Medicine and Health Sciences Commons^™

Calcium-Mediated Mechanisms Of Cystic Expansion, Shakila Abdul-Majeed, Surya M. Nauli

Pharmacy Faculty Articles and Research

In this review, we will discuss several well-accepted signaling pathways toward calcium-mediated mechanisms of cystic expansion. The second messenger calcium ion has contributed to a vast diversity of signal transduction pathways. We will dissect calcium signaling as a possible mechanism that contributes to renal cyst formation. Because cytosolic calcium also regulates an array of signaling pathways, we will first discuss cilia-induced calcium fluxes, followed by Wnt signaling that has attributed to much-discussed planar cell polarity. We will then look at the relationship between cytosolic calcium and cAMP as one of the most important aspects of cyst progression. The signaling of …

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 …

Multiple Protein Kinases Determine The Phosphorylated State Of The Small Heat Shock Protein, Hsp27, In Sh-Sy5y Neuroblastoma Cells, Linda A. Dokas, Amy M. Malone, Frederick E. Williams, Surya M. Nauli, William S. Messer Jr.

Pharmacy Faculty Articles and Research

In SH-SY5Y human neuroblastoma cells, the cholinergic agonist, carbachol, stimulates phosphorylation of the small heat shock protein 27 (HSP27). Carbachol increases phosphorylation of both Ser-82 and Ser-78 while the phorbol ester, phorbol-12, 13-dibutyrate (PDB) affects only Ser-82. Muscarinic receptor activation by carbachol was confirmed by sensitivity of Ser-82 phosphorylation to hyoscyamine with no effect of nicotine or bradykinin. This response to carbachol is partially reduced by inhibition of protein kinase C (PKC) with GF 109203X and p38 mitogen-activated protein kinase (MAPK) with SB 203580. In contrast, phosphorylation produced by PDB is completely reversed by GF 109203X or CID 755673, an …

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.

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 …

Development Of A Positive Psychology Intervention For Patients With Acute Cardiovascular Disease, Jeff C. Huffman, Carol A. Mastromauro, Julia K. Boehm, Rita Seabrook, Gregory L. Fricchione, John W. Denninger, Sonja Lyubomirsky

Psychology Faculty Articles and Research

The management of depression and other negative psychological states in cardiac patients has been a focus of multiple treatment trials, though such trials have not led to substantial improvements in cardiac outcomes. In contrast, there has been minimal focus on interventions to increase positive psychological states in cardiac patients, despite the fact that optimism and other positive states have been associated with superior cardiovascular outcomes. Our objective was to develop an 8-week, phone-based positive psychology intervention for patients hospitalized with acute cardiac disease (acute coronary syndrome or decompensated heart failure). Such an intervention would consist of positive psychology exercises adapted …

A Prospective Study Of Positive Psychological Well-Being And Coronary Heart Disease, Julia K. Boehm, Christopher Peterson, Mika Kivimaki, Laura D. Kubzansky

Psychology Faculty Articles and Research

Objective: Research suggests that positive psychological well-being is associated with cardiovascular health. However, much of this research uses elderly samples and has not determined the pathways by which psychological well-being influences cardiovascular disease or whether effects are similar for men and women. This study investigates the association between two aspects of well-being (emotional vitality and optimism) and coronary heart disease (CHD) in a sample of middle-aged men and women, and considers potential mediating factors.

Method: Between 1991 and 1994, well-being and coronary risk factors were assessed among 7,942 individuals without a prior cardiovascular event from the Whitehall II …

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.

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 …