Chemicals and Drugs Commons^™

Dextran-Methylprednisolone Succinate As A Prodrug Of Methylprednisolone: Plasma And Tissue Disposition, Xiaoping Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Plasma and tissue disposition of a macromolecular prodrug of methylprednisolone (MP), dextran (70 kDa)–methylprednisolone succinate (DMP), was studied in rats. Single 5‐mg/kg doses of DMP or unconjugated MP were administered into the tail veins of different groups of rats (n  = 4/group/time point). Blood (cardiac puncture) and tissues (liver, spleen, kidney, heart, lung, thymus, and brain) were collected at various times after DMP (0–96 h) or MP (0–2 h) injections. Concentrations of DMP and MP in samples were analyzed by size‐exclusion chromatography (SEC) and reversed‐phase high‐performance liquid chromatography (HPLC), respectively. Conjugation of MP with 70‐kDa dextran resulted in 22‐, …

Effect Of Monounsaturated Fat Rich Almonds On Hemostatic And Inflammatory Factors In Healthy Adults, Kristianne M. Connell

Loma Linda University Electronic Theses, Dissertations & Projects

Background: The frequent consumption of nuts is inversely associated with the incidence of cardiovascular disease. Nuts are known to decrease the risk of cardiovascular disease by reducing serum total and low-density lipoprotein (LDL) cholesterol. Markers of inflammation including C-reactive protein, E-selectin and interleukin-6 have been proposed to be newer risk factors for cardiovascular disease. However, the influence of nuts such as almonds on markers of inflammation and hemostasis that influence cardiovascular disease risk is not currently known.

Objective: The objective of this study was to determine the effect of almond consumption on markers of inflammation and hemostatic factors in healthy …

Evaluation Of Cholera Vaccines Formulated With Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant In Mice, Jia-Yan Wu, William F. Wade, Ronald K. Taylor

Dartmouth Scholarship

Cholera is an acute diarrheal disease that is caused by the gram-negative bacterium Vibrio cholerae. The low efficacy of currently available killed-whole-cell vaccines and the reactinogenicity coupled with potential reversion of live vaccines have thus far precluded widespread vaccination for the control of cholera. Recent studies on the molecular nature of the virulence components that contribute to V. cholerae pathogenesis have provided insights into possible approaches for the development of a defined subunit cholera vaccine. Genetic analysis has demonstrated that the toxin-coregulated pilus (TCP) is the major factor that contributes to colonization of the human intestine by V. cholerae. In …

Treatment Of Diabetes, John H.L. Playfair, Khalid M. Elased, Joseph B. De Souza

Pharmacology and Toxicology Faculty Publications

The present invention provides methods for using a killed malaria parasite or an extract thereof in the treatment of non-insulin dependent diabetes mellitus (NIDDM).

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- …

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.

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.

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.

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 …

Protein Adducts Of Iso[4]Levuglandin E2, A Product Of The Isoprostane Pathway, In Oxidized Low Density Lipoprotein, Robert G. Salomon, Wei Sha, Cynthia Brame, Kamaljit Kaur, Ganesamoorthy Subbanagounder, June O'Neil, Henry F. Hoff, L. Jackson Roberts Ii

Pharmacy Faculty Articles and Research

Levuglandin (LG) E₂, a cytotoxic seco prostanoic acid co-generated with prostaglandins by nonenzymatic rearrangements of the cyclooxygenase-derived endoperoxide, prostaglandin H₂, avidly binds to proteins. That LGE₂-protein adducts can also be generated nonenzymatically is demonstrated by their production during free radical-induced oxidation of low density lipoprotein (LDL). Like oxidized LDL, LGE₂-LDL, but not native LDL, undergoes receptor-mediated uptake and impaired processing by macrophage cells. Since radical-induced lipid oxidation produces isomers of prostaglandins, isoprostanes (isoPs), via endoperoxide intermediates, we postulated previously that a similar family of LG isomers, isoLGs, is cogenerated with isoPs. Now …

K-Cl Cotransport: Membrane Immunofluorescence Localization By Confocal Microscopy Of The Kcc1 Protein, Before And After Truncation Of The Cooh-Terminal Domain, In Human Embryonic Kidney (Hek293) Cells, Peter K. Lauf, Kenneth B.E. Gagnon, Jin Zhang, Eric Delpire, Robert E.W. Fyffe, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Quantitative Analysis Of Changes In Cell Volume And Intracellular Ph Induced By Ammonia And Ammonium In Neuroblastoma Cells Studied With Fluorescent Probes, Vania D. Rosas, G. Boyarsky, S. Marquez, Francisco J. Alvarez-Leefmans

Pharmacology and Toxicology Faculty Publications

No abstract provided.

New Mechanism Of Regulation Of K+-Cl- Cotransport, Norma C. Adragna, H. Ahmed, C. M. Ferrell, J. Filosa, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Nuclear Receptor Co-Repressor Gene Localizes To 17p11.2, A Frequently Deleted Band In Malignant Disorders, Michael W. Stacey, Jianxiang Wang, Rebecca L. Byrd, Johnson M. Liu, William G. Kearns

Bioelectrics Publications

The t(8;21) between the AML1 and ETO genes is a commonly seen genetic alteration in acute myeloid leukemia. Recently, we reported that the fusion partner ETO binds to the human nuclear receptor co-repressor (NCOR), a member of the NCOR/SIN3/histone deacetylase complex. This complex mediates transcriptional repression as a result of chromatin remodeling. Here, we used a combination of fluorescence in situ hybridization and hybrid panels to localize the human NCOR gene (NCOR) to chromosome band 17p11.2. The position of human NCOR on 17p11 raises the possibility of deranged transcriptional regulation in malignant disorders associated with deletions of 17p.

The Role Of Gap Junctions In Congenital Diseases Of The Heart, Scott Henry Britz-Cunningham

Loma Linda University Electronic Theses, Dissertations & Projects

Background. Gap junctions are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. Connexin43, the major protein of gap junctions in the heart, is targeted by several protein kinases that regulate myocardial cell-cell coupling. We hypothesized that mutations altering sites critical to this regulation would lead to functional or developmental abnormalities of the heart.

Methods. Connexin43 DNA from 25 normal subjects and 30 children with a variety of congenital heart diseases was amplified by the polymerase chain reaction and sequenced. Mutant DNA was expressed in cell culture and examined for its effect …

Developmental Expression Of Rat Target Of The Antiproliferative Antibody (Rtapa) Protein In The Brain, Clyde Dale Sullivan

Theses and Dissertations (ETD)

The present study defines the expression pattern of rTAPA (CD81) in the developing rat brain. rTAPA is a member of the tetramembrane spanning family of proteins, and like other members of this family, appears to be associated with the stabilization of cellular contacts. On immunoblots of the brain, rTAPA is present in higher levels than any other tissue examined: muscle, tendon, peripheral nerve, cartilage, liver, kidney, skin, and testicle. Immunohistochemical methods were used to define the distribution of rTAPA in the brain. This protein is expressed by ependyma, choroid plexus, astrocytes, and oligodendrocytes, and rTAPA is dramatically upregulated at the …

Vasodilators Activate Erythrocyte K-Cl Cotransport, Norma C. Adragna, H. Ahmed, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Significance Of The Kccl Cytoplasmic Cooh-Terminal Fragment For The Ph Dependence Of K-Cl Cotransport In Transfected Human Embryonic Kidney Cells, Norma C. Adragna, Jin Zhang, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Cellular Responses In Escherichia Coli To Lethal And Sublethal Doses Of Ozone, Indira Ruth Komanapalli

Loma Linda University Electronic Theses, Dissertations & Projects

Ozone is a major component of photochemical smog. High levels of this pollutant, sufficient to affect human health are found in many urban areas worldwide. Though limited studies in humans are supported by extensive findings from animal experiments, a difficulty in interpreting the results of these experiments has lead to an ambiguity on the biochemical mechanism of ozone toxicity. To elucidate the mechanism by which ozone causes cell damage and eventual cell death we conducted a comprehensive study using Escherichia coli K-12 as a model.

Studies on the comparative inactivation of bacteriophage lambda (λ), Escherichia coli, and Candida albicans …

Proton (H) Modulation Of K-Cl Cotransport Through Both Internal And External Sites In Dids-Ph-Clamped Low Magnesium Lk Sheep Erythrocytes, Peter K. Lauf, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

A Thermodynamic Study Of Electroneutral K-Cl Cotransport In Ph- And Volume-Clamped Low K Sheep Erythrocytes With Normal And Low Internal Magnesium, Peter K. Lauf, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

Swelling-Induced human erythrocyte K-Cl cotransport is membrane potential independent and capable of uphill transport. However, a complete thermodynamic analysis of basal and stimulated K-Cl cotransport, at constant cell volume, is missing, This study was performed in low K sheep red blood cells before and after reducing cellular free Mg into the nanomolar range with the divalent cation ionophore A23187 and a chelator, an intervention known to stimulate K-Cl cotransport. The anion exchange inhibitor 4,4'diisothiocyanato-2,2'disulfonic stilbene was used to clamp intracellular pH and Cl or NO3 concentrations. Cell volume was maintained constant as external and internal pH differed by more than …

Sidedness Of H+ Action On K-Cl Cotransport In Dids Ph(I)-Clamped Low K Sheep Red Blood Cells With Reduced Mg(I), Peter K. Lauf, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Dependence Of Thiol-Stimulated K-Cl Cotransport On Redox State Of Low K Sheep Red Blood Cells, Peter K. Lauf, Norma C. Adragna, Nihal S. Agar

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Hypoglycemia And Hyperinsulinemia In Rodent Models Of Severe Malaria Infection, Khalid M. Elased, J. H. L. Playfair

Pharmacology and Toxicology Faculty Publications

Severe hypoglycemia developed during nonlethal Plasmodium chabaudi and lethal P. yoelii blood stage malaria infection in mice, always in association with hyperinsulinemia. Supernatants of lethal P. yoelii incubated overnight induced hypoglycemia and hyperinsulinemia in normal mice. In murine malaria, hypoglycemia may be largely secondary to increased insulin secretion.

Cerebral Microcirculatory Effects Of Maturation, Scott R. Elliott

Loma Linda University Electronic Theses, Dissertations & Projects

The present studies demonstrate that in the second (2B) and fourth (4B) branches of newborn and adult sheep middle cerebral arteries, 5-HT2 serotonergic receptors mediate contractile responses to serotonin and that alpha-1 adrenergic receptors mediate contractile responses to norepinephrine. In addition, tissue sensitivity to 5-HT and NE decreases significantly with maturation, but does not vary with branch order. These age-related changes were associated with a decrease in affinity and maximum response in 2B and 4B segments of 5-HT and NE contracted arteries, respectively. Norepinephrine and 5-HT occupancy at the pD₂ rose significantly in 2B segments, but did not change …

Signal Transduction In Bacterial Chemotaxis, Edward Heath Rowsell

Loma Linda University Electronic Theses, Dissertations & Projects

This study investigated the site of ATP utilization in the signal transduction pathway of bacterial chemotaxis and localized the point of convergence of a methylation-independent system of chemotaxis with the methylation-dependent system. The identity of the signal originating from the phosphotransferase system was investigated by substituting the fructose-inducible HPr-like protein FPr for HPr in transport and chemotaxis. In addition, a novel chemoattractant, glycerol, was identified for Salmonella typhimurium. Histidine-auxotrophic S. typhimurium strains ST23 (hisF) and ST171 (hisF cheB) were depleted for ATP. The times required for the bacteria to adapt to a step increase in serine, …

N-Ethylmaleimide Treatment Of Low K Sheep Red-Blood-Cells At Different Temperatures Reveals Role Of Thiols And Mg For Activation And Inactivation Of K-Cl Cotransport, Peter K. Lauf, R. Moezzi, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.