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Articles 1 - 9 of 9
Full-Text Articles in Medical Pharmacology
Kras-Independent Factors Drive Pi3k Signaling And Circumvent The Necessity Of Kras-Driven Pi3k Activation In Pdac, Lucas Christopher Bialousow
Kras-Independent Factors Drive Pi3k Signaling And Circumvent The Necessity Of Kras-Driven Pi3k Activation In Pdac, Lucas Christopher Bialousow
MUSC Theses and Dissertations
Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest five-year survival rates among cancers and is characterized by near-ubiquitous occurrence of oncogenic KRAS mutations. Oncogenic KRAS activates several downstream pathways, including ERK 1/2 MAPK and PI3K, which are critical for PDAC. However, accumulating evidence suggests that PI3K activity can be maintained independent of oncogenic KRAS. The high prevalence of KRASG12R in PDAC challenges the prevailing model of KRAS-driven PI3K activation, as this mutant is defective in direct engagement with PI3Kα. These observations raise important questions regarding how PI3K signaling is sustained in PDAC. Here, we investigated KRAS-independent mechanisms that …
Ethanol Interactions With Dl-Methylphenidate Versus D-Methylphenidate In Humans, Owen Reeves
Ethanol Interactions With Dl-Methylphenidate Versus D-Methylphenidate In Humans, Owen Reeves
MUSC Theses and Dissertations
Adult Attention-Deficit/Hyperactivity Disorder (ADHD) affects~ 4.4% of the adult population, and patients with this disorder frequently have comorbid substance abuse disorders. Methylphenidate (MPH) is considered a first line pharmacotherapy agent in the treatment of ADHD, and is commonly used or co-abused with alcohol. Hydrolysis of oral racemic methylphenidate (dl-MPH) by carboxylesterase 1 (CES1) limits the bioavailability of the pharmacologically active d-MPH isomer to approximately 30% and that of the inactive 1-MPH isomer to only 1-2%. Co-administration of dl-MPH with ethanol results in elevated d-MPH plasma concentrations, as well as CES1 mediated enantioselective transesterification of 1-MPH to 1-ethylphenidate (EPH). The present …
Transdermal And Oral Dl-Methylphenidate-Ethanol Interactions In C57bl/6j Mice, Guinevere Hannah Bell
Transdermal And Oral Dl-Methylphenidate-Ethanol Interactions In C57bl/6j Mice, Guinevere Hannah Bell
MUSC Theses and Dissertations
The persistence of attention-deficit/hyperactivity disorder (ADHO) into adulthood has been increasingly recognized over the past few decades and the stimulant drug dl-methylphenidate (MPH) has remained a first-line pharmacotherapeutic agent in the treatment of ADHD. Many adult ADHD patients who are prescribed MPH report concomitant use with ethanol. In humans, coadministration of dl-MPH and ethanol results in pharmacokinetic and pharmacodynamic drug - drug interactions. Ethanol elevates biological concentrations of the pharmacologically active d-MPH isomer and yields the metabolic transesterification product ethylphenidate (EPH). EPH appears to be formed through the actions of carboxylesterase 1 (CES1) which exhibits I-MPH substrate enantioselectivity in both …
Effect Of Genetic Variation On The Formation Of Hepatocarcinogenic Metabolites Of Trichloroethylene Using Chloral Hydrate Studies (An Interdisciplinary Approach), Apryl Bronley-Delancey
Effect Of Genetic Variation On The Formation Of Hepatocarcinogenic Metabolites Of Trichloroethylene Using Chloral Hydrate Studies (An Interdisciplinary Approach), Apryl Bronley-Delancey
MUSC Theses and Dissertations
Trichloroethylene (TCE) is listed with the EPA as a suspected human carcinogen and is ubiquitous in the environment (US EPA 1992). Chloral hydrate (CH) is a sedative drug and a cytochrome P450 (CYP 450)-derived metabolite of TCE (Klaassen 2001). Chloral hydrate is metabolized in the liver to the rodent hepatocarcinogen trichloroacetate (TCA) by aldehyde dehydrogenase (ALDH), and to the non-carcinogenic metabolite trichloroethanol (TCEOH) by alcohol dehydrogenase (ADH) (Klaassen 2001). Both ALDH and ADH are polymorphic in humans which can presumably predict the disposition of chloral hydrate into the carcinogenic vs. non-carcinogenic pathways. The likelihood is then raised that subpopulations of …
Bioavailability Of The Tea Flavonoids Epicatechin And Epicatechin Gallate: Role Of Membrane Transport And Metabolism, Jaya Bharathi Vaidyanathan
Bioavailability Of The Tea Flavonoids Epicatechin And Epicatechin Gallate: Role Of Membrane Transport And Metabolism, Jaya Bharathi Vaidyanathan
MUSC Theses and Dissertations
Tea flavonoids, including (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) have been shown to have chemopreventive activity in cancer. Studies in animals and humans suggest that these dietary compounds have a very low oral bioavailability. However, the reason behind this limited bioavailability as well as the mechanisms underlying absorption is not clearly understood. The overall hypothesis of this dissertation project is that the human intestinal absorption of (-)-epicatechin (EC) and its gallate, (-)epicatechin- 3-gallate (ECG) is limited and regulated both by multiple transport mechanisms and metabolism. We used the Caco-2 cell monolayers, a well-established model to …
The Role Of The Central Nervous System In The Hypotensive Action Of Atenolol, Amy Kathryn Adams
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 …
Studies Of The Depolarization-Induced Release Of Beta Adrenergic Receptor Blocking Drugs From In Vitro Neural Preparations, Patricia Sherwood Bright
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 …
Studies Of Cardiovascular Energy Changes Occurring With Drug Administration Under Normal Acid Base Balance And During Hypercapnia, Ischemia, And Metabolic Acidosis, Earl E. Aldinger
MUSC Theses and Dissertations
Reflex autonomic changes occurring with the use of cardiovascular drugs may, as a side effect, increase cardiac work and oxygen demand. Improvement of coronary flow and/or a decrease in myocardial work load without increasing oxygen utilization are the desired effects of drugs used in the treatment of coronary insufficiency. The improvement of cardiac function is the purpose of drugs used in the treatment of heart failure. In either case the therapeutic effect may be accomplished through a direct myocardial effect and/or a decrease in cardiac pressure work load through extracardiac action. Through animal experimentation and patient correlation of the many …
A Study Of The Influence Of Acid-Base Changes On Myocardial And Vasopressor Responses To Arterenol And Epinephrine, Earl E. Aldinger
A Study Of The Influence Of Acid-Base Changes On Myocardial And Vasopressor Responses To Arterenol And Epinephrine, Earl E. Aldinger
MUSC Theses and Dissertations
It is well known that when the body is subjected to various stress conditions there is almost always a reflex release of certain neurohumoral substances in an attempt to compensate for these abnormal conditions. Acid-base changes, for example, are some of the most frequent occurring under these conditions. As mentioned throughout this thesis there is a direct correlation between acidosis end extreme hypotension or shock. The objective of these experiments was to investigate and determine the influence of acidosis on the cardiovascular response to the sympatho-adrenal hormones, arterenol and epinephrine, which are released in large amounts during shock. These studies …