Cardiovascular risks in hemodialyzed patients: could apelin have a role?

Apelin is a newly discovered adipocytokine and is produced by the white adipose tissue but is expressed, to a lesser extent in the kidney and heart. Apelin has recently been shown to be a potent positive inotropic agent in normal hearts. In addition, there is increasing evidence suggesting the role of apelin in the pathology of cardiovascular system. Cardiovascular disease is known to be a major contributor to the mortality and morbidity in patients with chronic renal failure. The aim of this study was to determine the apelin level in hemodialyzed patients and to assess its association to echocardiographic parameters among these patients. Forty uremic patients on maintenance hemodialysis were included in this study and compared with age and sex matched forty control subjects. Plasma apelin level, plasma nitrates and nitrites and routine biochemical investigations together with echocardiography were done for all subjects. Patients on hemodialysis showed significant lower level of apelin as compared to control group [5.59 +/- 2.97, 8.60 +/- 0.97 respectively, p<0.001]. Left ventricular internal end-diastolic dimension [LVIDd], Left ventricular internal end-systolic dimension [LVISd], interventricular septal thickness [IVS] were higher significantly among patients compared to control [p<0.001, <0.001, 0.02 respectively]. There was significant negative correlation between plasma apelin level and both LVIDd [p=0.003] and LVISd [p=0.046], suggesting the inotropic role of apelin. There was significant positive correlation between plasma apelin level and both plasma nitrates and nitrites [p<0.001] suggesting that apelin may mediate its effect via nitric oxide. Apelin level was significantly lower in hemodialysis patients. Apelin may be involved pathophysiology of cardiovascular disease in chronic renal failure. The therapeutic role of apelin as inotropic agent in uremic patients is to be investigated

Role of simvastatin, tetrandrine and candesartan in experimental induced liver fibrosis in rats

Liver fibrosis which insidiously and frequently develops to cirrhosis showed implications of manymitogenic and fibrogenic cytokines such as tumor necrosis factor a [TNF alpha] and transforming growth factor beta [TGF- beta] respectively. Moreover, the chemoattractant effect of reactive oxygen metabolites which recruit Kupffercells, hepatic stellate cells [HSCs]and other inflammatory cells makes more cytokine release and production ofextracellular matrix [ECM] proteins and myoflbroblast mitogens.In this study, three drugs were chosen, each of them is supposed to act by a quite differentmechanism in thioacetamide [TAA] experimental model of hepatic fibrosis in rats. Simvastatin, an example ofHMG Co A reductase inhibitor. Tetrandrine, an alkaloid with calcium channel blocking property and Candesartanas a receptor blacker for angiotensin II.This study was carried out on 40 male albino rats,8 rats served as normal controls, while in the other32 rats liver fibrosis was induced by intraperitonial TAA injection. The incidence of fibrosis or its protection wasassessed by intrasplenic pressure measurement, spleen /body weight ratio, liver hydroxyproline [HPO] contents,serum TNF alpha and TGF- beta levels, oxidative stress parameters as reduced glutathione [GSH] and malondialdehyde [MDA] levels were measured. In addition to liver transaminases and tissue inhibitor of matrix metalloproteinase [TIMP-1] activities.In the present study Six weeks administration of TAA resulted in significant rise in portal blood pressureas compared to saline control rats; associated with a significant reduction in hepatic GSH contents and asignificant increase in hepatic HPO and serum MDA concentration in TAA group as compared to all groups.Meanwhile, there were significant increases in serum levels of TNF- alpah, TGF- 01, and TIMP-lactivity in TAA ratsas compared to control group . There were also statistical significant reduction in the cytokine levels and inhibitorof metalloproteinase activities in Simvastatin, Tetrandrine and Candesartan groups as compared to TAA nontreated group.The same was the effect on liver function tests; there were significant higher serum activities of aspartateaminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALB] and y - glutamyl transferase [GGT] in TAA group as compared to saline control group. However, these serum enzymes activities showedsignificant reduction in the drug treated groups Simvastatin, Tetrandrine and Candesartan respectively. The studyfailed in detecting any significant statistical difference between the degree of protection against TAA inducedfibrosis that had been exerted by the three drugs used in the study.It was concluded that both Tetrandrine and Candesartan have marked protective effects in TAAinduced liver fibrosis by more than one mechanism .Simvastatin had a modest effect that may be by its antioxidanteffect. Clinical trials are recommended to support or disprove these results

Relationship between adiponectin, resistin and visceral obesity in type 2 diabetes mellitus in female Egyptians

The aim of this work was to study the possible physiological role of adiponectin and resistin as mediators linking obesity and insulin resistance in type 2 diabetes mellitus. Seventy-five female Egyptian subjects were enrolled in this study. They were divided into four groups as follows: obese nondiabetics [ONDM], obese diabetic type 2 [0DM], nonobese nondiabetic [NONDM] and nonobese diabetic [NODM]. Anthropometric measurements were taken. Abdominal ultrasound was also done to measure visceral fat [VF], subcutaneous fat [SCF] and visceral fat index [VFI]. Fasting blood samples were taken for analysis of serum insulin, blood glucose, plasma adiponectin and resistin. In the diabetic group adiponectin had an inverse correlation with resistin,VF and VFI [P < 0.01, P < 0.05, P < 0.01]. Resistin had a weak positive correlation only with VF, [P = 0.05] and RAI [resistin /adiponectin index] showed a positive correlation with VFI and SCF. In the nondiabetics adiponectin had no correlation with resistin, but had negative correlation with HOMA, age, VF and VFI, whereas resistin had no correlation with the same variables. RAI had a positive correlation with HOMA and SCF. In conclusion it can be said that resistin has no direct relation to insulin resistance either in diabetics or non diabetics. However, it may have a weak relation to visceral obesity only in diabetics. Hypoadiponectinemia is related to visceral obesity and increased resistin level in diabetics, while in non diabetics it is related to visceral obesity, insulin resistance and age. RAI is more informative than resistin which indicates a possible interaction between resistin and adiponectin especially in diabetics. RAI correlates positively with some anthropometrics but not to insulin resistance in diabetics, while it correlates positively with both variables in non diabetics

Steriod microdose therapy in rheumatoid arthritis patients: impact on bone metabolism

The anti-inflammatory and immuno-suppressive properties of GCs have prompted their extensive use in the management of various diseases including RA. However, the benefits derived from the use of GCs may be offset by the occurrence of GCs related side effects. One of the most important side effects of long-term use of GCs is osteoporosis. Steroid microdose therapy [simply called Microdose Therapy], a university-spin-off technology, is a physician-supervised, 3-step, education program for teaching patient control of GCs for controlling chronic inflammation in arthritic patients. This Microdose Therapy uses very low dose of prednisone [

Role of aspase-3 and soluble fas in neuronal apoptosis in the pilocarpine model of limbic system seizures in rats

The participation of specific pathway [s] in the mechanism of seizure induced brain injury remains poorly defined. Recent studies have implicated apoptotic process in this seizure related injury. Caspases are the final executioners of apoptotic cell death programme. Engagement of the cell death surface receptor Fas by Fas ligand [FasL] results in apoptolic cell death, mediated by caspase activation. Cell death mediated via Fas/Fasl interaction is blocked by soluble forms of Fas receptor [sFas]. Soluble Fas are produced by alternative splicing of Fas gene and by proteolytic cleavage of membrane Fas [mFas] receptor. The role of caspases in seizure-induced brain injury remains little explored. Therefore, the present study was designed to assess the role of caspase-3 enzyme activity and serum sFas level in the mechanism of neuronal apoptosis in the pilocarpine model of limbic system seizures in rats. Pilocarpine induced seizures reproduce most of the features of human temporal lobe epilepsy. Limbic seizures were induced in adult male rats by intraperitoneal [ip] injection of polocarpine [310-320mg/kg] and were terminated after 2-4 hours by diazepam [10-12mg/kg, ip] administration. Control rats were given an equal volume of saline, ip. Seizures were monitored behaviorally, most of rats developed seizures characterized by salivation, forelimb clonus, rearing and hindlmb clonus. After 6-8 hours of diazepam administration, blood was withdrawn for estimation of sFas level. In addition, brain limbic structures [Bilateral hippocampi and cingulate gyri] were quickly dissected and handled to estimate levels of caspase-3 enzyme activity and% DNA fragmentation in neurons within the vulnerable limbic areas. The results revealed a significant increase of caspase-3 protease activity expressed as fold increase of induced/non induced ratio as well as a significant increase of% DNA fragmentation detected in neurons of limbic structures of serizure rats as compared to control rats. In addition, a significant decrease of sFas serum level was found in epileptic rats compared with controls. The decrease serum sFas level may suggest decreased Fas mRNA splicing variants and increased full length Fas mRNA and membrane Fas, and may promote Fas mediated apoptosis. The increased receptor mediated consumption of Fas/Apo-1 in induction of apoptosis may further contribute to decreased serum sFas level. Our findings implicate increased caspase-3 protease activity in the mechanism of seizure-induced neuronal death within limbic structures possibly triggered by enhanced Fas mediated apoptosis. Therefore, control of factors regulating apoptosis may facilitate future attempts to decrease delayed brain damage induced by seizures