Aperito Journal of Drug Designing and Pharmacology

The study aim was to evaluate whether the Mineralocorticoid Receptors (MR) antagonist eplerenone, effects circulating microparticles originated from apoptotic and activated endothelial cells (EMP) in Chronic Heart Failure (CHF) patients. 

Methods: The study population consisted of 152 consecutive patients with CHF who underwent angiography or PCI between April 2010 and June 2014, and post-myocardial infarction subjects. All subjects enrolled in the study were divided into two cohorts: eplerenone treated (n=45) or placebo (n=107) for 52 weeks. Patients were treated with optimal dose of eplerenone (25-50 mg daily) adjusted to plasma potassium. All biomarkers were determined at the beginning (baseline) and at the termination of the study. Endothelial derived Microparticles (EMPs) were phenotyped by flow cytometry using a High-Definition Fluorescence Activated Cell Sorter. 

Results: At baseline, there was not difference in EMPs between groups. Eplerenone treatment reduced EMPs (CD144+/ CD31+/annexin V+ and CD31+/annexin V+) when compared with placebo. But activated CD62E+ EMP numbers were significantly increased by 24.3%.

The striking efficiency of enzyme catalysis has inspired many organic chemists to explore enzyme mechanism(s) by studying certain intramolecular processes (enzyme models) which proceed faster than their intermolecular counterparts. This editorial describes the use of computational methods such as quantum mechanics and molecular mechanics to explore the mechanisms of various enzyme models for assigning the factors affecting the rate-limiting step and determining the mode and action of the reaction. Among the enzyme models discussed herein are: (a) proton transfer between two oxygen atoms and proton transfer between nitrogen and oxygen in Kirby’s enzyme model; (b) intramolecular acid-catalyzed hydrolysis in some of Kirby’s N-alkylmaleamic acids; (c) proton transfer between two oxygen atoms in Menger’s rigid system; (d) acid-catalyzed lactonization of hydroxy acids as studied by Cohen and (e) SN2-based cyclization as studied by Bruice. These enzyme models were utilized as linkers to be covalently attached to commonly used drugs having poor bioavailability or/and bitter sensation. The conversion rate of the prodrug to its active form is solely determined on the structural features of the linker

Introduction: The quest for treatment of insomnia without side effects has been elusive and thus has led to herbal therapies. Two such supplements are Ayurvedic-based herbs, Ashwagandha and valerian. Even though the anti-inflammatory and antioxidant properties of Ashwagandha have been investigated, its sleep enhancing properties have not been studied. It was hypothesized that Ashwagandha would have sleep quality enhancing effects similar to those of valerian and would be more beneficial than the placebo. Further, a smart phone app based sleep assessment technology was utilized to monitor the participants in this 
study.  

Methods: Thirty-three participants were given either Ashwagandha, valerian, or placebo for 4 weeks (single blinded and randomized) and their sleep quality was monitored using a smart phone app or with questionnaires. After this study period and a brief washout period, the same procedure was repeated except the participants did not take any supplement, serving as a comparison measurement. 

Results: Sleep quality improved significantly in participants who took Ashwagandha (P<0.0001) when compared to valerian and placebo. They also appeared to have a higher percentage of deep sleep than the other groups. A much greater sleep quality increase was observed during the study period than during the later  comparison period in both of the herbal groups (p=0.02) but not in the placebo group. In addition, the app-based sleep monitoring system appeared feasible in this study. 

Conclusions: The results suggest that Ashwagandha may be an effective sleep-enhancing supplement. Its exact clinical relevance is not known and further investigation would be required to elucidate these findings.Samuel J Asirvatham (2014), A Randomized Trial of Ayurvedic Herbal Remedies for Sleep Quality: An App-Based Assessment. Aperito J Drug Design Pharmacol 1:109