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Articles 7531 - 7560 of 8643
Full-Text Articles in Medicine and Health Sciences
Chronic Health Conditions Of Individuals In Public Housing, Alicia A. Arnett
Chronic Health Conditions Of Individuals In Public Housing, Alicia A. Arnett
Theses and Dissertations--Nutrition and Food Systems
A majority of low-income individuals living in public housing today are working or receiving some kind of assistance, but still struggle to make ends meet. Previous studies show that cost and availability are barriers to healthy eating for low-income individuals. The purpose of this study was to determine relationships among nutrition habits, health status, sources of income, and food and living resources for low-income residents in public housing. The study utilizes data collected over five years on the impact of the revitalization of the families. The sample was randomly selected from residents of the housing property in a Kentucky city. …
Attention-Deficit/Hyperactivity Disorder In Childhood Is Associated With Cognitive Test Profiles In The Geriatric Population But Not With Mild Cognitive Impairment Or Alzheimer's Disease, N. Ivanchak, Erin L. Abner, S. A. Carr, S. J. Freeman, A. Seybert, John Ranseen, Gregory A. Jicha
Attention-Deficit/Hyperactivity Disorder In Childhood Is Associated With Cognitive Test Profiles In The Geriatric Population But Not With Mild Cognitive Impairment Or Alzheimer's Disease, N. Ivanchak, Erin L. Abner, S. A. Carr, S. J. Freeman, A. Seybert, John Ranseen, Gregory A. Jicha
Sanders-Brown Center on Aging Faculty Publications
The frequency of ADHD in the aging population and its relationship to late-life cognitive decline has not been studied previously. To address this gap in our understanding, the Wender-Utah ADHD Rating scale (WURS) was administered to 310 geriatric subjects with cognitive status ranging from normal cognition to mild cognitive impairment to overt dementia. The frequency of WURS-positive ADHD in this sample was 4.4%. WURS scores were not related to cognitive diagnoses, but did show nonlinear associations with tasks requiring sustained attention. The frequency of ADHD appears stable across generations and does not appear to be associated with MCI or dementia …
Traumatic Brain Injury: Cyclophilin D As A Therapeutic Target And The Neuropathology Caused By Blast, Ryan Douglas Readnower
Traumatic Brain Injury: Cyclophilin D As A Therapeutic Target And The Neuropathology Caused By Blast, Ryan Douglas Readnower
University of Kentucky Doctoral Dissertations
With an estimated incidence of 1.5 million each year, traumatic brain injury (TBI) is a major cause of mortality and morbidity in the United States. Opening of the mitochondrial permeability transition pore (mPTP) is a key event contributing to TBI pathology. Cyclophilin D (CypD), a matrix peptidyl-prolyl cis-trans isomerase, is believed to be the regulating component of the mPTP. Cyclosporin A, an immunosuppressant drug, inhibits CypD and blocks mPTP formation and has been shown to be neuroprotective following TBI. However, it is unclear if CsA’s neuroprotective mechanism is due to inhibition of CypD and/or immuno-suppression. Therefore to directly assess the …
Development And Characterization Of Novel Monoclonal Antibodies For Studying Prion Pathogenesis, Chu-Chun Weng
Development And Characterization Of Novel Monoclonal Antibodies For Studying Prion Pathogenesis, Chu-Chun Weng
University of Kentucky Master's Theses
Monoclonal antibodies (mAbs) recognizing different regions of PrP are potential tools in the study of prion diseases and immunotherapy. We used shuffled recombinant prion protein containing elk and mouse PrP as antigen to produce monoclonal antibodies in mice. We found that mAb 5C6 mapped to a discontinuous epitope comprised of amino acid 132 and 158 (mouse numbering). Monoclonal anibody 9E9 which maps to a unique N-terminal epitope at amino acid preferentially recognized cervid PrP. In contrast, the epitope of mAb 9H9 is located in the C-terminus and only reacted with mouse and hamster. The epitope for mAb 7H11 appears to …
Should Pseudoephedrine (Pse) Be Moved From Behind The Counter To Prescription-Only? An Analysis Of Pse As An Otc Medication And A Precursor For Methamphetamine Production, Jerry Dillon
MPA/MPP/MPFM Capstone Projects
Kentucky State Senator Tom Jensen recently sponsored Senate Bill 45, which would change pseudoephedrine (PSE) from an over-the-counter to a schedule V prescription-only drug. The bill failed, but the debate continues as to whether Kentucky should make PSE, a precursor required to manufacture illicit methamphetamine, a controlled drug that is available by prescription only.
Methamphetamine abuse has been increasing in Kentucky as well as in the rest of the country, despite efforts to control the sale of PSE through federal and state legislation. The Combat Methamphetamine Epidemic Act (CMEA) of 2006 and Kentucky’s initiative to electronically monitor the sales of …
The Incidence Of Hip Fracture Associated With Proton Pump Inhibitor (Ppi) And/Or H2 Receptor Antagonist (H2ra) Use In The Kentucky Medicaid Population, Timothy C. Umeh
The Incidence Of Hip Fracture Associated With Proton Pump Inhibitor (Ppi) And/Or H2 Receptor Antagonist (H2ra) Use In The Kentucky Medicaid Population, Timothy C. Umeh
MPA/MPP/MPFM Capstone Projects
No executive summary.
Towards The Total Synthesis Of The Capuramycin Family Of Natural Products, Jesse M. Jacobsen
Towards The Total Synthesis Of The Capuramycin Family Of Natural Products, Jesse M. Jacobsen
University of Kentucky Master's Theses
Despite over a century of advancement, tuberculosis remains a grave threat to world health. In particular, third world countries continue to struggle with the crushing weight of the disease. Furthermore, the emergence of drug resistance in TB strains poses a significant threat to the first world where incidence and mortality is low. The dwindling efficacy of current drug regimens necessitates research into new small molecules capable of arresting the growth and spread of TB. The capuramycin family of nucleoside antibiotics shows strong potential to become part of this new generation of anti-TB small molecules. Indeed, their ability to inhibit Translocase …
Analysis Of Student & Teacher Outcomes From Pre-Existing Data Obtained Through The Low Incidence Initiative: Teaching Academic Age-Appropriate Learning Via Communication Project, April M. Holman
University of Kentucky Master's Theses
Students with significant cognitive disabilities frequently exhibit reduced communicative and academic competence. The Low Incidence Initiative (LII) project was a professional development model designed to train school-based teams to facilitate increased communicative and academic competence with such students via distance-technology coaching. This study analyzed pre-existing data from year one of the LII. Data were analyzed to determine effectiveness of the project on communication status of students and on training school personnel to accurately identify student levels of communication, and for overall satisfaction with the project. Results indicated that all student participants demonstrated improvement in expressive communication output. 100% of students …
Strategies For Targeting Lentiviral Vectors, Christopher Matthew Trimby
Strategies For Targeting Lentiviral Vectors, Christopher Matthew Trimby
University of Kentucky Doctoral Dissertations
Lentiviral gene therapy has held great promise for treating a wide range of neurological disorders due to its ability to stably integrate into the genome of nondividing cells like neurons, in addition to dividing cells. The nervous system is a complex and highly heterogeneous system, and while a therapeutic intervention may have beneficial effects in one population of cells it may have severe side effects in another. For this reason, specific targeting of lentiviral vectors is crucial for their ultimate utility for research and clinical research use.
Two different approaches for focusing the targeting of lentiviral vectors were employed in …
Regulation Of Abcg5 And Abcg8 Sterol Transporters In Biliary Cholesterol Elimination, Reverse Cholesterol Transport And Dyslipidemia, Nadezhda Steliyanova Sabeva
Regulation Of Abcg5 And Abcg8 Sterol Transporters In Biliary Cholesterol Elimination, Reverse Cholesterol Transport And Dyslipidemia, Nadezhda Steliyanova Sabeva
University of Kentucky Doctoral Dissertations
ATP-binding cassette transporters ABCA1 and ABCG1 initiate reverse cholesterol transport generating HDL particles, whereas ABCG5/G8 promote biliary cholesterol secretion thereby facilitating the last step of reverse cholesterol transport. Mutations in the leptin axis result in obesity and dyslipidemia in ob/ob and db/db mice. These mice have defective HDL clearance, increased plasma cholesterol and decreased biliary cholesterol elimination. My studies demonstrate that ABCG5/G8 protein is low in these animals and can be restored with caloric restriction or leptin replacement. To directly test whether ABCG5/G8 alone is able to correct reverse cholesterol transport defect, liver specific ABCG5/G8 expression was achieved in db/db …
Role Of Pi3k-Akt Pathway In The Age Associated Decline In Tlr Mediated Activation Of Innate And Adaptive Immune Responses, Mosoka Papa Fallah
Role Of Pi3k-Akt Pathway In The Age Associated Decline In Tlr Mediated Activation Of Innate And Adaptive Immune Responses, Mosoka Papa Fallah
University of Kentucky Doctoral Dissertations
Immunosenescence results in reduced immune response to infections with Streptococcus pneumoniae as well as to pneumococcal polysaccharide vaccines. The antibody response to the capsular polysaccharide (CPS) provides protection against S. pneumoniae infection. CPS immunoresponse is T cell independent and needs the macrophage-derived cytokines such as IL-12, IL-6 and IL-1β to elicit an antibody response. We showed a cytokine dysregulation, i.e. a decrease in IL-12, IL-6 and TNF-α but an increase in IL-10, in the aged (18-24 months old comparable to >65 years in human) compared to young adult mouse (8-12 weeks less than 65 years old) splenic macrophages (SM) or …
Isolation And Elucidation Of The Chrysomycin Biosynthetic Gene Cluster And Altering The Glycosylation Patterns Of Tetracenomycins And Mithramycin-Pathway Molecules, Stephen Eric Nybo
Isolation And Elucidation Of The Chrysomycin Biosynthetic Gene Cluster And Altering The Glycosylation Patterns Of Tetracenomycins And Mithramycin-Pathway Molecules, Stephen Eric Nybo
University of Kentucky Doctoral Dissertations
Natural products occupy a central role as the majority of currently used antibiotic and anticancer agents. Among these are type-II polyketide synthase (PKS)-derived molecules, or polyketides, which are produced by many representatives of the genus Streptomyces. Some type-II polyketides, such as the tetracyclines and the anthracycline doxorubicin, are currently employed as therapeutics. However, several polyketide molecules exhibit promising biological activity, but due to toxic side effects or solubility concerns, remain undeveloped as drugs.
Gilvocarcin V (GV) (topoisomerase II inhibitor) has a novel mechanism of action: [2+2] cycloaddition to thymine residues by the 8-vinyl side chain and cross-linking of histone …
The Influence Of Antidiabetic Medications On The Development And Progression Of Prostate Cancer, Anna Elizabeth Hitron
The Influence Of Antidiabetic Medications On The Development And Progression Of Prostate Cancer, Anna Elizabeth Hitron
University of Kentucky Master's Theses
The development of prostate tumors has been linked to co-morbid diabetes mellitus (DM) in several studies, potentially through the stimulation of insulin-like growth factor receptor (IGFR). This study evaluates the effect of anti-diabetic medication use on the development of high grade tumors and time to tumor progression compared to non-diabetics. This retrospective, nested case control study identified patients with prostate cancer (PCa) from the Kentucky Medicaid Database. Cases were diagnosed with PCa and DM and using at least one of the following antidiabetic medications; sulfonylureas, insulin, metformin or TZDs. Cases were further stratified on their insulin exposure resulting from therapy. …
Lipopolysaccharide Animal Models For Parkinson's Disease, Mei Liu, Guoying Bing
Lipopolysaccharide Animal Models For Parkinson's Disease, Mei Liu, Guoying Bing
Neuroscience Faculty Publications
Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, acts as a potent stimulator of microglia and has been used to study the inflammatory process in the pathogenesis of Parkinson's disease (PD) and anti-inflammatory therapy for PD treatment. Here, we review the growing body of literature on both in vitro and in vivo LPS PD models. Primary cell cultures from mesencephalic tissue were exposed to LPS in vitro; LPS was stereotaxically injected into the substantia nigra, striatum, or globus pallidus of brain or injected into the peritoneal cavity of the animal in vivo. In conclusion, the LPS PD models are summarized as …
Mitochondria, Amyloid Β, And Alzheimer's Disease, Ryan Douglas Readnower, Andrew David Sauerbeck, Patrick G. Sullivan
Mitochondria, Amyloid Β, And Alzheimer's Disease, Ryan Douglas Readnower, Andrew David Sauerbeck, Patrick G. Sullivan
Spinal Cord and Brain Injury Research Center Faculty Publications
Hypometabolism is a hallmark of Alzheimer's disease (AD) and implicates a mitochondrial role in the neuropathology associated with AD. Mitochondrial amyloid-beta (Aβ) accumulation precedes extracellular Aβ deposition. In addition to increasing oxidative stress, Aβ has been shown to directly inhibit mitochondrial enzymes. Inhibition of mitochondrial enzymes as a result of oxidative damage or Aβ interaction perpetuates oxidative stress and leads to a hypometabolic state. Additionally, Aβ has also been shown to interact with cyclophilin D, a component of the mitochondrial permeability transition pore, which may promote cell death. Therefore, ample evidence exists indicating that …
Expedient Treatment Of A Collodion Baby, Michael Chung, Jaime Pittenger, Stuart Tobin, Andrew Chung, Nirmala Desai
Expedient Treatment Of A Collodion Baby, Michael Chung, Jaime Pittenger, Stuart Tobin, Andrew Chung, Nirmala Desai
Pediatrics Faculty Publications
Only ~270 cases of collodion babies have been reported in the literature since 1892. As the name suggests, the term "collodion baby" refers to a phenotype that can be characterized by a yellow, shiny, tight parchment-like membrane stretched over the skin. Although the collodion membrane is only an evanescent condition of the newborn, neonatal complications can occur in 45% of all collodion babies, leading to a mortality rate of ~11% in the first few weeks of life. Most children born as collodion babies will spontaneously desquamate within 2 weeks, but may be as long as 3 months. Eventually, these children …
Factors Associated With Tobacco Use Among Rural And Urban Pregnant Women, Whitney Jeanne Katirai
Factors Associated With Tobacco Use Among Rural And Urban Pregnant Women, Whitney Jeanne Katirai
University of Kentucky Doctoral Dissertations
The purpose of this study was to investigate the influences of smoking on rural and urban pregnant women. More specifically, the variables of the knowledge of health effects, health provider recommendations, subscores from the Health Belief Model (HBM), and social support were explored in relation to the smoking behavior of pregnant women. A secondary purpose was to investigate the accuracy of self-reported smoking during pregnancy using biochemical validation. Pregnant women (N=71) completed an anonymous questionnaire, designed by the researcher, to identify variables that predicted smoking for urban and rural women. Participants also gave a saliva sample for cotinine testing.
Approximately …
Genotoxin-Induced Acetylation Of The Werner Syndrome Protein (Wrn) And Effect On Its Dna Metabolic Function, Enerlyn Meliza Lozada Santiago
Genotoxin-Induced Acetylation Of The Werner Syndrome Protein (Wrn) And Effect On Its Dna Metabolic Function, Enerlyn Meliza Lozada Santiago
University of Kentucky Doctoral Dissertations
Loss of function of the WRN protein causes the genetic disorder Werner Syndrome that is characterized by increased cancer and premature aging. WRN belongs to the RecQ helicase family that plays key roles in preventing genome instability. In response to treatment with genotoxins, WRN is subject to post-translational modification. The relationship of post-translational modification of WRN with its function in DNA metabolism is unknown. There is accumulating evidence suggesting that WRN contributes to the maintenance of genomic integrity through its involvement in DNA replication. Consistent with this notion, WS cells are sensitive to DNA replication inhibitors and DNA damaging agents …
Effect Of Azithromycin On Macrophage Phenotype During Pulmonary Infections And Cystic Fibrosis, Theodore James Cory
Effect Of Azithromycin On Macrophage Phenotype During Pulmonary Infections And Cystic Fibrosis, Theodore James Cory
University of Kentucky Doctoral Dissertations
Azithromycin improves clinical outcomes in patients with cystic fibrosis (CF), specifically in patients infected with Pseudomonas aeruginosa. Azithromycin shifts macrophage programming away from a pro-inflammatory classical (M1) phenotype, and towards an anti-inflammatory alternative (M2) phenotype; however, little is known about this mechanism, nor of its impact upon immune response to pulmonary infection. We set out to determine the mechanism by which azithromycin is able to alter macrophage phenotype, and assess the effect of azithromycin induced macrophage polarization on inflammation during pulmonary infections.
Utilizing macrophage cell culture, we found that azithromycin increased IKKβ, a signaling molecule in the NFκB pathway, which …
Molecular And Genomic Approaches To Understanding Host-Virus Interactions In Shaping The Outcome Of Equine Arteritis Virus Infection, Yun Young Go
University of Kentucky Doctoral Dissertations
Equine arteritis virus (EAV) is the causal agent of equine viral arteritis, a disease of equids. During natural outbreaks of the disease, EAV can cause abortion in pregnant mares and persistent infection in stallions. Understanding how host cellular proteins interact with viral RNA and viral proteins, as well as their role in viral infection, will enable better characterization of the pathogenesis of EAV and establishment of persistent infection in stallions. Accordingly, we hypothesized that both viral factors and host genetically related factors could influence the outcome of EAV infection in horses. To test this hypothesis, we first combined contemporary molecular …
Polyamine Modulation In Alcoholism: Examination Using A Novel Screening Procedure Designed To Predict Anti-Relapse And Neuroprotective Efficacy, J. Ben Lewis
University of Kentucky Doctoral Dissertations
Alcohol dependence is a major public health concern. Despite the FDA’s approval of multiple anti-relapse drugs, relapse rates remain unacceptably high. Furthermore, cognitive deficits among chronic drinkers are evident and are suggested to contribute to relapse risk. Current evidence suggests that several critical features of alcoholism and alcohol-associated neurodegeneration are mechanistically linked to glutamatergic actions; specifically, they appear positively affected by glutamatergic inhibition, particularly inhibition via polyamine modulation of a subpopulation of n-methyl-d-aspartate receptors. The current project was designed to evaluate the performance of two putative polyamine modulators (JR-220 and CP-101,606) in a variety of screens designed …
What Makes People Generally Satisfied With Mental Health Services? Findings Of 2010 Consumer Satisfaction Survey In Kentucky Community Mental Health Centers, Minji Sohn
MPA/MPP/MPFM Capstone Projects
Problem: In 2010, the Kentucky Cabinet for Health and Family Services, Department for Behavioral Health Developmental and Intellectual Disabilities (BHDID) conducted a survey to evaluate consumers’ satisfaction with services delivered at the Community Mental Health Centers (CMHCs) in Kentucky. The purpose of this study is to identify factors that predict clients’ perception on General Satisfaction using responses of the survey.
Research Design: Two separate logistic regression analysis were performed for adult and youth survey respondents, respectively. For the Adult survey, respondents’ characteristics and their responses about several aspects of services were included as potential explanatory variables. For the Youth survey, …
Dental Service Utilization In An Academic Setting: An Analysis For Improved Oral Health, Paula R. Sandford
Dental Service Utilization In An Academic Setting: An Analysis For Improved Oral Health, Paula R. Sandford
MPA/MPP/MPFM Capstone Projects
The National Oral Health Surveillance System (NOHSS) is the result of a collaborative effort between the Centers for Disease Control and Prevention and the Association of State and Territorial Dental Directors which is designed to monitor aspects of oral health and disease on both a national and state level. The NOHSS ranks Kentucky at or near the bottom in most oral health indicators. The primary message of the Surgeon General’s May 2000 report on Oral Health in America was to emphasize the link between oral health and overall health including the effect on day‐to‐day activities such as work and school …
Computational Analyses Of The Uptake And Distribution Of Carbon Monoxide (Co) In Human Subjects, Kinnera Chada
Computational Analyses Of The Uptake And Distribution Of Carbon Monoxide (Co) In Human Subjects, Kinnera Chada
University of Kentucky Doctoral Dissertations
Carbon monoxide (CO) is an odorless, colorless, tasteless gas that binds to hemoglobin with high affinity. This property underlies the use of low doses of CO to determine hemoglobin mass (MHb) in the fields of clinical and sports medicine. However, hemoglobin bound to CO is unable to transport oxygen and exposure to high CO concentrations is a significant environmental and occupational health concern. These contrasting aspects of CO—clinically useful in low doses but potentially lethal in higher doses—mandates a need for a quantitative understanding of the temporal profiles of the uptake and distribution of CO …
Rit Gtpase Signaling Mediates Oxidative Stress Resistance And Survival Of Adult Newborn Neurons After Traumatic Brain Injury, Weikang Cai
Theses and Dissertations--Molecular and Cellular Biochemistry
The small GTPases function as molecular switches to control diverse signaling cascades. The mammalian Rit and Rin, along with Drosophila Ric, comprise an evolutionarily conserved subfamily of the Ras-related GTPases. Previous studies using cultured cell models suggested that Rit was involved in the control of cell proliferation, transformation, neuronal differentiation, morphogenesis, and cell survival, but the principal physiological function of Rit remained uncharacterized.
To address this outstanding question, we employed a genetic approach, engineering a Rit knockout mouse. Using this animal model, we demonstrate a central role of Rit in governing cell survival in a p38-dependent fashion. Primary mouse embryonic …
Intrapsychic Predictors Of Professional Quality Of Life: Mindfulness, Empathy, And Emotional Separation, Jacky T. Thomas
Intrapsychic Predictors Of Professional Quality Of Life: Mindfulness, Empathy, And Emotional Separation, Jacky T. Thomas
University of Kentucky Doctoral Dissertations
A growing literature documents the inherently stressful nature of working with persons who are suffering or traumatized, and the potential for the development of stress disorders among social workers and other helpers. Previous studies of compassion fatigue and burnout have provided important information about professional and workplace variables that might influence risk, but little attention has been given to studying intrapersonal skills/abilities that might reduce risk and/or increase resilience and work satisfaction among helping professionals. This exploratory study asked whether levels of mindfulness, empathy, and emotional separation would influence professional quality of life, including compassion fatigue, burnout, and compassion satisfaction. …
Trichloroethylene Exposure And Traumatic Brain Injury Interact And Produce Dual Injury Based Pathology And Pioglitazone Can Attenuate Deficits Following Traumatic Brain Injury, Andrew David Sauerbeck
Trichloroethylene Exposure And Traumatic Brain Injury Interact And Produce Dual Injury Based Pathology And Pioglitazone Can Attenuate Deficits Following Traumatic Brain Injury, Andrew David Sauerbeck
University of Kentucky Doctoral Dissertations
The development of Parkinson's disease (PD) in humans has been linked to genetic and environmental factors for many years. However, finding common single insults which can produce pathology in humans has proved difficult. Exposure to trichloroethylene (TCE) or traumatic brain injury (TBI) has been shown to be linked to PD and it has also been proposed that multiple insults may be needed for disease development.
The present studies show that exposure to TCE prior to a TBI can result in pathology similar to early PD and that the interaction of both insults is required for impairment in behavioral function, and …
Assessing The Perceptions Of Environmental Pollutants, Health And Nutrition Behavior To Improve Risk Communications In Kentucky, Elizabeth Virginia Willett
Assessing The Perceptions Of Environmental Pollutants, Health And Nutrition Behavior To Improve Risk Communications In Kentucky, Elizabeth Virginia Willett
University of Kentucky Master's Theses
Nutrition interventions are an effective way to improve the dietary habits and lifestyle choices and reduce the risk of chronic disease. The Researchers in the UK-SRP Community Engagement Core develop nutrition programs for communities affected by environmental pollutants. Risk communication is a discipline that can be used to develop targeted nutrition interventions that will yield positive behavior change. The purpose of this study was to examine knowledge, risk perception, and actions concerning environmental pollutants and nutrition behavior. Data was collected using a modified survey instrument based on the validated Environmental Health Engagement Profile (EHEP). Survey participants from diverse regions of …
The Relationship Of Anxiety, Coping, Thinking Style, Life Satisfaction, Social Support, And Selected Demographics Among Young Adult College Students, Jihan Saber Raja Mahmoud
The Relationship Of Anxiety, Coping, Thinking Style, Life Satisfaction, Social Support, And Selected Demographics Among Young Adult College Students, Jihan Saber Raja Mahmoud
University of Kentucky Doctoral Dissertations
Anxiety is prevalent among 13 % of young adult college students and is associated with emotional and behavioral consequences that adversely affect their mental and physical well-being. The major challenge for implementing evidence-based interventions is the lack of a multidimensional approach for evaluating anxiety in this population.
The purpose of this dissertation was to develop an evidence-based theoretical framework for studying the phenomenon of anxiety in young adult college students. Three studies were conducted to achieve this purpose. First, the psychometric properties of the 21-item shortened version of the Depression Anxiety and Stress Scale (DASS-21) were evaluated in a sample …
Combinatorial Biosynthetic Derivatization Of The Antitumoral Agent Gilvocarcin V, Micah Douglas Shepherd
Combinatorial Biosynthetic Derivatization Of The Antitumoral Agent Gilvocarcin V, Micah Douglas Shepherd
University of Kentucky Doctoral Dissertations
Gilvocarcin V (GV), the principal product of Streptomyces griseoflavus Gö 3592 and other Streptomyces spp., is the most prominent member of a distinct class of antitumor antibiotics that share a polyketide derived coumarin-based aromatic core. GV and other members of this class including polycarcin V from Streptomyces polyformus, often referred to as gilvocarcin-like aryl C-glycosides, are particularly interesting because of their potent bactericidal, virucidal and antitumor activities at low concentrations while maintaining low in vivo toxicity. Although the precise molecular mechanism of GV bioactivity is unknown, gilvocarcin V has been shown to undergo a photoactivated [2+2] cycloaddition of …