Effect of recombinant growth hormone [rh-GH] on glycerol induced acute renal failure [ARF] in rats

Experimental studies showed that acute uremia is characterized by reduced GH and IGF-l messenger RNA expression and is manifested as resistance to human rh-GH. However the administration of high doses of several anabolic agents including rh-GH have been proposed as a potential therapy for several catabolic conditions including acute renal failure [ARF]. Therefore this study was conducted to reveal the renoprotective and ameliorating effects of GH on glycerol-induced ARF in rats, by exploring its effects on generating IGF-l, decreasing ROS, improving kidney function and its effect on the generation of the vasodilator nitric oxide [NO]. The present study included four groups of albino rats, the first group [control group] was injected with saline, the second group [AFR group], in which 50% of glycerol was injected intramuscularly [im]. The third group was injected with the vehicle of growth hormone and the fourth group was injected with rh-GH [2 mg/day] for 5 days subcutaneously [sc] 48 hr after induction of ARF. The results showed 3.79 and 4.09 folds increase in blood urea and serum creatinine, respectively for the ARF group compared to the control group. These values in group IV deceased by 79.5 and 49% after rh-GH hormone treatment compared to their controls [group III]. Also the increased mean value of plasma malondialdehyde [MDA] and deceased mean value of plasma nitric oxide [NO] in the ARF group as compared to controls were markedly corrected after rh-GH treatment. The greatly increased level of IGF-l after rh-GH injection suggests that it may be the actual player behind these ameliorating effects of rh-GH on glycerol-induced ARF in rats. The therapeutic uses of rh-GH in ameliorating the effects of ARF that has already happened [as early as possible] and its protective effects in expected cases is therefore recommended

Role of oxytocin as regulator of leptin secretion and its relation to biochemical markers [OPG and SRANKL] of bone resorption and formation

Increasing evidences demonstrated many new targets for the hypothalamic hormone oxytocin [OT] supporting the presence of a central neuroendocrine and/or humoral factors that control bone remodeling. The present study was carried out to test the effect of OT on serum leptin level and on the regulation of skeletal homeostasis through measurement of serum levels of osteoprotogerin OPG [secreted glycoprotein of the tumour necrosis receptor superfamily], sRANKL [soluble decoy receptor activator of nuclear factor kappa filigand], calcium and phosphorus. Fifty adult male albino rats used in this study. They were divided into three groups: group I which was subdivided into 3 subgroups, subgroup IA untreated control, IB injected with DM SO [0.16 ml/kg, b.wt x 6 weeks], 1C injected with DMSO [0.08 ml/kg b.wt for 12 weeks]. II OT treated [40 micro/kg b.wt x6 weeks] group. Ill OT [8 micro/kg b.wt x 12 weeks] group. The results obtained showed very high significant increase in OPG level in group [II] compared with subgroups I A and IB and high significant increase of OPG in group [III] compared with subgroup 1C. On the other hand, non significant change was detected in serum levels of sRANKL. As regards serum leptin, a high significant increase was found in group II as compared with subgroups IA and IB and a high significant increase was detected in group [III] compared with IA and 1C subgroups. Serum calcium and phosphorus levels showed very high significant decrease in group [II] compared with IA and IB subgroups and high significant decrease in group [HI] compared with subgroup IA. Also, significant increase in OPG/sRANKL ratio in group [II] compared with IA subgroup. A negative correlation between sRANKL and OPG/sRANKL ratio was obtained in both OT treated groups.The OPG and sRANKL levels obtained in OT treated rats favor increased osteoblast over osteoclast activity and may explain, in part, the imbalance in bone remodeling in favor of bone formation. 'The rise in OPG serum level is probably a homeostatic mechanism to limit bone loss. We can say that leptin should be reappraised as an indicator of energy supplies available for homeostasis, which now includes bone remodeling. We can conclude that the stimulating effect of OT on serum leptin together with increased OPG synthesis indicate anabolic effect on osteoblastic cells to support bone formation and indicate the important role of OPG in bone remodeling and it may be useful for the treatment of osteoporosis associated with increased osteoclast function. OT and leptin can now be added to the array of bone modulating signalling molecules

Glucose-dependent insulin-releasing peptide [GIP] in patients with type 2 diabetes mellitus with and without autonomic neuropathy

This study was conducted to investigate the role of glucose-dependent insulin-releasing peptide or gastric inhibitory polypepetide [GIP] in the control of glycemic state in patients with type 2 diabetes mellitus in the presence and absence of autonomic neuropathy. Twenty patients with type 2 jiabetes mellitus and 10 healthy normal subjects were studied. The diabetic patients were divided into 2 equal groups: one group with autonomic neuropathy [AN] and the other without AN according to cardiovascular autonomic function tests. Patients and controls were subjected to clinical examination and determination of HbA[1c]%, fasting blood sugar and basal insulin level. One-hour after ingestion of standard mixed meal [50 gm carbohydrate and 8% amino acid in 400 ml water] blood samples were collected for determination of glucose, insulin, and GIP plasma levels. Insulin resistance index was calculated from the homeostasis model assessment equation [HOMA]. A significantly impaired postprandial GIP and insulin levels as well as their responses to the ingestion of the mixed meal in the type 2 diabetics with AN was observed compared to those without AN. Postprandial GIP level was found to be correlated negatively with postprandial glucose level [r=-0.54] and positively with postprandial insulin level [r=-0.45], P < 0.05 for all diabetic patients. In diabetic patients with AN, significant -negative correlations were detected between duration of diabetes and postprandial GIP level [r= -0.66], absolute GIP response [r= -0.74], as well as% GIP response [r=- 0.71] [P < /= 0.05 for all.]. GIP plays an important role in the physiologic control of postprandial glucose homeostasis. GIP responses were lower in the diabetics as a group compared with healthy subjects despite similar basal levels. Moreover, In diabetic patients with autonomic neuropathy, there was a delayed and impaired GIP response to the mixed meal. Their absolute and% GIP responses were significantly lower than those of control subjects and patients without autonomic neuropathy

effect of gralic on nitric oxide level in diabetic rats

The increase in number of diabetic patients motivated scientists to find new methods to control such disease. In the present study, the action of Garlic [Allium sativum] was studied on normal and streptozotocin [STZ]-induced diabetic rats. Experimental group included 60 male albino rats divided equally into control group, control group given oral daily dose of garlic [100 mg/kg B.wt] for 16 weeks, STZ-induced diabetic untreated group, and diabetic garlic-treated group included STZ-induced diabetic rats given the daily oral dose of the garlic for 16 weeks. Blood samples were collected for determination of blood glucose, nitric oxide [NO], malondialdehyde [MDA], and lipid profile [triglycerides [TG], cholesterol [C], high density lipoprotein-cholesterol [HDL-C], and low density lipoprotein-cholesterol [LDL-C]]. Supplementation of garlic to non-diabetic rats had produced no significant differences as regards any of the parameters including glucose, lipid profile, nitric oxide, and lipid peroxidation end product malondialdehyde [MDA] levels when compared with the control group. The diabetic rats showed significant elevation in serum glucose, NO, MDA, TG, C, and LDL-C. Concomitantly significant decrease in HDL-C was detected when compared with their corresponding values of controls. However, supplementation of garlic to the diabetic rats had shown a significant decrease in serum glucose, TG, C, LDL-C, NO, [and MDA] levels, while elevation in HDL-C level was detected. Thus, from the present study it is assumed that garlic treatment decreases the blood glucose level. Antioxidant garlic may protect B cells against toxic effect of ROS [reactive oxygen species] provoked due to hyperglycemia. This was indicated by the significant decrease of oxidative stress after garlic treatment in the studied group. It is concluded that garlic supplementation improves blood lipid profiles, strengthens blood oxidant potential, and causes significant reduction in blood glucose; NO; and MDA levels. These results suggest that garlic exerted antioxidant and antihyperglycemic effects

Relationship between hyperprolactinemia and bone metabolic markers in breast cancer patients

The understanding of the pathophysiology and the monitoring of metastatic bone disease remain unsatisfactory. Therefore, this study aimed at identification of the relationship between serum prolactin [PRL] levels and some bone metabolic markers [osteocalcin [OC] serum alkaline phosphatase [SAP], calcium [Ca], and inorganic phosphorus [Pi]] in early stages of breast cancer. Thirteen breast cancer patients in whom serum prolactin [PRL] levels had been determined were stratified into 2 groups according to their serum prolactin levels. Breast cancer I [BCI] included those with hyperprolactinemia and breast cancer II [BCII] included those with normal levels. Also a control group matched for age was taken. The bone markers of these groups were analyzed and compared. The study demonstrated that 6 patients [46%] "BCI" had a hyperprolactinemia and 7 patients [54%] "BCII" had a normal level of PRL. One way ANOVA test revealed significant differences in PRL, OC, SAP, Ca, and Pi between the three groups. OC is significantly reduced in the hyperprolactinemic patients reflecting diminished bone formation. SAP and Pi were significantly higher in all patients of breast cancer than that of the controls. The level of Ca tended to be higher in hyperprolactinemic patients than that of the controls. In the breast cancer patients, negative correlation between PRL and OC [R=-0.56, p<0.05] was found. On the contrary, positive correlation between PRL and SAP [r=0.60, p<0.05]was detected. It was concluded that the role of PRL in bone metabolism must be taken into consideration. Further wide scale studies are needed in a trial to uncover the exact role of hyperprolactinemia in patients with bone metastasis. This study could help in understanding bone disorders that may occur in breast cancer patients specially those with hyperprolactinemia

protective role of the angiotensin-converting enzyme inhibitor enalapril against gamma radiation induced organ toxicity in the rat

The present study was designed to evaluate the radioprotective efficacy of the angiotensin-converting enzyme inhibitor enalapril and the possible mechanisms of this radioprotection. This included the ability of prophylactic enalapril treatment to prevent or retard gamma radiation-induced organ toxicity and to protect tissue' antioxidant enzymes in the rat. Prior to irradiation rats were randomized to groups receiving enalapril or no treatment, in addition to a control group of non-irradiated, non-treated rats. Enalapril was administered intraperitoneally [0.1 mg/ kg body weight / day], 4 weeks before and 12 weeks after irradiation. Both groups were exposed to a single dose of 7GY gamma radiation. Irradiation induced significant elevations in the levels of blood urea nitrogen and serum creatinine and serum activities of lactate dehydrogenase [LDH], creatine kinase [CK], alanine amino transferase [ALT] and aspartate amino transferase [AST] compared to control values, indicative of renal, cardiac and hepatic injury. Also there was an increase in the serum levels of triglycerides, total cholessterol and LDL-cholesterol. On the contrary, HDL-cholesterol level was decreased. The heart, kidney and liver antioxidant enzymes including total glutathione peroxidase [total-GPX], glutathione reductase [GR] and superoxide dismutase [SOD] activities were inhibited, while malondialdehyde [MDA] level in these organs was elevated, indicative of increased lipid peroxidation. These data confirm the role of oxidative stress in radiation-induced organ toxicity and points to the possible antioxidative mechanisms of the radioprotective action of enalapril, which might be mediated by improving the balance between reactive oxygen species and antioxidant enzymes. Moreover, the beneficial effect of enalapril on serum lipid profile is suggested to be an additional mechanism of radioprotection

Role of leptin in premenopa usal and postmenopausal obese women

Leptin, the product of ob gene, is thought to play a key role in the regulation of body fat mass, body weight and energy expenditure . Malfunction of this mechanism could lead to obesity. Thirty six healthy obese females with body mass index [BMI]>27 Kg/m[2] were divided into two groups: premenopausal and postmenopausal group, each group is further subdivided according to waist to hip ratio [WHR] into upper body [android] and tower body [gynoid] obese groups. Control groups with matching age were taken. Anthropometric parameters [weight, height, BMI, WHR], serum leptin, testosterone, lipids and lipoproteins were determined for all groups. In premenopausal females one way AN OVA test revealed significant differences in leptin, testosterone, BMI, WHR, triglycerides and VLDL between the three groups. In postmenopausal females the significant difference was found in leptin, testosterone, weight, height, BMI and WHR. Positive correlations between leptin and BMI [r =0.81, p<0.05] and WHR [r=0.78, p<0.05] were found in the android premenopausal female group.Leptin is also correlated positively with testosterone in the gynoid premenopausal group [r =0.86, p <0.05] but negatively in the android postmenopausal female group [r=-0.76, p<0.05]. The above data suggest hyperleptinemia and leptin resistance in the two types of obesity but the association between leptin and body fat content was found to be in the android premenopausal group only, the same group showed hypertriglyceridemia and increase in VLDL indicating that premenopausal females with higher WHR are more liable to cardiovascular risks

Study of antioxidants defense system, lipid pattern and left ventricular geometry in hypertensive patients

Free radical activity oxidative stress has been implicated in the pathogenesis of a variety of human diseases. In an attempt to define the role of oxidative stress, dyslipidemia and geometric changes in hypertensive patients [HT], we studied 44 patients, 20 [45.5%] Essential hypertensive [EH], 14 [31.8%] diabetic hypertensive [DH] and 10[22.7%] renal hypertensive [RH]. They were assessed by measurement of some free radicals and antioxidants, serum lipids and echocardiography, the data was compared with 10 age and sex matched normal subjects. There was a significant decrease in important natural antioxidant vitamins C, E, A and reduced glutathione [RG] and a significant increase in lipid peroxide level [LPO] in all groups of hypertensive patients as compared to control. The mean value of cholesterol [C] concentrations in all the hypertensive patients was significantly higher than in controls [P<0.001] Triglycerides [TG] were significantly higher in diabetic hypertensive patients in comparison to controls [P<0.001], HDL-C mean values were reduced significantly in [EH], [RH] groups. LDL-C mean values in all groups of hypertensive were significantly increased [P<0.01]. 38.6% of our patients had concentric left ventricular hypertrophy [CLVH], 13.6% had eccentric left ventricular hypertrophy [ELVH], 13.6% had concentric remodeling [CR] and 34% had normal geometry. We conclude that oxidative stress was observed in all groups of hypertensive patients and we recommend the use of antioxidants as an adjunct to antihypertensive therapy