Background: Dry cough is the most common adverse effect and limiting factor of all angiotensin converting-Enzyme inhibitors (ACEIs). Prostaglandins have been pinpointed as playing an important role in the genesis of this problem. This double blind clinical trial desinged to study the efficacy of 500 milligram (mg) of aspirin comparing with placebo in controlling Enalapril-induced cough. Methods: The subjects were 32 patients who had developed Enalapril-induced cough. They were randomized into two groups: a group of daily dose of aspirin, 500 mg and a group of placebo for a treatment period of 4 weeks. Mean of cough severity was compared between two groups before treatment and weekly, until 4 weeks. Results: Mean of cough severity in aspirin and placebo groups before and at the end of first week of treatment did not show any significant difference. After the second, third, and fourth weeks, cough severity scores were significantly reduced in aspirin group (p<0.001). Conclusion: 500mg aspirin, once daily, can suppress or abolish Enalapril-induced cough and this finding proposes alternative therapeutic approach for ACEIs-induced related cough.        

Background: Inhibition of the renin-angiotensin system in patients with diabetic nephropathy can reduce proteinuria and slow down renal impairment. In this study, we aimed to evaluate the preventive effects of prescribing both angiotensin converting Enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) for renal disease progression compared with administrating each of these two medications alone in patients with type 2 diabetes.Methods: 90 patients with diabetic nephropathy were randomized into three groups: receiving captopril, losartan, and losartan in combination with captopril. Proteinuria was measured before, 2, 6 and 12 months after intervention, and creatinine clearance was measured before and after intervention. Repeated measures ANOVA, Fisher's least significant difference (Fisher's LSD), and t-test were used for data analysis by SPSS software.Findings: Proteinuria was improved in all groups who received medication (P<0.001). This reduction in the group who received losartan in combined to captopril was more than other groups (P=0.026). Creatinine clearance was not significantly different between all groups.Conclusion: Administration of ACEI or ARBs reduced proteinuria in patients suffering from diabetic nephropathy (due to type 2 diabetes) but prescribing both drugs had a significantly better outcome. However, creatinine clearance was not significantly improved in any of the groups.

Objective: Alzheimer's disease (AD) is a progressive neurodegenerative disease which endothelil cell can be affected by this disease. In brain, functional changes in endothelial cells contribute to reductions in resting blood flow and following progression of neurologic disorders. Furthermore, Angiotensin-converting Enzyme inhibitors (ACE-I) have beneficial effects on endothelial dysfunction. This is the first study which presents direct experimental evidence associating to endothelial apoptosis as a basis of AD pathogenesis and response to an ACE-I therapy.Materials and Methods: Human umbilical vein endothelial cells (HUVECs) were treated with sera from AD patients and sera from healthy volunteers (each n=10). Apoptosis was determined by annexin V-propidium iodide staining and cell death detection kit. The effect of 50mM Enalapril as a ACE-I drug on EC apoptosis was assessed. Nitrite (NO2-) levels were determined in the culture supernatants.Results: Enalapril suppressed the induction of apoptosis by the serum of patients only when used before treating HUVECs with the sera of AD. Mean ± SD of apoptosis induction in the control group was 6.7 ± 3.69; in the group treated with sera of AD for 24 hours was 47.78±0.65; in the group wherein sera from AD was added (pretreatment) after exposure of HUVECs by 50 mM enalapril for 24 hours was 26.6±2.63; and in the group where in HUVECs were exposed in the sera of AD for 24 hours and then 50mM enalapril was added to these cells for another 24 hours (post treatment) was 56.87±5.51. Also, the mean ± SD of NO2 concentration showed significantly greater levels of dissolved NO2/NO3 metabolite in the culture media of untreated HUVECs by enalapril (1.03±0.06) as compared with control (0.26±0.13; p<0.05), while the rate of nitric oxide (NO) significantly decreased when enalapril was presented in culture both in the pretreatment (0.07±0.003) and in the post treatment group (0.06±0.005; p<0.05).Conclusion: It could be concluded that EC treated with sera from AD patients activates apoptosis in HUVECs; this effect was reversed by enalapril pretreatment. This can be proposed as a therapeutic approach for Alzheimer’s patients.

Introduction: Cox2 selective inhibitors such as celecoxib, rofecoxib and valdecoxib are recently used to reduce inflammatory response. There is still a need to develop more potent Cox2 inhibitors. This study was conducted to introduce new structures with more affinity to Cox2 Enzyme.Materials & methods: Chemical structures with 80% similarity to celecoxib was collected by using PubChem at NCBI database. The PDB file of Cox2 Enzyme (6COX) obtained from RCSB PDB website in bounding with ligand SC-558 as reference ligand. Docking of ligands to SC-558 site of Cox2 performed with lead IT software (version 2.1.0 BioSolveIT, GmbH, Germany) and the interaction energy of different compounds was obtained. IC50 value of selected compounds identified by using in vitro screening against Cox2 Enzyme. The cytotoxicity assay was performed by using MTT method.Findings: Screening results in PubChem database was 5000 molecules similar to celecoxib. 24 compounds had better energy scores than 6COX bound co-crystallized ligand SC-558.The ligands were docked with the binding pocket that they showed interaction with Leu352, Phe518, Met522, Val523, Ala527 and Ser353. By visual inspection, compounds showed orientation and hybrid mode similar to SC-558.Discussion & Conclusion: our findings strengthened the computational procedure the discovery of new compounds with anti-inflammatory activity and less toxicity than Cox2 general inhibitors.

Carbonic Anhydrase (CA) is an Enzyme having Zinc metal that catalyzes the reversible reaction of conversion of carbon dioxide to Bicarbonate. This Enzyme is vital for Biological systems such as the human body. In this research, the inhibitory mechanism of action of coumarin and some of its sugar derivatives with carbon anhydrase XII & II have been investigated. The most stable conformer of these Inhibitories was selected for calculations and their interaction with these two Enzymes was investigated. All calculations have been done by density functional theory (DFT) in the level of B_3LYP with basic set 6-31G* and with Minnesota function M06 with basic set 6-31+G*. In the following the thermodynamic variables of such reaction 〖 ∆ S〗 _(r×n)° , 〖 ∆ H〗 _(r×n)° , 〖 ∆ G〗 _(r×n)° have been calculated. Results show that the reaction between this family of Inhibitories and Carbonic Anhydrase Enzyme is not of the type of direct and syndetic but the Enzyme inactivates with the spacing effect.

Background- Dry coughs are the most common adverse effect and limiting factor of all angiotensin converting-Enzyme inhibitors (ACEI). Prostaglandins have been pinpointed as playing an important role in the genesis of this problem. This double blind clinical trial was desinged to compare the efficacy of 500 miligram (mg) aspirin versus placebo in controlling ACEI-induced coughs.Methods-The subjects were 32 patients, who had developed ACEI-induced coughs. They were randomized to a daily dose of 500 mg aspirin or placebo for a treatment period of 4 weeks. The means of cough severity before and each week for 4 weeks were compared in the two groups.Results- Means of cough severity in the aspirin and placebo groups before and at the end of the first week of treatment did not show any significant difference. After the second, third and fourth weeks, the cough severity score was significantly reduced in the aspirin group (p<0.001).Conclusion-500 mg aspirin once daily can suppress or abolish ACEI-induced coughs, and this finding proposes alternative therapeutic approaches for ACEI-related coughs.