Medical Pharmacology Commons^™

Drugs, Devices, And Desires: A Problem-Based Learning Course In The History Of Medicine, Sarah Levitt, Anne Mckeage, P. K. Rangachari

Interdisciplinary Journal of Problem-Based Learning

Problem-based learning (PBL) is well suited for courses in the history of medicine, where multiple perspectives exist and information has to be gleaned from different sources. A student, an archivist, and a teacher offer three perspectives about a senior level course where students explored the antecedents and consequences of medical technology. Two active learning strategies were used: (a) PBL to explore the historical basis of procedures used to diagnose, prevent and treat a single disease, tuberculosis, and (b) a concurrent inquiry-based component that permitted individual exploration of other medical technologies and demonstration of learning through diverse options (book reviews, conversations, …

Role Of Garlic Usage In Cardiovascular Disease Prevention: An Evidence-Based Approach, Waris Qidwai, Tabinda Ashfaq

Department of Family Medicine

Introduction:.Rapidly growing prevalence of cardiovascular disease is a major threat for the developed as well as developing world warranting urgent need of intervention. Complementary and alternative medicines are gaining popularity among general population because of their safety profile and easy administration. Garlic, in particular, is considered to be one of the best disease-preventive foods because of its potent and widespread effects. This study was done to find out the role of garlic usage in cardiovascular disease prevention.

Methodology : .Major databases including Google, PubMed,MEDLINE, and Cochrane library view were used for the literature search. Clinical trials conducted on humans assessing …

Engineering A Bcr-Abl–Activated Caspase For The Selective Elimination Of Leukemic Cells, Manabu Kurokawa, Takahiro Ito, Chih-Sheng Yang, Chen Zhao

Dartmouth Scholarship

Increased understanding of the precise molecular mechanisms involved in cell survival and cell death signaling pathways offers the promise of harnessing these molecules to eliminate cancer cells without damaging normal cells. Tyrosine kinase oncoproteins promote the genesis of leukemias through both increased cell proliferation and inhibition of apoptotic cell death. Although tyrosine kinase inhibitors, such as the BCR-ABL inhibitor imatinib, have demonstrated remarkable efficacy in the clinic, drug-resistant leukemias emerge in some patients because of either the acquisition of point mutations or amplification of the tyrosine kinase, resulting in a poor long-term prognosis. Here, we exploit the molecular mechanisms of …

Properties Of Ribbon And Non-Ribbon Release From Rod Photoreceptors Revealed By Visualizing Individual Synaptic Vesicles., Minghui Chen, Matthew J. Van Hook, David Zenisek, Wallace B. Thoreson

Journal Articles: Pharmacology & Experimental Neuroscience

Vesicle release from rod photoreceptors is regulated by Ca(2+) entry through L-type channels located near synaptic ribbons. We characterized sites and kinetics of vesicle release in salamander rods by using total internal reflection fluorescence microscopy to visualize fusion of individual synaptic vesicles. A small number of vesicles were loaded by brief incubation with FM1-43 or a dextran-conjugated, pH-sensitive form of rhodamine, pHrodo. Labeled organelles matched the diffraction-limited size of fluorescent microspheres and disappeared rapidly during stimulation. Consistent with fusion, depolarization-evoked vesicle disappearance paralleled electrophysiological release kinetics and was blocked by inhibiting Ca(2+) influx. Rods maintained tonic release at resting membrane …

Ethanol Regulation Of Serum Glucocorticoid Kinase 1 Expression In Dba2/J Mouse Prefrontal Cortex, Blair N. Costin, Seth M. Dever, Michael F. Miles

Pharmacology and Toxicology Publications

Background

We previously identified a group of glucocorticoid-responsive genes, including Serum Glucocorticoid kinase 1 (Sgk1), regulated by acute ethanol in prefrontal cortex of DBA2/J mice. Acute ethanol activates the hypothalamic pituitary adrenal axis (HPA) causing release of glucocorticoids. Chronic ethanol dysregulates the HPA response in both humans and rodents, possibly contributing to important interactions between stress and alcoholism. Because Sgk1regulates ion channels and learning and memory, we hypothesized that Sgk1 contributes to HPA-dependent acute and adaptive neuronal responses to ethanol. These studies characterized acute and chronic ethanol regulation of Sgk1 mRNA and protein and their relationship with ethanol actions …

Cannabinoid Cb2 Receptors Regulate Central Sensitization And Pain Responses Associated With Osteoarthritis Of The Knee Joint, James J. Burston, David R. Sagar, Pin Shao, Mingfeng Bai, Emma King, Louis Brailsford, Jenna M. Turner, Gareth J. Hathway, Andrew J. Bennett, David A. Walsh, David A. Kendall, Aron H. Lichtman, Victoria Chapman

Pharmacology and Toxicology Publications

Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies.

Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that …

Association Between The Luteinizing Hormone/Chorionic Gonadotropin Receptor (Lhcgr) Rs4073366 Polymorphism And Ovarian Hyperstimulation Syndrome During Controlled Ovarian Hyperstimulation, Travis J. O'Brien, Mariah M. Kalmin, Arthur F. Harralson, Adam M. Clark, Ian Gindoff, Samuel J. Simmens, David Frankfurter, Paul Gindoff

Pharmacology and Physiology Faculty Publications

Background

The aim of this study was to determine the relationship between a purported luteinizing hormone/chorionic gonadotropin (LHCGR) high function polymorphism (rs4539842/insLQ) and outcome to controlled ovarian hyperstimulation (COH).

Methods

This was a prospective study of 172 patients undergoing COH at the Fertility and IVF Center at GWU. DNA was isolated from blood samples and a region encompassing the insLQ polymorphism was sequenced. We also investigated a polymorphism (rs4073366 G > C) that was 142 bp frominsLQ. The association of the insLQ and rs4073366 alleles and outcome to COH (number of mature follicles, …

Fyn-Dependent Gene Networks In Acute Ethanol Sensitivity, Sean P. Farris, Michael F. Miles

Pharmacology and Toxicology Publications

Studies in humans and animal models document that acute behavioral responses to ethanol are predisposing factor for the risk of long-term drinking behavior. Prior microarray data from our laboratory document strain- and brain region-specific variation in gene expression profile responses to acute ethanol that may be underlying regulators of ethanol behavioral phenotypes. The non-receptor tyrosine kinase Fyn has previously been mechanistically implicated in the sedative-hypnotic response to acute ethanol. To further understand how Fyn may modulate ethanol behaviors, we used whole-genome expression profiling. We characterized basal and acute ethanol-evoked (3 g/kg) gene expression patterns in nucleus accumbens (NAC), prefrontal cortex …

Contribution Of Nadph Oxidase To Membrane Cd38 Internalization And Activation In Coronary Arterial Myocytes, Ming Xu, Xiao-Xue Li, Joseph K. Ritter, Justine M. Abais, Yang Zhang, Pin-Lan Li

Pharmacology and Toxicology Publications

The CD38-ADP-ribosylcyclase-mediated Ca2+ signaling pathway importantly contributes to the vasomotor response in different arteries. Although there is evidence indicating that the activation of CD38-ADP-ribosylcyclase is associated with CD38 internalization, the molecular mechanism mediating CD38 internalization and consequent activation in response to a variety of physiological and pathological stimuli remains poorly understood. Recent studies have shown that CD38 may sense redox signals and is thereby activated to produce cellular response and that the NADPH oxidase isoform, NOX1, is a major resource to produce superoxide (O2·−) in coronary arterial myocytes (CAMs) in response to muscarinic receptor agonist, which uses CD38-ADP-ribosylcyclase …

Androgen Receptor-Target Genes In African American Prostate Cancer Disparities, Bi-Dar Wang, Qi Yang, Kristin Ceniccola, Fernando Bianco, Ramez Andrawis, Thomas W. Jarrett, Harold A. Frazier, Steven R. Patierno, Norman H. Lee

Pharmacology and Physiology Faculty Publications

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter …

Characterization Of Induced Neural Progenitors From Skin Fibroblasts By A Novel Combination Of Defined Factors., Changhai Tian, Qiang Liu, Kangmu Ma, Yongxiang Wang, Qiang Chen, Randall Ambroz, David L. Klinkebiel, Yuju Li, Yunlong Huang, Jianqing Ding, Jie Wu, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

Recent reports have demonstrated that somatic cells can be directly converted to other differentiated cell types through ectopic expression of sets of transcription factors, directly avoiding the transition through a pluripotent state. Our previous experiments generated induced neural progenitor-like cells (iNPCs) by a novel combination of five transcription factors (Sox2, Brn2, TLX, Bmi1 and c-Myc). Here we demonstrated that the iNPCs not only possess NPC-specific marker genes, but also have qualities of primary brain-derived NPCs (WT-NPCs), including tripotent differentiation potential, mature neuron differentiation capability and synapse formation. Importantly, the mature neurons derived from iNPCs exhibit significant physiological properties, such as …

Molecular Staging Of Node Negative Patients With Colorectal Cancer., Terry Hyslop, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Metastatic disease is the principle cause of death from colorectal cancer. In that context, the most significant indicator of overall survival and therapeutic response to adjuvant chemotherapy is the presence of metastatic tumor cells in regional lymph nodes. Although histopathologic analysis of lymph nodes is central to all colorectal cancer staging paradigms, its prognostic and predictive value is limited. Indeed, about 30% of patients with histopathology-negative lymph nodes (pN0) die from metastatic disease, reflected by microscopic lymph node metastases that are overlooked by standard techniques. These unrecognized tumor cells are especially important when considering racial disparities in outcomes in colorectal …

Regulation Of Alpha Synuclein Following Chronic Methamphetamine Administration In Guinea Pigs: Correlation With Memory And Synaptic Plasticity, Adnouse Blanc

PCOM Biomedical Studies Student Scholarship

Methamphetamine (METH) is a highly addictive drug of abuse that has a severe impact on neuronal changes in the brain including modulations of plasticity, cognitive dysfunction, as well as memory impairment. These changes can be seen as modifications in the expression of biochemical markers associated with synaptic plasticity. One such marker associated with memory impairment is alpha synuclein (α-syn). Alteration of α-syn expression has been linked to memory impairment in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Here we assess the effect of chronic METH treatment in correlation to cognitive functions.

Twenty-nine guinea pigs (male, 150-250 g) were …

Rational Use Of Antibiotics--A Quality Improvement Initiative In Hospital Setting, Sidrah Nausheen, Rabia Hammad, Ambreen Khan

Department of Obstetrics & Gynaecology

Objectives: To minimise irrational use of antibiotics by implementing guidelines for antibiotic usage in obstetrics and Gynaeocology.
Methods: The observational study was conducted from January to December 2010 at the maternity unit of Aga Khan Hospital for Women and children, Kharadar, a secondary care facility in Karachi, Pakistan. Data was collected from medical records related to the study period. Prophylactic antibiotics were given according to the American College of Obstetricians and Gynaecologists recommendation 2009. Surveillance was done by surgical site infection rates and infectious morbidity. Data was analysed on SPSS 13.
Results: Therapeutic antibiotic use was rationalized, reducing the use …

Is Administration Of Depot Medroxyprogesterone Acetate Injections Every Three Months Effective In Decreasing Pain Associated With Endometriosis In Premenopausal Women?, Maria Kern

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic EBM review is to determine whether or not the administration of depot medroxyprogesterone acetate injections every three months are effective in decreasing pain associated with endometriosis in premenopausal women.

STUDY DESIGN: A review of two randomized controlled trials and one randomized comparative trial comparing pain improvement from depot medroxyprogesterone acetate (DMPA) injections at different time intervals and/or in comparison to other hormonal birth control methods in premenopausal patients suffering from endometriosis.

DATA SOURCES: Randomized controlled trials and a randomized comparative trial were found using PubMed and Ovid MEDLINE databases.

OUTCOME MEASURED: Outcomes were …

Is Oral Rivaroxaban Safe And Effective In The Treatment Of Patients With Symptomatic Dvt?, Ami A. Patel

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not oral rivaroxaban is safe and effective in the treatment of patients with symptomatic DVT.

STUDY DESIGN: Review of three English language primary randomized controlled trial studies published from 2007-2011.

DATA SOURCES: Three randomized controlled trials studying the effectiveness and safety of rivaroxaban in the treatment of patients with symptomatic DVT in comparison to enoxaparin and placebo.

OUTCOMES MEASURED: Outcomes measured were episodes of recurrent DVT and bleeding. Patients were monitored for the proposed treatment period and seen at fixed intervals that were matching …

Are Triptan Drugs Safe And Effective For Use In The Prevention Of Menstrually Related Migraines (Mrms)?, Christina Ponzio

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Triptan drugs are safe and effective for use in the prevention of menstrually related migraines (MRMs).

STUDY DESIGN: Review of two English language randomized controlled trials and one pilot randomized control trial.

DATA SOURCES: Randomized controlled trials comparing Triptan drugs to a placebo group were found using Medline, PubMed, and OVID.

OUTCOMES MEASURED: Incidence of MRM based on patient self-report; number of relapses; patients’ subjective evaluations of effectiveness based on questionnaire; adverse effects of Triptan treatment.

RESULTS: Two randomized controlled trials …

Is Pramipexole Safe And Effective In Reducing Depressive Symptoms In Patients With Mild To Moderate Parkinson’S Disease And Depression?, Corinne J. Kern

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not pramipexole (Mirapex) is a safe and effective drug to treat depression in patients with mild to moderate Parkinson’s Disease (PD).

STUDY DESIGN: Review of three English language primary randomized controlled trials and one randomized prospective, observational study published between 2003-2010.

DATA SOURCES: Three randomized controlled trials and one randomized prospective, observational study comparing the efficacy of pramipexole to placebo, sertraline (an SSRI) and other dopamine agonists (pergolide) in the treatment of PD related depression symptoms were found using PubMed.

OUTCOME(S) MEASURED: Each of the …

Is Rimonabant A Safe And Effective Treatment For Patients With Alcohol Dependence?, Samantha L. Hughes

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Rimonabant is a safe and effective treatment for patients with alcohol dependence.

STUDY DESIGN: Systematic review of three English language randomized control trials published in 2005, 2008 and 2010.

DATA SOURCES: Three double-blind, placebo controlled randomized trials comparing Rimonabant or Naltrexone to placebo were found using PubMed, OVID, Medline and Cochrane.

OUTCOMES MEASURED: Outcomes measured include event rate of heavy drinking days using the timeline follow back method, which facilitates self-reporting of drinking habits by utilizing calendars and personal recall. Other outcomes measured include …

Does The Addition Of Muramyl Tripeptide To Chemotherapy Improve Overall Survival For Patients With Osteosarcoma?, Jennifer Jones

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the addition of muramyl tripeptide to chemotherapy improve overall survival for patients with osteosarcoma?”

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2005 and 2009.

DATA SOURCES: Randomized controlled trials evaluating the addition of muramyl tripeptide (MTP) to chemotherapy for patients with osteosarcoma were found using Medline/PubMed databases.

OUTCOMES MEASURED: Event-free survival (EFS) and overall survival were the outcome measures used to determine the effectiveness of the additional chemotherapy treatment in osteosarcoma patients. EFS was defined as …