The potential effect of ambrisentan as monotherapy and combined with tadalafil on diabetic erectile dysfunction in rats.

INTRODUCTION: This study investigated the role of ambrisentan; the selective endothelin type-A receptor (ETAR) blocker on experimental diabetic erectile dysfunction in rats. MATERIALS AND METHODS: Eighty-four adult male Sprague Albino rats were divided randomly into 7 groups. Three control groups received 1 mL saline, 0.2 mg/kg/d ambrisentan and 1.5 mg/kg/d tadalafil, respectively orally for 4 weeks. The remaining four groups were fed high fat diet for 14 days. Diabetes was induced by a single intra-peritoneal injection of 40 mg/kg streptozotocin. After 72 h, diabetes was confirmed by plasma glucose level ⩾250 mg/dL. Diabetic rats were divided randomly into four groups, numbered from 4 to 7. The fourth group was the diabetic-control group, while the fifth and sixth groups received ambrisentan and tadalafil respectively. The seventh group received a combination of both drugs. Treatment continued for 4 weeks then, copulatory, intracavernous pressure measurement, and laboratory tests were conducted. RESULTS: In diabetic rats, ambrisentan and tadalafil improved fasting glucose, insulin, insulin resistance, testosterone, nitric oxide, and rho kinase (ROCK) values compared to diabetic group with the maximum improvement achieved in ambrisentan/tadalafil group (p < 0.05). Ambrisentan also enhanced ICP and improved latency to erection and number of mounts with a tolerable SBP. Yet, ambrisentan/tadalafil combined therapy resulted in deterioration in SBP with consecutive worsening in ICP and mating indices. CONCLUSION: Ambrisentan showed significant therapeutic potential to prevent and improve diabetic ED in rats comparable to tadalafil.

Study of the possible effect of sacubitril/valsartan combination versus valsartan on the cognitive function in Alzheimer's disease model in rats.

Objectives: Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder. The proportion of elderly individuals at risk for AD and cardiovascular problems increases by raising life expectancy. The present study was designed to investigate the effect of the sacubitril/valsartan combination compared to that of valsartan alone in a rat model of AD. Methods: 72 male adult Wistar rats were divided into seven groups; control untreated rats received saline, control valsartan-treated rats received valsartan orally, control sacubitril/valsartan treated rats received sacubitril/valsartan orally, model rats received aluminum chloride i.p., model valsartan treated rats received aluminum chloride i.p. and valsartan orally and model sacubitril/valsartan treated rats received aluminum chloride i.p. and sacubitril/valsartan combination orally. All previous treatments continued on a daily basis for 6 weeks. At the second, fourth, and sixth weeks of the experiment, behavioral changes were evaluated using the Morris water maze and novel object recognition tests, and systolic blood pressure was measured. In the end, rat brain malondialdehyde and amyloid-beta 1-42 levels were measured, and the isolated hippocampus was evaluated histopathologically. Results: Valsartan improved AD symptoms in the aluminum-induced rat model, while the sacubitril/valsartan combination significantly worsened all tested parameters in both control and model rats compared with untreated and valsartan-treated animals. Conclusion: Based on the current study's findings, valsartan did not increase the risk for AD development in control rats and improved AD symptoms in a rat model, while sacubitril/valsartan combination increased the risk of AD in control rats and worsened the condition in a rat model.

Efficacy of carvedilol versus propranolol versus variceal band ligation for primary prevention of variceal bleeding.

BACKGROUND AND AIMS: Band ligation and propranolol are the current therapies for primary prevention of variceal bleeding. Carvedilol is a rising nonselective beta-blocker used for reducing portal pressure with favorable outcome. The aim of this study to assess the efficacy of carvedilol, propranolol, and band ligation for primary prevention of variceal bleeding based on the effect of each regimen on progression of Child score and portal hypertensive gastropathy after 1 year. METHODS: The study included 264 cirrhotic patients with medium/large-sized varices who were candidates for primary prophylaxis of variceal bleeding. Patients were randomly divided into three groups: group I: band ligation; group II: propranolol; group III: carvedilol. RESULTS: Group I showed higher success rate of 75 %, followed by group III with 70.2 % and group II with 65.2 %. Risk of bleeding was comparable between the three groups, with group II carrying the highest rate of complications (34.7 %) followed by group III (14.2 %) and finally group I (5.7 %). After 1 year of follow-up, Child score did not improve in any of the studied groups, while portal hypertensive gastropathy significantly increased in group I but decreased in groups II and III. CONCLUSIONS: Band ligation is the best treatment option for primary prevention of variceal bleeding with minimal complications. Carvedilol is a good pharmaceutical alternative medicine to propranolol with lesser side-effects. Progress of liver disease as represented by Child score is not affected by any of the primary variceal prophylactic regimens, although medical treatment reduces portal hypertensive gastropathy. Choice of treatment depends on patient will, compliance with treatment, and endoscopist competence.

Comparison between the effect of glibenclamide and captopril on experimentally induced diabetic nephropathy in rats.

HYPOTHESIS: This study aimed to elucidate the role of glibenclamide in the prevention of diabetic nephropathy and to compare it with a reference drug captopril in rats. MATERIALS AND METHODS: There were two main groups of rats. Control group (I) was subdivided into four subgroups which received distilled water, vehicle of streptozotocin, glibenclamide or captopril. The streptozotocin-diabetic Group (II) was subdivided into three subgroups: untreated, glibenclamide or captopril treated. Measurement of arterial blood pressure, serum glucose and creatinine levels, 24 h urinary protein and albumin/creatinine ratio, kidney weight and its histological examination were done after 1, 2, 4, 8, 12 and 16 weeks of treatment. RESULTS: In treated diabetic rats captopril reduced blood pressure significantly, while no significant change in the mean arterial blood pressure or blood glucose level was recorded with glibenclamide treatment. Glibenclamide and captopril-treated diabetic rats showed significant decrease in serum creatinine level, urine volume, urinary protein excretion, albumin:creatinine ratio and kidney:body weight ratio compared with the diabetic non-treated group. Histological examination of diabetic kidneys treated with either glibenclamide or captopril showed reduced glomerular hypertrophy, glomerulosclerosis, tubular degeneration and interstitial fibrosis compared with untreated diabetic rats. CONCLUSION: Glibenclamide attenuated some biochemical and histological changes produced by diabetic nephropathy, despite persistent hyperglycemia and hypertension.