Diseases Commons^™

Characterization Of The Mechanism Of Pparγ-Mediated Neointima Formation In Rodents, Ryoko Tsukahara

Theses and Dissertations (ETD)

Lysophosphatidic acid (LPA) and its ether analog alkyl glycerophosphate (AGP) elicit arterial wall remodeling when applied intralumenally into the uninjured carotid artery. LPA is the ligand of eight GPCRs and the peroxisome proliferator-activated receptor γ (PPARγ). We pursued a gene knockout strategy to identify the LPA receptor subtypes necessary for the neointimal response in a non-injury model of carotid remodeling and also compared the effects of AGP and the PPARγ agonist rosiglitazone (ROSI) on balloon injury-elicited neointima development. In the balloon injury model AGP significantly increased neointima; however, rosiglitazone application attenuated it. AGP and ROSI were also applied intralumenally for …

Compound 49b: A Novel Beta-Adrenergic Receptor Agonist In The Treatment Of Diabetic Retinopathy, Kimberly Williams-Guy

Theses and Dissertations (ETD)

Diabetic retinopathy is the leading cause of blindness in working Americans. While there are therapeutic regimens for the disease, more effective methods are needed. We have previously shown that a non-specific beta-adrenergic receptor agonist, isoproterenol, was effective in preventing functional and morphological changes associated with diabetic retinopathy in the rat. Isoproterenol also produced left ventricle remodeling suggesting it entered the systemic circulation. We therefore synthesized various novel beta-adrenergic receptor compounds and screened these compounds in vitro for their ability to reduce markers of inflammation and apoptosis. Of the various compounds tested, Compound 49b was able to reduce both inflammation and …

Neuroprotective Effects Of Bilobalide Are Accompanied By A Reduction Of Ischemia-Induced Glutamate Release In Vivo, Dorothee Lang, Cornelia Kiewert, Alexander Mdzinarishvili, Tina Maria Schwarzkopf, Rachita K. Sumbria, Joachim Hartmann, Jochen Klein

Pharmacy Faculty Articles and Research

Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 h of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40–50% when given at 10 mg/kg 1 h prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1 h past stroke induction. Sensorimotor function in mice was improved by bilobalide as shown by corner and chimney tests. When brain metabolism in situ was monitored by microdialysis, MCAO caused a rapid disappearance of extracellular glucose in the …

Hiv-1 Matrix Protein Binding To Rna, Ayna Alfadhli, Henry Mcnett, Seyram Tsagli, Hans Peter Bachinger, David H. Peyton

Chemistry Faculty Publications and Presentations

The matrix (MA) domain of the HIV-1 precursor Gag (PrGag) protein plays multiple roles in the viral replication cycle. One essential role is to target PrGag proteins to their lipid raft-associated phosphatidylinositol-(4,5)-bisphosphate (PI[4,5]P2) assembly sites at the plasma membranes (PMs) of infected cells. In addition to this role, several reports have implicated nucleic acid binding properties to retroviral MAs. Evidence indicates that RNA binding enhances the binding specificity of MA to PI(4,5)P2-containing membranes, and supports a hypothesis in which RNA binding to MA acts as a chaperone that protects MA from associating with inappropriate cellular membranes prior to PrGag delivery …

Antivirulence Potential Of Tr-700 And Clindamycin On Clinical Isolates Of Staphylococcus Aureus Producing Phenol-Soluble Modulins, Jason Yamaki, Timothy Synold, Annie Wong-Beringer

Pharmacy Faculty Articles and Research

Staphylococcus aureus strains (n = 50) causing complicated skin and skin structure infections produced various levels of phenol-soluble modulin alpha-type (PSMα) peptides; some produced more than twice that produced by the control strain (LAC USA300). TR-700 (oxazolidinone) and clindamycin strongly inhibited PSM production at one-half the MIC but exhibited weak to modest induction at one-fourth and one-eighth the MICs, primarily in low producers. Adequate dosing of these agents is emphasized to minimize the potential for paradoxical induction of virulence.

Inflammatory Proteins, Genetic Variation, And Environmental Influences On Health Care Associated Infection Development In Sepsis, Reba Antoinette Umberger

Theses and Dissertations (ETD)

The purpose of this study was to determine the impact of baseline systemic inflammation (pro‑inflammatory cytokine, anti‑inflammatory cytokine, and their ratio), genetic variability, and environment on the development of health care associated infections (HAI) among sepsis patients during their ICU stay (up to 28 days).

Methods: A prospective observation study was conducted at the Veterans Affairs Medical Center in the Medical Intensive Care Unit over an 18 month period. A total of 78 patients were enrolled within 72 hours of presenting to the ICU with sepsis. Patient were excluded if they were receiving immunosuppressants (chemotherapy or greater than one mg/kg …

Self-Reported Exercise And Risk Of Osteoporosis In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Lori J. Mennen-Winchell

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate cancer is stimulated to grow in response to testosterone. Androgen deprivation therapy (ADT) leads to chemical castration and suppression of prostate cancer cell production. Testosterone levels less then 300ng/ml decreases bone mineral density and could result in osteoporosis. Studies have shown that during the first year of ADT, fracture risk, mainly in hips and spine increases about 50%. In men, 40% of hip fractures result in death. Exercise may reduce the risk of osteoporosis and thus contribute to the prevention of hip and other fractures. There is limited data regarding whether exercise is associated with a reduced risk of …

Characterization Of Amino Acid Residues Integral To Neuronal Binding Of Amyloid Beta Protein In Alzheimer’S Disease, Nicole C. Olson

Chemistry and Biochemistry

Purpose:  Alzheimer’s Disease is a neurodegenerative disease resulting from over-production and neuronal accumulation of amyloid-beta proteins (Aβ40/Aβ42). The glycine residue at position 33 and histidine residues at positions 13 and 14 are involved with binding and internalization of these proteins, actions potentially inhibited by substituting or sterically hindering these residues with an antibody specific to positions 2-11 (IgG-4.1). Rat pheochromocytoma (PC12) cells differentiated with nerve growth factor were used as a neuronal model to determine whether substitution and/or antibody block amyloid-beta’s neuronal interactions.

Methods:  PC12 cells were incubated with fluorescein-labeled-amyloid-beta-40 (F-Aβ40) or substituted F-Aβ40 derivatives (F-Aβ40-H13,14G, F-Aβ40-H13,14G;G33A), with or without …

A Survey Of Oxidative Paracatalytic Reactions Catalyzed By Enzymes That Generate Carbanionic Intermediates: Implications For Ros Production, Cancer Etiology, And Neurodegenerative Diseases, Victoria Bunik, John Schloss, John T. Pinto, Natalia Dudareva, Arthur J L Cooper

NYMC Faculty Publications

Enzymes that generate carbanionic intermediates often catalyze paracatalytic reactions with O2 and other electrophiles not considered “normal” reactants. For example, pyridoxal 5′-phosphate (PLP)—containing pig kidney dopa decarboxylase oxidizes dopamine with molecular O2 to 3,4-dihydroxyphenylacetaldehyde at about 1% of the rate at which it catalyzes nonoxidative dopa decarboxylation. The mutant Y332F enzyme, however, catalyzes stoichiometric conversion of dopa to 3,4-dihydroxyphenylacetaldehyde, suggesting that even minor structural changes may alter or initiate paracatalytic reactions catalyzed by certain enzymes. Carbanions generated by several thiamine diphosphate (ThDP)—dependent enzymes react with different electrophiles, transforming some xenobiotics and endogenous compounds into potentially biologically hazardous products. The detrimental …

Unifying The Mathematical Modeling Of In Vivo And In Vitro Microdialysis, Peter M. Bungay, Rachita K. Sumbria, Ulrich Bickel

Pharmacy Faculty Articles and Research

A unifying approach is presented for developing mathematical models of microdialysis that are applicable to both in vitro and in vivo situations. Previous models for cylindrical probes have been limited by accommodating analyte diffusion through the surrounding medium in the radial direction only, i.e., perpendicular to the probe axis, or by incomplete incorporation of diffusion in the axial direction. Both radial and axial diffusion are included in the present work by employing two-dimensional finite element analysis. As in previous models, the nondimensional clearance modulus (Θ) represents the degree to which analyte clearance from the external medium influences diffusion through the …

Inhibition Of Multi-Drug Resistant Hiv-1 Reverse Transcriptase By Nucleoside Beta-Triphosphates, Chandravanu Dash, Yousef Ahmadibeni, Michael J. Hanley, Jui Pandhare, Mathias Gotte, Stuart F. J. Le Grice, Keykavous Parang

Pharmacy Faculty Articles and Research

Despite the success of potent reverse transcriptase (RT) inhibitors against human immunodeficiency virus type 1 (HIV-1) in combination regimens, the development of drug resistant RTs constitutes a major hurdle for the long-term efficacy of current antiretroviral therapy. Nucleoside β-triphosphate analogs of adenosine and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), and 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T)) were synthesized and their inhibitory activities were evaluated against wild-type and multidrug resistant HIV-1 RTs. Adenosine β-triphosphate (1) and AZT β-triphosphate (2) completely inhibited the DNA polymerase activity of wild type, the NRTI multi resistant, and nonnucleoside RT inhibitors (NNRTI) resistant HIV-1 RT at 10 …

Does Tranexamic Acid Effectively And Safely Reduce Menstrual Blood Loss (Mbl) In Women With Menorrhagia Or Iud Induced Mbl?, Veronica W. Chang

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine if Tranexamic Acid effectively and safely reduce menstrual blood loss (MBL) in women with Menorrhagia or IUD induced MBL?

The Role Of Ghrelin And Leptin In Obesity: Is Exogenous Administration Of These Hormones A Possible Drug Therapy?, Peri Eckstein

The Science Journal of the Lander College of Arts and Sciences

Ghrelin and leptin are two hormones that have been recognized to have a major influence on energy balance. Leptin is a mediator of long term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin, on the other hand, is a fast acting hormone, playing a role in meal initiation. As a growing number of people suffer from obesity, understanding the mechanisms by which various hormones and neurotransmitters influence energy balance has been a subject of intense research. This paper provides background on leptin and ghrelin hormones, their role in food intake and body weight in humans, …

Synthesis Of 3-Phenylpyrazolopyrimidine-1,2,3-Triazole Conjugates And Evaluation Of Their Src Kinase Inhibitory And Anticancer Activities, Anil Kumar, Israr Ahmad, Bhupender S. Chhikara, Rakesh Tiwari, Deendayal Mandal, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of two classes of 3-phenylpyrazolopyrimidine-1,2,3-triazole conjugates were synthesized using click chemistry approach. All compounds were evaluated for inhibition of Src kinase and human ovarian adenocarcinoma (SK-Ov-3), breast carcinoma (MDA-MB-361), and colon adenocarcinoma (HT-29). Hexyl triazolyl-substituted 3-phenylpyrazolopyrimidine exhibited inhibition of Src kinase with an IC50 value of 5.6 µM. 4-Methoxyphenyl triazolyl-substituted 3-phenylpyrazolopyrimidine inhibited the cell proliferation of HT-29 and SK-Ov-3 by 73% and 58%, respectively, at a concentration of 50 µM.

Trends In The Clinical Characteristics Of Hiv Infected Patients Initiating Antiretroviral Therapy In Kenya, Uganda And Tanzania Between 2002 And 2009, Elvin H. Geng, Peter W. Hunt, Lameck O. Diero, Sylvester Kimaiyo, Geofrey R. Somi, Pius Okong, David R. Bangsberg, Mwebesa B. Bwana, Craig R. Cohen, Juliana A. Otieno, Deo Wabwire, Batya Elul, Denis Nash, Philippa J. Easterbrook, Paula Braitstein, Beverly S. Musick, Jeffrey N. Martin, Constantin T. Yiannoutsos, Kara Wools-Kaloustian

Publications and Research

Background: East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIVinfected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described.

Methods: We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of ART initiation …

A Comparison Of Pharmacist Travel-Health Specialists' Versus Primary Care Providers' Recommendations For Travel-Related Medications, Vaccinations, And Patient Compliance In A College Health Setting, Melissa J. Durham, Jeffery A. Goad, Lawrence S. Neinstein, Mimi Lou

Pharmacy Faculty Articles and Research

Background. Pretravel medication and vaccination recommendations and receipt were compared between primary care providers (PCPs) without special training and clinical pharmacists specializing in pretravel health.

Methods. A retrospective chart review of patients seen for pretravel health services in a pharmacist-run travel clinic (PTC) compared to PCPs at a University Student Health Center. Vaccine/medication recommendations were assessed for consistency with national/international guidelines. Medical/pharmacy records were queried to determine the receipt of medications/vaccinations.

Results. The PTC recommended antibiotics for travelers' diarrhea were given more often when indicated (96% vs 50%, p < 0.0001), and patients seen in the PTC received their medications more often (75% vs 63%, p = 0.04). PCPs prescribed more antibiotics for travelers' diarrhea that were inconsistent with guidelines (not ordered when indicated 49% vs 6%, p < 0.0001 and ordered when not indicated 21% vs 3%, p < 0.0001). The PTC prescribed antimalarials more often when indicated (98% vs 81%, p < 0.0001), while PCPs prescribed more antimalarials that were inconsistent with guidelines (not ordered when indicated 15% vs 1%, p < 0.0001 and ordered when not indicated 19% vs 2%, p < 0.0001). The PTC ordered more vaccines per patient when indicated (mean = 2.77 vs 2.31, p = 0.0012). PTC patients were more likely to receive vaccines when ordered (mean = 2.38 vs 1.95, p = 0.0039). PCPs recommended more vaccines per patient that were inconsistent with guidelines (not ordered when indicated: mean = 0.78 vs 0.12, p < 0.0001, ordered when not indicated: mean 0.18 vs 0.025, p < 0.0001).

Conclusions. A pharmacist-run pretravel health clinic can …

Is Sildenafil Citrate A Safe And Effective Treatment For Pulmonary Hypertension In Adults?, Atekelt Tadese

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine whether or not the Phosphodiesterase inhibitors drug Sildenafil Citrate is safe and effective treatment for Pulmonary Hypertension in adults

Are Proton Pump Inhibitors A Safe And Effective Treatment For Gastroesophageal Reflux Disease In Infants Less Than Twelve Months Old?, Mariah Smith

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not proton pump inhibitors are a safe and effective treatment for gastroesophageal reflux disease in infants less than twelve months old.

Is 5% Imiquimod Cream More Efficacious At Sustained Clearance Of Genital Warts At 3 Months Compared To 1% Imiquimod, Ablation Therapy, And A Placebo Vehicle Cream?, David A. Smith

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not 5% Imiquimod is more efficacious at sustained treatment of genital warts at 3 months compared to 1% Imiquimod, ablation, and a placebo vehicle cream.

Is Opt-80 A Safe And Effective Treatment For Patients With C.Difficile Infection?, Heather A. Shupp

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: Objective of this systematic review is to determine whether or not OPT-80 is a safe and effective treatment for patients with C.difficile infection.

Is Topical 1% Pimecrolimus Cream An Effective Treatment For Rosacea?, Lauren Sloan

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not topical 1% pimecrolimus cream is an effective treatment for rosacea.

The Effectiveness And Safety Of Antibiotic Treatment In Healing Tympanic Membrane Perforation In Aboriginal Children, Shannon M. Rice

PCOM Physician Assistant Studies Student Scholarship

The objective of this systematic review is to determine whether or not antibiotic treatment is safe and effective in healing tympanic membrane (TM) perforation in Aboriginal children diagnosed with chronic suppurative otitis media and otitis media with effusion less than 16 years of age.

Is Alitretinoin (9-Cis-Retinoic Acid) Safe And Effective For Use In Hand Eczema?, Jeanne K. Seeberger

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine if Alitretinoin is a safe and effective alternative to current treatments in reducing the symptoms of Hand Eczema (HE)

Is Liraglutide Safe And Effective As A Monotherapy For The Treatment Of Obesity In Type 2 Diabetics And Healthy Individuals?, Erica Sheeran

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not liraglutide is safe and effective as a monotherapy for the treatment of obesity in type 2 diabetics and healthy individuals.

Is L-Carnitine An Effective Treatment To Improve The Quality Of Life For Patients With Rett Syndrome?, Bernadette Mason

PCOM Physician Assistant Studies Student Scholarship

Objective: To determine “Is L-carnitine an effective treatment to improve the quality of life for patients with Rett Syndrome?”

Is Esomeprazole (Nexium) More Effective Than Omeprazole (Prilosec) In Reducing Heartburn And In Increasing The Rate Of Esophageal Healing In Adults With Endoscopically Diagnosed Erosive Esophagitis (Ee)?, Shawn P. Mahoney

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether Esomeprazole (Nexium) is more safe and effective than Omeprazole (Prilosec) in reducing Heartburn and in increasing the rate of esophageal healing in adults with endoscopically diagnosed Erosive Esophagitis (EE)

How Safe And Effective Is Infliximab In The Treatment Of Children With Moderate To Severe Crohn’S Disease?, Jackie Linh

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this systematic review is to determine whether or not “how safe and effective is infliximab in treatment of children with moderate to severe Crohn’s disease?”

Is Monotherapy Treatment Of Etanercept Effective Against Plaque Psoriasis?, Joseph Devito

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this systematic review is to determine whether or not monotherapy treatment of etanercept is effective against plaque psoriasis.

Is Besifloxacin Ophthalmic Suspension 0.6% Safe And Effective For The Treatment Of Bacterial Conjunctivitis?, Hetal R. Desai

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not besifloxacin ophthalmic suspension 0.6% is safe and effective for the treatment of bacterial conjunctivitis.

Is Vitamin E Supplementation Effective In Reducing Mortality Related To Cardiovascular Events In People With Type 2 Diabetes Mellitus?, Payal Amin

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not Vitamin E is effective in reducing the mortality related to cardiovascular event in patients with Type 2 Diabetes mellitus.