Pharmacology, Toxicology and Environmental Health Commons^™

Response Of Monovalent Cation Transporters To Pro-Apoptotic Protein Kinase C Modulators In Human Lens Epithelial Cells, Michael Anthony Lepera

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Protein kinase inhibition by staurosporine causes apoptotic volume decrease involving potassium (K) channels in immortalized human B3 lens epithelial cells (LECs). Here, the effect of two pro-apoptotic protein kinase C (PKC) inhibitors [12-O-tetradecanoyl-phorbol-13-acetate (TPA) and chelerythrine (CET)] were studied on membrane K transport in a fetal human LEC line (FHL124) by western blotting, immunofluorescence, ion flux, ATP, apoptosis, and biotinylation assays. Long term TPA exposure (0-6 h) inhibited 75% of Na-K-2Cl cotransport (NKCC). In contrast, short term (0-20 min) exposure to 50 μM CET reduced Na/K pump and NKCC by >90% and >70%, respectively, without retrieval from the membrane into …

Differentiation Of Megakaryocytes/Platelets And Neurons From Human Endometrial Stromal Progenitor Cells, Jinju Wang

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Human endometrium is a high dynamic tissue that contains stem/progenitor cells. These endometrial stromal progenitor cells (hESCs) have been differentiated into a number of mesodermal lineages. There is limited information on differentiating hESCs into neurons, and no information on differentiating hESCs into megakaryocytes (MKs) and platelets (PLTs). The aim of this work was to investigate the possibility of differentiating hESCs into two distinct lineages: MKs, with subsequent PLT formation, and neurons.

We isolated hESCs from human endometrial tissue and cultured the cells for 4-6 passages. Before each differentiation experiment, the purity of hESCs was confirmed by flow cytometry analysis which …

Role Of Hyperglycemia And Aldosterone On Renal Ace2 And Albuminuria In Db/Db Mice, Harshita Chodavarapu

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Diabetic nephropathy (DN) is one of the microvascular complications of type II diabetes and a leading cause for the development of end stage renal disease. Renin angiotensin system (RAS) plays a pivotal role in the development and progression of diabetic nephropathy. Hyperglycemia activates RAS and increases tissue and circulating levels of angiotensin II (Ang II) and aldosterone. A new component of RAS, angiotensin converting enzyme 2 (ACE2), has been shown to be renoprotective in early stages of diabetes. The aim of this study is to test the hypothesis that strict glycemic control using rosiglitazone or treatment with mineralocorticoid receptor (MR) …

Analysis Of Archived Dried Blood Spots By Mass Spectrometry For Vitamin D And Real-Time Pcr For Its Enzymes And Receptor, Amod N. Joshi

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Vitamin D is an essential micronutrient required for maintenance of the skeletal system and its deficiency leads to diminished availability of calcium for maintaining bone mineralization. Vitamin D deficiency (VDD) during pregnancy and/or in early infancy can lead to rickets and a fragile bone state resulting in fractures with minimal forces. Such multiple unexplained fractures (MUF) present in infants at less than 6 months of age are often misdiagnosed as cases of child abuse. Therefore, it is important to evaluate the status of vitamin D in early infancy. The analysis of dried blood spots (DBS) provides a unique screening method …

Response Of Neuroinflammatory And Neurodegenerative Markers Following Sub-Lethal Sarin Exposure And Subsequent Treatment Via An In-Vivo Caspase Inhibitor, Douglas F. Chmura

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Organophosphorus nerve agents are amongst the most deadly chemical compounds ever synthesized. Sarin is an organophosphate (OP) ester that irreversibly forms a phosphoester bond at the active site of acetylcholinesterase and thereby induces a rapid and lethal cholinergic crisis. It remains an active threat to vulnerable civilian populations due to its ease of synthesis and known use by rogue nations and terrorist groups. Death is the most extreme consequence of sarin toxicity. Current treatments fail to provide protection against progressive cognitive impairments years after mild exposure. Q-VD-OPh is an in-vivo caspase inhibitor with potent anti-apoptotic and anti-inflammatory properties. In this …

Synthesis, Characterization And Manipulation Of Creighton Silver Nanoparticles For Future Cytotoxicity Studies, Sesha Lakshmi Paluri

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Nowadays, 24% of the nanomaterial-based consumer products contain silver nanoparticles (AgNPs) and exploit the well-known antimicrobial properties of silver. Although AgNPs have a wide range of biomedical research and industrial applications, very little is known about their toxicity. The main goal of this study is to synthesize, characterize and manipulate Creighton colloidal AgNPs for future cytotoxicity studies. These "naked" AgNPs were free from chemically aggressive capping/stabilizing agents, reaction byproducts or organic solvents. To achieve this goal, colloidal AgNPs were successfully: a) synthesized in large volumes (5L) using a slightly modified Creighton method by the reduction of silver nitrate with sodium …

Low Dose Nerve Agent Sarin Causes Dilated Cardiomyopathy And Autonomic Imbalance In Mice, Swapnil Vijay Shewale

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Sarin, a lethal chemical nerve agent, may be a causative factor in multifactorial syndrome implicated in the Gulf War and Tokyo terrorist attacks. While high dose results in seizure and death, low dose exposure may lead to autonomic imbalance and chronic cardiac pathologies. In the present study, echocardiography and electrocardiography were used to examine the late onset effects of a low dose sarin on cardiac structure and function in mice. Stress responsiveness of the hypothalamic pituitary adrenal (HPA) axis was also tested. Findings demonstrate changes consistent with a dilated cardiomyopathy, including left ventricular dilatation, reduced contractility, and altered electrophysiological and …