Medicine and Health Sciences Commons^™

Effects Of Antihistamines On The Function Of Human Alpha-7 Nicotinic Acetylcholine Receptors, Seyedeh Soha Khanian

Theses

The effect of histamine H1 receptor (H1R) antagonists (antihistamines), namely, promethazine (PMZ), orphenadrine (ORP), chlorpheniramine (CLP), pyrilamine (PYR), diphenhydramine (DPH), cetirizine (CTZ), and triprolidine (TRP) were tested on the function of the cloned α₇subunit of the human nicotinic acetylcholine receptor (α₇-nAChR) expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Antihistamines inhibited the α₇-nAChR in the order of PYR > CLP > TRP > PMZ > ORP ≥ DPH ≥ CTZ. Among antihistamines, PYR showed the highest reversible inhibition of acetylcholine (100 µM) - induced current with IC₅₀ value of 6.2 µM. In contrast, the standard H2-H4R …

Screening For Novel Inhibitors Of Alpha-Ynuclein Seeded Nucleation-Dependent Aggregation And Toxicity As A Potential Therapeutic Strategy For Parkinson’S Disease, Mustafa Taleb Ardah

Theses

α-Synuclein aggregation is the key pathogenic event in several important neurological disorders including Parkinson’s Disease, dementia with Lewy bodies and multiple system atrophy, giving rise to a distinct group of neurodegenerative diseases known as synucleinopathies. Although the molecular basis of α – syn toxicity is mediated by a nucleation-dependent aggregation process. To elucidate the structural basis of α-synuclein mediated toxicity, we developed various methods to prepare different α-synuclein species of a defined size and morphology distribution, and we investigated their toxicity in different human dopaminergic cell lines. We observed that crude α-synuclein oligomers preparations, containing both monomeric and heterogeneous mixtures …

Effects Of Sodium/Glucose Co-Transporter Inhibitors On Contractility And Ca2+ Signalling In Ventricular Myocytes From Streptozotocin-Induced Diabetic Rats., Norin Nabil Fathalla Hamouda

Theses

The prevalence of diabetes mellitus is increasing at an alarming rate worldwide. Cardiovascular (CV) disease is the major cause of morbidity and mortality in diabetic patients. The search for new treatments has led to developing alternative insulin-independent treatment strategies such as sodium/glucose co-transporter (SGLT) inhibitors. Inhibition of intestinal SGLT1 impairs dietary glucose absorption, while inhibition of renal SGLT2 promotes glucose excretion leading to calorie loss and improved glycemic control. In this study, we hypothesized that inhibiting cardiac SGLTs may alter Ca²⁺ mobilization in myocytes. The effects of Phlorizin (PHLOR) (non-selective SGLT1 and 2 inhibitor), Quercetin-3-O-glucoside (QUER-3-G) (selective SGLT1 inhibitor), …

Genotypes Frequencies Of Rs9923231 And Rs7294 Snps In The Vkorc1 Gene Among Emiratis And Their Implications For Warfarin Dosage, Hayat Saad Al-Jaibeji Al-Jaibeji

Theses

Warfarin is the most commonly used oral anticoagulant medication given as a prophylaxis and/or treatment of venous and arterial thromboembolic disorders. Warfarin doses vary up to 10-fold among patients due to pharmacokinetics, pharmacodynamics and pharmacogenomics factors. In addition, Warfarin has a low therapeutic index with the risk of developing serious side effects such as severe bleeding or failure of therapy. Therefore, the main challenge to achieve the therapeutic goal in Warfarin treatment is estimating the appropriate dose for each patient. It is estimated that pharmacogenomic factors contribute to more than 60% of dose variability. The gene encoding for the target …

The Effects Of Cannabidiol On The Electrical And Contractile Properties Of Cardiomyocytes, Ramez Ali Mansour

Theses

In earlier studies, cannabidiol (CBD), a major nonpsychotropic cannabinoid found in cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrical properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the fluorescent indicator fura-2 AM. CBD (1 μM) caused a significant decrease in the amplitudes of electrically-evoked myocyte shortening and Ca2+ transients. However, the amplitudes of caffeine-evoked Ca2+ transients and the rate of recovery of electrically-evoked Ca2+ transients …

Genotypes Frequencies Of Rs9923231 And Rs7294 Snps In The Vkorci Gene Among Emiratis And Their Implications For Warfarin Dosage, Hayat Saad Al-Jaibeji

Theses

Warfarin is the most commonly used oral anticoagulant medication given as a prophylaxis and/or treatment of venous and arterial thromboembolic disorders. Warfarin doses vary up to 10-fold among patients due to pharmacokinetics, pharmacodynamics and pharmacogenomics factors. In addition, Warfarin has a low therapeutic index with the risk of developing serious side effects such as severe bleeding or failure of therapy. Therefore, the main challenge to achieve the therapeutic goal in warfarin treatment is estimating the appropriate dose for each patient. It is estimated that pharmacogenomics factors contribute to more than 60% of dose variability. The gene encoding for the target …

Hydrodynamic Cfd Modeling Of A Pharmaceutical Reactor Vessel Provided With A Retreat-Blade Impeller Under Different Baffling Conditions, Christopher G. Foehner

Theses

In the pharmaceutical industry, glass-lined reactors and vessels are often utilized to carry out a variety of different unit operations. Within these systems, both the vessel and impellers are typically glass-lined in order to provide superior corrosion resistance, prevent product contamination, and enhance cleanability. This approach, in turn, often requires the use of different, and sometimes sub-optimal, baffling conditions, which affect the hydrodynamics of the vessels and the reactor performance.

Computational Fluid Dynamics (CFD) is a computational tool that employs numerical methods and algorithms to discretize and numerically solve partial differential equations (PDEs) representing mass, energy, and momentum conservation equations …

Dispersion And Dissolution Kinetics Of Api Particles In Pharmaceutical Hot Melt Extrusion, Wang Zhan

Theses

Pharmaceutical Hot Melt Extrusion (HME) is essentially a special case of polymer compounding. The elementary steps involved in traditional plastics melt processing are handling of particulates, melting, dispersive and distributive mixing, devolatilization and stripping, and finally pressurization and pumping. However, for pharmaceutical HME, the dissolution of the API (Active Pharmaceutical Ingredient) is an additional and very important elementary step, along with the melting of the polymeric excipient that precedes it, and mixing which accelerates the dissolution process. A major concern in pharmaceutical HME is the thermal degradation of the API. To avoid overexposure of API to heat while ensuring complete …

Experimental Determination Of The Mixing Requirements For Solid Suspension In Pharmaceutical Stirred Tank Reactors, Anqi Zhou

Theses

Glass and glass-lined, stirred-tank reactors are of significant importance in the pharmaceutical and related industries. Because of fabrication issues, a retreat blade impeller (RBI) with a low impeller clearance off the tank bottom is commonly used in glass-lined reactors, typically combined with a single baffle (providing only partial baffling conditions) mounted from the top of the reactor. In addition, these reactors are often provided with a torispherical bottom. Other configurations are also used, including full baffling or no baffles at all, hemispherical bottoms, and different impeller types. Despite their common use, some of the most important mixing characteristics of this …

Assessment Of A Marine Polysaccharide For Use As Excipient In Pharmaceutical Hot-Melt Extrusion, Qing Ye

Theses

Pharmaceutical Hot Melt Extrusion (HME) is currently investigated by both industry and academia as a method for manufacturing solid oral dosages with improved bioavailability of poorly-water soluble active pharmaceutical ingredients (APIs) and control drug release of water-soluble APIs. Although HME is traditionally utilizing synthetic polymers to produce such dosages, biopolymers constantly gain ground by virtue of renewability, biocompatibility and in some cases biodegradability. In this work, the possibility of using Keltone, a marine polysaccharide derived from brown seaweed, as a polymeric excipient for pharmaceutical HME is explored. Keltone is insoluble in acidic pH and soluble in basic pH, therefore making …

Role Of Myd88 Protein In The Maintenance Of Immunological Self-Tolerance: Induction Of Autoimmunity By Salmonella Infection Consequent To Myd88 Deficiency., Jincy Merin Issac

Theses

Activation of the innate immune system is a prerequisite for the induction of adaptive immune responses to both infectious and non-infectious agents. Toll-like receptors (TLRs) are a family of proteins important for recognizing pathogen associated molecular patterns. MyD88 is an adaptor molecule whose function is critical in TLR signaling. MyD88-deficient (MyD88^-/-) mice exhibit heightened susceptibility to infections, even by attenuated strains of Salmonella enterica serovar Typhimurium. Paradoxically, despite their hypersusceptibility, infected MyD88^-/- mice produce elevated serum levels of anti-Salmonella antibodies regardless of the route of infection. This hypergammaglobulinemia was observed with both Th1-driven (IgG2c and IgG3) …

Ventricular Myocyte Contraction, Calcium Transport And Expression Of Genes Encoding Cardiac Muscle Proteins In Type 2 Diabetic Rats Fed A Sucrose-Enriched Diet, Eslam Mohamed Gaber El Nebrisi

Theses

Diabetes Mellitus (DM) is currently the fastest growing disease in the world. The prevalence of DM has increased worldwide and is expected to double within 20 years. The UAE is ranked 15^th worldwide, with 18.98% of the UAE population living with diabetes. Six Middle East North Africa (MENA) region countries – Bahrain, Egypt, Kuwait, Oman, Saudi Arabia, and United Arab Emirates (UAE) - are among the world’s 10 highest for prevalence of diabetes and impaired glucose tolerance. This represents a huge cost to society in terms of morbidity and mortality, and economically through lost productivity and cost burden on …

Molecular Characterization Of Vim Carbapenemases In The Arabian Peninsula, Nour Yahfoufi

Theses

The emergence and global spread of carbapenem resistant Enterobacteriaceae is alarming world-wide phenomenon that also affects the Middle East due to limited treatment options for such infections and their common association with high level of fatality. The most important mechanism of such resistance is caused by the production of various carbapenemase enzymes. In the Arabian Peninsula, so far, NDM and OXA48-like carbapenemases have been reported, while elsewhere other enzymes, e.g. VIM, IMP and KPC are also commonly found. Our aim was to systematically look for the VIM-type carbapenemases among local isolates and to characterize their genetic background.

Initially, screening isolates …

The "Globesity" Trend: Exploring The Ethical Concerns Of Registered Nurses Caring For Bariatric Surgery Patients, Casey L. Lowden-Crook

Theses

Obesity is a major global health problem. The comorbidities associated with obesity (for example: diabetes mellitus type 2 and cardiovascular disease) are multisystem and require continual medical management which places a great strain on the healthcare system. Australia is ranked the 5th most obese population in the world and deaths associated with obesity and obesity related illnesses are estimated at 7,200 per year (Medibank, 2010). This lifestyle disease is now the leading cause of premature death in Australia. The obesity epidemic is blamed on changes in the social, economic and physical environment (obesogenic environments) which have influenced people to over-consume …

The Effect Of Exercise Intensity On Physiological And Psychological Outcomes In Breast And Prostate Cancer Survivors: A Controlled Study, Eric Martin

Theses

Introduction

Research has identified a need to explore the components of exercise prescription for cancer survivors, particularly the most effective exercise intensity. The main purpose of this research was to examine whether exercise intensity modulates a range of physiological and psychological outcomes for breast and prostate cancer survivors. The primary outcomes were related to peak oxygen consumption (VO2peak) and quality of life (QOL). VO2peak is a highly sensitive measure that indicates overall health. QOL references the general wellbeing of individuals, and is an outcome of great importance in cancer rehabilitation research.

Pilot Study

A pilot study involving breast cancer survivors …

Noongar Women's Birth Experience, Judith Pamela Wilson

Theses

This qualitative study used a descriptive interpretive approach that drew heavily on the methodological underpinnings of interpretive phenomenology in order to explore the lived experience of Noongar women in childbirth. The aim of the study was to give voice to Noongar women, who despite having poorer outcomes than the wider population, remain marginalised and mute in childbirth reform. The purpose of the study was to acknowledge as authoritative, Noongar women’s wisdom and understanding of their childbirth experience.

This study was conducted at the cultural interface, by a non-Indigenous researcher who implemented a collaborative and power sharing model of enquiry. Ten …

Molecular Markers Of Weight Loss In Sleeve Gastrectomy Patients: A Prospective Cohort Study, Tamara C. Preda

Theses

Background:

Obesity is a polymorphic chronic disease that has reached epidemic proportions. Bariatric surgery including sleeve gastrectomy (SG) has an increasingly important role in long-term management of these patients. The molecular mechanisms post SG are complex and not fully understood.

Aims:

The primary study aim is to investigate the hormonal mechanisms by which SG effects weight loss and related health benefits by examining the association between SG weight loss and biochemical/hormone levels. A secondary aim was to assess the improvements in obesity related chronic disease states following SG.

Methods:

We conducted a prospective cohort study of obese patients undergoing SG …

Early Onset Dementia : Individual, Family And Professional Perspectives On Experiences And Support Strategies., Caroline Kilty

Theses

As of 2016 there will be as many as 5,000 people with EOD (early onset dementia) in Ireland (Haase, 2005). This group experiences depression, changes to relationships, in how they relate to friends and their community (Alzheimer’s Australia, 2007) as well as a gradual reduction in social contact with friends and relatives (Haase, 2005). Approximately half of EOD caregivers will have symptoms akin to anxiety and depression (Bentham & La Fontaine, 2005). However, younger people with EOD are marginalised in society (Keady & Nolan, 1994), and there has been little research into interventions and strategies from the perspective of those …

Young People’S Mental Health Awareness (Including An Evaluation Of A Mental Health Promoting Pilot Project Developed In Connaught), Pamela Kent

Theses

Adolescence is a particularly vulnerable life stage during which mental health challenges can occur and “in order to create a positive state of mental health and well-being it is imperative for young people to be able to recognise which aspects of life have a positive and damaging effect on their mental health” (HSE, 2007: 14). Irish research states that “Positive mental health enables young people to live fulfilling lives and promoting the mental health and wellbeing of our young people is a shared responsibility and is everybody’s business” (Department of Education and Skills & Health Service Executive & Department of …

الصحة النفسية، والقلق والاكتئاب لدى مجهولي النسب في دولة الإمارات العربية المتحدة, موزة علي خلفان النعيمي

Theses

هدفت الدراسة الحالية إلى التعرف على مستويات القلق، والاكتئاب والصحة النفسية لدى مجهولي النسب في دولة الإمارات العربية المتحدة، وعلاقتها ببعض المتغيرات الديموغرافية والمتمثلة بالجنس (النوع الاجتماعي).

تكونت عينة الدراسة من (73) فرد من مجهولي النسب والمقيمين في دار زايد للرعاية الأسرية في إمارة أبو ظبي (أبو ظبي والعين). وتم تطبيق قائمة بيك للاكتئاب، واختبار سمة القلق لسبيلبيرغر، ومقياس الصحة النفسية العامة، تم استخراج المتوسطات الحسابية والانحرافات المعيارية والتكرارات واختبار ( ) للإجابة عن أسئلة الدراسة.

توصلت الدراسة إلى وجود مستويات من القلق والاكتئاب لدى أفراد العينة حيث بلغت نسبة الأفراد الذين يعانون من الاكتئاب (المتوسط إلى الشديد) (28.7%) والأفراد …

The Role Of Social Marketing In Salt Reduction, Michael Barry

Theses

More people die from cardiovascular disease than any other cause in Ireland (Department of Health, 2013). A direct correlation exists between high salt intake and high blood pressure and ensuing cardiovascular diseases (He and MacGregor, 2010). This thesis focuses on the use of social marketing to educate people on the dangers of high salt intake with the eventual aim of making recommendations to aid in the reduction of high blood pressure. In-depth interviews were conducted with twelve leading personnel from salt reduction and social marketing fields. All interviewees reached similar conclusions suggesting that salt reduction as a health issue needs …

The Impact Of Different Types Of Core Training In Stable And Unstable Environments On Markers Of Athletic Performance, Gerry Fitzpatrick

Theses

Background: Research suggests that core stability and strength is important in facilitating athletes to effectively transfer force to the lower and upper extremities of the body. The purpose of the current research was to evaluate the impact of an eight week intervention of core training on stable and unstable surfaces, and in vertical and horizontal alignments, on markers of athletic performance relevant to team sports.

Methods: The athletic performance markers selected were bounce depth jump, counteiTnovement Jump, agility (T-test), 10 meter sprint, 30 meter sprints, and IRM leg strength as identified by Cressey (2007). Core stability and strength were measured …