Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons™

Open Access. Powered by Scholars. Published by Universities.®

Virginia Commonwealth University

Discipline
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 2911 - 2940 of 5384

Full-Text Articles in Medicine and Health Sciences

Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis Using A Breast Cancer Mouse Model, Aiman Alhazmi Jul 2012

Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis Using A Breast Cancer Mouse Model, Aiman Alhazmi

Theses and Dissertations

Understanding the impact of epigenetic mechanisms on tumorigenesis is essential, as epigenetic alterations are associated with tumor initiation and progression. Because epigenetic changes are reversible, they are potential targets for cancer therapy. Nucleosome Remodeling Factor (NURF) is a chromatin-remodeling complex that regulates gene expression by changing nucleosome positioning along the DNA sequence. Previous studies have shown a role for NURF in embryonic development as well as regulating genes involved in tumor progression. In this work we investigated the impact of eliminating NURF function in tumorigenesis in vivo. BALB/c mice challenged with syngeneic 67NR breast cancer cell lines, injected into the …

Go to article

Cell Death And Growth Arrest Pathways Mediating The Actions Of Stilbene 5c In Hct-116 Colon Cancer Cells, Moureq Alotaibi Jul 2012

Cell Death And Growth Arrest Pathways Mediating The Actions Of Stilbene 5c In Hct-116 Colon Cancer Cells, Moureq Alotaibi

Theses and Dissertations

Abstract The stilbene derivative, cis-3, 4’, 5-trimethoxy-3’-aminostilbene (stilbene 5c), is a potentially potent antitumor agent that acts via binding to the colchicine-binding pocket in microtubules. Earlier studies have shown that stilbene 5c induces cell death in ovarian cancer cells and leukemic cells. The present study was designed to investigate the effectiveness of this microtubule poison against the HCT-116 human colon cancer cell line and its mechanisms of action. Time course studies demonstrated that stilbene 5c produces a biphasic decrease in cell viability. The capacity of the cells to proliferate was not restored upon removal of the drug after 6 days …

Go to article

Small Molecules As Negative Allosteric Modulators Of Alpha7 Nachrs, Osama Alwassil Jul 2012

Small Molecules As Negative Allosteric Modulators Of Alpha7 Nachrs, Osama Alwassil

Theses and Dissertations

Alpha7 Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in essential physiological functions and play a role in disorders such as Alzheimer’s disease. MD-354 (3-chlorophenylguanidine; 21), the first small–molecule negative allosteric modulator (NAM) at alpha7 nAChRs, served as a lead in developing structure–activity relationships for NAMs at a7 nAChRs. MD-354 (21) also binds at 5-HT3 receptors. Analogs of MD-354 with structural features detrimental to 5-HT3 receptor affinity were evaluated in patch-clamp recordings and an aniline N-methyl analog resulted in a more potent and selective NAM than MD-354. A new N-methyl series of compounds was synthesized in which the 3-position was replaced …

Go to article

Transferrin Binding Protein B Structure, Function, And Export In Neisseria Gonorrhoeae, Meredith L. Weck Jul 2012

Transferrin Binding Protein B Structure, Function, And Export In Neisseria Gonorrhoeae, Meredith L. Weck

Theses and Dissertations

Iron, an essential nutrient for most microorganisms, is sequestered in the host by iron-binding proteins, such as lactoferrin and transferrin. Neisseria gonorrhoeae utilizes transferrin as an iron source and its iron acquisition system is composed of two transferrin binding proteins: TbpA and TbpB. TbpA is a TonB-dependent, outer membrane transporter and TbpB is a bilobed, surface exposed lipoprotein. TbpB can distinguish between apo- and holo-transferrin which is involved in increasing the efficiency of iron uptake through the Tbps. It is anchored in the outer leaflet of the outer membrane by its lipid moiety. We aimed to identify the mechanism of …

Go to article

The Role Of Tetraspanin-8 In Astrocyte Elevated Gene-1 Mediated Progression Of Hepatocellular Carcinoma, Maaged Akiel Jul 2012

The Role Of Tetraspanin-8 In Astrocyte Elevated Gene-1 Mediated Progression Of Hepatocellular Carcinoma, Maaged Akiel

Theses and Dissertations

Hepatocellular carcinoma (HCC) is a devastating form of liver cancer that accounts for 80% of liver cancers. HCC has a poor prognosis with five-year survival of less than 12% in the United States. We in previous studies have identified Astrocyte Elevated Gene-1 (AEG-1) as an aberrantly overexpressed gene in many cancers including HCC, regulating tumor progression. Microarray studies identified the small transmembrane protein, tetraspanin8 (TSPAN8) as a downstream of AEG-1. TSPAN8 belongs to the family of TETRASPANINS with the characteristic of crossing the membrane four times, and regulating a wide range of cellular phenomena. TSPAN8 is implicated in metastasis and …

Go to article

Angiogenesis In Response To Varying Fiber Size In An Electrospun Scaffold In Vivo., Damien Brown Jul 2012

Angiogenesis In Response To Varying Fiber Size In An Electrospun Scaffold In Vivo., Damien Brown

Theses and Dissertations

Injury to the spinal cord results in partial or complete loss of sensory perception and motor function. After spinal cord injury (SCI), damaged tissue dies and a cavity will form. This cavity prevents the regeneration of tissue and any functional recovery. One way to address the cavity is the insertion of an electrospun scaffold that our lab has created. This provides a substrate for regenerating tissue to grow on, and it is thought that reestablishing the blood supply within the scaffold will allow cells necessary for regeneration to thrive. This could ultimately lead to meaningful recovery for patients who have …

Go to article

Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib Jun 2012

Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib

Theses and Dissertations

Increasingly the role of epigenetic machinery as a bridge between underlying DNA sequence and cellular phenotype is being discovered. The establishment of a myriad of unique cellular types sharing identical gene sequences in a multicellular organism gives a broad sense for the inherent role of epigenetic influence on cell differentiation. Importantly, the epigenetic mechanisms involved in establishing cell identity unsurprisingly contribute to diseased states, including cancer. Recent research continues to elucidate contributory roles of epigenetic mechanisms, such as DNA methylation, histone modification, and microRNA regulation, in human cancers. Additionally, chromatin remodelers, such as the Nucleosome Remodeling Factor (NURF), have been …

Go to article

Cohort Membership, Dental Insurance And Utilization Of Dental Services In Adults Age 47 And Over Receiving Dental Care At Virginia Commonwealth University’S School Of Dentistry, Patricia Brown Bonwell Jun 2012

Cohort Membership, Dental Insurance And Utilization Of Dental Services In Adults Age 47 And Over Receiving Dental Care At Virginia Commonwealth University’S School Of Dentistry, Patricia Brown Bonwell

Theses and Dissertations

This cross-sectional, non-experimental study evaluates associations between cohort membership, type of dental coverage, and utilization of dental services in all patients age 47 and over who received dental care at Virginia Commonwealth University’s (VCU) School of Dentistry in 2011. Structural Lag Theory poses that society’s institutions lag behind the actuality of a healthy and capable older adult population. The two dynamisms of the Structural Lag Theory were used for this study. The Dynamism of Changing Lives is represented by Cohort differences. Cohort differences include cohort size, people living longer and retaining more of their natural teeth along with different attitudes …

Go to article

Development And Comparison Of Risk-Adjusted Models To Benchmark Antibiotic Use In The University Healthsystem Consortium Hospitals, Omar Moh'd Musa Ibrahim Jun 2012

Development And Comparison Of Risk-Adjusted Models To Benchmark Antibiotic Use In The University Healthsystem Consortium Hospitals, Omar Moh'd Musa Ibrahim

Theses and Dissertations

Background. Infectious diseases societies recommend that hospitals risk-adjust their antimicrobial use before comparing it to their peers, a process called benchmarking. The purpose of this investigation is to apply and compare 3 risk-adjustment procedures for benchmarking hospital antibacterial consumption (AbC). Two standardization of rates procedures, direct and indirect standardization, are compared with one another as well as with regression modeling. Methods. Total aggregate adult AbC for 52 systemic antibacterial agents was measured in 70 hospitals that subscribed to the University HealthSystem Consortium Clinical Resource Manager database in 2009 and expressed as days of therapy (DOTs) per either 1000 patients days …

Go to article

Elucidating Genetic And Environmental Influences On Alcohol-Related Phenotypes, Jacquelyn Meyers Jun 2012

Elucidating Genetic And Environmental Influences On Alcohol-Related Phenotypes, Jacquelyn Meyers

Theses and Dissertations

Decades of work has led researchers to believe that risk for complex behavioral phenotypes, such as alcohol use disorders, is likely influenced by multiple genes of small effect acting in conjunction with each other and the environment. Currently, the field of psychiatric genetics is developing methodologies for the identification of genetic risk variants that predispose individuals to the development of complex behavioral disorders. Several challenges related to the complex and polygenic nature of these phenotypes, must be considered. This dissertation study attempts to address these important challenges in the context of alcohol use disorders and related phenotypes. A rich twin …

Go to article

Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy Jun 2012

Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy

Theses and Dissertations

UNIQUE FEAUTRES OF ORGANIZATION AND NEURONAL PROPERTIES IN A MULTISENSORY CORTEX Multisensory processing is a ubiquitous sensory effect that underlies a wide variety of behaviors, such as detection and orientation, as well as perceptual phenomena from speech comprehension to binding. Such multisensory perceptual effects are presumed to be based in cortex, especially within areas known to contain multisensory neurons. However, unlike their lower-level/primary sensory cortical counterparts, little is known about the connectional, functional and laminar organization of higher-level multisensory cortex. Therefore, to examine the fundamental features of neuronal processing and organization in the multisensory cortical area of the posterior parietal …

Go to article

Otx But Not Mitf Transcription Factors Are Required For Zebrafish Rpe Development, Brandon Lane May 2012

Otx But Not Mitf Transcription Factors Are Required For Zebrafish Rpe Development, Brandon Lane

Theses and Dissertations

Mitf and Otx transcription factors have been identified as essential to the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific role in the RPE developmental pathway have not been clearly defined. The role of the two Mitf transcription factors (Mitfa and Mitfb) and two Otx transcription factors (Otx1a and Otx2) in zebrafish RPE development was explored in these experiments. The loss of Mitf activity in mitfa, mitfb, or double mitf null mutant fish lines had no effect on RPE pigmentation or development. The loss of Otx2 activity through morpholino knockdown produced a …

Go to article

The Regulation Of Mitochondrial Dnmt1 During Oxidative Stress, Joyce Balinang May 2012

The Regulation Of Mitochondrial Dnmt1 During Oxidative Stress, Joyce Balinang

Theses and Dissertations

Epigenetics is the study of heritable gene expression due to alterations in the DNA structure other than the underlying DNA sequence. DNA methylation is one of the three types of epigenetic modifications found in the eukaryotic system. It involves the incorporation of a methyl group at the 5-position of cytosine residues in the DNA. DNA methylation is associated with several notorious disorders and diseases including Fragile X Syndrome, neurodegenerative disease (Parkinson’s, Alzhiemer, etc), diabetes and cancer. Cytosine methylation of mitochondrial DNA (mtDNA) was first demonstrated several decades ago but the mechanism of generating cytosine modification and its functional importance remain …

Go to article

The Antinociceptive Effects Of Alpha 7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulators In Different Animal Pain Models, Kelen Freitas May 2012

The Antinociceptive Effects Of Alpha 7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulators In Different Animal Pain Models, Kelen Freitas

Theses and Dissertations

The α7 nicotinic acetylcholine receptor (nAChR) subtype is abundantly expressed in the central nervous system (CNS) and in the periphery. Positive allosteric modulators (PAMs) of the α7 increase the response to an agonist and are divided into two types depending on whether they also decrease desensitization of the receptor (type II) or not (type I). Therefore, this study aims to investigate whether the enhancement of endogenous α7 nAChR function will result in a beneficial effect in nociceptive, inflammatory and chronic neuropathic pain models. While NS1738 and PNU-120596 were not active to reduce acute thermal pain, measured by hot-plate and tail-flick …

Go to article

Periodontal Resident Self-Assessment Of Ergonomics Before And After Videotaped Surgeries, Corin Marantz May 2012

Periodontal Resident Self-Assessment Of Ergonomics Before And After Videotaped Surgeries, Corin Marantz

Theses and Dissertations

Objective: To examine whether self-assessment of videotaped surgeries helps improve periodontal residents’ ergonomics. Methods: Residents (n=8) provided self-assessments of their own ergonomics while performing periodontal surgery using a questionnaire with open and closed items. Results were analyzed using quantitative and qualitative means. Results: Comparison of responses resulted in a change between Pre-video Surgery 1 and PSV1 (p<0.05) and between the three occasions for flat foot and horizontal shoulder positions (p<0.05). Resident goals were most numerous for improving positions of shoulder, back and neck and most notable responses for failure to achieve goals were the need for surgical access and being too focused the procedure. Conclusions: Videotape review is a valid means of self-assessment. Intervention solely in the form of a questionnaire and videotape review was insufficient in its ability to change the residents’ ergonomics. Barriers to implementation of proper ergonomics were identified.

Go to article

T-Bet-Dependent Regulation Of T Cell Responses During Trypanosoma Cruzi Infection, Dustin Cobb May 2012

T-Bet-Dependent Regulation Of T Cell Responses During Trypanosoma Cruzi Infection, Dustin Cobb

Theses and Dissertations

The human pathogen Trypanosoma cruzi is an intracellular parasite and the etiological agent of Chagas disease. Protective immune responses to T. cruzi are highly dependent on T helper 1 and CD8+ T cells which produce interferon-gamma. A deficiency in these responses has severe consequences on the ability to control infection. Our investigation into the role of the Th1 transcription factor, T-bet, during murine T. cruzi infection revealed that T-bet is required for resistance. Contrary to our expectations, T-bet was not required for the development of Th1 immunity during infection, as T-bet-deficient mice still developed interferon-gamma-producing T cells. However, T-bet was …

Go to article

Validation Of 3'-Deoxy-3'-[18f]-Fluorothymidine Positron Emission Tomography For Image-Guidance In Biologically Adaptive Radiotherapy, Marian Axente May 2012

Validation Of 3'-Deoxy-3'-[18f]-Fluorothymidine Positron Emission Tomography For Image-Guidance In Biologically Adaptive Radiotherapy, Marian Axente

Theses and Dissertations

Accelerated tumor cell repopulation during radiation therapy is one of the leading causes for low survival rates of head-and-neck cancer patients. The therapeutic effectiveness of radiotherapy could be improved by selectively targeting proliferating tumor subvolumes with higher doses of radiation. Positron emission tomography (PET) imaging with 3´-deoxy-3´-[18F]-fluorothymidine (FLT) has shown great potential as a non-invasive approach to characterizing the proliferation status of tumors. This thesis focuses on histopathological validation of FLT PET imaging specifically for image-guidance applications in biologically adaptive radiotherapy. The lack of experimental data supporting the use of FLT PET imaging for radiotherapy guidance is addressed by developing …

Go to article

The Pharmacist Supply In The United States, 1994-2009: A Population Ecology Perspective, Kevin S.J. Lett May 2012

The Pharmacist Supply In The United States, 1994-2009: A Population Ecology Perspective, Kevin S.J. Lett

Theses and Dissertations

The U.S. healthcare system is a complex segment of our society that is constantly evolving with changes to various areas such as education, financing, safety, and health. There continues to be a critical examination of how healthcare professionals are trained and utilized as healthcare demands increase. One category of healthcare professionals that has evolved over time to address societal needs is pharmacists. Pharmacists have kept their traditional function of dispensing medications while expanding into multiple areas of expertise and training from patient counseling and drug therapy, to being part of multidisciplinary teams treating acute care patients. According to the National …

Go to article

Symptom Clusters In Lung Cancer Patients, Debra Rattican May 2012

Symptom Clusters In Lung Cancer Patients, Debra Rattican

Theses and Dissertations

SYMPTOM CLUSTERS IN LUNG CANCER PATIENTS By Debra Rattican, PhD, RN A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2012 Major Director: Debra E. Lyon, PhD. Professor and Chair Family and Community Health Nursing The purpose of the study was to examine selected relationships among symptoms common to individuals with lung cancer. The specific aims were: 1) To examine the relationship between the symptoms of dyspnea and anxiety in patients with lung cancer. 2) To examine the relationships among the symptoms of dyspnea, anxiety, and …

Go to article

Synthesis And Biological Evaluation Of Second Generation Anibamine Analogues As Novel Anti-Prostate Cancer Agents, Shilpa Singh May 2012

Synthesis And Biological Evaluation Of Second Generation Anibamine Analogues As Novel Anti-Prostate Cancer Agents, Shilpa Singh

Theses and Dissertations

Prostate cancer is the most prevalent non-cutaneous cancer among men. Since the 19th century when Virchow first introduced the concept of inflammation in cancer, chemokines and their receptors have garnered a lot of interest. Chemokine receptor CCR5 has been especially implicated in many disease states and recently found to be over expressed in prostate cancer cell lines. Anibamine, a natural CCR5 antagonist discovered in 2004, has been found to have significant anti-prostate cancer activity at micromolar level. To optimize this compound and also discover a novel pharmacophore, exploration of the original structure was carried out. Significant modifications were made to …

Go to article

Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen May 2012

Function Of Insulin-Like Growth Factor Binding Protein 7 (Igfbp7) In Hepatocellular Carcinoma, Dong Chen

Theses and Dissertations

Title of Dissertation: FUNCTION OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 7(IGFBP7) IN HEPATOCELLULAR CARCINOMA By Dong Chen. Purpose: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment, thus requiring the development of innovative and effective targeted therapies. The oncogene Astrocyte Elevated Gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates Insulin-like Growth Factor Binding Protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function. Experimental Design: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarrays by real-time PCR …

Go to article

Predictors Of Sexual Relationship Power, Communication And Sexual Decision Making Among Latino Couples, Yui Matsuda May 2012

Predictors Of Sexual Relationship Power, Communication And Sexual Decision Making Among Latino Couples, Yui Matsuda

Theses and Dissertations

Unintended pregnancy (UP) is increasing among Latinos in the United States. Unintended pregnancy contributes to many negative consequences for infants, mothers and families. Concurrently, various factors affect Latino couples’ sexual relationship power, communication and decision making about family planning, including sexual relationship power, relationship commitment, dyadic adjustment, individual background, and cultural characteristics. Previous research has not focused on understanding the factors that affect Latino couples’ sexual relationship power, communication and sexual decision making from each partner’s perspective. The purpose of this study was to examine the association between sexual relationship power, communication, and sexual decision making from each partner’s perspective …

Go to article

Combining Electrospun Polydioxanone Scaffolds, Schwann Cells, And Matrigel To Improve Functional Recovery After A Complete Spinal Cord Transection In Rats, Ashok Kannan May 2012

Combining Electrospun Polydioxanone Scaffolds, Schwann Cells, And Matrigel To Improve Functional Recovery After A Complete Spinal Cord Transection In Rats, Ashok Kannan

Theses and Dissertations

Spinal cord injury (SCI) has presented itself as a multifaceted pathology that is largely inhibitory to regeneration, and therefore to functional recovery, even though spinal cord neurons have been found to be innately regenerative. Thus, having identified the key players in the inhibition of this innate regeneration, SCI researchers have focused on two major types of approaches: (1) blocking inhibitory cues and (2) promoting innate regeneration. Schwann cells (SCs) have long been shown to promote and enhance functional recovery after SCI through providing supplemental myelination and trophic and tropic factors to regenerating axons, though singular approaches rarely address the complex …

Go to article

Comparison Of Root Canal Irrigation Systems In Reducing Intracanal Microorganisms Using Saline-An In Vitro Study, Pranav Desai May 2012

Comparison Of Root Canal Irrigation Systems In Reducing Intracanal Microorganisms Using Saline-An In Vitro Study, Pranav Desai

Theses and Dissertations

Mechanical and chemical debridement plays an important role in reducing intracanal microorganisms. Effective root canal irrigation depends on both the root canal irrigant and irrigation system. The objective of this study was to evaluate the debridement efficiency of four root canal irrigation systems, Endovac®, PiezoFlow™, EndoActivator® and traditional needle irrigation using saline as an irrigant. Seventy-five, single canal, extracted, mature teeth were selected. Teeth were standardized to canal lengths of 15 mm and instrumented to Master Apical File size #40 with 4% taper. Teeth were mounted in a centrifuge tube using PVS impression material. Teeth were randomly divided into four …

Go to article

Radiation Sensitization Of Breast Cancer Cells By Vitamin D Through The Promotion Of Autophagic Cell Death, Eden Wilson May 2012

Radiation Sensitization Of Breast Cancer Cells By Vitamin D Through The Promotion Of Autophagic Cell Death, Eden Wilson

Theses and Dissertations

Radiation therapy is a widely used tool in cancer therapy and is frequently offered as the first line of treatment for cancers of the breast. While radiotherapy is often initially effective in killing tumor cells or suppressing their growth, there are factors that confer tumor cell resistance to irradiation. Development of resistance may lead to disease recurrence despite the use of surgery, chemotherapy and radiation therapy. A primary goal of the studies in Dr. Gewirtz’s laboratory is to develop strategies to overcome resistance to radiation (and chemotherapy) in breast cancer, with the ultimate goal of preventing or attenuating disease recurrence. …

Go to article

Therapeutic Drug Monitoring Of Factor Viii Prophylaxis Using Its Plasma Coagulant Activity And Global Hemostasis Biomarkers: A Pharmacokinetic/Pharmacodynamic Pilot Study, Hawaj Maitham Al Apr 2012

Therapeutic Drug Monitoring Of Factor Viii Prophylaxis Using Its Plasma Coagulant Activity And Global Hemostasis Biomarkers: A Pharmacokinetic/Pharmacodynamic Pilot Study, Hawaj Maitham Al

Theses and Dissertations

Background: The current clinical practice of factor VIII (FVIII) prophylaxis revolves around converting patients with severe hemophilia A, hereafter simply referred to as hemophilia, phenotype (defined as plasma factor VIII coagulant activity [FVIII:C] <1 IU dL-1) to moderate hemophilia phenotype (defined as plasma FVIII:C from 1–5 IU dL-1). However, a wide inter-individual variation in bleeding tendency is observed despite changes in plasma FVIII:C (pharmacokinetic [PK] changes). Therefore, monitoring FVIII prophylaxis by global hemostasis biomarkers (pharmacodynamic [PD] response) can potentially be beneficial. Objective: To conduct appropriate PK/PD modeling using plasma FVIII:C and global hemostasis (platelet function and blood viscoelastic) biomarkers in severe hemophilia. Methods: Nine non-bleeding severe hemophiliacs (plasma FVIII:C <1 IU dL-1) with variant bleeding tendency (5 frequent bleeders and 4 infrequent bleeders) were infused with a recombinant factor FVIII (rFVIII) prophylactic dose (mean = 32.1 international units per kilogram [IU kg-1]). Blood was collected at baseline and 0.5-, 1-, 2-, 4-, 8-, 12-, 24- and 48-hours (h) post-dose for plasma FVIII:C, platelet function (platelet contractile force [PCF], clot elastic modulus [CEM] and force onset time [FOT]) and blood viscoelastic (reaction-time [R], kinetics-time [K] and maximum amplitude [MA]) biomarkers and activated partial thromboplastin time (aPTT). Non-compartmental analysis (NCA) was performed using standard methods. Compartmental analysis (CA) and PK/PD modeling were performed by non-linear regression. Correlation and analysis of variance (ANOVA) were used to explore the role of clinically relevant modifiers of bleeding tendency, as appropriate. ANOVA was used to assess inter-group differences in pertinent PK and PD parameters. P value <0.05 significance level was pre-specified for all statistical tests. Results: Mean (±SD) volume of distribution at steady state (Vss), total clearance (CLtot) and terminal half-life (t1/2) from NCA were 40.5 (±11.2) milliliter per kilogram (mL kg-1), 2.9 (±1.2) milliliter per hour per kilogram (mL h-1 kg-1) and 11.6 (±6.2) h, respectively. Mean (±SD) Vss and CLtot from the one-compartment body model (CA) were 39.6 (±8.9) mL kg-1 and 3.1 (±1.3) mL h-1 kg-1, respectively. The mean (±SD) baseline effect (E0) and slope from the PK/PD linear modeling were: for aPTT, 48.9 (±4.4) seconds (sec) and -0.025 (±0.009) second deciliter per international unit (sec dL IU-1), respectively; for PCF, 0.3 (±0.3) kilodynes (kdynes) and 0.008 (±0.004) kilodynes deciliter per international unit (kdynes dL IU-1), respectively; and for CEM, 0.0 (±0.0) kilodynes per square centimeter (kdynes cm-2) and 0.032 (±0.016) kilodynes deciliter per international unit per square centimeter (kdynes dL IU-1 cm-2), respectively. The mean (±SD) maximum effect (Emax) and half the maximum effective concentration (EC50) from the PK/PD sigmoidal Emax model were: for FOT, 70.1 (±16.9) % reduction and 87.8 (±31.4) IU dL-1 for FOT, respectively; for R, 74.9 (±26.0) % reduction and 68.5 (±28.4) IU dL-1, respectively; and for K, 73.2 (±36.4) % reduction and 67.2 (±29.0) IU dL-1, respectively. MA was not PK/PD modeled due to its low sensitivity. Conclusions: Plasma FVIII:C remained ≥1 IU dL-1 over the prophylactic interval. FOT and R were the most sensitive biomarkers at lower plasma FVIII:C. PCF and CEM were more sensitive than K and aPTT at lower plasma FVIII:C. MA was the least sensitive biomarker. Correlation and inter-group differences did not reach statistical significance (small sample size). These results may be used to assess risk of bleeding and dose-optimize FVIII prophylaxis in severe hemophilia.

Go to article

Inhibition Of Injury-Induced Cell Proliferation In The Dentate Gyrus Impairs Cognitive Recovery Following Traumatic Brain Injury, Teresa Daniels Apr 2012

Inhibition Of Injury-Induced Cell Proliferation In The Dentate Gyrus Impairs Cognitive Recovery Following Traumatic Brain Injury, Teresa Daniels

Theses and Dissertations

Traumatic brain injury (TBI) induces a robust cellular proliferative response among neural stem/progenitor cells (NS/NPCs) in the dentate gyrus of the hippocampus. This proliferative effect is thought to contribute to the innate cognitive recovery observed following TBI. Inhibition of hippocampal neurogenesis impairs cognitive function. Furthermore, enhancement of injury-induced hippocampal neurogenesis via intraventricular administration of basic fibroblast growth factor (bFGF) improves cognitive function in animals following TBI. In this experiment, we investigated the direct association between injury-induced hippocampal neurogenesis and cognitive recovery utilizing an antimitotic agent, arabinofuranosyl cytidine (Ara-C). In this study, adult rats received a moderate lateral fluid percussion injury …

Go to article

Quantitative Analysis Of Multiple Charged Large Molecules In Human Or Rat Plasma Using Liquid Chromatography Tandem Mass Spectrometry, Matthew Halquist Apr 2012

Quantitative Analysis Of Multiple Charged Large Molecules In Human Or Rat Plasma Using Liquid Chromatography Tandem Mass Spectrometry, Matthew Halquist

Theses and Dissertations

Immunoassays have traditionally been employed for the determination of plasma concentration-time profiles for pharmacokinetic studies of therapeutic proteins and peptides. These ligand binding assays have high sensitivity but require significant time for antibody generation (1 to 2 years) for assay development. Despite high sensitivity, these assays suffer from cross-reactivity that can lead to inaccurate results. As an alternative to immunoassays, this dissertation was focused on the development and validation of assays that can be used for quantitative analysis of peptides or proteins in plasma using liquid chromatography tandem mass spectrometry (LC-MS/MS). Two approaches were considered for measurement of proteins and …

Go to article

Perceived Social Attributes Of College Students With Ideal Versus Non-Ideal Dental Esthetics Judged By Peers., David Jones Apr 2012

Perceived Social Attributes Of College Students With Ideal Versus Non-Ideal Dental Esthetics Judged By Peers., David Jones

Theses and Dissertations

The purpose of this study was to determine the influence of dentofacial appearance on perceived social attributes of college-aged adult males and females as judged by their peers. Specifically, the objective was to determine if ideal smile esthetics positively influenced this age group’s perception of opposite-sex peers based on ratings of the following psychosocial characteristics: attractiveness, desire to spend time with, desire to date, and desire for a long-term relationship. Evaluators were shown digital photographs of subjects with ideal and nonideal smiles and asked to rate those 4 attributes using a visual analogue scale (VAS). The subjects’ photographs with ideal …

Go to article

The Effect Of Minocycline Treatment On Cell Proliferation And Neurogenesis In The Hippocampus In Young And Aged Brains Following Traumatic Brain Injury, Ashley Harvin Apr 2012

The Effect Of Minocycline Treatment On Cell Proliferation And Neurogenesis In The Hippocampus In Young And Aged Brains Following Traumatic Brain Injury, Ashley Harvin

Theses and Dissertations

Following traumatic brain injury, there is an enhanced cell proliferative and neurogenic response in the young adult hippocampus, which may be associated with innate cognitive recovery. However, in the aged brain, an increased level of inflammatory cell responses was observed following injury concomitant to decreased hippocampal neurogenesis and cognitive recovery in the aging population. This suggests that excessive inflammation produced in the injured aging brain has a detrimental effect on neurogenesis and cognitive function. In this study, we examined the effect of anti-inflammatory treatment with minocycline on cell proliferation and generation of new neurons in the dentate gyrus (DG) of …

Go to article

First Prev Next Last