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Articles 3481 - 3510 of 4193
Full-Text Articles in Medicine and Health Sciences
Age-Related Genetic And Epigenetic Chromosomal Changes: A Twin Study, Kimberly Jones
Age-Related Genetic And Epigenetic Chromosomal Changes: A Twin Study, Kimberly Jones
Theses and Dissertations
The primary aims of this study were to examine acquired genetic and epigenetic changes that occur in individuals with increasing age and to determine how these changes are influenced by genetic/environmental factors. Acquired genetic changes were assessed by determining the frequency and chromosomal contents of spontaneously occurring micronuclei in identical and fraternal twins. A total of 115 individuals (48 twin pairs and 19 singletons) were evaluated, ranging in age from 7 to 85 years. As expected, micronuclei frequencies, which are indicative of genomic damage, significantly increased with age (p<0.0001, r=0.446). The majority of micronuclei (32%) contained sex chromosomes and the frequency of sex chromosome-bearing micronuclei significantly increased with age (p<0.0001). The frequency of autosome-containing micronuclei was not significantly influenced by age or gender. However, some autosomes were seen more (chromosomes 4, 8, and 9) or less (chromosomes 17 and 22) frequently than expected by chance (p<0.05). An evaluation of the numerical contents of the sex chromosome-containing micronuclei and their corresponding binucleates showed that the majority of the binucleates had an abnormal chromosomal complement (either hypodiploid or hyperdiploid), with the subset of binucleates having a normal chromosomal complement decreasing with age for both the Y chromosome in males and the X chromosome in females. Model fitting, implemented in Mx, showed the variation in the frequency of micronuclei to be best explained by either additive genetic and unique environmental components, or common and unique environmental factors. Specific environmental exposures and health conditions that were shown to influence micronuclei frequencies, included: multivitamins, leafy green vegetables, fruit, vitamin E supplements, arthritis, heart disease, allergies, and alcohol. To assess acquired epigenetic changes, global methylation profiles of two identical twin pairs were compared and found to differ, indicating that individuals do develop alterations in their methylation profiles with age. Furthermore, the twin pair having a significant difference in their micronuclei frequencies and environmental exposures had more differences in their methylation pattern compared to the twin pair whose micronuclei frequencies and environmental factors did not differ. Overall, genetic and epigenetic changes were shown to occur with age and to be influenced by genetic and lifestyle factors.
Impact Of Statin Therapy On Outcomes In Aneurysmal Subarachnoid Hemorrhage Patients, Abdulkhaliq Alsalman
Impact Of Statin Therapy On Outcomes In Aneurysmal Subarachnoid Hemorrhage Patients, Abdulkhaliq Alsalman
Theses and Dissertations
There is conflicting data on the effects of statins on cerebral vasospasm and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH) patients. In this retrospective cohort study, patients were divided into those who received pravastatin (PRAV group) 40mg/d and those who did not (NP group). Data were analyzed using multivariate logistic regression. Eighty-one patients met inclusion criteria. There was a statistically significant decreased in the incidence of vasospasm in the PRAV group; however, this association did not retain significance after adjusting for WFNS, race, elevated WBC, and clipping (59% PRAV vs. 88% NP, p=0.08). There was no statistically significant difference in …
Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti
Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti
Theses and Dissertations
Status epilepticus (SE) is a major clinical emergency resulting in continuous seizure activity that can cause brain injury and many molecular and pathophysiologic changes leading to neuronal plasticity. The neuronal plasticity following SE-induced brain injury can initiate epileptogenesis and lead to the ultimate expression of acquired epilepsy (AE), characterized clinically by spontaneous, recurrent seizures. Epileptogenesis is the process wherein healthy brain tissue is transformed into hyperexcitable neuronal networks that produce AE. Understanding these alterations induced by brain injury is an important clinical challenge and can lend insight into possible new therapeutic targets to halt the development of AE. Currently there …
Genes And Symptoms Of Schizophrenia: Modifiers, Networks, And Interactions In Complex Disease, Sarah Bergen
Genes And Symptoms Of Schizophrenia: Modifiers, Networks, And Interactions In Complex Disease, Sarah Bergen
Theses and Dissertations
Understanding the genetic foundations of schizophrenia and the resultant symptom manifestations is an important step as we work toward development of new prevention and treatment strategies. This work has sought better understanding of this disease through use of three subject cohorts and two studies using simulated data exploring features of complex disease. First, we probed the symptoms of schizophrenia in subjects of African and European ancestry drawn from the Genetic Association Information Network (GAIN) schizophrenia study and found significant differences between groups, particularly in affective symptoms. The genetic basis of symptom variation was then explored in a selection of candidate …
Effect Of Renin Angiotensin System Inhibition On Cardiovascular Sequelae In Elderly Hypertensive Patients With Insulin Resistance, Hala Zreikat
Theses and Dissertations
Background: Insulin resistance may play a pathogenic role in cardiovascular disease (CVD). Resistance to insulin has been associated with obesity, hypertension, and abnormal glucose and lipid metabolism. The constellation of these features among insulin resistant subjects has been called the metabolic syndrome. Prevalence of the metabolic syndrome increases with age and is most common in the elderly. Different criteria have been proposed to define the metabolic syndrome (ATP, WHO, AACE, EGIR). Current management of metabolic syndrome focuses on the specific risk factors that the patient may have without targeting the underlying insulin resistance. Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin …
Therapeutic Strategies Aimed To Facilitate Axonal Regeneration And Functional Recovery Following Traumatic Spinal Cord Injury, Woon Chow
Theses and Dissertations
Traumatic spinal cord injury (SCI) is a physically debilitating, emotionally devastating, financially costly, and life-changing condition that afflicts more than 1,000,000 people in the United States alone. Owing to the characteristic neuropathology and low regenerative capacity of the central nervous system, many victims of SCI are left permanently paralyzed. Though the tissue damage caused by the initial insult almost certainly cannot be reversed, intensive research in recent years to elucidate the cellular and molecular events that follows has provided new grounds for optimism. Accordingly, in this dissertation, we present a number of potential treatment strategies aimed to address some of …
Exploring The Stress Response In New Army Nurses, Laureen Otto
Exploring The Stress Response In New Army Nurses, Laureen Otto
Theses and Dissertations
The study of stress is limited in professional nursing, but it is nearly non-existent in professional military nursing. The purpose of this study was to explore the relationships among psychological, environmental, biological and demographic factors of stress in new Army nurses during the Army Medical Department’s 8-week Officer Basic Leadership Course (OBLC). Using a descriptive prospective, correlational repeated measures design, 33 study participants completed two psychological stress measures (Perceived Stress Scale [PSS] and the Impact of Event Scale – Revised[IES-R]), an environmental measure (Life Experiences Survey [LES]), a biologic measure (salivary cortisol) and a demographic questionnaire at three different time …
Identification Of Clinical, Laboratory And Genetic Covariates For Pharmacokinetics, Efficacy And Toxicity Of Sorafenib In Patients With Solid Tumors, Lokesh Jain
Theses and Dissertations
The goal of this research work was to understand the clinical-pharmacology based treatment approaches for sorafenib. Treatment with sorafenib is associated with high inter-patient variability in pharmacokinetic exposures, efficacy and toxicity. We explored the demographic, laboratory, clinical and pharmacogenetic factors to elucidate the sources of variability. In addition, we examined the impact of pharmacogenetic variation in VEGFR2, an important mediator of the VEGF pathway, on risk of prostate cancer. To support these investigations, (mainly single-dose) pharmacokinetic, pharmacogenetic, efficacy and toxicity information were collected from patients with solid tumors, enrolled in five phase I / II clinical trials at National Cancer …
Automated Identification Of Noun Clauses In Clinical Language Samples, Britney Richey Manning
Automated Identification Of Noun Clauses In Clinical Language Samples, Britney Richey Manning
Theses and Dissertations
The identification of complex grammatical structures including noun clauses is of clinical importance because differences in the use of these structures have been found between individuals with and without language impairment. In recent years, computer software has been used to assist in analyzing clinical language samples. However, this software has been unable to accurately identify complex syntactic structures such as noun clauses. The present study investigated the accuracy of new software, called Cx, in identifying finite wh- and that-noun clauses. Two sets of language samples were used. One set included 10 children with language impairment, 10 age-matched peers, …
Development Of Psychometrically Equivalent Speech Audiometry Materials For Testing Children In Mongolian, Meghan Elizabeth Caldwell
Development Of Psychometrically Equivalent Speech Audiometry Materials For Testing Children In Mongolian, Meghan Elizabeth Caldwell
Theses and Dissertations
The purpose of this study was to develop, digitally record, evaluate, and equate Mongolian monosyllabic and bisyllabic child-appropriate words which can be used in the measurement of word recognition scores and speech-reception threshold (SRT) in children who are native speakers of Mongolian. Based on data collected from a survey of Mongolian child language professionals, a subset of child-appropriate materials was adapted from a set of materials developed for Mongolian adults. Two lists of 50 monosyllabic words and four half-lists of 25 words each were developed for testing the word recognition abilities of Mongolian children. The developed lists and half-lists were …
Patterns Of Vowel Production In Speakers Of American English From The State Of Utah, Larkin Hopkins Reeves
Patterns Of Vowel Production In Speakers Of American English From The State Of Utah, Larkin Hopkins Reeves
Theses and Dissertations
The English spoken in the United States has traditionally been divided into six dialect regions: New England, Mid-Atlantic, Southern, Midland, Northern, and Western. The acoustic properties of American English spoken in the Southern and Northern dialect regions have been the subject of intense research, but the acoustic properties of the Western dialect region have not been analyzed as thoroughly. The umbrella term, Western American English, includes the English spoken in a large geographic area that stretches from Montana, Wyoming, Colorado, and New Mexico to the Pacific coast. Research that has focused on the Western dialect has included participants from several …
The Withdrawn And Sociable Behaviors Of Children With Specific And Nonspecific Language Impairment, Heather Haskin
The Withdrawn And Sociable Behaviors Of Children With Specific And Nonspecific Language Impairment, Heather Haskin
Theses and Dissertations
Recently researchers have identified a group of children with language impairment (LI) whose IQ scores are below the typical IQ cutoff of 85 for specific language impairment (SLI) but above the IQ cutoff of 70 for intellectual disability (Weismer et al., 2000). This group is referred to as having nonspecific language impairment (NLI). Eleven children with NLI, eleven same-age peers with SLI, and eleven same-age typical peers were compared on withdrawn and sociable behaviors demonstrated in the classroom setting using the Teacher Behavior Rating Scale (Hart & Robinson, 1996). Three subtypes of withdrawal (solitary-active, solitary-passive, reticent) and two subtypes of …
Adenosine Dimethyltransferase Ksga: Biochemical Characterization Of The Protein And Its Interaction With The 30s Subunit, Pooja Desai
Theses and Dissertations
Ribosomes form the core of the protein biosynthesis machinery and are essential to life. Ribosome biogenesis is a complex cellular process involving transcription of rRNA, pre-rRNA processing, rRNA modification and simultaneous assembly of ribosomal proteins. RNA nucleotide modification is observed in all domains of life. While there is enormous conservation of ribosome structure, very few post-transcriptional rRNA modifications have been conserved throughout evolution. A notable example of such rare conservation is the dimethylation of two adjacent adenosines in the 3’-terminal helix, a highly conserved region of the small subunit rRNA. Enzymes that carry out these dimethylations are equally conserved and …
Mutagenesis And Spectroscopic Studies Of Mycobacterium Tuberculosis Sterol 14alpha Demethylase., Anuja R. Modi
Mutagenesis And Spectroscopic Studies Of Mycobacterium Tuberculosis Sterol 14alpha Demethylase., Anuja R. Modi
Theses and Dissertations
P450s are heme containing enzymes which affect oxidation of substrates via catalytic intermediates having transient lifetimes. These oxidative catalytic intermediates are formed by a sequential interplay of electrons and protons at the active site of the enzyme bearing molecular dioxygen. The proton transfer to the active site from bulk solvent is coordinated by an “acid-alcohol” pair of active site residues which are conserved in all P450s. Sterol 14α-demethylases (CYP51) are P450 enzymes which catalyze oxidative deformylation of lanosterol in the cholesterol/ergosterol biosynthetic pathway. Both cholesterol and ergosterol are important regulators of membrane fluidity. CYP51 differs from other P450s in that …
Age-Related Differences In In-Vitro Sensitivity To Inhibition Of Human Red Blood Cell Acetylcholinesterase And Plasma Butyrylcholinesterase By The Cholinesterase Inhibitors Physostigmine (Phys), Pyridostigmine (Pyr), Donepezil (Don) And Galantamine (Gal), David Lee
Theses and Dissertations
Alzheimer’s disease (AD) is a chronic, progressive neurodegenerative disorder, characterized clinically by a progressive loss of memory, cognitive function, ability to care for oneself and psychiatric symptoms. First-line agents for the treatment of AD are ChE inhibitors (DON, GAL), whose modest clinical efficacy and the high incidence of dose-limiting toxicities limit their clinical utility. In addition to AD, ChE inhibitors (PYR) are used for other medical conditions, such as myasthenia gravis (MG). Furthermore, ChE inhibitors (PYR) are used by military personnel prophylactically if impending exposure to chemical warfare agents, e.g., soman, is suspected. The purpose of this research project was …
To Evaluate The Level Of Agreement Between Two Self-Reported Medication Adherence Scales And Prescription Refill Records In Older Adults, Priyanka Kakad
To Evaluate The Level Of Agreement Between Two Self-Reported Medication Adherence Scales And Prescription Refill Records In Older Adults, Priyanka Kakad
Theses and Dissertations
Objective: To evaluate the level of agreement between two self-reported medication adherence scales and prescription refill records in older adults. Design: Cross-sectional study Setting: Imperial Plaza; a retirement community located in Richmond, Virginia. Participants: 32 independent-living older adults, taking anti-hypertensive medications and filling their prescriptions at on-site Plaza Professional Pharmacy were recruited in the study. Methods: Participants’ 6 months refill records were obtained and Medication Possession Ration (MPR) was calculated. Participants were interviewed using Morisky Medication Adherence Scale (MMAS) & Brief Medication Questionnaire (BMQ). Kappa statistics was used to evaluate the level of agreement. Results: Poor level of agreement was …
Chaperone Expression And Effects Of Its Inhibition On Breast Cancer Sensitization, Malissa Diehl
Chaperone Expression And Effects Of Its Inhibition On Breast Cancer Sensitization, Malissa Diehl
Theses and Dissertations
Breast cancer is one of the most prevalent and deadly forms of cancer in women and is not restricted by race or ethnicity. Although a wealth of knowledge has been amassed on the biology of breast cancer, including its risk factors, diagnosis, prognosis, prevention, and treatment, it remains a serious health concern and active area of research. Initial response to standard chemotherapeutic and radiotherapeutic regimens is generally strong for many patients, yet breast tumors often recur, leading to more aggressive and resistant tumors. Because recurrence is such a clinical issue, more effective therapeutic approaches are needed to eliminate partial clinical …
The Potential Role For Capb In Pathogenesis Of Francisella Tularensis, Eric Fleming
The Potential Role For Capb In Pathogenesis Of Francisella Tularensis, Eric Fleming
Theses and Dissertations
Francisella tularensis was a facultative intracellular pathogen and a gram-negative coccobacillus which has been categorized by the CDC as a potential class A select agent due to its highly infectious properties and high mortality rates. Francisella tularensis was also responsible for the zoonotic disease tularemia, which was usually transmitted by arthropod vectors or via contact with infected animals. Francisella tularensis subspecies novicida has been used by many researchers in genetic pathogenesis experiments to try to elucidate genes responsible for virulence factors. One of these virulence factors was a capsular material which has been thought to be involved in either increasing …
Specific Levels Of Therapeutic Ultrasound Stimulate The Release Of Inflammatory And Angiogenic Mediators From Macrophages In Culture, Thomas Turner
Specific Levels Of Therapeutic Ultrasound Stimulate The Release Of Inflammatory And Angiogenic Mediators From Macrophages In Culture, Thomas Turner
Theses and Dissertations
Therapeutic ultrasound (TUS) is a treatment modality that is used to accelerate tissue healing. TUS is thought to affect cellular processes of tissue healing, especially those that occur in the inflammatory and early proliferative phases. TUS can be applied using various parameter selections including intensity, wavelength, duty cycle and treatment duration and no clear consensus exists on optimal parameters for healing enhancement. Macrophages are important mediators of inflammation and their actions are critical to normal progression into the proliferative phase of healing. They complete many functions during these periods of tissue healing, among those being release of cytokines and growth …
Effect Of Posture On Acromiohumeral Distance With Arm Elevation In Subjects With And Without Rotator Cuff Disease Using Ultrasonography, Nitin Kalra
Theses and Dissertations
Objectives: To examine the effects of posture on subacromial (SA) space with arm elevation in patients with rotator cuff disease (RCD) and healthy subjects. Background: Poor posture has been linked to altered scapular mechanics, theorized to lead to excessive SA space narrowing. However, no study has examined the direct effects of posture on SA space using ultrasonography. We hypothesize that when compared to a neutral posture, upright posture will increase SA space and slouched posture will decrease SA space. Methods: Subjects with painful RCD (n=31) and healthy (n=29) shoulders participated. SA space was measured on ultrasound generated images using the …
Novel Allosteric Inhibitors Of Thrombin, Bijoy Desai
Novel Allosteric Inhibitors Of Thrombin, Bijoy Desai
Theses and Dissertations
Thrombin is a critical enzyme involved in blood coagulation and haemostasis. For this reason the study of its interactions with substrates, inhibitors and modulator is essential. It is also a unique enzyme in the serine protease family because unlike enzymes like trypsin and chymotrypsin its activity is modulated by various endogenous and exogenous ligands. This is due to the presence of “exosites” on the thrombin surface. Exosite II, unlike exosite-I, has not been characterized for its allosteric effect. In order to understand the structural basis of interaction and inhibition of inhibitor 4AS, which possibly interacts with exosite-II, native bovine thrombin …
Behavioral And Molecular Analysis Of Individual Variation In Ethanol Drinking, Jennifer Wolstenholme
Behavioral And Molecular Analysis Of Individual Variation In Ethanol Drinking, Jennifer Wolstenholme
Theses and Dissertations
A majority of Americans regularly consume alcohol, but the risk factors leading to excessive drinking and alcohol abuse are unevenly distributed throughout the population. Genetic differences can account for only 40-60% of this variability. While variations in ethanol preference drinking in rodent models have been reported, the neurobiological factors underlying these behaviors are still not completely understood. Thus, these studies were designed to determine behavioral and molecular factors associated with the initiation of ethanol drinking preference in an inbred mouse model. We harnessed the power of inter-individual variation of ethanol drinking within an inbred mouse strain to essentially eliminate genetic …
Chaperone Association With Telomere Binding Proteins, Amy Depcrynski
Chaperone Association With Telomere Binding Proteins, Amy Depcrynski
Theses and Dissertations
The Hsp90 chaperone complex associates with the telomerase enzyme, facilitating the assembly of the ribonucleoprotein complex. While previous data from our laboratory indicate that Hsp90 and p23 remain stably associated with (functionally active) telomerase, more recent experiments suggest that these chaperones associate with telomeres independent of telomerase, presumably through a specific interaction with telomere binding proteins. The current study examines the novel interactions between TRF2, TRF1, TIN2 and TPP1 and molecular chaperones (Hsp90, Hsp70, p23). In vitro and in cell experiments have shown an interaction between TRF1 and TRF2 and the molecular chaperones Hsp90 and Hsp70. Inhibition of Hsp90 using …
Relationship Among Stress Of Labor, Support, And Childbirth Experience In Postpartum Mothers, Sasamon Srisuthisak
Relationship Among Stress Of Labor, Support, And Childbirth Experience In Postpartum Mothers, Sasamon Srisuthisak
Theses and Dissertations
Background: Due to the profound and life-changing aspects of giving birth and to each woman’s individualized birthing experience, it is important to understand the myriad of factors that contribute to a positive childbirth experience. The aims of this study were to: (1) identify factors related to a positive childbirth experience; (2) to examine relationships among women’s perceptions and personal evaluations of their childbirth experience, stress associated with labor pain, support from the nursing staff, initial contact with the baby following birth, support from partners, education, age, and obstetric history; and (3) to identify predictors of a positive childbirth experience. Method: …
Exploring The Methylation Status Of Rai1 And The Rai1 Consensus Binding Sequence, Eri Kamura
Exploring The Methylation Status Of Rai1 And The Rai1 Consensus Binding Sequence, Eri Kamura
Theses and Dissertations
Smith Magenis Syndrome (SMS) is a multiple congenital anomalies/ mental retardation disorder caused by deletion or mutation of the RAI1 gene on chromosome 17p11.2. The majority of patients with SMS phenotypes have a deletion or mutation of RAI1. However, some patients have been observed with SMS-like phenotypes and yet have no deletions or mutations in the RAI1 gene. One possible explanation could be aberrant methylation of RAI1 since RAI1 is present and yet may be silenced. In order to study this possibility, patient cell lines were treated with 5-Aza-2’-deoxycytidine. RNA was extracted and real-time PCR was used to check the …
Retinoic Acid Induced 1 Gene Analysis In Humans And Zebrafish, Bijal Vyas
Retinoic Acid Induced 1 Gene Analysis In Humans And Zebrafish, Bijal Vyas
Theses and Dissertations
Smith-Magenis syndrome (SMS) is a complex mental retardation syndrome caused by deletion of 17p11.2 region or mutation of the RAI1 gene (retinoic acid induced 1). Individuals with SMS typically exhibit speech and motor delays, mental retardation, characteristic craniofacial and skeletal anomalies, and a distinct neurobehavioral phenotype that includes sleep disturbances, stereotypes, and maladaptive and self-injurious behaviors. RAI1 is thought to be a transcription factor modulating the expression of genes involved in a variety of cellular functions. Previous studies have shown the RAI1 gene being induced by retinoic acid (RA), a derivative of vitamin A. RA plays a significant role in …
Structural Interactions Between The Α3Β1 Integrin And Mmp-2: A Potential Functional Role In Cell Adhesion, James Bowman
Structural Interactions Between The Α3Β1 Integrin And Mmp-2: A Potential Functional Role In Cell Adhesion, James Bowman
Theses and Dissertations
During cardiac development and in cardiac disease changes in hemodynamic load initiate events leading to remodeling of the ECM. This study addresses the hypothesis that interactions between Integrins and Metalloprotienases function to modulate cell adhesion in the cultured cardiac fibroblast. The fibroblast is positioned to detect and respond to changes in the mechanical load on the heart. Functionally the cardiac fibroblast is the primary cell type responsible for the production, maintenance, and remodeling of the cardiac interstitium. Matrix Metalloproteinases, specifically the Gelatinases, are expressed in concert during development and in disease with changes in the hemodynamic loading of the heart. …
Synthesis And Biochemical Studies On Sulfated Monomers Of Low Molecular Weight Lignins, Jenson Verghese
Synthesis And Biochemical Studies On Sulfated Monomers Of Low Molecular Weight Lignins, Jenson Verghese
Theses and Dissertations
Anticoagulants are used as the first line therapy for management and prevention of thrombotic disorders. Thrombin and factor Xa have been the prime targets for regulation of the coagulation cascade. In this work, a small library of 17 benzofuran derivatives were synthesized and screened against thrombin and factor Xa. The derivatives that displayed inhibitory potential were docked on the exosite-II of factor Xa using a docking protocol that was developed in our research group. These compounds were based on the β-5 structural unit found in the oligomer -'CDSO3‘, which was prepared in our lab and was found to inhibit both …
Development Of Hint Based Computational Tools For Drug Design: Applications In The Design And Development Of Novel Anti-Cancer Agents, Ashutosh Tripathi
Development Of Hint Based Computational Tools For Drug Design: Applications In The Design And Development Of Novel Anti-Cancer Agents, Ashutosh Tripathi
Theses and Dissertations
The overall aim of the research is to develop a computational platform based on HINT paradigm for manipulating, predicting and analyzing biomacromolecular-ligand structure. A second synergistic goal is to apply the above methodology to design novel and potent anti-cancer agents. The crucial role of the microtubule in cell division has identified tubulin as an interesting target for the development of therapeutics for cancer. Pyrrole-containing molecules derived from nature have proven to be particularly useful as lead compounds for drug development. We have designed and developed a series of substituted pyrroles that inhibit growth and promote death of breast tumor cells …
Enzymatic Regulation Of Opioid Antinociception And Tolerance, Lynn Hull
Enzymatic Regulation Of Opioid Antinociception And Tolerance, Lynn Hull
Theses and Dissertations
ENZYMATIC REGULATION OF OPIOID ANTINOCICEPTION AND TOLERANCE By Lynn C. Hull, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2009 Director: William L. Dewey, Ph.D. Department of Pharmacology and Toxicology The involvement of kinases in opioid actions has long been established. The acute actions of opioids, through the Gi/Go G-proteins, cause the inhibition of adenylyl cyclase and therefore a decrease in protein kinase A (PKA) activation. Additionally, acute opioid administration may cause the G-protein to activate the phospholipase C (PLC)-mediated cascade leading to the …