Medical Sciences Commons^™

The Relationship Between Reactivity Of Metabolites Of Pyrrolizidine Alkaloids And Extrahepatic Toxicity, R. A. Cooper, R. J. Huxtable

Roland A. Cooper

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.

Regulation Of The Rat Liver Sodium-Dependent Bile Acid Cotransporter Gene By Prolactin. Mediation Of Transcriptional Activation By Stat5, Tanmoy C. Ganguly, Michelle L. O'Brien, Saul J. Karpen, James F. Hyde, Fredrick J. Suchy, Mary Vore

Toxicology and Cancer Biology Faculty Publications

The intracellular mechanism(s) underlying the upregulation of the hepatic Na+/taurocholate cotransporting polypeptide (ntcp) by prolactin (PRL) are unknown. In this report, we demonstrate a time-dependent increase in nuclear translocation of phosphorylated liver Stat5 (a member of the ignal ransducers and ctivators of ranscription family) that correlated with suckling-induced increases in serum PRL levels. In electrophoretic mobility gel shift assays, nuclear Stat5 exhibited specific DNA-binding ability towards IFN-gamma-activated sequence (GAS)-like elements (GLEs; 5'TTC/A-PyNPu-G/TAA-3') located in the -937 to -904 bp region of the ntcp promoter. Transient cotransfections in HepG2 cells revealed that PRL inducibility (2.5-3-fold) required coexpression of the long form …

Dna-Protein Cross-Linking By Pyrrolizidine Alkaloids, Gail L. Drew

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Pyrrolizidine alkaloids (PAs) are natural plant compounds found in hundreds of plant species worldwide and are reported to have cytotoxic, carcinogenic, antimitotic, and genotoxic activity. PAs are metabolized by the cytochrome P450 (CYP) system to the pyrrole or the N-oxide form. The pyrroles are bifunctional electrophilic alkylators that bind cellular nucleophiles such as DNA and proteins and sirupt normal cell processes, including DNA replication and gene transcription and can cause megalocytosis. The pyrroles dehydrosenecionine (DHSN) and dehydromonocrotaline (DHMO) are among the most potent PA cross-linkers and inducers of megalocytosis. DHSN and DHMO-induced cross-links in cultured normal (MDBK) and neoplastic (MCF7) …

Aflatoxin B1 Metabolism In Mammalian Pulmonary Tissue, J. Michael Eichelberger

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Aflatoxin B₁ (AFB₁) is a potent dietary hepatocarcinogen and may be a lung carcinogen when inhaled. To study the relative ability of lung and liver to metabolize AFB₁, a susceptible (Swiss-Webster rat) and resistant species (Syrian golden hamster) were pretreated with inducing agents in order to identify specific AFB₁ metabolizing enzymes in each tissue.

Analysis of AFB₁-exo-epoxide (AFBO) formation, O-dealkynation assays, and protein immunoblots demonstrated that cytochrome P450 (CYP) 1A proteins were overexpressed in both the lung and liver of hamsters pretreated with 3-methylchyolanthrene (3-MC). Only CYP1A1 was expressed in the lung …

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.

The Protective Role Of Manganese Superoxide Dismutase Against Adriamycin-Induced Acute Cardiac Toxicity In Transgenic Mice, Hsiu-Chuan Yen, Terry D. Oberley, Satit Vichitbandha, Ye-Shih Ho, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Adriamycin (ADR) is a potent anticancer drug known to cause severe cardiac toxicity. Although ADR generates free radicals, the role of free radicals in the development of cardiac toxicity and the intracellular target for ADR-induced cardiac toxicity are still not well understood. We produced three transgenic mice lines expressing increased levels of human manganese superoxide dismutase (MnSOD), a mitochondrial enzyme, as an animal model to investigate the role of ADR-mediated free radical generation in mitochondria. The human MnSOD was expressed, functionally active, and properly transported into mitochondria in the heart of transgenic mice. The levels of copper-zinc SOD, catalase, and …

A Simple Procedure For Determining The Aqueous Half-Lives Of Pyrrolic Metabolites Of Pyrrolizidine Alkaloids, R. A. Cooper, R. J. Huxtable

Roland A. Cooper

Physicochemical And Metabolic Basis For The Differing Neurotoxicity Of The Pyrrolizidine Alkaloids, Trichodesmine And Monocrotaline, R. J. Huxtable, C. C. Yan, S. Wild, S. Maxwell, Roland Cooper

Roland A. Cooper

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 …

The Sea Anemone Purine, Caissarone: Adenosine Receptor Antagonism, Roland A. Cooper, Josecarlos De Freitas, Frank Porreca, Cynthia M. Eisenhour, Ronald Lukas, Ryan J. Huxtable

Roland A. Cooper

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.

Comparative Toxicities Of Aminonitriles, Timothy Lester Lacy

Theses and Dissertations - UTB/UTPA

This study examined the comparative toxicities and metabolism of four selected aminonitriles namely aminoacetonitrile, $\beta$-aminopropionitrile, $N,N\sp\prime$-dimethylaminopropionitrile, and $\beta ,\beta\sp\prime$-iminodipropionitrile. Various experiments in this study include time course of the metabolism of these nitriles to cyanide, thiocyanate, and cyanoacetic acid. All of the nitriles studied were metabolized to cyanide and thiocyanate and the levels of these metabolites remained at a significantly high level even 5 days after dosing. Except aminoacetonitrile all the nitriles were metabolized to cyanoacetic acid. Experiments on the role of vehicles on the toxicity and metabolism of nitriles showed that all of the vehicles studied significantly affected nitrile …

Quinine And Quinidine Inhibit K-Cl Cotransport In Low K Sheep Erythrocytes, Norma C. Adragna, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Reactive Oxygen-Dependent Dna Damage Resulting From The Oxidation Of Phenolic Compounds By A Copper-Redox Cycle Mechanism, Y. Li, M. A. Trush

Osteopathic Medicine, Jerry M. Wallace School of

No abstract provided.

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.

Risk Assessment For Developmental Toxicity: Airborne Occupational Exposure To Ethanol And Iodine, Donald R. Mattison

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

Dean Mattison explains hazard identification, hazard characterization and exposure characterization as furnishing a foundation for Risk assessment generally. He then illustrates their application in assessing the fetal Risk posed by two common substances. Ultimately, he argues that only after Risks have been so examined can women of child bearing age (or anyone) decide what if any measures are appropriate to avoid them.

Book Reviews, Thomas G. Field Jr.

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

Reviews of the following two books: VALUING HEALTH Risks. COSTS, AND BENEFITS FOR ENVIRONMENTAL DECISION MAKING (P. Brett Hammond and Rob Coppock, eds.) THE LIABILITY MAZE: THE IMPACT OF LIABILITY LAW ON SAFETY AND INNOVATION (Peter W. Huber And Robert E. Litan, eds.)

Fertile Women May Now Apply: Fetal Protection Policies After Johnson Controls, Barbara Ruhe Grumet

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

In its recent interpretation of Title VII of the Civil Rights Act, the U.S. Supreme Court leaves little room for permissible occupational sex discrimination. However, its decision has wider implications. Here, Professor Grumet takes a look at some of them from both a legal and a social perspective, including matters such as employees' reproductive freedom and employers' potential liability for a variety of possible injuries to employees' offspring.

Sodium Pump And Leaks In Cultured Vascular Endothelial Cells, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Effect Of Dietary Aluminum Sulfate On Calcium And Phosphorus Metabolism Of Broiler Chicks, Akmed S. Hussein, Austin H. Cantor, Thomas H. Johnson, Robert A. Yokel

Animal and Food Sciences Faculty Publications

The effect of dietary aluminum sulfate on Ca and P metabolism was studied using 1-day-oldmale broiler chicks. In Experiment 1, practical diets providing .90% Ca plus .45% available P (P_av), .90% Ca plus .78% P_av, 1.80% Ca plus .45% P_av, or 1.80% Ca plus .90% P_av were fed with 0 or .392% Al as aluminum sulfate for 21 days. The control diet (.90% Caplus .45% P_av) without added A1 was fed to all chicks during Days 22 to 49. In general, Al significantly (Pi), tibia breaking strength, tibia weight, percentage of …

Relationship Of Dietary Aluminum, Phosphorus, And Calcium To Phosphorus And Calcium Metabolism And Growth Performance Of Broiler Chicks, Akmed S. Hussein, Austin H. Cantor, Thomas H. Johnson, Robert A. Yokel

Animal and Food Sciences Faculty Publications

Dietary treatments providing three levels of added Al (0, .196, or .392%) as aluminum sulfate and of available phosphorus (P_av) (.45, .68, or .78%) in a factorial arrangement were administered to day-old chicks in Experiment 1. Plasma inorganic phosphorus (P_i) was significantly (P < .05) elevated by increasing P_av and was decreased by Al. Body weight gain, feed intake, and the gain:feed ratio at Day 21 were significantly decreased by increased concentrations of Al, but were unaffected by the P_av concentrations. Decreases of 39 and 73% in weight gain and of 34 and 66% in feed intake resulted from feeding …

Passive Cation Transport In Reversibly Sickling Deer Red Blood Cells, Norma C. Adragna, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

The Role Of Homeostatic Imbalance In The Reported Immunomodulation Of T-2 Toxin, Michael Jay Taylor

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

T-2 toxin (T-2), produced by the genus Fusarium, is a cytotoxic trichothecene mycotoxin, a feed contaminant, and has been shown to be immunomodulatory. It is suspected that T-2-associated immunomodulation is mediated partly through the hypothalamic-pituitary-adrenal axis. The presence of endotoxin, a bacterial product capable of activating the hypothalamic-pituitary-adrenal axis as well as the levels of several hormones, also associated with activation of the hypothalamic-pituitary-adrenal axis, were determined in both vehicle- and toxin-treated animals. Endotoxemia was evident twenty-four hours after a single oral exposure to T-2. Blood levels of adrenocorticotropic hormone and corticosterone, parameters of the stress response, also increased …

Policy For Identifying And Assessing The Health Risks Of Toxic Substances, Maine Bureau Of Health

Maine Collection

Policy for Identifying and Assessing the Health Risks of Toxic Substances

by Norman T. Anderson, Environmental Toxicology Program, Division of Disease Control, Bureau of Health (February, 1988).

Contents: Section I: Introduction / Section II: Methods / Section III: Exposure Assessment / Section IV: Hazard Identification / Section V: Hazard Assessment / Section VI: Risk Characterization / List of Figures / List of Tables

Kinetics Of Na/Li Exchange In High-K (Hk) And Low-K (Lk) Sheep Red Cells (Src), K. H. Ryu, Norma C. Adragna, D. Bradley, Peter K. Lauf

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Optimal Isolation Conditions For Ion-Transport Studies In Pig Aortic Endothelial-Cells, Norma C. Adragna

Pharmacology and Toxicology Faculty Publications

No abstract provided.