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

study of the cytoprotective effect of clarithromycin on the induced gastric mucosal injury in rats

Clarithromycin, a macrolide antibiotic has been used successfully with antiulcer agents to prolong duodenal ulcer remission and this has been shown to be related to the eradication of Helicobacter pylori. However, it is not well known if clarithromycin possess cytoprotective effects. The aim of the present study was to examine whether clarithromycin may have gastroprotective effect against 96% ethanol-induced gastric lesion in rats and to elucidate the role played by opiate receptors, afferent sensory nerve fibers, alpha and beta-adrenoceptors, endogenous prostaglandins, sulfhydryls, fluid volume and mucous volume retained in the gastric lumen, in the mechanism of protection offered by intragastric clarithromycin against ethanol-induced mucosal injury. Gastric mucosal lesions were induced by 96% ethanol in rats, then the effect of intragastric clarithromycin [50-400 mg/kg b.wt.] on the ethanol-induced lesion was studied. The effect of naloxone [8 mg/kg.b.wt. intraperitoneal], capsaicin [125 mg/kg b. wt. subcutaneous], prazosin [0.5 mg/kg b. wt. subcutaneous], yohimbine [5 mg/kg b. wt. subcutaneous], metoprolol [2 mg/kg b. wt. intraperitoneal], butoxamine [4 mg/kg b. wt. intraperitoneal], indomethacin [5mg/kg b. wt. subcutaneous] and iodoacetamide [100 mg/kg. b.wt. subcutaneous] on the protective effect of clarithromycin was examined. In addition, the effect of clarithromycin on the volume of gastric content was also investigated. Each study was carried out using six rats per group. It has been found that intragastric administration of clarithromycin protected the rat gastric mucosa against 96% ethanol-induced lesion in a dose dependent manner. The inhibition of lesions was 31.86, 51.33, 79.65 and 91.15% at doses of 50, 100, 200 and 400 mg/kg b.wt. respectively. The gastroprotective effect of clarithromycin was not significantly modified by pretreatment with either naloxone; or capsaicin. Subcutaneous pretreatment of rats with prazosin or intraperitoneal pretreatment with metoprolol or butoxamine, did not significantly modify the gastroprotective effect of clarithromycin, However, clarithromycin protection was significantly diminished, although not completely abolished by subcutaneous yohimbine. Clarithromycin protection was not significantly modified by pretreatment with either subcutaneous indomethacin, or iodoacetamide. In addition there was a dose dependent increase in fluid volume and in the mucous volume at 50-400 mg/kg b. wt. of clarithromycin at 30 min. Yohimbine significantly reduced both basal and clarithomycin-stimulated gastric mucous secretion. It could be concluded that the mechanism mediating the intragastric clarithromycin protective effect against 96% ethanol-induced mucosal lesion is independent of opiate receptors, capsaicin-sensitive afferent sensory nerve fibers, alpha[1], beta[1]-, beta[2]-adrenoceptors, endogenous prostaglandins, and sulfhydryl compounds of the gastric mucosa. However, the increase in luminal gastric mucous and fluid volume may contribute to the protective effect of intragastric clarithromycin against 96% ethanol-induced gastric lesion, alpha[2]-adrenoceptos possibly are involved in such protection by a mucous dependent mechanism

possible role of nitric oxide [NO] in ovarian steroidogenesis, ovulation and implantation in the rat

Evaluation of the effects of nitric oxide [NO] on the ovarian functions including ovulation and steriodogensis [serum 17-beta estradiol and progesterone concentrations] and to verify if nitric oxide is an essential mediator in embryonic implantation in the rat. Fifty female albino rats devided into 2 major groups, group [1] and group [2]: group [I] consisted of thirty prepubertal female rats injected with 5IU pregnant mare's serum gonadotropin [PMSG] intraperitoneal [I.P.], followed after 48h by I.P. injection of 5IU human chorionic gonadotropin [hCG], this group was further subdivided into 3 subgroups each of ten rats: Group IA saline treated group served as control, group IB [L-NAME treated group], group IC [L-NAME + sodium nitroprusside [SNP] treated group] both groups injected I.P. in a single dose. Twenty four hour later, blood samples were collected to measure levels of serum total nitrite, progesterone and 17 beta estradiol concentration then both ovaries removed and weighted, the ratio of ovarian weight / total body weight was obtained, number of ovarian and graafian follicles rupture sites were assessed as well. Group II consists of 20 mature pregnant rats divided into 2 sub groups [IIA, IIB] on the third day of pregnancy both uterine horns were exposed and [L-NAME] was injected [Group IIA] and [L-NAME+SNP] in the second [group IIB] into one of the uterine horns, animals allowed to recover on the eighth day of pregnancy, gravid uteri were dissected out and inspected for implantation sites. In group I [hCG] administration after [PMSG] in prepubertal rats produce superovulation. Injection of [L-NAME] [I.P.] after [PMSG] and [hCG] administration, showed a significant reduction in serum total nitrite concentration, serum progesterone and estradiol were elevated, also there was a decrease in ovarian and graafian follicles rupture sites. Ovarian weight was decreased although body weight was not changed indicating the specific effect of NO on ovarian tissue. NO generator [SNP], reverse the inhibitory action of L-NAME on the serum total nitrite levels, ovulatory process and the stimulatory action on steriodogensis as no significant difference was detected in ovarian and graafian follicles rupture sites, ovarian weight, serum progesterone and estradiol concentration compared to control group. In group II: administration of L-NAME on the third day of pregnancy significantly reduced the implantation sites. Coadministration of [SNP] with [L-NAME] showed that SNP reversed the anti-implantation effect of L-NAME. [1] Nitric oxide plays an important role in the regulation of steriodogensis and ovulation. This is evident as after injection of [NOS] inhibitor [L-NAME] there was reduction in the number of both ovarian and graafian follicles rupture sites. Also decrease in ovarian weight and ovarian/body weight ratio was observed. Level of serum 17 beta estradiol and progesterone were elevated, the reversal of these effects by coadministration of a [NO] donor SNP plus L-NAME was present. [2] Nitric oxide is involved in embryonic implantation as inhibition of NOS by L-NAME led to and implantation failure where as co-treatment with [SNP] abolished this inhibitory effect

Possible protective mechanisms of some antioxidants against different type of induced gastric ulcer in rats: implications of nitric oxide synthase

This work studied the involvement of free radicals in pathogenesis of different types of induced ulcer and the protective effect of some antioxidants. Some of the possible protective mechanisms of antioxidants [zinc sulfate, sodium selenite, N-acetylcysteine and vitamin E] were investigated against ethanol, indomethacin and across induced ulcer in rats. A group of six normal rats served as a control group. It was concluded that antioxidants zinc sulfate, sodium selenite, N-acetylcysteine and vitamin E can protect gastric mucosa against ethanol, indomethacin and stress induced ulcer in rats. The protective effect against gastric mucosal damage may be done through inhibition of lipid peroxidation of the cell membrane in association with hydroxyl radical scavenging activity, prevention of glutathione depletion, improvement of antioxidant capacity or preservation of NOS activity