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Emotional Climate, Feeding Practices, And Feeding Styles: An Observational Analysis Of The Dinner Meal In Head Start Families, Sheryl O Hughes, Thomas G Power, Maria A Papaioannou, Matthew B Cross, Theresa A Nicklas, Sharon K Hall, Richard M Shewchuk Jun 2011

Emotional Climate, Feeding Practices, And Feeding Styles: An Observational Analysis Of The Dinner Meal In Head Start Families, Sheryl O Hughes, Thomas G Power, Maria A Papaioannou, Matthew B Cross, Theresa A Nicklas, Sharon K Hall, Richard M Shewchuk

Faculty, Staff and Students Publications

BACKGROUND: A number of studies conducted with ethnically diverse, low-income samples have found that parents with indulgent feeding styles had children with a higher weight status. Indulgent parents are those who are responsive to their child's emotional states but have problems setting appropriate boundaries with their child. Because the processes through which styles impact child weight are poorly understood, the aim of this study was to observe differences in the emotional climate created by parents (including affect, tone of voice, and gestures) and behavioral feeding practices among those reporting different feeding styles on the Caregiver's Feeding Styles Questionnaire. A secondary …


Addressing The Challenges Of Reporting On Childhood Asthma In A Changing Health Care System: Building Better Evidence For High Performance, Meagan Lyon, Anne Rossier Markus, Maya Tuchman Gerstein, Sara J. Rosenbaum Jun 2011

Addressing The Challenges Of Reporting On Childhood Asthma In A Changing Health Care System: Building Better Evidence For High Performance, Meagan Lyon, Anne Rossier Markus, Maya Tuchman Gerstein, Sara J. Rosenbaum

Geiger Gibson/RCHN Community Health Foundation Research Collaborative

Childhood asthma is a serious and costly chronic disease that burdens children and families as well as the health care systems that serve them. A key element to improving asthma outcomes is access to timely and useful data that can improve the quality of care and inform programs and policies to best serve those communities most burdened by asthma. This Policy Brief examines the nation’s data collection framework for childhood asthma and considers steps that might be taken to strengthen it, including the development, collection and refinement of community-level data to inform local health care systems. Through a review of …


The Huntington's Disease High-Wire Act, Kenneth P. Serbin Jun 2011

The Huntington's Disease High-Wire Act, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.


Successful Aging And The Epidemiology Of Hiv, David E. Vance, Teena Mcguinness, Karen Musgrove, Nancy Ann Orel, Pariya L. Fazeli Jun 2011

Successful Aging And The Epidemiology Of Hiv, David E. Vance, Teena Mcguinness, Karen Musgrove, Nancy Ann Orel, Pariya L. Fazeli

Gerontology Faculty Publications

By 2015, it is estimated that nearly half of those living with HIV in the US will be 50 years of age and older. This dramatic change in the demographics of this clinical population represents unique challenges for patients, health care providers, and society-at-large. Fortunately, because of highly active antiretroviral therapy (HAART) and healthy lifestyle choices, it is now possible for many infected with HIV to age successfully with this disease; however, this depends upon one’s definition of successful aging. It is proposed that successful aging is composed of eight factors: length of life, biological health, cognitive efficiency, mental health, …


Chd Knowledge And Risk Factors Among Filipino-Americans Connected To Primary Care Services, Alona Dalusung-Angosta Jun 2011

Chd Knowledge And Risk Factors Among Filipino-Americans Connected To Primary Care Services, Alona Dalusung-Angosta

Nursing Faculty Presentations

Problem:

Despite growing numbers of FAs in the U.S. and high CHD prevalence, only limited studies are available in the the literature.

Contributing factors?

  • Lack of knowledge
  • Sociodemographic (SD)/Socioeconomic (SE) variables


Ischemia Impairs Vasodilation In Skeletal Muscle Resistance Artery, Kyle Remington Struthers Jun 2011

Ischemia Impairs Vasodilation In Skeletal Muscle Resistance Artery, Kyle Remington Struthers

Master's Theses

Functional vasodilation in arterioles is impaired with chronic ischemia. We sought to examine the impact of chronic ischemia and age on skeletal muscle resistance artery function. To examine the impact of chronic ischemia, the femoral artery was resected from young (2-3mo) and adult (6-7mo) mice and the profunda femoris artery diameter was measured at rest and following gracilis muscle contraction 14 days later using intravital microscopy. Functional vasodilation was significantly impaired in ischemic mice (14.4±4.6% vs. 137.8±14.3%, p<0.0001 n=8) and non-ischemic adult mice (103.0±9.4% vs. 137.8±14.3%, p=0.05 n=10). In order to analyze the cellular mechanisms of the impairment, a protocol was developed to apply pharmacological agents to the experimental preparation while maintaining tissue homeostasis. Endothelial and smooth muscle dependent vasodilation were impaired with ischemia, 39.6 ± 13.6% vs. 80.5 ± 11.4% and 43.0 ± 11.7% vs. 85.1 ± 10.5%, respectively. From this data, it can be supported that smooth muscle dysfunction is the reason for the observed impairment in arterial vasodilation.


Chronic Disease Self-Management Programs: Relevance For Persons With Dementia, Nina M. Silverstein, Alison S. Gottlieb Jun 2011

Chronic Disease Self-Management Programs: Relevance For Persons With Dementia, Nina M. Silverstein, Alison S. Gottlieb

Gerontology Institute Publications

The context for this study is the work of the Healthy Brain Initiative. The CDC has established a cooperative agreement with the Alzheimer’s Association to develop and implement a multifaceted approach to look at cognitive health as a public health issue. Late in 2010, the Association commissioned a review of the major chronic disease prevention programs from a systems approach to begin to understand the source of findings that Medicare beneficiaries with Alzheimer’s and related disorders are much higher cost than those simply with a single chronic disease and no AD. This led to the conclusion that Chronic Disease Self‐Management …


The Role Of Protein Kinase C Epsilon In Hydrogen Peroxide And Nitric Oxide Release During Oxidative Stress Caused By Extracorporeal Shockwave Lithotripsy, Edward S. Iames Jun 2011

The Role Of Protein Kinase C Epsilon In Hydrogen Peroxide And Nitric Oxide Release During Oxidative Stress Caused By Extracorporeal Shockwave Lithotripsy, Edward S. Iames

PCOM Biomedical Studies Student Scholarship

Clinical extracorporeal shock wave lithotripsy (ESWL) treatment to ablate kidney stones can cause acute damage to the renal microvasculature. Accumulation of continued treatment with shockwave therapy can lead to chronic damage to the kidney, and lead to clinical hypertension. Shockwaves have been shown to stimulate endothelial cells to release superoxide (SO), which is converted to hydrogen peroxide (H2O2), and reacts with nitric oxide (NO) to produce peroxynitrite anion (OONO-), creating a powerful oxidant that increases oxidative stress while simultaneously reducing NO bioavailability. Increased oxidative stress during events such as ESWL, also uncouples NO production …


Femoroacetabular Impingement: Saving The Joint, Ronald Huang, Javad Parvizi Jun 2011

Femoroacetabular Impingement: Saving The Joint, Ronald Huang, Javad Parvizi

Department of Orthopaedic Surgery Faculty Papers

Many factors have been linked to the development of osteoarthritis (OA) of the hip, but often, cases are still considered “idiopathic.” Femoroacetabular impingement (FAI) has been suggested as a possible etiologic factor for the otherwise “idiopathic” cases. It is theorized that the subtle morphologic abnormalities seen at the head-neck junction and acetabulum in FAI may lead to labral tears, chondral damage, and subsequent progression of OA. Prevalence of FAI has been suggested to be as high as 14% in the general population. It often presents in young active patients that subject their hip joint to repetitive micro trauma associated with …


Surgical Management Of Complete Atrioventricular Septal Defect: Associations With Surgical Technique, Age, And Trisomy 21., Andrew M. Atz, John A. Hawkins, Minmin Lu, Meryl S. Cohen, Steven D. Colan, James Jaggers, Ronald V. Lacro, Brian W. Mccrindle, Renee Margossian, Ralph S. Mosca, Lynn A. Sleeper, L Luann Minich, Pediatric Heart Network Investigators, Girish S. Shirali Jun 2011

Surgical Management Of Complete Atrioventricular Septal Defect: Associations With Surgical Technique, Age, And Trisomy 21., Andrew M. Atz, John A. Hawkins, Minmin Lu, Meryl S. Cohen, Steven D. Colan, James Jaggers, Ronald V. Lacro, Brian W. Mccrindle, Renee Margossian, Ralph S. Mosca, Lynn A. Sleeper, L Luann Minich, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: We sought to evaluate the contemporary results after repair of a complete atrioventricular septal defect and to determine the factors associated with suboptimal outcomes.

METHODS: The demographic, procedural, and outcome data were obtained within 1 and 6 months after repair of a complete atrioventricular septal defect in 120 children in a multicenter observational study from June 2004 to 2006.

RESULTS: The median age at surgery was 3.7 months (range, 9 days to 1.1 years). The type of surgical repair was a single patch (18%), double patch (72%), and a single atrial septal defect patch with primary ventricular septal defect …


Renin-Angiotensin-Aldosterone Genotype Influences Ventricular Remodeling In Infants With Single Ventricle., Seema Mital, Wendy K. Chung, Steven D. Colan, Lynn A. Sleeper, Cedric Manlhiot, Cammon B. Arrington, James F. Cnota, Eric M. Graham, Michael E. Mitchell, Elizabeth Goldmuntz, Jennifer S. Li, Jami C. Levine, Teresa M. Lee, Renee Margossian, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali May 2011

Renin-Angiotensin-Aldosterone Genotype Influences Ventricular Remodeling In Infants With Single Ventricle., Seema Mital, Wendy K. Chung, Steven D. Colan, Lynn A. Sleeper, Cedric Manlhiot, Cammon B. Arrington, James F. Cnota, Eric M. Graham, Michael E. Mitchell, Elizabeth Goldmuntz, Jennifer S. Li, Jami C. Levine, Teresa M. Lee, Renee Margossian, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

Background: We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function, and response to enalapril in infants with single ventricle.

Methods and results: Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with renin-angiotensin-aldosterone system upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate, and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high risk), and those …


S.O.S. For Huntington's Disease Families, And An Important Bill In Congress, Kenneth P. Serbin May 2011

S.O.S. For Huntington's Disease Families, And An Important Bill In Congress, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.


Variations In Mre11/Rad50/Nbs1 Status And Dna Damage-Induced S-Phase Arrest In The Cell Lines Of The Nci60 Panel, Kristen M. K. Garner, Alan Eastman May 2011

Variations In Mre11/Rad50/Nbs1 Status And Dna Damage-Induced S-Phase Arrest In The Cell Lines Of The Nci60 Panel, Kristen M. K. Garner, Alan Eastman

Dartmouth Scholarship

The Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity.


Hivtoolbox, An Integrated Web Application For Investigating Hiv, David P. Sargeant, Sandeep Deverasetty, Yang Luo, Angel Villahoz Baleta, Stephanie Zobrist, Viraj Rathnayake, Jacqueline C. Russo, Jay Vyas, Mark A. Muesing, Martin Schiller May 2011

Hivtoolbox, An Integrated Web Application For Investigating Hiv, David P. Sargeant, Sandeep Deverasetty, Yang Luo, Angel Villahoz Baleta, Stephanie Zobrist, Viraj Rathnayake, Jacqueline C. Russo, Jay Vyas, Mark A. Muesing, Martin Schiller

Life Sciences Faculty Research

Many bioinformatic databases and applications focus on a limited domain of knowledge federating links to information in other databases. This segregated data structure likely limits our ability to investigate and understand complex biological systems. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and allows virologists and structural biologists to access sequence, structure, and functional relationships in an intuitive web application. HIV-1 integrase protein was used as a case study to show the utility of this application. We show how data integration facilitates identification of new questions and hypotheses much more rapid …


Holding The Potential Cure In My Hand, Kenneth P. Serbin May 2011

Holding The Potential Cure In My Hand, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.


Childhood Meat Eating And Inflammatory Markers: The Guangzhou Biobank Cohort Study, Mary Schooling, Chao Q. Jiang, Tai H. Lam, W. S. Zhang, Kar Keung Cheng, Gabriel M. Leung May 2011

Childhood Meat Eating And Inflammatory Markers: The Guangzhou Biobank Cohort Study, Mary Schooling, Chao Q. Jiang, Tai H. Lam, W. S. Zhang, Kar Keung Cheng, Gabriel M. Leung

Publications and Research

Background
We hypothesized that socio-economic development could, via nutritionally driven levels of pubertal sex-steroids, promote a pro-inflammatory state among men but not women in developing countries. We tested this hypothesis, using recalled childhood meat eating as a proxy for childhood nutrition, in southern China.

Methods
We used multivariable linear regression in the Guangzhou Biobank Cohort Study phase 3 (2006-8) to examine the adjusted associations of recalled childhood meat eating, <1/week (n = 5,023), about once per week (n = 3,592) and almost daily (n = 1,252), with white blood cell count and its differentials among older (≥50 years) men (n = 2,498) and women (n = 7,369).

Results
Adjusted for age, childhood socio-economic position, education and smoking, childhood meat eating had sex-specific associations with white blood cell count and lymphocyte count, but not granulocyte count. Men with childhood …


The Effects Of Computer-Based Education On Children's Knowledge About Asthma, Matyt L. Adler May 2011

The Effects Of Computer-Based Education On Children's Knowledge About Asthma, Matyt L. Adler

Evidence-Based Practice Project Reports

Asthma is a global health problem affecting people of all ages that can cause severe limitations when uncontrolled. In the United States, asthma was the most prevalent chronic disease among children and youth in 2008 (U.S. Department of Health and Human Services, 2009). Because day-to-day management of asthma is the responsibility of the child or the parent, education of patients is one of four crucial components to effectively provide quality asthma care. Changes in workload complexities with primary care visits has increased and visit duration decreased, resulting in less available time to address individual patient needs including the education aspect …


The Huntington’S Community Rising And Converging, Kenneth P. Serbin May 2011

The Huntington’S Community Rising And Converging, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.


Influenza And Bacterial Coinfections In The 20th Century, Xuan-Yi Wang, Paul E. Kilgore, Kyung Ah Lim, Song-Mei Wang, Jeongseok Lee, Wei Deng, Mei-Qi Mo, Batmunkh Nyambat, Jing-Chen Ma, Michael O. Favorov, John D. Clemens May 2011

Influenza And Bacterial Coinfections In The 20th Century, Xuan-Yi Wang, Paul E. Kilgore, Kyung Ah Lim, Song-Mei Wang, Jeongseok Lee, Wei Deng, Mei-Qi Mo, Batmunkh Nyambat, Jing-Chen Ma, Michael O. Favorov, John D. Clemens

Department of Pharmacy Practice

To help understand the potential impact of bacterial coinfection during pandemic influenza periods, we undertook a far-reaching review of the existing literature to gain insights into the interaction of influenza and bacterial pathogens. Reports published between 1950 and 2006 were identified from scientific citation databases using standardized search terms. Study outcomes related to coinfection were subjected to a pooled analysis. Coinfection with influenza and bacterial pathogens occurred more frequently in pandemic compared with seasonal influenza periods. The most common bacterial coinfections with influenza virus were due to S. pneumoniae, H. influenzae, Staphylococcus spp., and Streptococcus spp. …


Bin Laden And Hd, Kenneth P. Serbin May 2011

Bin Laden And Hd, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.


Strategies To Reduce Disease Burden From Diabetes And Hypertension In Developing World, Waris Qidwai May 2011

Strategies To Reduce Disease Burden From Diabetes And Hypertension In Developing World, Waris Qidwai

Department of Family Medicine

No abstract provided.


Inflammatory Proteins, Genetic Variation, And Environmental Influences On Health Care Associated Infection Development In Sepsis, Reba Antoinette Umberger May 2011

Inflammatory Proteins, Genetic Variation, And Environmental Influences On Health Care Associated Infection Development In Sepsis, Reba Antoinette Umberger

Theses and Dissertations (ETD)

The purpose of this study was to determine the impact of baseline systemic inflammation (pro‑inflammatory cytokine, anti‑inflammatory cytokine, and their ratio), genetic variability, and environment on the development of health care associated infections (HAI) among sepsis patients during their ICU stay (up to 28 days).

Methods: A prospective observation study was conducted at the Veterans Affairs Medical Center in the Medical Intensive Care Unit over an 18 month period. A total of 78 patients were enrolled within 72 hours of presenting to the ICU with sepsis. Patient were excluded if they were receiving immunosuppressants (chemotherapy or greater than one mg/kg …


High-Risk Human Papillomavirus (Hpv): An Emerging Health Issue For Women And Minorities, Dierdre O. Turner May 2011

High-Risk Human Papillomavirus (Hpv): An Emerging Health Issue For Women And Minorities, Dierdre O. Turner

UNLV Theses, Dissertations, Professional Papers, and Capstones

The human papillomavirus (HPV) is the cause of nearly all cases of cervical cancers worldwide. HPV viral DNA is found in more than 99% of cervical cancers. In addition to cervical cancer, HPV is also associated with some breast and oral cancers. White women have been showing a decline in breast cancer rates while black women are continuously showing higher rates of mortality from both breast and cervical cancer. Minority women are also more likely to receive a late diagnosis and are showing increased incidence of oral cancer, which makes study of HPV in women and minorities significant.

To date, …


Bioarchaeology Of Compassion: Exploring Extreme Cases Of Pathology In A Bronze Age Skeletal Population From Tell Abraq, U.A.E., Jamie D. Vilos May 2011

Bioarchaeology Of Compassion: Exploring Extreme Cases Of Pathology In A Bronze Age Skeletal Population From Tell Abraq, U.A.E., Jamie D. Vilos

UNLV Theses, Dissertations, Professional Papers, and Capstones

Tell Abraq is a Bronze Age archaeological site located in the modern day United Arab Emirates and was occupied from the 3rd millennium BC to the 1st century AD. The coastal location provided access to both marine and agricultural resources as well as trade routes and foreign exchange. The tomb at the site was in use for 200 years (2200-2000 BC) and housed the commingled remains of a minimum of 286 adults. These individuals lived hard lives, dependent on good health to maintain a life-line of sustenance for themselves and each other. A number of individuals with severe expressions of …


Evaluation Of Kawasaki Disease Risk-Scoring Systems For Intravenous Immunoglobulin Resistance., Lynn A. Sleeper, L Luann Minich, Brian M. Mccrindle, Jennifer S. Li, Wilbert Mason, Steven D. Colan, Andrew M. Atz, Beth F. Printz, Annette Baker, Victoria L. Vetter, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali May 2011

Evaluation Of Kawasaki Disease Risk-Scoring Systems For Intravenous Immunoglobulin Resistance., Lynn A. Sleeper, L Luann Minich, Brian M. Mccrindle, Jennifer S. Li, Wilbert Mason, Steven D. Colan, Andrew M. Atz, Beth F. Printz, Annette Baker, Victoria L. Vetter, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess the performance of 3 risk scores from Japan that were developed to predict, in children with Kawasaki disease, resistance to intravenous immunoglobulin (IVIG) treatment.

STUDY DESIGN: We used data from a randomized trial of pulsed steroids for primary treatment of Kawasaki disease to assess operating characteristics of the 3 risk scores, and we examined whether steroid therapy lowers the risk of coronary artery abnormalities in patients prospectively classified as IVIG resistant.

RESULTS: For comparability with published cohorts, we analyzed the data of 99 patients who were not treated with steroids (16% IVIG-retreated) and identified male sex, lower …


Self-Reported Exercise And Risk Of Osteoporosis In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Lori J. Mennen-Winchell May 2011

Self-Reported Exercise And Risk Of Osteoporosis In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Lori J. Mennen-Winchell

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate cancer is stimulated to grow in response to testosterone. Androgen deprivation therapy (ADT) leads to chemical castration and suppression of prostate cancer cell production. Testosterone levels less then 300ng/ml decreases bone mineral density and could result in osteoporosis. Studies have shown that during the first year of ADT, fracture risk, mainly in hips and spine increases about 50%. In men, 40% of hip fractures result in death. Exercise may reduce the risk of osteoporosis and thus contribute to the prevention of hip and other fractures. There is limited data regarding whether exercise is associated with a reduced risk of …


Atm Signaling To Tsc2: Mechanisms And Implications For Cancer Therapy, Angela Alexander May 2011

Atm Signaling To Tsc2: Mechanisms And Implications For Cancer Therapy, Angela Alexander

Dissertations and Theses (Open Access)

Ataxia telangiectasia mutated (ATM) is a critical component of the cellular response to DNA damage, where it acts as a damage sensor, and signals to a large network of proteins which execute the important tasks involved in responding to the damage, namely inducing cell cycle checkpoints, inducing DNA repair, modulating transcriptional responses, and regulating cell death pathways if the damage cannot be repaired faithfully. We have now discovered that an additional novel component of this ATM-dependent damage response involves induction of autophagy in response to oxidative stress. In contrast to DNA damage-induced ATM activation however, oxidative stress induced ATM, occurs …


To Consult Or Not To Consult? Investigating Barriers To Dysparenia Treatment-Seeking In Young Women, Robyn L. Donaldson May 2011

To Consult Or Not To Consult? Investigating Barriers To Dysparenia Treatment-Seeking In Young Women, Robyn L. Donaldson

UNLV Theses, Dissertations, Professional Papers, and Capstones

Little is known about mediators of treatment-seeking in dyspareunia. The general health belief literature as well as some existing qualitative data specific to dyspareunia, however, suggests a number of potentially significant barriers that may delay or prevent women from enlisting the aid of health care professionals. The aim of this study was to investigate influences on dyspareunia treatment-seeking behavior in young women, for whom the consequences of treatment avoidance are hypothesized to be the greatest. Given the lack of standardized health behavior measures relevant to intercourse pain, we constructed a measure assessing potential barriers to dyspareunia treatment-seeking. An exploratory principal …


Insights Into P53-Dependent Apoptotic Signaling And Cell Fate Vis-A-Vis Functional Cooperation Among Bcl-Xl, Cytoplasmic P53, And Puma, John C. Fisher May 2011

Insights Into P53-Dependent Apoptotic Signaling And Cell Fate Vis-A-Vis Functional Cooperation Among Bcl-Xl, Cytoplasmic P53, And Puma, John C. Fisher

Theses and Dissertations (ETD)

Following DNA damage, nuclear p53 induces the expression of PUMA (p53 upregulated modulator of apoptosis), a BH3‑only protein that binds and inhibits the anti‑apoptotic BCL‑2 repertoire, including BCL‑xL. Structural investigations of PUMA and the BCL‑xL×PUMA BH3 domain complex by X‑ray crystallography and nuclear magnetic resonance (NMR) spectroscopy reveal a novel, PUMA‑induced, domain‑swapped dimerization of BCL‑xL that requires a π‑stacking interaction between PUMA W71 and BCL‑xL H113. PUMA is an intrinsically disordered protein, but upon interaction with BCL‑xL, PUMA W71 and the PUMA BH3 domain residues fold into an alpha helix and subtly remodel BCL‑xL to trigger its dimerization. Wild type …


Pharmacokinetic And Pharmacodynamic Studies Of A Novel Spectinamide Series Of Antituberculosis Agents, V. N. R. Pavan Kumar Vaddady May 2011

Pharmacokinetic And Pharmacodynamic Studies Of A Novel Spectinamide Series Of Antituberculosis Agents, V. N. R. Pavan Kumar Vaddady

Theses and Dissertations (ETD)

Spectinamides are novel amide derivatives of the antibiotic spectinomycin that have emerged as a new class of agents to treat tuberculosis. These agents showed potent in vitro activity against Mycobacterium tuberculosis (MTB) compared to spectinomycin and in a preliminary in vivo study in interferon gamma (IFN‑γ) knockout mice, spectinamide Lee1329 reduced the lung bacillary load of TB comparable to streptomycin. We hypothesized that the application of an iterative pharmacokinetics and pharmacodynamics (PK/PD) guided approach would facilitate the optimization of these lead compounds suitable for further development.

A series of in vitro experiments including parallel artificial membrane permeability assay (PAMPA), microsomal …