Medical Sciences Commons^™

Dashing Away Hypertension: Evaluating The Efficacy Of The Dietary Approaches To Stop Hypertension Diet In Controlling High Blood Pressure, Preeya Shah Phd, Kyle D. Maxwell, Joseph I. Shapiro Md

Biochemistry and Microbiology

The dietary approaches to stop hypertension (DASH) diet has been developed and popularized as a non-pharmaceutical intervention for high blood pressure reduction since 1995. However, to date, a comprehensive description of the biochemical rationale behind the diet’s principal guidelines has yet to be compiled. With rising interest for healthy and reliable life-style modifications to combat cardiovascular disease, this review aims to compile the most recent and relevant studies on this topic and make an informed assessment as to the efficacy of and underlying mechanisms operant in the DASH diet. Specifically, the merits of lowering dietary intake of sodium and saturated …

A Disease-Based Approach To The Vertical And Horizontal Integration Of A Medical Curriculum, Charles A. Gullo Phd, Brian R. Dzwonek, Bobby L. Miller

Biochemistry and Microbiology

As medical disciplines have become increasingly interdisciplinary and evidenced-based medicine is widely practiced, there is a need for curricula that reflect these changes. The newly revised LCME standards 1.1 Strategic Planning and Continuous Quality Improvement and 8.3 Curricular Design, Review, Revision/Content Monitoring require ongoing curricular review to assure accreditation compliancy. We have completed a comprehensive review of our curriculum and have moved from a discipline-based curriculum to that of one that focuses on a systems/disease-based model. The approach allows for a more horizontally integrated curriculum in the preclinical years, while the use of 115 distinct disease and eight themes creates …

Sh2 Ligand-Like Effects Of Second Cytosolic Domain Of Na/K-Atpase Α1 Subunit On Src Kinase, Moumita Banerjee, Qiming Duan, Zijian Xie

Pharmaceutical Science and Research

Our previous studies have suggested that the α1 Na/K-ATPase interacts with Src to form a receptor complex. In vitro binding assays indicate an interaction between second cytosolic domain (CD2) of Na/K-ATPase α1 subunit and Src SH2 domain. Since SH2 domain targets Src to specific signaling complexes, we expressed CD2 as a cytosolic protein and studied whether it could act as a Src SH2 ligand in LLC-PK1 cells. Co-immunoprecipitation analyses indicated a direct binding of CD2 to Src, consistent with the in vitro binding data. Functionally, CD2 expression increased basal Src activity, suggesting a Src SH2 ligand-like property of CD2. Consistently, …

Adolescent Intermittent Alcohol Exposure: Deficits In Object Recognition Memory And Forebrain Cholinergic Markers, H. Scott Swartzwelder, Shawn K. Acheson, Kelsey M. Miller, Hannah G. Sexton, Wen Liu, Fulton T. Crews, Mary-Louise Risher

Biomedical Sciences

The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational …

Cross-Sectional Survey Of Relevant Literatures As To The Current Proposed Disease Mechanisms And Treatments Of Amyotrophic Lateral Sclerosis (Als), Zachary Sanford

Marshall Journal of Medicine

Amyotrophic Lateral Sclerosis (ALS), more commonly referred to as Lou Gehrig’s disease, is a progressively degenerative neuromuscular disorder affecting both the upper and lower motor neurons and preferentially affecting males in their forties to seventies. Although the pathology of ALS has been clearly elucidated elsewhere, the precise mechanisms by which the disease progresses and the means by which it is acquired are still poorly understood areas of medicine. Current genomic and proteomic studies in human and animal models have yielded exciting and promising new findings that may help elucidate this pathology. It is the purpose of this review article to …

Interrater Variability In Identifying Ventilator Associated Pneumonia Using Six Different Definitions, Ahmad Nusair, Md, Balwinder Singh, Md, Ms., Shifang Ding, Md, Phd., Ognjen Gajic, Md, Guangxi Li, Md

Marshall Journal of Medicine

Objective

There is no widely accepted standard definition for Ventilator Associated Pneumonia (VAP). The reliability of the current definitions in use remains controversial. Our objective was to assess the reliability of six commonly used VAP definitions: The Loose, The Rigorous, The Modified Clinical Pulmonary Infection Score (CPIS), The Canadian Critical Care Trials Group (CCCTG), The International Sepsis Forum Consensus (ISFC) and The Center for Disease Control and Prevention (CDC).

Design

We examined the electronic health records of all the consecutively admitted adult patients at our institution who received invasive mechanical ventilation (IMV) for ≥ 48 hours, from January 2006 through …

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Biochemistry and Microbiology

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed …

Autophagy Protects Against Cyp2e1/Chronic Ethanol-Induced Hepatotoxicity, Yongke Lu, Arthur I. Cederbaum

Pharmacology, Physiology and Toxicology

Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver …

Cerium Oxide Nanoparticle Treatment Ameliorates Peritonitis-Induced Diaphragm Dysfunction, Shinichi Asano, Ravikumar Arvapalli, Nandini D. Manne, Mani Maheshwari, Bing Ma, Kevin M. Rice, Vellaisamy Selvaraj, Eric Blough

MIIR Faculty Research

The severe inflammation observed during sepsis is thought to cause diaphragm dysfunction, which is associated with poor patient prognosis. Cerium oxide (CeO₂) nanoparticles have been posited to exhibit anti-inflammatory and antioxidative activities suggesting that these particles may be of potential use for the treatment of inflammatory disorders. To investigate this possibility, Sprague Dawley rats were randomly assigned to the following groups: sham control, CeO₂ nanoparticle treatment only (0.5 mg/kg iv), sepsis, and sepsis+CeO₂ nanoparticles. Sepsis was induced by the introduction of cecal material (600 mg/kg) directly into the peritoneal cavity. Nanoparticle treatment decreased sepsis-associated impairments in …

We Are… Bridging Medicine And Science, Vol. 1, Issue 4, Fall 2015, Marshall University Biomedical Sciences

We Are... Bridging Medicine Science

No abstract provided.

Myricetin Inhibits Proliferation Of Cisplatin-Resistant Cancer Cells Through A P53-Dependent Apoptotic Pathway, Haizhi Huang, Allen Y. Chen, Xingqian Ye, Bingyun Li, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatinresistant cancer …

Platelet-Activating Factor Receptor Affects Food Intake And Body Weight, Wei Li, Thomas M. Mcintyre

Biomedical Sciences

“Let’s Move!” is a comprehensive initiative, launched by the First Lady, Michelle Obama, dedicates to solving problems of obesity, which is growing in child. The life behaviors do affect obesity; however, the mechanistic insight in molecular level is still not clear. In this study, by continually monitoring mouse body weight under chow and high fat western diets as well as metabolic, physical activity and food intake behaviors assessed in a CLAMS Comprehensive Lab Animal Monitoring System, we demonstrated that the platelet-activating factor receptor (PTAFR) contributes to modification of life behaviors. PTAFR does not affect metabolism of ingested dietary fat and …

The Tri-State Experience: Outcome Analysis Of Patients With Triple Negative Breast Cancer Treated At Marshall University, Laurie Matt Md, Mph, Mohammad Mozayen Md, Todd W. Gress Md, Maria Tria Tirona Md

Internal Medicine

Breast cancer is the most frequently diagnosed malignancy in women in the United States. It is the second most common malignancy to cause death, with approximately 39,000 women dying of breast cancer in the United States in 2013. Triple negative breast cancer is defined as the absence of estrogen, progesterone and human epidermal growth factor receptor 2 receptors. It has been associated with a higher incidence in African American women, a younger age and a more advanced stage at diagnosis, and an inferior overall survival. To recognize the differences of our West Virginia community population when compared to the national …

Myricetin Inhibits Proliferation Of Cisplatin-Resistant Cancer Cells Through A P53-Dependent Apoptotic Pathway, Haizhi Huang, Allen Y. Chen, Xingqian Ye, Bingyun Li, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmaceutical Science and Research

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatin-resistant cancer …

Gallic Acid, A Phenolic Compound, Exerts Anti-Angiogenic Effects Via The Pten/Akt/Hif-1Α/Vegf Signaling Pathway In Ovarian Cancer Cells, Zhiping He, Allen Y. Chen, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmaceutical Science and Research

Gallic acid (GA), a polyphenol, is widely found in numerous fruits and vegetables, particularly in hickory nuts. In the present study, we found that gallic acid, a natural phenolic compound isolated from fruits and vegetables, had a more potent growth inhibitory effect on two ovarian cancer cell lines, OVCAR-3 and A2780/CP70, than the effect on a normal ovarian cell line, IOSE-364. These results demonstrated that GA selectively inhibits the growth of cancer cells. Gene expression was examined by ELISA and western blot analysis, and gene pathways were examined by luciferase assay. It was found that GA inhibited VEGF secretion and …

Differences In Health-Related Behaviors And Attitudes Between Urban, Rural, And Isolated Households In Western West Virginia, Michael Newsome Phd, Tim Hazelett, Monika Sawhney Phd, Msw

Economics Faculty Research

This study uses data from a 2013 survey of 275 randomly sampled households across nine counties in western West Virginia to examine the significant differences between the health behaviors and attitudes of rural and isolated populations. The results show that age, education, and income are significant factors in explaining differences in health-related behaviors and attitudes for all urban, rural and isolated respondents. However, after controlling for socio-demographic differences, isolation is found to have only a few significant effects, and some of the effects run counter to stereotypes of isolated populations. Rural respondents are significantly more likely than isolated respondents to …

The Sox9 Upstream Region Prone To Chromosomal Aberrations Causing Campomelic Dysplasia Contains Multiple Cartilage Enhancers, Baojin Yao, Qiuqing Wang, Chia-Feng Liu, Pallavi Bhattaram, Wei Li, Timothy J. Mead, James F. Crish, Véronique Lefebvre

Biomedical Sciences

Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized skeleton malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. In contrast, the mechanisms whereby translocations in the –350/–50-kb region 5 of SOX9 cause severe disease and whereby SOX9 expression is specified in chondrocytes remain scarcely known. We here screen this upstream region and uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9 expression domain. Three of them are primarily active in chondrocytes. E250 (located at – 250 kb) confines its activity to condensed prechondrocytes, …

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated By Ho-1-Sirt1 Module In Murine Hepatocytes And Mice Fed A High Fructose Diet, Komal Sodhi, Nitin Puri, Gaia Favero, Sarah Stevens, Charles Meadows, Nader G. Abraham, Rita Rezzani, Hayden A. Ansinelli, Edward Lebovics, Joseph I. Shapiro

Biochemistry and Microbiology

Background

Oxidative stress underlies the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), obesity and cardiovascular disease (CVD). Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1) belongs to the family of NAD-dependent de-acyetylases and is modulated by cellular redox.

Hypothesis

We hypothesize that fructose-induced obesity creates an inflammatory and oxidative environment conducive to the development of NAFLD and metabolic syndrome. The aim of this study is to determine whether HO-1 acts through SIRT1 to form a functional module within hepatocytes to attenuate steatohepatitis, hepatic fibrosis and cardiovascular dysfunction.

Methods …

Robotic Joint Replacement Surgery: Does Technology Improve Outcomes, Chelsea Hill, Reem El-Bash, Leslie Johnson, Alberto Coustasse

Management Faculty Research

Introduction: Osteoarthritis is a common disease that leads patients to seek Total Joint Replacement (TJR). Component misalignments leads to failure of TJR. Computer navigation enhances the precision of component alignment, but the addition of robotic guidance, can boost TJR to a higher level of accuracy.

Methodology: This literature reviewed 29 English language peer reviewed articles from 2002 – 2013 and one website. A conceptual framework was adapted to explain benefits and barriers of adoption of robotic TJR.

Results: A total of ten studies were reviewed with focus on more precise alignment, outcomes, length of stay, and costs. Cost to obtain …

Cerium Oxide Nanoparticles Inhibit Lipopolysaccharide Inducedmap Kinase/Nf-Kb Mediated Severe Sepsis, Mani Maheshwari, Nandini Manne Phd, Shinichi Asano, Eric Blough, Kevin M. Rice, Niraj Nepa,, Erin Fankhanel

Pharmaceutical Science and Research

The life threatening disease of sepsis is associated with high mortality. Septic patient survivability with currently available treatments has failed to improve. The purpose of this study was to evaluate whether lipopolysaccharide (LPS) induced sepsis mortality and associated hepatic dysfunction can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the methods processing of raw data related to our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In press) and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press). The data present here provides confirmation …

Epigenetics As An Answer To Darwin’S “Special Difficulty,” Part 2: Natural Selection Of Metastable Epialleles In Honey Bee Castes, Douglas M. Ruden, Pablo E. Cingolani, Arko Sen, Wen Qu, Luan Wang, Marie-Claude Senut, Mark D. Garfinkel, Vincent E. Sollars, Xiangyi Lu

Biochemistry and Microbiology

In a recent perspective in this journal, Herb (2014) discussed how epigenetics is a possible mechanism to circumvent Charles Darwin’s “special difficulty” in using natural selection to explain the existence of the sterile-fertile dimorphism in eusocial insects. Darwin’s classic book “On the Origin of Species by Means of Natural Selection” explains how natural selection of the fittest individuals in a population can allow a species to adapt to a novel or changing environment. However, in bees and other eusocial insects, such as ants and termites, there exist two or more castes of genetically similar females, from fertile queens to multiple …

Cancer Stem Cells In The Screening Of Anticancer Drugs For Central Nervous System Tumors, Sarah Elizabeth Daron-Mathis

Theses, Dissertations and Capstones

There is a growing need (in the medical field) to design personalized therapy for cancer patients. Decades of cancer research have found no silver bullet that can cure all or even most patients. This study evaluated four patients affected by central nervous system (CNS) tumors (Ependymoma and Glioblastoma), and found that tumors with the same histology had unique responses to treatment. Each sample presented different levels of heterogeneity in expressed biomarkers and responded to drugs at varying levels.

Oncologists conventionally treat cancer patients with drugs tested in large clinical trials. However, often patients do not experience positive outcomes following treatments …

Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer, Rounak Paramjeet Nande

Theses, Dissertations and Capstones

A major challenge for effective gene therapy is systemic delivery of viruses carrying therapeutic genes into affected tissue. The immunogenic nature of human adenoviruses (Ads) limits their use for intratumoral (IT) injection in gene therapy. Ads transfection is further hampered by the fluctuating presence of Coxsackie and Adenovirus Receptor (CAR) and integrins on the cells’ surface. To circumvent these limitations we developed a novel approach wherein Ads are encapsulated inside the shell of lyophilized, lipid-encapsulated, perfluorocarbon microbubbles (MBs)/ultrasound (US) contrast agents, which act as delivery vehicles for a sitespecific gene transfer system.

We performed infection studies with Ad.GFP (Green Fluorescent …

Epigenetic Role Of Ptip In Mouse Spermatogenesis, Chengjing Liu

Theses, Dissertations and Capstones

In mammals, spermatogenesis is a biological process inside the testis to produce spermatozoa from spermatogonia. This process is governed by both genetic and epigenetic mechanisms and thus is a powerful system for epigenetic research. Methylation of histone 3 lysine 4 (H3K4) is an epigenetic mark, which has been found to be dynamically modulated in mouse male germ cells during spermatogenesis. Pax2 Transactivation domain Interaction Protein (PTIP) has been recently identified as part of a H3K4 methyltransferase complex. In this study, I hypothesize that PTIP is an essential epigenetic regulator in mouse spermatogenesis. To test this hypothesis, I first established a …

Cerium Oxide Nanoparticles Attenuate Polymicrobial Sepsis Induced Splenic Damage In Male Sprague Dawley Rats, Venkata Vinay Kumar Bandarupalli

Theses, Dissertations and Capstones

Sepsis is a serious life threatening medical emergency which, if not treated properly, oftentimes results in organ failure and death. Current sepsis treatment protocols are largely centered on the use of antibiotics and supportive care. Recent studies have suggested that antibiotics fail to be effective for sepsis treatment when administered during hypo-dynamic phase of sepsis that is usually characterized by the presence of a cytokine storm. As such, there is an urgent need to develop novel therapeutic drugs that target the inflammatory cytokines that are secreted as a result of increased reactive oxygen species. Cerium oxide nanoparticles (CeO2) have been …

Isolated Candida Infection Of The Lung, Yousef Shweihat Md, James Perry, Darshana T. Shah Phd

Biochemistry and Microbiology

Candida pneumonia is a rare infection of the lungs, with the majority of cases occurring secondary to hematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or skin. We report a case of a 77-year-old male who is life-long smoker with a history of rheumatoid arthritis and polymyalgia rheumatica, but did not take immunosuppressants for those conditions. Here, we present an extremely rare case of isolated pulmonary parenchymal Candida infection in the form pulmonary nodules without evidence of systemic disease which has only been described in a few previous reports.

Ascorbic Acid And Ascorbate-2-Phosphate Decrease Hif Activity And Malignant Properties Of Human Melanoma Cells, Sarah Miles, Adam P. Fischer, Sandeep J. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background: Hypoxia inducible factor-1 alpha (HIF-1α) is thought to play a role in melanoma carcinogenesis. Posttranslational regulation of HIF-1α is dependent on Prolyl hydroxylase (PHD 1–3) and Factor Inhibiting HIF (FIH) hydroxylase enzymes, which require ascorbic acid as a co-factor for optimal function. Depleted intra-tumoral ascorbic acid may thus play a role in the loss of HIF-1α regulation in melanoma. These studies assess the ability of ascorbic acid to reduce HIF-1α protein and transcriptional activity in metastatic melanoma and reduce its invasive potential.

Methods: HIF-1α protein was evaluated by western blot, while transcriptional activity was measured by HIF-1 HRE-luciferase reporter …