Medicine and Health Sciences Commons^™

Impaired Fast-Spiking, Suppressed Cortical Inhibition, And Increased Susceptibility To Seizures In Mice Lacking Kv3.2 K+ Channel Proteins, David Lau, Eleazar Vega-Saenz De Miera, Diego Contreras, Alan Chow, Richard Paylor, Christopher S. Leonard, Bernardo Rudy

NYMC Faculty Publications

Voltage-gated K(+) channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to -10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one …

Ryanodine Receptor Adaptation, Michael Fill, A. Zahradníková, Carlos A. Villalba-Galea, I. Zahradník, A. L. Escobar, S. Györke

School of Pharmacy Faculty Articles

In the heart, depolarization during the action potential activates voltage-dependent Ca²⁺ channels that mediate a small, localized Ca²⁺ influx (I_Ca). This small Ca²⁺ signal activates specialized Ca²⁺ release channels, the ryanodine receptors (RyRs), in the sarcoplasmic reticulum (SR). This process is called Ca²⁺-induced Ca²⁺ release (CICR). Intuitively, the CICR process should be self-regenerating because the Ca²⁺ released from the SR should feedback and activate further SR Ca²⁺ release. However, the CICR process is precisely controlled in the heart and, consequently, some sort of negative control mechanism(s) must exist to …

Glucocorticoid Regulation Of Insulin Like Growth Factor Binding Protein-5 Gene Transcription In Human Osteoblasts, Xiaoying Wang

Loma Linda University Electronic Theses, Dissertations & Projects

Glucocorticoids (GCs) inhibit bone formation in vivo and inhibit osteoblast proliferation and collagen synthesis in vitro. These effects may be mediated by alterations in the insulin-like growth factor (IGF) system. In the present study of normal human osteoblast-like (HOB) cells, we tested the hypothesis that dexamethasone (Dex) inhibits the expression of IGF binding protein-5 (IGFBP-5). Dex decreased IGFBP-5 mRNA levels to 54% of control after 4 hr. Dex did not modify the decay of IGFBP-5 mRNA in transcriptionally arrested osteoblast cells. Dex decreased IGFBP-5 hnRNA levels to 67% of control after 2 hr, and the activity of the human IGFBP- …

Studies On The Purification And Role Of Igfbp-5 Protease In Bone, H. Garrett Rush Thompson

Loma Linda University Electronic Theses, Dissertations & Projects

Osteoporosis is a disease characterized by low bone density and deterioration of mineralized bone leading to enhanced susceptibility to fracture. Several growth factors have been implicated in the coupling of formation to resorption during the bone remodeling process. The net bone forming activity of many growth factors has prompted numerous studies focused on the regulation of osteoblast cell proliferation, differentiation and activity. The current study focuses on the insulin-like growth factor (IGF) system, an important growth factor system involved in the regulation of bone formation and bone resorption.

IGF binding protein -5 (IGFBP-5), the most abundant IGF binding protein in …

Trends. The Politics Of Psychopathology: Ritalin Conspiracy As Paranoia Or As Good Business?, Ibpp Editor

International Bulletin of Political Psychology

This article discusses the intersection of science, pharmaceuticals, and politics in the context of Ritalin and an alleged over-diagnosis of attention deficit disorder (ADD).

Structured Treatment Interrupion (Sti) With Nevirapine (Nvp) And Two Nucleoside Reverse Transciptase Inhibitors (Nsrti): Is Re-Suppression Achieved Following Treatment Interruption?, Joseph L. Yozviak Do, Facp, R Eric Doerfler Np, Cch, William C. Woodward Do

Department of Medicine

No abstract provided.

Antiretroviral Therapy (Art) In Clinical Practice: Effectiveness And Tolerability Of Necvirapine (Nvp), Stavudine (D4t) And Lamivudine (3tc), Joseph L. Yozviak Do, Facp, R Eric Doerfler Np, Cch, William C. Woodward Do

Department of Medicine

No abstract provided.

Antiretroviral Therapy (Art) In Clinical Practice: Ethnic Variability In Effectiveness And Tolerability Of Nelfinavir And Two Nucleoside Reverse Transcriptase Inhibitors, Joseph L. Yozviak Do, Facp, B Moran, R Eric Doerfler Np, Cch, William C. Woodward Do

Department of Medicine

No abstract provided.

Expression And Requirement Of Epithelial Fatty Acid- Binding Protein In Neuronal Axon Growth, Gregory William Allen

Loma Linda University Electronic Theses, Dissertations & Projects

Epithelial fatty acid-binding protein (E-FABP) is expressed in the dorsal root ganglia following sciatic nerve injury and in migrating and differentiating neurons during neuronal development. It was hypothesized that E-FABP expression is required for the robust outgrowth of axons from developing and regenerating neurons. To test this hypothesis, E-FABP expression in both PC12 cells and primary retinal neurons was examined. In PC12 cells, NGF induces E-FABP mRNA and protein during the period of neurite outgrowth, and E-FABP localizes to the perinuclear cytoplasm, nucleus, and growth cone. Furthermore, E-FABP-deficient cell lines exposed to NGF were less differentiated and had shorter neurites …

Trends. On Drugs? Response To The Peruvian Elections, Ibpp Editor

International Bulletin of Political Psychology

This article discusses electoral "dirty tricks" in the Peruvian election between President Alberto Fuimori and Mr. Alejandro Toledo. The article also discusses comments made by the head of the United States (US) Office of National Drug Policy and Control, General Barry R. McCaffrey.

Tricresyl Phosphate Neurotoxicity Potential, George William Sherk

RISK: Health, Safety & Environment (1990-2002)

Mr. Sherk discusses the potential effects of ongoing human exposure to ordinary doses of neurotoxicants.

A Case For Caution: An Evaluation Of Calabrese And Baldwin's Studies Of Chemical Hormesis, Kevin C. Elliott

RISK: Health, Safety & Environment (1990-2002)

Suggesting a need for more research, Mr. Elliott argues that it is too soon for risk-assessment policy to account for recent challenges to a toxicological linear dose-response assumption.

Comparing The Epa Indoor Air Quality Personal Computer Model And Field Data, Arash Behravesh, Wilbur A. Spaul

RISK: Health, Safety & Environment (1990-2002)

The authors recommend caution in using an EPA model for reconstructing past exposure events as well as for predicting future exposures.

Cation-Anion-Coupled Cotransport In An Immortalized Neuronal Cell Line (C6 Glioma), Kenneth B. E. Gagnon, Norma C. Adragna, Robert E.W. Fyffe, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Transient Nature Of The Stimulatory" Nem-Effect" On K-Cl Cotransport In Kccl-Transfected Hek293 And Primary Rat Aortic Smooth Muscle Cells, Peter K. Lauf, Jin Zhang, Jing Zhang, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Drug Of Choice As A Predictor Of Program Completion In A 12-Week Intensive Outpatient Program And Continuing Care Program, James R. Myers

Theses, Dissertations and Capstones

This study consisted of a one year examination of a twelve week Intensive Outpatient Program (IOP), followed by continuing care treatment, coupled with required attendance to a Twelve Step AA/NA Program. This study detailed the treatment plan available at a local Intensive Outpatient Program in Southern West Virginia. A sample, separating alcoholics from other substance abusers to obtain an estimated completion rate was used.

Tills thesis comprised a one-year history of subjects (6/30/98 -07/01/99). A total of 84 subjects entered into the Intensive Outpatient Program (IOP) within the above time frame. Determination of completion rates was based on a categorical …

Nh4+ Inhibits K-Cl Cotransport In Low K Sheep Red Blood Cells, Peter K. Lauf, Suhail Ahmed, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Novel Approaches For Designing 5'-O-Ester Prodrugs Of 3'-Azido-2'3'-Dideoxythymidine (Azt), Keykavous Parang, Leonard I. Wiebe, Edward E. Knaus

Pharmacy Faculty Articles and Research

3'-Azido-2'3'-dideoxythymidine (AZT, 1, zidovudine, RetrovirTM) is used to treat patients with human immunodeficiency virus (HIV) infection. AZT, after conversion to AZT-5'-triphosphate (AZT-TP) by cellular enzymes, inhibits HIV-reverse transcriptase (HIV-RT). The major clinical limitations of AZT are due to clinical toxicities that include bone marrow suppression, hepatic abnormalities and myopathy, absolute dependence on host cell kinase-mediated activation which leads to low activity, limited brain uptake, a sort half-life of about one hour in plasma that dictates frequent administration to maintain therapeutic drug levels, low potential for metabolic activation and/or high susceptibility to catabolism, and the rapid development of resistance by HIV-1. …

Modulation Of The Pharmacokinetics And Pharmacodynamics Of Proteins By Polyethylene Glycol Conjugation, Reza Mehvar

Pharmacy Faculty Articles and Research

With the rapid advances in the field of biotechnology during the last decade, many peptides and proteins have been produced and evaluated for therapy of various diseases, including cancer. However, rapid clearance and the possibility of immunogenicity after the in vivo administration of these biotechnology-driven products have impeded their marketing. To circumvent these problems, synthetic and natural polymers such as polyethylene glycol (PEG) and dextrans, respectively, have been covalently attached to proteins, and some of these protein-polymer conjugates have shown promising therapeutic results. The conjugation of proteins with polymers usually causes a reduction in the recognition of the protein by …

Cellular Release Of And Response To Atp As Key Determinants Of The Set-Point Of Signal Transduction Pathways, Rennolds S. Ostrom, Caroline Gregorian, Paul A. Insel

Pharmacy Faculty Articles and Research

The determinants of “basal” activity of signaling pathways regulating cellular responses are poorly defined. One possibility is that cells release factors to establish the set-point of such pathways. Here we show that treatment of Madin-Darby canine kidney cells with the nucleotidase apyrase decreases basal arachidonic acid release and cAMP production 30–40% and that inhibitors of P2Y receptor action also affect basal and forskolin-stimulated cAMP accumulation. Changing medium prominently increases extracellular levels of ATP in Madin-Darby canine kidney, COS-7, and HEK-293 cells. Mechanical stimulation of ATP release likely occurs in virtually every experimental protocol with cultured cells, implicating such release and …