high after CdCl[2] injection. On the other hand, serum osteocalcin levels were significantly reduced especially in group 2 as compared to the other groups. The present study showed that administration of 1,25 [OH][2] D[3] to group 3 lead to reduction in levels of urinary Dpd and increased levels of serum osteocalcin but did not affect levels of serum transaminases. It was concluded that CdCl[2] induced hepatocellular injury is associated with increased bone resorption and decreased bone formation. Administration of 1.25 [OH][2] D[3] can stop these changes by preventing the progression of bone dystrophy associated with hepatocellular damage

Effect of quercetin on brain protein kinase C-alpha expression and serotonin level in streptozotocin-induced diabetic rats

Hyperglycemia is a key factor in diabetic complications. However, the mechanism of hyperglycemia-induced brain changes remains poorly understood. The aim of the present study was to investigate the effect of diabetes on serotonin [5-hydroxytryptamine; 5-HT] levels and protein kinase C-alpha [PKC-alpha] expression in brain. The potential protective effect of quercetin [QE]; as phytochemical on diabetic brain was additionally studied. This study was carried out on 60 adult male albino rats divided into three main groups; group I [control] included 20 vehicle-treated rats, group II [diabetic] consisted of 20 rats injected once intraperitonially with streptozotocin [STZ; 50mg/kb body weight] amid group III [insulin-treated diabetic] comprised 20 diabetic rats injected subcutaneously with insulin [SIU/kg/day]. Each group was subdivided into 2 subgroups; subgroup I [non-QE treated] and subgroup 2[QE-treated]. QE was administered orally [10mg/kg/day]. At the end of the implemental period, all rats were sacrificed, blood samples were withdrawn and their brains were rapidly removed and dissected. 5-HT was extracted from brain samlples and their concentrations were estimated fluorophotometrically. PKC-alpha expression was quantitated by immunoblot from extracted brain samples. The STZ-induced diabetic rats showed significant marked hyperglycemia and higher brain PKC-alpha expression as compared to both control and insulin-treated diabetic groups. However, brain 5-HT concentrations did not differ significantly between the three studied groups. Only in diabetic rats, QE administration produced a significant increase in 5-HT concentrations and a decrease in PKC-alpha expression but with no effect on blood glucose levels. A highly significant direct correlation was found between blood glucose and PKC-alpha expression levels. However, 5-HT did not correlate with either blood glucose or PKC-alpha expression. it could be concluded that STZ-induced chronically hyperglycemic rats were associated with enhanced PKC-alpha expression as well as unaltered neurotransmitter; 5-HT in brain. QE seems to act perfectly in diabetic rats by mechanisms other than antihyperglycemic action. The neuroprotective effect of QE in diabetics was suggested to be through both elevating 5-HT and lowering PKC-alpha expression. Consequently, controlling hyperglycemia is still the most essential approach for primary prevention of diabetic complications

Fecal calprotectin, novel index for assessing the pathophysiological mechanisms of inflammatory bowel disease in rats treated by glutathione

In this study, the role of fecal calprotectin [FC] as a recent non-invasive diagnostic aid of inflammatory bowel disease [IBD] was evaluated and the effect of glutathione as a preventive and therapeutic factor in acetic acid induced colitis has been studied. Forty albino rats were divided into four groups; group I: acetic acid induced colitis group. Group II: before the induction of colitis, rats were given a preventive dose of glutathione [200 mg/kg, i.p]. Group III: after colitis induction rats were treated with glutathione for one week [50 mg/kg,i.p.]. Group IV: control group. At the end of experimental period, rats were sacrificed and fecal caiprotectin was assessed in the different groups, the level of antioxidant system in the intestine was evaluated and the severity of inflammation was histopathologically scored. Colitis induction was associated with significant increase in the colonic level of FC, which was significantly reduced with glutathione prevention. Glutathione level was decreased significantly in the intestine after colitis induction, however, it was significantly high in the prevention 'group. There was significant reduction in the antioxidant enzyme system after colitis induction. However, glutathione prevention was associated with higher antioxidant enzymes compared to treatment. Various histopathological changes as inflammation, ulceration and dysplasia were detected after colitis induction, group III, however, showed no ulceration and mild inflammation. Fecal caiprotectin can be used as a non-invasive and early marker for IBD. Glutathione prevention appeared to be beneficial for the acute stage of IBD than glutathione treatment. Moreover, intestinal antioxidant enzymes were correlated negatively with FC level