Medical Pharmacology Commons^™

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 …

Studies On Bronchodilator And Cardiac Stimulant Activities Of Urginea Indica, Samra Bashir, Saima Abbas, Aslam Khan, Anwar H. Gilani

Department of Biological & Biomedical Sciences

This study was designed to evaluate bronchodilator and cardio-tonic effects of Urginea indica to provide rational for these medicinal uses. U. indica bulb extract was studied on rabbit tracheal and guinea-pig atrial preparations mounted in tissue baths under simulated physiological conditions. U. indica inhibited carbachol (1 µM) and K⁺ (80 mM)-induced contractions in rabbit trachea, similar to dicyclomine, suggesting the presence of anticholinergic and calcium channel blocking (CCB) mechanisms in U. indica. Anticholinergic and CCB effects of U. indica were respectively confirmed when it shifted the carbachol and Ca²⁺ concentration-response curves rightwards, similar to dicyclomine. U. indica (0.01-1 …

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 …

Possible Steps Of Complete Disassembly Of Post-Termination Complex By Yeast Eef3 Deduced From Inhibition By Translocation Inhibitors., Shinya Kurata, Ben Shen, Jun O Liu, Nono Takeuchi, Akira Kaji, Hideko Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosomes, after one round of translation, must be recycled so that the next round of translation can occur. Complete disassembly of post-termination ribosomal complex (PoTC) in yeast for the recycling consists of three reactions: release of tRNA, release of mRNA and splitting of ribosomes, catalyzed by eukaryotic elongation factor 3 (eEF3) and ATP. Here, we show that translocation inhibitors cycloheximide and lactimidomycin inhibited all three reactions. Cycloheximide is a non-competitive inhibitor of both eEF3 and ATP. The inhibition was observed regardless of the way PoTC was prepared with either release factors or puromycin. Paromomycin not only inhibited all three reactions …

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 …

Early Adolescent Nicotine Exposure Has Long-Lasting Effects On Cocaine-Induced Behaviors In Mice, Mai Alajaji

Theses and Dissertations

Nicotine is one of the most commonly used drugs among adolescent populations. Given the fact that adolescence is a unique developmental stage, during which nicotine has long-term effects on future drug-taking behavior, it is essential to understand how early exposure to nicotine during adolescence may affect the abuse liability of other drugs. We hypothesize that repeated exposure to low doses of nicotine in adolescence induce age-specific enhancement of the rewarding effects of several drugs of abuse in the conditioned place preference (CPP) test. Furthermore, we predict that these changes in behavioral responses are mediated by nicotine-induced brain region-specific increases in …

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 …

Is Dabigatran Superior To Warfarin In Treating Patients With Atrial Fibrillation?, Kelly Higgins

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Dabigatran is superior to Warfarin in patients with atrial fibrillation.

STUDY DESIGN: Review of three English language primary studies published in 2007, 2009, and 2010.

DATA SOURCES: Three randomized control trials found using Cochrane Database.

OUTCOME(S) MEASURED: Outcomes measured were presence or absence of stroke or systolic embolism and intracranial hemorrhage. The absence of these events preserved neurologic function in patients with atrial fibrillation.

RESULTS: In both VKA-naïve and VKA-experienced patients, Dabigatran 150 mg was superior to Warfarin in both the prevention of stroke …

Does Ranibizumab Improve Best Corrected Visual Acuity In Adults With Diabetic Macular Edema Compared To Those Without Ranibizumab?, James E. Huang

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective evidence based medicine (EBM) review is to determine whether or not ranibizumab improves best corrected visual acuity (BCVA) in adults with diabetic macular edema compared to patients who do not receive ranibizumab.

STUDY DESIGN: The selective review examined best corrected visual acuity values reported from published, primary literature sources that examined the efficacy of ranibizumab in diabetic macular edema.

DATA SOURCES: Two double blind randomized controlled trials and one case control study were selected and reviewed.

OUTCOMES MEASURED: Best corrected visual acuity (BCVA) as measured from Early Treatment Diabetic Retinopathy Study visual …

Does Daily Intake Of Glucosamine Supplements Prevent The Need For Knee Replacements Later In Life For Adult Patients Predisposed To Osteoarthritis?, Nancy Helmy

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not daily intake of glucosamine supplements prevents the need for knee replacements later in life for adults predisposed to osteoarthritis.

STUDY DESIGN: Review of three English language primary randomized controlled trial studies published between 2001 and 2008

DATA SOURCES: Three double blind randomized control trials comparing glucosamine supplements to placebo were found using PubMed.

OUTCOMES MEASURED: Outcomes were measured using radiographic studies of the knees, joint space measurements, and symptoms were evaluated using Lequesne and WOMAC indexes.

RESULTS: The Reginster (2001) and Pavelka (2002) studies demonstrated no …

Is Fentanyl Pectin Nasal Spray Safe And Effective For Patients With Breakthrough Cancer Pain?, Salina G. Elengical

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether fentanyl pectin nasal spray (FPNS) is safe and effective treatment for patients with breakthrough cancer pain.

STUDY DESIGN: Review of three English language primary randomized controlled trials published 2010-2011.

DATA SOURCES: Multicenter, randomized, double-blind, double-dummy, placebo-controlled trials comparing fentanyl pectin nasal spray, immediate-release morphine sulfate, and/or nasal spray placebo were found using PubMed, COCHRANE, and Medline databases.

OUTCOME MEASURED: All three studies essentially used similar parameters to measure effectiveness and safety of fentanyl pectin nasal spray compared to oral immediate-release morphine sulfate and/or placebo. Baseline pain intensity …