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Articles 1 - 30 of 155
Full-Text Articles in Medicine and Health Sciences
The Effects Of Age And Heterochromatin On Frequencies Of Acquired Chromosomal Aneuploidy In Uncultured Human Leukocytes, Noran Aboalela
The Effects Of Age And Heterochromatin On Frequencies Of Acquired Chromosomal Aneuploidy In Uncultured Human Leukocytes, Noran Aboalela
Theses and Dissertations
While age-related sex chromosomal aneuploidy is a well-characterized phenomenon, the relationship between autosomal loss and age remains unclear. The emergence of the specific and highly sensitive fluorescence in situ hybridization (FISH) technology has enabled investigators to study interphase cells, thereby overcoming problems inherent with the study of metaphase spreads for acquired aneuploidy assessment. Despite all the advantages of this technique, there are some limitations that could be misleading when scoring interphase autosomal aneuploidy. In this study we show that sex chromosomal hypoploidy is correlated with age. By using a twin study design, we evaluated Y chromosome hypoploidy frequencies and found …
An Evaluation Of Cardiorespiratory Responses And Ventilatory Efficiency During Treadmill And Cycling Exercise In Overweight Adolescents, Amanda Scheps
An Evaluation Of Cardiorespiratory Responses And Ventilatory Efficiency During Treadmill And Cycling Exercise In Overweight Adolescents, Amanda Scheps
Theses and Dissertations
The assessment of ventilatory efficiency (VE/VCO2 slope) is increasingly being utilized to complement traditional cardiorespiratory fitness testing during graded exercise. The purpose of this study was to compare cardiorespiratory responses and ventilatory efficiency in obese children during a progressive exercise test to volitional fatigue performed on a treadmill and a cycle ergometer. Fifteen obese male (N=3) and female (N=12) adolescents aged 10 to 18 years were recruited in the study and completed both the treadmill and cycle ergometer trials. Mean age and BMI of the sample was 13.3 years and 38.0 kg/m2, respectively. Maximal oxygen consumption (VO2max) and ventilatory efficiency …
Mother-Infant Synchrony During Infant Feeding, Barbara Reyna
Mother-Infant Synchrony During Infant Feeding, Barbara Reyna
Theses and Dissertations
MOTHER-INFANT SYNCHRONY DURING INFANT FEEDING By Barbara A. Reyna, PhD A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2010. Major Director: Rita H. Pickler, PhD Endowed Nursing Alumni Professor Department of Family and Community Health Nursing, School of Nursing Synchrony between a mother and her infant is fundamental to their developing relationship. Feeding is an essential activity that provides an opportunity for interaction between a mother and her infant and may lead to synchronous interaction. The purpose this study was to develop and test a …
Haploinsufficiency Of Rai1 And Its Effect On Bdnf Expression, Sun Kim
Haploinsufficiency Of Rai1 And Its Effect On Bdnf Expression, Sun Kim
Theses and Dissertations
Smith-Magenis Syndrome (SMS) [OMIM, #182290] is a congenital anomaly and mental retardation (MCA/MR) syndrome associated with deletion of chromosome17p11.2 [1]. The clinical phenotype has been well described and includes minor craniofacial anomalies, self-injurious behaviors as well as sleep disturbances, speech delays, and obesity [1,2,3]. The incidence of SMS is estimated to be ~ 1:15,000 - 25,000 births [2,6]. Among SMS patients, ~90% are comprised of 17p11.2 deletions, while ~10% have RAI1 mutations [8]. All 17p11.2 deletions associated with SMS include RAI1 deletion [10]. RAI1 is thought to function as a transcriptional factor although its cellular role is still unclear. First, …
Facial Expression Discriminates Between Pain And Absence Of Pain In The Non-Communicative, Critically Ill Adult Patient, Mamoona Arif-Rahu
Facial Expression Discriminates Between Pain And Absence Of Pain In The Non-Communicative, Critically Ill Adult Patient, Mamoona Arif-Rahu
Theses and Dissertations
BACKGROUND: Pain assessment is a significant challenge in critically ill adults, especially those unable to communicate their pain level. At present there is no universally accepted pain scale for use in the non-communicative (cognitively impaired, sedated, paralyzed or mechanically ventilated) patient. Facial expressions are considered among the most reflexive and automatic nonverbal indices of pain. The facial expression component of pain assessment tools include a variety of facial descriptors (wincing, frowning, grimacing, smile/relaxed) with inconsistent pain intensity ratings or checklists of behaviors. The lack of consistent facial expression description and quantification of pain intensity makes standardization of pain evaluation difficult. …
An Analysis Of Ada Title I Allegations Of Workplace Discrimination As Filed With The Eeoc By Persons With Mental Illness, Jessica E. Hurley
An Analysis Of Ada Title I Allegations Of Workplace Discrimination As Filed With The Eeoc By Persons With Mental Illness, Jessica E. Hurley
Theses and Dissertations
ABSTRACT AN ANALYSIS OF ADA TITLE I ALLEGATIONS OF WORKPLACE DISCRIMINATION AS FILED WITH THE EEOC BY PERSONS WITH MENTAL ILLNESS Jessica Erin Hurley A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Health Related Sciences—Rehabilitation Leadership Virginia Commonwealth University, 2011 Dissertation Chair: Brian T. McMahon, Ph.D., CRC This study explores employment discrimination as experienced by persons with mental illness who filed allegations under Title I (the employment provisions) of the Americans with Disabilities Act (ADA) of 1990. The entire universe of employment discrimination allegations filed under Title I of the ADA …
Approaches To Identify Surface Proteins Of Anaplasma Phagocytophilum Dense-Cored Organisms As Adhesins To Human P-Selectin Glycoprotein Ligand-1, Matthew Troese
Approaches To Identify Surface Proteins Of Anaplasma Phagocytophilum Dense-Cored Organisms As Adhesins To Human P-Selectin Glycoprotein Ligand-1, Matthew Troese
Theses and Dissertations
Anaplasma phagocytophilum is an obligatory intracellular bacterium that infects neutrophils to cause human granulocytic anaplasmosis. Sialyl Lewis x (sLex)-modified P-selectin glycoprotein ligand-1 (PSGL-1) is the confirmed receptor utilized by A. phagocytophilum to bind and invade human neutrophils and myeloid cell lines. As an obligate intracellular pathogen, the binding of A. phagocytophilum to a host cell receptor is a prerequisite step for entry and replication, and thus its survival. However, the bacterial adhesins mediating this process have yet to be identified. In this study, we sought to identify surface proteins of A. phagocytophilum as putative adhesins. A. phagocytophilum undergoes a biphasic …
Inhibition Of Cytomegalovirus Genome Maturation By The Halogenated Benzimidazoles, Anne Sauer
Inhibition Of Cytomegalovirus Genome Maturation By The Halogenated Benzimidazoles, Anne Sauer
Theses and Dissertations
Current FDA approved anti-cytomegalovirus antivirals are ganciclovir, foscarnet, and cidofovir. These drugs target the viral polymerase to inhibit DNA synthesis. Halogenated benzimidazoles target a step later in viral replication during packaging and cleavage of the viral genome. The compounds 2-Bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (BDCRB) and 2,5,6-trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB) are novel inhibitors of human cytomegalovirus (HCMV) and resistance to these compounds are found within the human cytomegalovirus viral terminase. Terminase is unique to the virus and in theory provides a good target for antiviral development. Beginning with a BDCRB resistant guinea pig cytomegalovirus observations found a single mutation located in the viral terminase gene UL89 …
Intrinsic Features Of The Multisensory Cortical Area Lrss In The Ferret, Alexandru Ioan Cojanu
Intrinsic Features Of The Multisensory Cortical Area Lrss In The Ferret, Alexandru Ioan Cojanu
Theses and Dissertations
Environmental events simultaneously transduced by more than one sensory modality underlie multisensory processing in the CNS. While most studies of multisensory processing examine functional effects, none have evaluated the influence of local or columnar circuitry. The goal of the present study is to examine of local features of the ferret lateral rostral suprasylvian sulcus (LRSS), a multisensory cortex. Immunostaining revealed the cytoarchitectonic features of the LRSS: thick supragranular layers, a narrow layer IV, and moderately stained but differentiated infragranular layers. Golgi-Cox techniques were used with light microscopy and digital reconstruction to document neuronal morphology. Among the 90 reconstructed neurons, 4 …
Do General, Community Hospitals Compete By Specializing In High Volume, High Revenue-Generating Service Lines?, Nancy J. Muller
Do General, Community Hospitals Compete By Specializing In High Volume, High Revenue-Generating Service Lines?, Nancy J. Muller
Theses and Dissertations
To determine if general, community hospitals show evidence of specializing in the nation's six highest volume, highest revenue-generating service lines, 2003-2007 data of hospitals throughout Florida, Virginia, and Nevada were analyzed using backward deletion, stepwise regression. Service lines selected for study were cardiac surgery, cardiology, invasive cardiology, orthopedics, labor and delivery, and pulmonary services. Results do show evidence of specialization, but characteristics of hospitals vary by service line. Findings suggest that the general, community hospital, traditionally a full-service provider, may be undergoing transformation including specialization. The study demonstrates the usefulness of studying specialization at the service line level.
Characterization And Development Of A Stroke-Induced Model Of Acquired Epilepsy In Organotypic Hippocampal Slice Cultures: Role Of The Cannabinoid Cb1 Receptors In Modulation Of Neuronal Excitation And Inhibition, Julie Ziobro
Theses and Dissertations
Stroke is the most common cause of acquired epilepsy in persons 35 and older. The massive increase in extracellular glutamate during stroke causes a cascade of intracellular events that can lead to cell death or the molecular changes that initiate the development of epilepsy. In addition, many studies point to a modulatory role of the endocannabinoid system in controlling seizures. Animal models of stroke induced acquired epilepsy have been difficult to develop. Therefore, this dissertation was initiated to develop an organotypic hippocampal slice culture model of acquired epilepsy and examine the changes in distribution and function of the endogenous CB1 …
The Impact Of Hurricane Katrina On The Nurse Anesthesia Community In New Orleans, Marjorie Geisz-Everson
The Impact Of Hurricane Katrina On The Nurse Anesthesia Community In New Orleans, Marjorie Geisz-Everson
Theses and Dissertations
Hurricane Katrina devastated New Orleans in 2005. Certified Registered Nurse Anesthetists (CRNAs) and Student Registered Nurse Anesthetists (SRNAs) were impacted by the storm. CRNAs were required to be on duty during the storm and SRNAs’ education was disrupted by the storm. This dissertation is a compilation of three papers that represent the initial exploratory research into the impact of natural disasters on CRNAs and future CRNAs. The first article was a focused ethnography utilizing focus groups and described the shared experiences of CRNAs who were on duty in New Orleans during Hurricane Katrina and the psychosocial impact the storm had …
Determination Of Structure Of Hepatitis B Virus E Antigen, Asheel Patel
Determination Of Structure Of Hepatitis B Virus E Antigen, Asheel Patel
Theses and Dissertations
Hepatitis B virus is a member of the hepadnavirus family. The hepatitis B virus core gene codes for two proteins viz. core protein and pre-core protein. These proteins assemble to form particles viz. HBcAg and HBeAg respectively. The structure of the HBcAg has been widely studied but very little is known about the structure of HBeAg. Therefore, the aim of this study was to identify the disulfide bonding patterns in HBeAg. Recombinant HBeAg was isolated from E.coli and used for this study along with various mutants of HBeAg. There are four cysteines present in HBeAg each at position -7, 48, …
Brachytherapy Seed And Applicator Localization Via Iterative Forward Projection Matching Algorithm Using Digital X-Ray Projections, Damodar Pokhrel
Brachytherapy Seed And Applicator Localization Via Iterative Forward Projection Matching Algorithm Using Digital X-Ray Projections, Damodar Pokhrel
Theses and Dissertations
Interstitial and intracavitary brachytherapy plays an essential role in management of several malignancies. However, the achievable accuracy of brachytherapy treatment for prostate and cervical cancer is limited due to the lack of intraoperative planning and adaptive replanning. A major problem in implementing TRUS-based intraoperative planning is an inability of TRUS to accurately localize individual seed poses (positions and orientations) relative to the prostate volume during or after the implantation. For the locally advanced cervical cancer patient, manual drawing of the source positions on orthogonal films can not localize the full 3D intracavitary brachytherapy (ICB) applicator geometry. A new iterative forward …
Utilization Patterns And Economic Impact Of Iv Iron And Erythropoiesis Stimulating Agents In Chronic Kidney Disease Patients: A Multi-Hospital Study, Avani Joshi
Theses and Dissertations
Background: Chronic kidney disease (CKD) affects approximately 20 million Americans and is the cause of significant morbidity and mortality. Anemia, common in CKD, develops early in the disease process. It contributes to increased risk of cardiovascular disease, hospitalization, mortality, and diminishes health-related quality of life. Intravenous iron and Erythropoiesis Stimulating Agents (ESAs) are recommended for anemia management in CKD. The utilization patterns of IV iron and ESA, and their impact on hospital costs and length of stay merits investigation. Objectives: There were five general objectives of this investigation. The rate and extent of utilization of IV iron in anemic CKD …
Antifolate Modulators Of Amp-Activated Protein Kinase Signaling As Cancer Therapeutics, Scott Rothbart
Antifolate Modulators Of Amp-Activated Protein Kinase Signaling As Cancer Therapeutics, Scott Rothbart
Theses and Dissertations
Since its discovery, it was appreciated that the antifolate pemetrexed had multiple targets within folate metabolism. This laboratory was instrumental in showing that pemetrexed elicited its primary action as a thymidylate synthase inhibitor. Unusual for an antifolate, pemetrexed showed significant clinical activity against malignant pleural mesothelioma and non-small cell lung cancer. Accordingly, the FDA recently issued first-line approvals for pemetrexed in these diseases, leading us to question whether the effects of pemetrexed on other folate-dependent targets could explain this atypical clinical activity of the drug. Studies in this dissertation showed that in addition to thymidylate synthase inhibition, pemetrexed was also …
B Cell Adam10 Activity Is Increased By Kainate Receptor Activation: Potential Role Of This Pathway In Th2 Immunity And Cancer, Jamie Sturgill
B Cell Adam10 Activity Is Increased By Kainate Receptor Activation: Potential Role Of This Pathway In Th2 Immunity And Cancer, Jamie Sturgill
Theses and Dissertations
CD23 has long been appreciated to be a natural, negative regulator of IgE synthesis. This understanding is due in part to animal models in which CD23 deficient or CD23 transgenic animals display exacerbated or reduced IgE levels respectively. Interestingly, CD23 is susceptible to proteolytic cleavage from the cell surface. When this occurs, CD23 loses its regulatory capability and the solubilized form can lead to pro-inflammatory events through its cytokinergic activity on macrophages. Thus, targeting this specific cleavage would be beneficial to the control of allergic disease by stabilizing CD23 at the cell surface. Inhibitor studies performed by our group as …
Mechanisms Of Rotator Cuff Disease: Alterations Of Scapular Kinematics On Subacromial Space, Amee Seitz
Mechanisms Of Rotator Cuff Disease: Alterations Of Scapular Kinematics On Subacromial Space, Amee Seitz
Theses and Dissertations
Rotator cuff disease is multi-factored and has been attributed to both intrinsic and extrinsic factors. Extrinsic factors contribute to compression of the rotator cuff tendons. Intrinsic factors that contribute to rotator cuff tendon degradation with tensile/shear overload include alterations in biology, mechanical properties, morphology, and vascularity. Subacromial impingement is related to factors that encroach upon the subacromial space, while internal impingement affects the articular side of the tendons adjacent to glenoid. While the mechanisms of impingement are varied, further research is necessary to improve treatment and patient outcomes. Chapter 2 is a thorough review of literature on the mechanisms of …
Development And Applications Of The Hint Forcefield In Prediction Of Antibiotic Efflux And Virtual Screening For Antivirals, Aurijit Sarkar
Development And Applications Of The Hint Forcefield In Prediction Of Antibiotic Efflux And Virtual Screening For Antivirals, Aurijit Sarkar
Theses and Dissertations
This work was aimed at developing novel tools that utilize HINT, an empirical forcefield capable of quantitating both hydrophobic and hydrophilic (hydropathic) interactions, for implementation in theoretical biology and drug discovery/design. The role of hydrophobicity in determination of macromolecular structure and formation of complexes in biological molecules is undeniable and has been the subject of research across several decades. Hydrophobicity is introduced, with a review of its history and contemporary theories. This is followed by a description of various methods that quantify this all-pervading phenomenon and their use in protein folding and contemporary drug design projects – including a detailed …
Adam10 Is A Critical Regulator Of B Cell Development, Antibody Production, And Myeloid-Derived Suppressor Cell Expansion: Effects Of B Cell-Specific Adam10 Deletion And Overexpression In Vivo., David Gibb
Theses and Dissertations
Proteolytic processing of transmembrane receptors and ligands can have dramatic effects on cell signaling and subsequent cellular responses. Previous studies demonstrated that a disintegrin and metalloproteinase 10 (ADAM10) may cleave numerous B cell-expressed receptors, including the low affinity IgE receptor (CD23). However, lethality of ADAM10-deficient embryos has limited examination of these cleavage events in lymphocytes. To investigate their role in B cell development and function, we generated B cell-specific ADAM10 knockout mice. Intriguingly, deletion prevented development of the entire marginal zone B cell (MZB) lineage. Further analysis revealed that ADAM10 is required for S2 cleavage of the Notch2 receptor and …
Adherence To The American College Of Surgeons (Acs) Recommendation On Double Gloving, Hand Free Zone And Blunt Suture Needle Use Among Surgeon Ranks, Akbar Nassiry
Theses and Dissertations
Background: The American College of Surgeons guidelines suggest the use of intact gloves, double gloving, hands-free zone technique to pass sharp instruments, and blunt tip suture needles to protect patients, as well as the surgical team. This study estimates the extent to which these guidelines are followed in a large academic health system. Methods: Over a two-month period in the spring of 2010, 320 general surgical attendings, subspecialty surgical attendings, and surgical resident physicians practicing at a large academic health system, were approached during or after surgical conferences to participate in a cross-sectional study. Nearly 1/3rd completed an anonymous and …
Cannabinoid Receptors In The 3d Reconstructed Mouse Brain: Function And Regulation, Peter Nguyen
Cannabinoid Receptors In The 3d Reconstructed Mouse Brain: Function And Regulation, Peter Nguyen
Theses and Dissertations
CB1 receptors (CB1R) mediate the psychoactive and therapeutic effects of cannabinoids including ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent in marijuana. However, therapeutic use is limited by side effects and tolerance and dependence with chronic administration. Tolerance to cannabinoid-mediated effects is associated with CB1R adaptations, including desensitization (receptor-G-protein uncoupling) and downregulation (receptor degradation). The objectives of this thesis are to investigate the regional-specificity in CB1R function and regulation. Previous studies have investigated CB1Rs in a subset of regions involved in cannabinoid effects, but an inclusive regional comparison of the relative efficacies of different classes of cannabinoids to activate G-proteins has not …
Environmental Responses Of Two-Component Systems In Streptococcus Sanguinis, Jenishkumar Patel
Environmental Responses Of Two-Component Systems In Streptococcus Sanguinis, Jenishkumar Patel
Theses and Dissertations
The gram-positive bacterium Streptococcus sanguinis is a member of human indigenous oral microbialflora and has long been recognized as a key player in the bacterial colonization of the mouth. S. sanguinis is also the most common viridians streptococcal species implicated in infective endocarditis. Although many studies have focused on two-component systems in closely related Streptococcus species such as S. mutans, S. pneumoniae and S. gordonii; the mechanism of the response regulator in S. sanguinis is still unknown. The ability of S. sanguinis to adapt and thrive in hostile environments suggests this bacterium is capable of sensing and responding to various …
Volumetric Growth Model Of Human Medulloblastoma In The Nude Mouse Cerebellum, Thomas Gavigan
Volumetric Growth Model Of Human Medulloblastoma In The Nude Mouse Cerebellum, Thomas Gavigan
Theses and Dissertations
Medulloblastoma is the most common brain tumor in children, accounting for 10-20% of primary central nervous system (CNS) neoplasms and approximately 40% of all posterior fossa tumors. It is a highly invasive embryonal neuroepithelial tumor that typically arises in the cerebellar vermis and has a tendency to disseminate throughout the CNS early in its course. The molecular mechanisms of the disease largely remain uncharacterized, as the clinical treatment is still associated with mortality and severe side effects. The development of a clinically relevant in vivo model is important not only to further understand the disease but also to provide a …
Novel Roles For Reelin In Retinogeniculate Targeting, Cheryl Haner
Novel Roles For Reelin In Retinogeniculate Targeting, Cheryl Haner
Theses and Dissertations
In the developing visual system, the axon of a pre-synaptic cell must be guided to a post-synaptic partner. Retinal ganglion cells (RGCs) in the eye are an excellent model to study this process. Multiple classes exist that respond to specific types of light input, and these project to different destinations in the brain that process distinct types of information. The RGC axons that navigate to the lateral geniculate nucleus (LGN) do so in a class-specific manner. Axons from RGCs that mediate non-image forming functions innervate the ventral LGN (vLGN) and the intergeniculate leaflet (IGL). Axons from RGCs that process image-forming …
Factors Affecting Gingival Excess, Altered Passive Eruption And Recession In The Mandibular Anterior And Premolar Sites, William Bohlen
Factors Affecting Gingival Excess, Altered Passive Eruption And Recession In The Mandibular Anterior And Premolar Sites, William Bohlen
Theses and Dissertations
Abstract FACTORS AFFECTING GINGIVAL EXCESS, ALTERED PASSIVE ERUPTION AND RECESSION IN THE MANDIBULAR ANTERIOR AND PREMOLAR SITES By William F Bohlen, D.M.D. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Dentistry at Virginia Commonwealth University. Virginia Commonwealth University, 2010 Major Director: Thomas Waldrop, DDS, MS Program director, Department of Periodontics, Virginia Commonwealth University AIM: The aim of this study was to determine the factors affecting gingival excess, altered passive eruption and recession. METHODS: 100 subjects were examined clinically and models of their mandible were fabricated. Demographic, periodontal and cast measurements were …
Klf2/Klf4 Double Knock-Out Mouse Embryos Show Cranial Bleeding With Endothelial Disruption Of The Primary Head Vein, Benjamin Curtis
Klf2/Klf4 Double Knock-Out Mouse Embryos Show Cranial Bleeding With Endothelial Disruption Of The Primary Head Vein, Benjamin Curtis
Theses and Dissertations
Krüppel-like factors (KLFs) are a family of 3 Cys2/His2 zinc finger transcription factors with a diverse set of roles in cellular differentiation, cell cycle regulation, tumor suppression, erythropoiesis, angiogenesis, and other processes. During embryonic development, KLF2 has a role in vessel maturation. Adult conditional KLF4 knockout mouse embryos have thickened arterial intima follow vascular injury. Breeding KLF2+/- and KLF4+/- mice resulted in the generation of KLF2/KLF4 double knockout (DKO) embryos. KLF2/KLF4 DKO embryos died by E10.5 with cranial bleeding. Using immunohistochemistry, embryo whole-mounts were examined for differences in gross vascularization between wild-type (WT), KLF2-/- and KLF2/KLF4 (DKO embryonic day 9.5 …
Assessing Economic And Hrql Burden Of Food Allergy And Anaphylaxis In The U.S., Dipen Patel
Assessing Economic And Hrql Burden Of Food Allergy And Anaphylaxis In The U.S., Dipen Patel
Theses and Dissertations
Background: Food allergy, an abnormal immunologic response to food protein, has an estimated prevalence of 6% in young children and 3.7% in adults in the U.S. The only proven therapy for food allergy is strict elimination of the offending allergens. As a result, caregivers and patients could experience constant anxiety and stress that affects their quality of life. Additionally, food allergy can lead to significant economic impact on the health care system, since severe reactions often lead to ED visits and hospitalizations. Objectives: The first major objective was to determine the economic burden of Food Allergy and Anaphylaxis (FAA) patients …
The Impact Of Adolescent Nicotine Exposure On Drug Dependence In Adulthood, Mai Alajaji
The Impact Of Adolescent Nicotine Exposure On Drug Dependence In Adulthood, Mai Alajaji
Theses and Dissertations
Nicotine is one of the first and most commonly abused drugs in adolescence. According to The Center for Disease Control, every day more than 6000 adolescents try their first cigarette and over 3000 of them become daily smokers. Smoking among adolescents is a strong predictor of future drug abuse and dependence in adulthood. A number of studies has suggests that adolescents pre-exposed to nicotine may suffer permanent disruption of the brain’s reward systems through changes in dopamine receptor function. We hypothesize that nicotine exposure during adolescence causes long lasting neurobiological alterations that increase the likelihood of cocaine use in adulthood. …
Investigation And Optimization Of A Solvent / Anti-Solvent Crystallization Process For The Production Of Inhalation Particles, Swati Agrawal
Investigation And Optimization Of A Solvent / Anti-Solvent Crystallization Process For The Production Of Inhalation Particles, Swati Agrawal
Theses and Dissertations
Dry powder inhalers (DPIs) are commonly used to deliver drugs to the lungs. The drug particles used in these DPIs should possess a number of key properties. These include an aerodynamic particle size < 5μm and particle crystallinity for long term formulation stability. The conventionally used micronization technique to produce inhalation particles offers limited opportunities to control and optimize the particle characteristics. It is also known to induce crystalline disorder in the particles leading to formulation instability. Hence, this research project investigates and optimizes a solvent/anti-solvent crystallization process capable of directly yielding inhalation particles using albuterol sulfate (AS) as a model drug. Further, the feasibility of the process to produce combination particles of AS and ipratropium bromide monohydrate (IB) in predictable proportions and in a size suitable for inhalation is also investigated. The solvent / anti-solvent systems employed were water / ethyl acetate (EA) and water / isopropanol (IPA). Investigation and optimization of the crystallization variables with the water / EA system revealed that particle crystallinity was significantly influenced by an interaction between the drug solution / anti-solvent ratio (Ra ratio), stirring speed and crystal maturation time. Inducing a temperature difference between the drug solution and anti-solvent (Tdrug solution > Tanti-solvent) resulted in smaller particles being formed at a positive temperature difference of 65°C. IPA was shown to be the optimum anti-solvent for producing AS particles (IPA-AS) in a size range suitable for inhalation. In vitro aerosol performance of these IPA-AS particles was found to be superior compared to the conventionally used micronized particles when aerosolized from the Novolizer®. The solvent / anti-solvent systems investigated and optimized …