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Examination Of Nucleoside Transport In The Mammalian Nervous System, Kenneth William Jones
Examination Of Nucleoside Transport In The Mammalian Nervous System, Kenneth William Jones
Digitized Theses
In rabbit and guinea pig cortical synaptosomes, the nucleoside transport inhibitors nitrobenzylthioinosine and dipyridamole were used to test the hypotheses that the nitrobenzylthioinosine-sensitive and -resistant ({dollar}\sp3{dollar}H) dipyridamole binding sites are associated with the es and ei nucleoside transporters, respectively. In addition, the hypothesis that the es and ei nucleoside transporters in rabbit cortical synaptosomes differ in their selectivity for compounds besides nitrobenzylthioinosine was tested, Nitrobenzylthioinosine-sensitive ({dollar}\sp3{dollar}H) dipyridamole binding and ({dollar}\sp3{dollar}H) nitrobenzylthioinosine binding involved the same site on the es transporter. The relative proportions and inhibitor sensitivities of nitrobenzylthioinosine-resistant ({dollar}\sp3{dollar}H) dipyridamole binding could not be correlated with nitrobenzylthioinosine-resistant nucleoside transport. This, …
Postsynaptic Cholinergic Control Of Cardiac Function In Aging, Na Su
Postsynaptic Cholinergic Control Of Cardiac Function In Aging, Na Su
Digitized Theses
The present study using isolated constant flow-perfused heart from adult (8 month-old) and aged (26 month-old) Fischer 344 rats for the first time demonstrated a striking enhancement of the negative chronotropic, inotropic and coronary vasoconstriction responses of the aging heart to postsynaptic cholinergic stimulation.;The approaches used and the results demonstrated were the following. (i) Acetylcholinesterase activity measured by the method of Ellman et al (1961) declined significantly in the atria and ventricles of the aged compared to adult rats. (ii) No age-related difference was seen in muscarinic receptor number in the atria and ventricles as assessed by {dollar}\lbrack\sp3\rm H\rbrack QNB{dollar} …
Role Of Protein Kinase C In Mediating The Effects Of Physiological And Pathophysiological Interventions In The Heart, Christopher Andrew Ward
Role Of Protein Kinase C In Mediating The Effects Of Physiological And Pathophysiological Interventions In The Heart, Christopher Andrew Ward
Digitized Theses
Protein kinase C has been implicated as a mediator of myocardial function following both physiological and pathophysiological stimuli. The purpose of the present study was to examine the functional effects of PKC in mediating phorbol esters as well as receptor-induced effects in myocardial tissues. Additionally, the possible role of PKC in mediating cardiac pathophysiology was assessed under conditions which mimicked aspects of myocardial ischemia/reperfusion. The effects of phorbol esters on cardiac function were assessed in isolated perfused guinea pig hearts. The effects of phorbol esters, acidosis/realkalinization and hydrogen peroxide were assessed in isolated guinea pig ventricular myocytes to determine PKC-dependent …
Comparative Studies Of The Effects Of Menogaril And Adriamycin On Cell Morphology And Membrane Function Of Parental And Multidrug Resistant Cells, Stewart E. Daly
Comparative Studies Of The Effects Of Menogaril And Adriamycin On Cell Morphology And Membrane Function Of Parental And Multidrug Resistant Cells, Stewart E. Daly
Digitized Theses
This project was initiated to obtain a better understanding of the cellular mode of action of the anthracycline drug menogaril. Comparative experiments demonstrated that menogaril was as cytotoxic as adriamycin against parental AUX B1 Chinese hamster ovary cells (CHO), however, multidrug resistant (MDR) CH{dollar}\sp{lcub}\rm R{rcub}{dollar}C5 CHO cells, which are characterized by the overexpression of P-glycoprotein relative to the parental cells, were less resistant to menogaril. When parental and MDR cells were exposed to equitoxic concentrations of both drugs, menogaril accumulated to a higher level, however, both drugs accumulated to a significantly higher level in the MDR cells. Immediately after exposure …
Isozyme-Selective, Lung-Selective Mechanism-Based Inhibitors Of Cytochrome P-450 And Determination Of P450 Isozyme Specificity For Arachidonic Acid Metabolism, Leah Christine Knickle
Isozyme-Selective, Lung-Selective Mechanism-Based Inhibitors Of Cytochrome P-450 And Determination Of P450 Isozyme Specificity For Arachidonic Acid Metabolism, Leah Christine Knickle
Digitized Theses
1-Aminobenzotriazole (ABT) and its N-benzyl (BBT) and N-{dollar}\alpha{dollar}-methylbenzyl ({dollar}\alpha{dollar}MB) derivatives were compared as isozyme-selective, lung-selective (vs liver) mechanism-based inhibitors of P450 in guinea pigs 4 hr following i.v. administration. Monooxygenase activities selective for guinea pig orthologues of rabbit P450 1A1, 2B4 and 4B1 (1A1, 2Bx and 4Bx, respectively) were determined in pulmonary and hepatic microsomes. BBT and {dollar}\alpha{dollar}MB inactivated pulmonary P450 in an isozyme-selective manner. In non-induced and phenobarbital-induced animals the order of inactivation was 2Bx {dollar}>{dollar} 1A1 {dollar}>>>>{dollar} 4Bx whereas in {dollar}\beta{dollar}-naphthoflavone-induced animals {dollar}\alpha{dollar}MB specifically inhibited 2Bx. BBT and {dollar}\alpha{dollar}MB were also highly selective for the inactivation …
An In Vitro Examination Of Surface Tension Reduction By Pulmonary Surfactant In The Presence And Absence Of Inhibitory Agents, Amanda M. Cockshutt
An In Vitro Examination Of Surface Tension Reduction By Pulmonary Surfactant In The Presence And Absence Of Inhibitory Agents, Amanda M. Cockshutt
Digitized Theses
The surface activity of Lipid Extract Surfactant (LES), a clinical preparation used for the treatment of Neonatal Respiratory Distress Syndrome, and the effects of addition of surfactant-associated protein A (SP-A) and palmitic acid were assayed in vitro in the presence and absence of challenge by inhibitory agents. Measurements of surface activity were made with the pulsating bubble surfactometer and the captive bubble technique. The addition of SP-A to LES enhances the surface activity of the preparation, especially at low surfactant concentrations. SP-A accelerates the adsorption of surfactant lipids from the aqueous subphase to the air-liquid interface and causes enrichment of …
Role Of Metallothionein In Chemical Toxicity Mediated By Reactive Intermediates Generated From Xenobiotic And Oxygen Metabolism, Zacharias Emmanuel Suntres
Role Of Metallothionein In Chemical Toxicity Mediated By Reactive Intermediates Generated From Xenobiotic And Oxygen Metabolism, Zacharias Emmanuel Suntres
Digitized Theses
This research was concerned with the role of metallothionein (MT) in chemical toxicity mediated by reactive intermediates generated from xenobiotic and oxygen metabolism. Metallothionein(s) are ubiquitous, low molecular weight, cysteine-rich (30% of total amino acids), metal binding proteins. These proteins have been shown to be important in the regulation of essential metal metabolism and in the detoxication of toxic metals. In the present research it was hypothesized that (i) because of its high cysteinyl thiolate concentration, MT is reactive towards intermediates generated from xenobiotic metabolism; and (ii) the metal (Zn, Cu) released from MT concomitant with the inactivation of metal …
The Effects Of High Pressures Of Inert Gases And Of Anaesthetics On Rat Striatal Dopamine In Vitro, Margaret Lorraine Paul
The Effects Of High Pressures Of Inert Gases And Of Anaesthetics On Rat Striatal Dopamine In Vitro, Margaret Lorraine Paul
Digitized Theses
Operational deep-sea diving is complicated by two conditions affecting the Central Nervous System. One of these, known as Inert Gas Narcosis (IGN), is due to the presence of nitrogen (N{dollar}\sb2{dollar}) in the breathing gas, and presents signs and symptoms of progressive CNS depression similar to anaesthesia as pressure (depth) is increased. The other, referred to as the High Pressure Neurological Syndrome (HPNS) was observed when non-narcotic helium (He) was substituted for N{dollar}\sb2{dollar} to circumvent the problem of IGN. The effects are attributed to pressure per se and include, in man, tremor, EEG changes, and motor incoordination. The precise neurological changes …
Studies On Adenosine-Mediated Neuromodulation In The Enteric Nervous System, Fedias Leontiou Christofi
Studies On Adenosine-Mediated Neuromodulation In The Enteric Nervous System, Fedias Leontiou Christofi
Digitized Theses
Although the role of adenosine in the inhibition of acetylcholine release from myenteric neurons of the small intestine is firmly established, the classification and characteristics of such receptors have not been adequately described. Unlike in the central nervous system, it is not clear if heterogeneity of adenosine receptors exists, or if nucleoside-mediated inhibition of the release of other neuromediators occurs in the enteric nervous system. The studies reported in this thesis were directed at these questions.;Adenosine recognition sites were characterized in ligand binding studies at purified myenteric varicosities. The receptor nature of the binding sites labelled by selective adenosine analogs …
Investigations Of The Mechanism Of Alcohol-Induced Cardiomyopathy, David Christopher King
Investigations Of The Mechanism Of Alcohol-Induced Cardiomyopathy, David Christopher King
Digitized Theses
Investigations into the mechanism of severe, subacute ethanol induced cardiomyopathy in the rat were performed in animals that were severely intoxicated for 48 hours. This treatment produced increases in cardiac wet weight, dry weight and protein content. Determination of cardiac DNA content and water content showed that the increase in heart size resulted from hypertrophy and not hyperplasia nor edema.;In a time effect study of intracellular events it was found that cardiac ornithine decarboxylase activity was enhanced after eight hours of intoxication and remained elevated through 24 hours. RNA content was elevated by eight hours and remained high through the …
Investigation Of The Mechanism Of Contraction Of The Isolated Guinea Pig Pulmonary Venule Induced By Hypoxia Or Anoxia, Wayne Ross Tracey
Investigation Of The Mechanism Of Contraction Of The Isolated Guinea Pig Pulmonary Venule Induced By Hypoxia Or Anoxia, Wayne Ross Tracey
Digitized Theses
Since small pulmonary arteries are thought to be the major site of hypoxic pulmonary vasoconstriction (HPV), the response of pulmonary veins to hypoxia has not been thoroughly investigated. Therefore, the response of isolated guinea-pig pulmonary venules to hypoxia (bath Po{dollar}\sb2{dollar}: 25 torr) and anoxia (bath Po{dollar}\sb2{dollar}: 0 torr) was characterized. Pulmonary venules (effective lumen radius (ELR): 119 {dollar}\pm{dollar} 1 {dollar}\mu{dollar}m) responded to hypoxia and anoxia with a graded, sustained, and repeatable contraction (hypoxia: 3 {dollar}\pm{dollar} 1 mg/mm; anoxia: 27 {dollar}\pm{dollar} 3 mg/mm), while paired femoral venules (ELR: 184 {dollar}\pm{dollar} 7 {dollar}\mu{dollar}m) contracted to the initial anoxic challenge only (5 {dollar}\pm{dollar} …
Studies On The Factors Affecting The Renal Toxicity Of Cadmium Metallothionein And Cis-Diamminedichloroplatinum, Catherine Ann Suzuki
Studies On The Factors Affecting The Renal Toxicity Of Cadmium Metallothionein And Cis-Diamminedichloroplatinum, Catherine Ann Suzuki
Digitized Theses
The critical organ of toxicity after chronic cadmium (Cd) exposure is the kidney. This toxicity can be modified by intracellular interactions of Cd with metallothionein (MT) or glutathione (GSH). Since the Cd-bound form of MT (Cd-MT) is a potent nephrotoxic agent, Cd-MT was used as a model for investigations of Cd-induced renal disease.;After Cd-MT injection in rats, urinary enzymes were used as subcellular markers of renal damage. The maximal excretion of two brush border membrane (BBM) enzymes preceded the maximal excretion of a lysosomal enzyme indicating early damage to the BBM with subsequent lysosomal damage. Pretreatment with zinc (Zn) increased …
Amiodarone Toxicity: Relationships To Cumulative Dose And Serum Drug Concentrations With Preliminary Observations Of Changes In Superoxide Dismutase Activity, Paul Timothy Pollak
Amiodarone Toxicity: Relationships To Cumulative Dose And Serum Drug Concentrations With Preliminary Observations Of Changes In Superoxide Dismutase Activity, Paul Timothy Pollak
Digitized Theses
Amiodarone, a cardiac antiarrhythmic agent, provides greater efficacy, more convenient dosing, and produces fewer acute adverse effects than most other antiarrhythmic agents. Toxic effects do occur during chronic therapy, of which pulmonary fibrosis is the most serious. Relationships between adverse effects, serum drug concentrations and administered dose are not yet well understood. Lamellar inclusions observed in the lung with amiodarone pulmonary toxicity resemble those from damage by superoxide free radicals in paraquat-induced pulmonary fibrosis. Observation of superoxide dismutase (SOD) activity in patients receiving amiodarone was considered a possible source of preliminary evidence that amiodarone alters free radical metabolism. A liquid …
Some Studies Of Interactions At Biological Surfaces, Donald John Mciver
Some Studies Of Interactions At Biological Surfaces, Donald John Mciver
Digitized Theses
Interactions between biological surfaces are central events in a wide variety of biological processes, including ligand-receptor binding, adsorption of molecules from suspension onto interfaces, and adhesive interactions between whole cells or subcellular particles. Despite the chemical diversity of these reactions--for example, the wide range of ligand structures and binding behaviour--it is believed that the underlying physicochemical forces do not differ between all of these surface phenomena.;In this study, an approach based on classical equilibrium capillarity has been adapted to estimate the magnitude of the macroscopically observable resultant of these surface forces (the surface affinity or work of adhesion) between several …
Studies On The Effects Of Centrally Acting Drugs At Increased Pressures Of Air, G D. Fields
Studies On The Effects Of Centrally Acting Drugs At Increased Pressures Of Air, G D. Fields
Digitized Theses
This thesis examined the effect of selected "stimulant" and "depressant" drugs in mice and humans at increased pressures (4 and 7 ata) of air.;In mice, hyperbaric air acted to reduce amphetamine sulphate induced convulsive activity, lethality, and stereotyped licking/biting; in contrast, the locomotor stimulation was enhanced as was that produced by morphine suphate (15 and 30 mg/kg). With regard to the depressants, 7 ata air prolonged the sleep time induced by pentobarbital (45 mg/kg) but had no effect at the lower dose (35 mg/kg). Conversely exposure to hyperbaric air reduced the diphenhydramine (10, 20 mg/kg) - induced depression of activity, …
The Development Of Cardiac Hypertrophy During Sub-Chronic Ethanol Intoxication: The Role Of Adrenal Medullary Catecholamines, Michael Anthony Adams
The Development Of Cardiac Hypertrophy During Sub-Chronic Ethanol Intoxication: The Role Of Adrenal Medullary Catecholamines, Michael Anthony Adams
Digitized Theses
The development of cardiac hypertrophy and other changes were examined during sub-chronic ethanol intoxication in Sprague-Dawley rats. Several experimental manipulations were evaluated: adrenal medullectomy, peripheral sympathectomy and the administration of adrenergic antagonists, prazosin and metoprolol. Ethanol, given by gavage every eight hours for up to 96 hours, maintained the rats in an ataxic state. It was found that adrenal cortical tissue hypertrophied after ethanol exposure. The release of adrenal medullary catecholamines was stimulated, producing a decline in contents, particularly of adrenaline, which was reflected in elevations in urinary catecholamines. Cardiac noradrenaline levels were reduced. These changes were paralleled by cardiac …
Effects Of Opiates And Opioid Peptides In The Hypothalamus On Feeding And Temperature In The Rat, Fern Sheila Tepperman
Effects Of Opiates And Opioid Peptides In The Hypothalamus On Feeding And Temperature In The Rat, Fern Sheila Tepperman
Digitized Theses
Opiates were administered to the ventromedial hypothalamus (VMH), a brain site associated with feeding regulation, to provide some indication of the central component of opiate-induced feeding. The objectives of the investigation were to establish whether opiates given into the VMH could elicit dose-dependent feeding at stereospecific receptors, how this effect is mediated and whether changes in feeding and core temperature are interdependent. Also, feeding following injection of morphine into various brain sites was examined.;Male Sprague-Dawley rats were implanted stereotaxically with cannulae, and feeding and core temperature were monitored.;Injection of the opiates morphine and levorphanol and the quaternary opiate morphine methiodide …
Studies Of The Pharmacological Effects Of Benzoic Acid Analogs On Thrombosis And Inflammation, John Joseph Killackey
Studies Of The Pharmacological Effects Of Benzoic Acid Analogs On Thrombosis And Inflammation, John Joseph Killackey
Digitized Theses
Previous work in this laboratory demonstrated that a series of benzoic acid analogs, with only minor structural variations compared to ASA, displayed a wide variation in biological effects compared to ASA. The compounds studied include 2-propionyloxybenzoic acid (2-PBA), 3-propionyloxybenzoic acid (3-PBA), 2-acetylbenzoic acid (ABA), 3-methylphthalide (3-MP) and 3-hydroperoxy-3-methylphthalide (3HMP). The purpose of this study was to extend our knowledge of the effects of these compounds and the processes they modify by assessing the in vivo antithrombotic and anti-inflammatory activities and the inhibition of prostaglandin (PG) synthesis (including PGI(,2)) in related in vitro systems. The ultimate aim of this work is …
An Analysis Of Non-Adrenergic (Purinergic) Inhibitory Control Of The Mammalian Gastrointestinal Tract, Francis Kanayo Okwuasaba
An Analysis Of Non-Adrenergic (Purinergic) Inhibitory Control Of The Mammalian Gastrointestinal Tract, Francis Kanayo Okwuasaba
Digitized Theses
No abstract provided.
Comparison Of Actions And Interactions Of Dopamine-Based Isoquinolines And Their Noncyclized Progenitors, Alice Mary Marshall
Comparison Of Actions And Interactions Of Dopamine-Based Isoquinolines And Their Noncyclized Progenitors, Alice Mary Marshall
Digitized Theses
No abstract provided.
Disruptions Of Core Temperature And Feeding Responses In Rats By Narcotic Analgesics And Other Centrally-Acting Drugs, James Arthur Thornhill
Disruptions Of Core Temperature And Feeding Responses In Rats By Narcotic Analgesics And Other Centrally-Acting Drugs, James Arthur Thornhill
Digitized Theses
No abstract provided.
Effects Of Allopurinol On Platelet Function In Man And Experimental Animals, Richard Albert Wildeman
Effects Of Allopurinol On Platelet Function In Man And Experimental Animals, Richard Albert Wildeman
Digitized Theses
No abstract provided.
The Effect Of Decompression From Raised Pressures On Blood Enzymes And Hematology, David John Freeman
The Effect Of Decompression From Raised Pressures On Blood Enzymes And Hematology, David John Freeman
Digitized Theses
No abstract provided.
Toxicity And Related Pharmacological Action Of Acetylcholine Mustard, John Gilbert Clement
Toxicity And Related Pharmacological Action Of Acetylcholine Mustard, John Gilbert Clement
Digitized Theses
No abstract provided.
The Effects Of Some Salicylate Analogues On Human Blood Platelet Function, Donald Grant Mills
The Effects Of Some Salicylate Analogues On Human Blood Platelet Function, Donald Grant Mills
Digitized Theses
No abstract provided.
Effects Of Analgesics On Centrally-Induced "Pain" In Rats, Thea Christa Dubas
Effects Of Analgesics On Centrally-Induced "Pain" In Rats, Thea Christa Dubas
Digitized Theses
No abstract provided.
Reversal Of Neuromuscular Blockade By Exchanging Potassium Ions By Cesium Ions In The Isolated Rat Phrenic Nerve-Diaphragm Preparation, Andrew George Korey
Reversal Of Neuromuscular Blockade By Exchanging Potassium Ions By Cesium Ions In The Isolated Rat Phrenic Nerve-Diaphragm Preparation, Andrew George Korey
Digitized Theses
No abstract provided.
Pharmacological Actions Of A Mustard Derivative Of Acetylcholine, Clarence Harold Jackson
Pharmacological Actions Of A Mustard Derivative Of Acetylcholine, Clarence Harold Jackson
Digitized Theses
No abstract provided.
The Effects Of Cholinergic Drugs On Operant Behavior Of The Rat, William Arthur Mckim
The Effects Of Cholinergic Drugs On Operant Behavior Of The Rat, William Arthur Mckim
Digitized Theses
No abstract provided.
The Influence Of Beta-Adrenergic Receptor Blocking Agents In Experimental Coronary Occlusion In Conscious Dogs, Maidul Islam Khan
The Influence Of Beta-Adrenergic Receptor Blocking Agents In Experimental Coronary Occlusion In Conscious Dogs, Maidul Islam Khan
Digitized Theses
No abstract provided.