Sex-Dependent Anti-Stress Effect of an alpha 5 Subunit Containing GABA(A) Receptor Positive Allosteric Modulator

Rationale: Current first-line treatments for stress related disorders such as major depressive disorder (MDD) act on monoaminergic systems and take weeks to achieve a therapeutic effect with poor response and low remission rates. Recent research has implicated the GABAergic system in the pathophysiology of depression, including deficits in interneurons targeting the dendritic compartment of cortical pyramidal cells. Objectives: The present study evaluates whether SH-053-2'F-R-CH3 (denoted "alpha 5-PAM"), a positive allosteric modulator selective for (alpha 5-subunit containing GABA(A) receptors found predominantly on cortical pyramidal cell dendrites, has anti stress effects. Methods: Female and male C57BL6/J mice were exposed to unpredictable chronic mild stress (UCMS) and treated with alpha 5-PAM acutely (30 min prior to assessing behavior) or chronically before being assessed behaviorally. Results: Acute and chronic alpha 5-PAM treatments produce a pattern of decreased stress induced behaviors (denoted as "behavioral emotionality") across various tests in female, but not in male mice. Behavioral Z-scores calculated across a panel of tests designed to best model the range and heterogeneity of human symptomatology confirmed that acute and chronic alpha 5-PAM treatments consistently produce significant decreases in behavioral emotionality in several independent cohorts of females. The behavioral responses to alpha 5-PAM could not be completely accounted for by differences in drug brain disposition between female and male mice. In mice exposed to UCMS, expression of the Gabra5 gene was increased in the frontal cortex after acute treatment and in the hippocampus after chronic treatment with alpha 5-PAM in females only, and these expression changes correlated with behavioral emotionality. Conclusion: We showed that acute and chronic positive modulation of alpha 5 subunit containing GABA(A) receptors elicit anti-stress effects in a sex-dependent manner, suggesting novel therapeutic modalities

Aortic valve papillary fibroelastoma causing embolic strokes: a case report and review

Avraham Miller,1 Audrik Perez,1 Swathi Pabba,2 Vijay Shetty3 1Internal Medicine, Maimonides Medical Center, Brooklyn, NY, USA; 2Chalmeda Anand Rao Institute of Medical Sciences, Telangana, India; 3Department of Cardiology, Maimonides Medical Center, Brooklyn, NY, USA Abstract: Papillary fibroelastomas (PFEs) are the second most common benign neoplasms of the cardiac valves and are being recognized more frequently because of higher resolution imaging technology. PFEs are associated with substantial complications that are secondary to systemic embolism. Surgical resection should be offered to all patients who have symptoms and to asymptomatic patients who have pedunculated lesions or tumors larger than 1 cm in diameter. Herein, we present a patient who presented for a second time in 2 months with stroke symptoms. During his first admission, a transthoracic echocardiogram was performed and he was sent home after resolution of his symptoms and a grossly negative workup. During his second admission, a transesophageal echocardiogram was performed and the PFE was found and later excised. While this discussion reviews the literature with regard to detection and management, it will hopefully serve as a reminder to keep this on the differential when the workup has remained without an obvious source. Keywords: stroke, fibroelastoma, papillary, embolis

Measurement and Modeling of Solid-Liquid Equilibria of l -Glutamic Acid in Pure Solvents and Aqueous Binary Mixtures

The experimental solubility data of l-glutamic acid in pure water, formic acid, methanol, 1-propanol, 2-propanol, acetonitrile, and binary mixtures (formic acid + water, methanol + water, 2-propanol + water, acetonitrile + water) with different compositions were carried out at temperatures ranging from (283.15 to 328.15) K by the static analytic method. The solubility measurements showed that formic acid and its aqueous mixtures recorded a higher solubility than methanol + water, 2-propanol + water, and acetonitrile + water for the same composition at each temperature. Moreover, except formic acid the addition of methanol, 2-propanol, and acetonitrile to its aqueous mixtures resulted in the decrease in solubility of l-glutamic acid. The experimental data was fitted using different thermodynamic models such as the Buchowski-Ksiazczak equation, the Van't Hoff equation, the modified Apelblat equation, and the NRTL model, and the optimum values of the regressed parameters were obtained. The modified Apelblat equation, Buchowski-Ksiazczak equation, and NRTL activity coefficient model were fitted to the pure solvents solubility data, while the modified Apelblat, modified Apelblat-Jouyban-Acree, and NRTL models were used for the binary solvent systems. The results demonstrated formic acid as a cosolvent in the dissolution of l-glutamic acid in formic acid + water binary mixtures, while others exhibited an antisolvent effect on the solubilization of l-glutamic acid in their respective aqueous mixtures

Biosynthesis of silver nanoparticles from Schizophyllum radiatum HE 863742.1: their characterization and antimicrobial activity

Development of reliable and eco-friendly process for synthesis of silver nanoparticles is an important step in the field of application in nanotechnology. One of the options to achieve this objective is to use natural biological processes. They have an advantage over conventional methods involving chemical agents associated with environmental toxicity. This study demonstrates the extra-cellular synthesis of stable silver nanoparticles using the white rot fungus, Schizophyllum radiatum with GenBank Accession no HE 863742.1. The supernatant of the seed media obtained after separating the cells has been used for the synthesis of silver nanoparticles. The morphology and structure of synthesized silver nanoparticles were characterized using FT-IR, XRD, UV–visible spectrum of the aqueous medium containing silver ion showed a peak in the range of 420–430 nm corresponding to the Plasmon absorbance of silver nanoparticles. Scanning electron microscopy micrograph showed formation of well-dispersed silver nanoparticles in the range of 10–40 nm. The effect of different carbon sources and the time taken for formation particles and the anti-microbial activity of synthesized nanoparticles were carried and compared with silver nitrate solution and with standard streptomycin. The process of reduction being extra-cellular and fast may lead to the development of an easy bioprocess for synthesis of silver nanoparticles