Medical Sciences Commons^™

Modulation Of The Bursting Properties Of Single Mouse Pancreatic Β-Cells By Artificial Conductances, T.A. Kinard, G. De Vries, A. Sherman, L. S. Satin

Pharmacology and Toxicology Publications

Abstract

Glucose triggers bursting activity in pancreatic islets, which mediates the Ca²⁺ uptake that triggers insulin secretion. Aside from the channel mechanism responsible for bursting, which remains unsettled, it is not clear whether bursting is an endogenous property of individual β-cells or requires an electrically coupled islet. While many workers report stochastic firing or quasibursting in single cells, a few reports describe single-cell bursts much longer (minutes) than those of islets (15–60 s). We studied the behavior of single cells systematically to help resolve this issue. Perforated patch recordings were made from single mouseβ-cells or hamster …

2,4-Disulfo Phenyl Butyl Nitrone, Its Salt And Their Use As Pharmaceuticals, John M. Carney

Pharmacology and Nutritional Sciences Faculty Patents

2,4-disulfonyl α-phenyl-tert-butyl nitrone and its pharmaceutically acceptable salts are disclosed. These materials are useful as pharmaceutical agents for oral or parenteral, e.g. intravenous administration to patients suffering from acute central nervous system oxidation as occurs in a stroke or from gradual central nervous system oxidation which can exhibit itself as progressive central nervous system function loss. The materials are also used to ameliorate the side effects of oxidative-damage causing antineoplastic disease treatments.

The Effect Of Systemic Doxycycline On Alveolar Bone Loss Following Periradicular Surgery, G. Reed Cummings

Loma Linda University Electronic Theses, Dissertations & Projects

Studies have shown an average of 0.5 mm to over 1.0 mm of bone loss following full thickness flap reflection. Recent investigations have revealed that the tetracycline family of antibiotics can prevent bone loss. The purpose of this study was to determine the effect of systemic Doxycycline on crestal alveolar bone loss following periradicular surgery in Beagle dogs.

The experiment was divided into two phases. The first phase served as the control (Non-Doxycycline), the second phase as the experiment (Doxycycline). Full thickness flaps were reflected in the mandibular left or right quadrant (control side) of five Beagle dogs. Using a …

Murine Transporter Associated With Antigen Presentation (Tap) Preferences Influence Class I-Restricted T Cell Responses., A J Yellen-Shaw, C E Laughlin, R M Metrione, Laurence C. Eisenlohr

Department of Biochemistry and Molecular Biology Faculty Papers

The transporter associated with antigen presentation (TAP) complex shuttles cytosolic peptides into the exocytic compartment for association with nascent major histocompatibility complex class I molecules. Biochemical studies of murine and human TAP have established that substrate length and COOH-terminal residue identity are strong determinants of transport efficiency. However, the existence of these specificities in the intact cell and their influences on T cell responses have not been demonstrated. We have devised a method for studying TAP- mediated transport in intact cells, using T cell activation as a readout. The approach makes use of a panel of recombinant vaccinia viruses expressing …

Spin Trapping Compounds, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing as the active ingredient a spin-trapping reagent, preferably α-phenyl butyl nitrone (PBN) or spin-trapping derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient are disclosed for treating or preventing symptoms associated with aging or other conditions associated with oxidative tissue damage. Other spin-trapping agents can also be used, such as 5,5-dimethyl pyrroline N-oxide (DMPO) or α-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), and other spin-trapping derivatives thereof. These compositions and methods are useful in the treatment of age-related disorders, pre-surgical and/or pre-anesthetic preparation or administration of chemotherapeutic agents, and in the treatment of disorders or trauma of the brain, …

Effect Of Long-Term Hypoxia On Myocardial Alpha1- Receptors, Bihong T. Chen

Loma Linda University Electronic Theses, Dissertations & Projects

To determine the developmental changes in myocardial α₁-adrenergic receptor system, we employed [³H-Prazosin] binding technique to characterize α₁-adrenergic receptors in both fetal and adult sheep myocardial ventricular membrane preparations. Myocardial α₁-adrenergic receptor density (Bmax) declined during developmental process with both fetal left ventricle(LV) and fetal right ventricle(RV) having significantly more binding sites than respective adult ventricles. We also demonstrated that the positive inotropic response to the α₁-adrenergic agonist phenylephrine did not differ significantly between the fetal and adult ventricles.

The present study also investigated the effect of long-term high-altitude hypoxemia …

Spin Trapping Pharmaceutical Compositions And Methods For Use Thereof, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Spin trapping compositions in general have now been discovered to be effective in treating a variety of disorders, including disorders such as those arising from ischemia, infection, inflammation, exposure to radiation or cytotoxic compounds, not just of the central and peripheral nervous systems but of peripheral organ disease having a wide variety of etiologies. In the preferred embodiment, the compositions for treating tissue damage from ischemia contain PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for intravenous, oral, topical, or nasal/pulmonary administration. Many different disorders can be treated using these compounds, including diseases or disorders of the central …

Method And Compositions For Treating Age Related Disorders, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing as the active ingredient a spin-trapping reagent, preferably α-phenyl butyl nitrone (PBN) or spin-trapping derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient are disclosed for treating or preventing symptoms associated with aging or other conditions associated with oxidative tissue damage. Other spin-trapping agents can also be used, such as 5,5-dimethyl pyrroline N-oxide (DMPO) or α-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), and other spin-trapping derivatives thereof. These compositions and methods are useful in the treatment of age-related disorders, pre-surgical and/or pre-anesthetic preparation or administration of chemotherapeutic agents, and in the treatment of disorders or trauma of the brain, …

Anion Induced Blue To Purple Transition In Bacteriorhodopsin, Mrunalini Pattarkine, Anil K. Singh

Faculty Works

Purple membrane (PM, λ" role="presentation">λmax" role="presentation">max 570 nm) of H. halobium on treatment with sulphuric acid changes its colour to blue (λ" role="presentation">λmax" role="presentation">max 608 nm). The purple chromophore can be regenerated from the blue chromophore by exogeneous addition of anions such as CI−" role="presentation">− and HPO42−" role="presentation">2−4. Chloride ion is found to be more effective than the dibasic phosphate ion in regenerating the purple chromophore. Nevertheless, one thing common to the anion regeneration is that both CI−" role="presentation">− and HPO42−" role="presentation">2−4 show marked pH effect. At pH 1.0 the efficiency of …

Phenylbutyl Nitrone Compositions And Methods For Prevention Of Gastric Ulceration, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient, are disclosed for treating or preventing gastric ulceration caused by ingestion of non-steroidal anti-inflammatories. Based on animal studies, the dosage is in the range of 3 to 300 mg/kg and is administered prior to, simultaneously, or shortly after ingestion of the NSAID compounds(s). In the preferred embodiment, the range is between 10 and 30 mg/kg, depending on the dosage unit required to protect the mucosa. The preferred method of administration is orally, alone or in combination with the non-steroidal anti-inflammatory. It is believed …

2,4-Disulfonyl Phenyl Butyl Nitrone, Its Salt And Their Use As Pharmaceuticals, John M. Carney

Pharmacology and Nutritional Sciences Faculty Patents

2,4-disulfonyl α-phenyl-tert-butyl nitrone and its pharmaceutically acceptable salts are disclosed. These materials are useful as pharmaceutical agents for oral or parenteral, e.g. intravenous administration to patients suffering from acute central nervous system oxidation as occurs in a stroke or from gradual central nervous system oxidation which can exhibit itself as progressive central nervous system function loss. The materials are also used to ameliorate the side effects of oxidative-damage causing antineoplastic disease treatments.

2,4-Disulfonyl Phenyl Butyl Nitrone, Its Salt And Their Use As Pharmaceuticals Free Radical Traps, John M. Carney

Pharmacology and Nutritional Sciences Faculty Patents

2,4-disulfonyl α-phenyl-tert-butyl nitrone and its pharmaceutically acceptable salts are disclosed. These materials are useful as pharmaceutical agents for oral or intravenous administration to patients suffering from acute central nervous system oxidation as occurs in a stroke or from gradual central nervous system oxidation which can exhibit itself as progressive central nervous system function loss.

2,4-Disulfonyl Phenyl Butyl Nitrone, Its Salt And Their Use As Pharmaceuticals, John M. Carney

Pharmacology and Nutritional Sciences Faculty Patents

2,4-disulfonyl α-phenyl-tert-butyl nitrone and its pharmaceutically acceptable salts are disclosed. These materials are useful as pharmaceutical agents for oral or parenteral, e.g. intravenous administration to patients suffering from acute central nervous system oxidation as occurs in a stroke or from gradual central nervous system oxidation which can exhibit itself as progressive central nervous system function loss. The materials are also used to ameliorate the side effects of oxidative-damage causing antineoplastic disease treatments.

Phenyl Butyl Nitrone Compositions And Methods For Treatment Of Oxidative Tissue Damage, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions for treating tissue damage from ischemia contain PBN, or active derivatives thereof, which are active during ischemia in preventing ATP depletion of the cells which predisposes them to subsequent injury during reperfusion, and which are active during reperfusion as oxygen radical scavengers, in a suitable pharmaceutical carrier for systemic or local administration, especially to the CNS, spinal column and eyes. Based on animal studies, the dosage for treating damage due to stroke is in the range of 10 to 300 mg/kg. Similar dosages are useful in treating damage resulting from free radical generation during inflammation, either as a product …

Pbn, Dmpo, And Pobn Compositions And Method Of Use Thereof For Inhibition Of Age-Associated Oxidation, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing as the active ingredient a spin-trapping reagent, preferably α-phenyl butyl nitrone (PBN) or spin-trapping derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient are disclosed for treating or preventin symptoms associated with aging or other conditions associated with oxidative tissue damage. Other spin-trapping agents can also be used, such as 5,5-dimethyl pyrroline N-oxide (DMPO) or α-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), and other spin-trapping derivatives thereof. These compositions and methods are useful in the treatment of age-related disorders, pre-surgical and/or pre-anesthetic preparation or administration of chemotherapeutic agents, and in the treatment of disorders or trauma of the brain, …

Pharmacokinetics And Pharmacodynamics Of Recombinant Hirudin Variant 2 (Rhv2) In Animal Models, Lalitha Iyer

Dissertations

No abstract provided.

Inactivation Of Hit Cell Ca2+ Current By A Simulated Burst Of Ca2+ Action Potentials, L. S. Satin, S. J. Tavalin, P. D. Smolen

Pharmacology and Toxicology Publications

ABSTRACT A novel voltage-clamp protocol was developed to test whether slow inactivation of Ca2+ current occurs during bursting in insulin-secreting cells. Single insulin-secreting HIT cells were patch-clamped and their Ca2+ currents were isolated pharmacologically. A computed ,3-cell burst was used as a voltage-clamp command and the net Ca2+ current elicited was determined as a cadmium difference current. Ca2+ current rapidly activated during the computed plateau and spike depolarizations and then slowly decayed. Integration of this Ca2+ current yielded an estimate of total Ca influx. To further analyze Ca2+ current inactivation during a burst, repetitive test pulses to + 10 mV …

Phenylbutyl Nitrone Compositions And Methods For Prevention Of Gastric Ulceration, Robert A. Floyd, John M. Carney

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient, are disclosed for treating or preventing gastric ulceration caused by ingestion of non-steroidal anti-inflammatories. Based on animal studies, the dosage is in the range of 3 to 300 mg/kg and is administered prior to, simultaneously, or shortly after ingestion of the NSAID compound(s). In the preferred embodiment, the range is between 10 and 30 mg/kg, depending on the dosage unit required to protect the mucosa. The preferred method of administration is orally, alone or in combination with the non-steroidal anti-inflammatory. It is believed …

Phenyl Butyl Nitrone Compositions And Methods For Treatment Of Oxidative Tissue Damage, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions for treating tissue damage from ischemia contain PBN, or active derivatives thereof, which are active during ischemia in preventing ATP depletion of the cells which predisposes them to subsequent injury during reperfusion, and which are active during reperfusion as oxygen radical scavengers, in a suitable pharmaceutical carrier for systemic or local administration, especially to the CNS, spinal column and eyes. Based on animal studies, the dosage for treating damage due to stroke is in the range of 10 to 300 mg/kg. Similar dosages are useful in treating damage resulting from free radical generation during inflammation, either as a product …

7li Nmr Of Normal Human Erythrocytes, Rao P. Gullapalli, Roger M. Hawk, Richard A. Komoroski

Journal of the Arkansas Academy of Science

Lithium has been known to be an effective medication for people with bipolar disorder. The mechanisms of action of lithium in the brain is not very well understood. NMR spectroscopy and imaging are effective both in determining lithium levels in tissue and brain. We have monitored lithium levels in red blood cells. We have been able to separate intra- and extracellular compartments of lithium using shift reagents, thereby obtaining T^1 's of both the compartments. Lithium uptake as a function of hematocrit was monitored weekly over a 3 week period. The time constant of 50 mM lithium uptake at 25°C …

Camp Antagonizes Interleukin 2-Promoted T-Cell Cycle Progression At A Discrete Point In Early G1., Kirk W. Johnson, Bruce H. Davis, Kendall A. Smith

Dartmouth Scholarship

T lymphocytes are stimulated to proliferate in an autocrine/paracrine manner by the lymphokine interleukin 2 (IL-2). In seeking further insight into the mechanisms by which IL-2 induces progression of T cells through the G1 phase of the cell cycle, studies were performed with agents that increase cellular adenosine 3',5'-cyclic monophosphate (cAMP), a well-known inhibitor of lymphocyte growth. The addition of dibutyryl-cAMP, cholera toxin, forskolin, or 3-isobutyl-1-methylxanthine to an IL-2-dependent murine T-cell line evoked a dose-related suppression of S-phase transition without affecting cellular viability. Moreover, elevation of cAMP levels led to an accumulation of uniformly small cells, suggesting an arrest in …

Phloretin And Phlorizin Derivative Containing Compounds, Donald F. Diedrich, Susanne L. Diedrich

Pharmacology and Nutritional Sciences Faculty Patents

Compounds including phloretin and/or phlorizin derivatives coupled to an undigestible and non-absorbable matrix are provided. The compounds have pharmacological efficacies. They inhibit sugar uptake from the intestine and may be used in composition form in methods for treating diabetes and for promoting weight loss. A method for the manufacture of these compounds and a novel intermediate phlorizin derivative for making these compounds are also disclosed.

Neurokinin Regulation Of Midbrain Raphe Neurons: A Behavioral And Anatomical Study, Joseph Paris

Dissertations

No abstract provided.

Compositions And Method Of Treatment For Sickle Cell Anemia, Donald F. Diedrich, Christopher L. Maynard

Pharmacology and Nutritional Sciences Faculty Patents

The invention provides a new composition and method for the treatment of sickle cell anemia. . . .

To see the remainder of this abstract, please download this patent.

The Role Of The Central Nervous System In The Hypotensive Action Of Atenolol, Amy Kathryn Adams

MUSC Theses and Dissertations

The contribution of the central nervous system to the hypotensive action of atenolol was examined in spontaneously hypertensive rats and normotensive dogs. In the rat, atenolol produced a hypotensive response which was stereoselective for the ��-isomer after both central and peripheral administration. In addition, 10 µg ��-atenolol administered intra-cisternally produced a hypotensive response not observed after intravenous administration of the same dose. The hypotensive action of atenolol was further examined using a method developed for the quantita­tion of atenolol in plasma and cerebrospinal fluid (CSF) of dogs. Atenolol rapidly entered the CSF after intravenous administration, producing a hypotensive response in …

Regulation Of Luteinizing Hormone And Catecholamine Release, Benjamin Aaron Adler

Theses and Dissertations (ETD)

These studies tested the interrelated hypotheses that the ovarian hormones produce their positive feedback effects on luteinizing hormone (LH) secretion through activation of noradrenergic and adrenergic systems in specific hypothalamic regions. Furthermore, the ovarian hormones may alter the activity of opioid neuropeptide and Gamma-Aminobutyric Acid (GABA) systems to produce these alterations in catecholamine transmission and gonadotropin secretion. Radioimmunoassays were utilized to determine plasma LH and median eminence LHRH, and hypothalamic catecholamine concentrations were measured by radioenzymatic assay.

The first two studies tested whether epinephrine (EPI) synthesis inhibition blocks the accumulation of median eminence LHRH that precedes the ovarian hormone-induced LH …

Interferon Gamma Blocks The Growth Of Toxoplasma Gondii In Human Fibroblasts By Inducing The Host Cells To Degrade Tryptophan., E. R. Pfefferkorn

Dartmouth Scholarship

Treatment of human fibroblasts with human recombinant gamma interferon blocked the growth of Toxoplasma gondii, an obligate intracellular protozoan parasite. Growth of the parasite was measured by a plaque assay 7 days after infection or by the incorporation of [3H]uracil 1 or 2 days after infection. The antitoxoplasma activity induced in the host cells by gamma interferon was strongly dependent upon the tryptophan concentration of the medium. Progressively higher minimal inhibitory concentrations of gamma interferon were observed as the tryptophan concentration in the culture medium was increased. Treatment with gamma interferon did not make the cells impermeable to tryptophan. The …

Studies Of The Depolarization-Induced Release Of Beta Adrenergic Receptor Blocking Drugs From In Vitro Neural Preparations, Patricia Sherwood Bright

MUSC Theses and Dissertations

The objective of this study was to evaluate the hypothesis that nerve terminals may serve as a site for storage and release of beta adrenergic receptor blocking drugs. Experiments were conducted with two different in vitro neural preparations, cultured superior cervical ganglia from adult rats and synaptosomes prepared from rat cerebral cortex. The release of propranolol by depolarizing stimuli was examined and compared with the release of the more hydrophilic, cardioselective beta receptor antagonist atenolol. In both neuronal models, norepinephrine release was monitored as an index of exocytosis. Cultured superior cervical ganglia of the rat represent an in vitro model …

Physiology And Pharmacology: 1905-1977; Physiology: 1977-1983, Helge Ellis Ederstrom, Stanley J. Brumleve

UND Departmental Histories

This departmental history was written on the occasion of the UND Centennial in 1983.

Effects Of The Serotonin Depletor Parachlorophenylalanine Upon Shock-Induced Aggression And Pressing Responses In Rats, Robert G. Sewell

Masters Theses

The literature concerning the effects of d, l-parachlorophenylalanine (PCPA) upon shock-induced aggression (SIA) is reviewed and found to be inconsistent. PCPA, a known serotonin depletor, has behavioral effects in a variety of other procedures which collectively suggest that PCPA should produce SIA enhancement. The present study was designed to analyze PCPA (300 mg/kg) effects upon SIA in rats restrained spatially close to an inanimate target and panel operandum. The results showed marked increases in both aggressive biting and panel pressing for several days following each PCPA treatment for each subject tested. These data were interpreted to indicate that serotonin depletion …