Medicine and Health Sciences Commons^™

Structure-Activity Profiling Of Alkaloid Natural Product Pharmacophores Against A Schistosoma Serotonin Receptor, Jonathan S. Marchant, Wayne W. Harding, John D. Chan

Publications and Research

Serotonin (5-HT) is an important regulator of numerous aspects of flatworm biology, ranging from neuromuscularfunctionto sexualmaturationandegglaying. Intheparasiticblood flukeSchistosomamansoni,5-HTtargets several G-protein coupled receptors (GPCRs), one of which has been demonstrated to couple to cAMP and regulate parasite movement. This receptor, Sm.5HTRL, has been successfully co-expressed in mammalian cells alongside a luminescent cAMP-biosensor, enabling pharmacological profiling for candidate anti-schistosomal drugs. Here, we have utilized this assay to perform structure-activity investigations of 143 compounds containing previously identified alkaloid natural product pharmacophores (tryptamines, aporphines and protoberberines) shown to regulate Sm.5HTRL. These experiments mapped regions of the tryptamine pharmacophore amenable and intolerant to substitution, highlighting …

Burden Of Lipohypertrophy Among Insulin Dependent Diabetes Mellitus Patients In China: An Analysis Of Outcomes And Impact Of Pen Needle Reimbursement Policy, Arthi Chandran

Dissertations and Theses

Background

Diabetes is a global epidemic and with an aging population accompanied by rapid urbanization China ranks highest in disease prevalence and associated burden. Independent of diabetes type, insulin is an eventual and costly requirement for disease management. The consequences of insulin administration however are poorly understood. Lipohypertrophy (LH) is one such consequence. It is hypothesized that method of insulin delivery and poor delivery technique are significant risk factors for this condition which is believed to alter insulin pharmacodynamics. Subsequently, insulin pen needles are a critical component of care however access to pen needles varies across China.

Objective

The objective …

Incidence, Risk Factors, And Prediction Of Gastrointestinal And Intracranial Bleeding In A Cohort Of Older Veterans Prescribed Oral Anticoagulants, Angela Laurio

Dissertations and Theses

ABSTRACT

Incidence, Risk Factors, and Prediction of Gastrointestinal and

Intracranial Bleeding in a Cohort of Older Veterans Prescribed Oral Anticoagulants

by

Angela L. Laurio

Advisor: Marianne (Mimi) C. Fahs, PhD, MPH

Objectives:

The objectives of this dissertation were to: (1) describe and compare the incidence and odds of gastrointestinal and intracranial bleeding in veterans age 50 to 89 who were prescribed warfarin, direct oral anticoagulants, or no oral anticoagulants; (2) identify risk factors for gastrointestinal and intracranial bleeding among older veterans prescribed oral anticoagulants, and to calculate the relative risk of bleeding over time through time-to-event analysis; and (3) develop …

Chronic Voluntary Oral Methamphetamine Induces Deficits In Spatial Learning And Hippocampal Protein Kinase Mzeta With Enhanced Astrogliosis And Cyclooxygenase-2 Levels, Jorge A. Avila, Roseanna M. Zanca, Denis Shor, Nicholas Paleologos, Amber A. Alliger, Maria E. Figueiredo-Pereira, Peter A. Serrano

Publications and Research

Methamphetamine (MA) is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw)] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA) based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA. This VOMA model is useful for determining the lower limits necessary to produce neurotoxicity in the …

Bacterial Lps At The Immune Modulating Component In Juzen-Taiho-To, Diego Montenegro

Dissertations, Theses, and Capstone Projects

Juzen-taiho-to (JTT) is an immune-boosting herbal formulation with an ideal balance of safety and efficacy. For example, JTT is clinically used in Japan to stimulate the immunological functions of cancer patients undergoing chemotherapy and radiation. Although the clinical effects of JTT are recognized, the active compounds and mechanism of action are unknown. The studies conducted previously in our laboratory associated several phytosterols and plant glycolipids with the potent immunostimulatory activity of JTT: namely, β-sitosteryl β-D-glucoside (BSSG), glucocerebroside (GluCer), digalactosyldiacylglycerol (DGDG) and monogalactosyldiacylglycerol (MGDG). However, these compounds, when further purified, exhibited little or no immunostimulatory activity. This suggested that the immunostimulatory …