Other Medical Sciences Commons^™

Epoxyeicosatrienoic Acids Regulate Adipocyte Differentiation Of Mouse 3t3 Cells, Via Pgc-1Α Activation, Which Is Required For Ho-1 Expression And Increased Mitochondrial Function, Maayan Waldman, Lars Bellner, Luca Vanella, Joseph Schragenheim, Komal Sodhi, Shailendra P. Singh, Daohong Lin, Anand Lakhkar, Jiangwei Li, Edith Hochhauser, Michael Arad, Zbigniew Darzynkiewicz, Attallah Kappas, Nader G. Abraham

Biochemistry and Microbiology

Epoxyeicosatrienoic acid (EET) contributes to browning of white adipose stem cells to ameliorate obesity/diabetes and insulin resistance. In the current study, we show that EET altered preadipocyte function, enhanced peroxisome proliferation-activated receptor γ coactivator α (PGC-1α) expression, and increased mitochondrial function in the 3T3-L1 preadipocyte subjected to adipogenesis. Cells treated with EET resulted in an increase, P < 0.05, in PGC-1α and a decrease in mitochondria-derived ROS (MitoSox), P < 0.05. The EET increase in heme oxygenase-1 (HO-1) levels is dependent on activation of PGC-1α as cells deficient in PGC-1α (PGC-1α knockout adipocyte cell) have an impaired ability to express HO-1, P < 0.02. Additionally, adipocytes treated with EET exhibited an increase in mitochondrial superoxide dismutase (SOD) in a PGC-1α-dependent manner, P < 0.05. The increase in PGC-1α was associated with an increase in β-catenin, P < 0.05, adiponectin expression, P < 0.05, and lipid accumulation, P < 0.02. EET decreased heme levels and mitochondria-derived ROS (MitoSox), P < 0.05, compared to adipocytes that were untreated. EET also decreased mesoderm-specific transcript (MEST) mRNA and protein levels (P < 0.05). Adipocyte secretion of EET act in an autocrine/paracrine manner to increase PGC-1α is required for activation of HO-1 expression. This is the first study to dissect the mechanism by which the antiadipogenic and anti-inflammatory lipid, EET, induces the PGC-1α signaling cascade and reprograms the adipocyte phenotype by regulating mitochondrial function and HO-1 expression, leading to an increase in healthy, that is, small, adipocytes and a decrease in adipocyte enlargement and terminal differentiation. This is manifested by an increase in mitochondrial function and an increase in the canonical Wnt signaling cascade during adipocyte proliferation and terminal differentiation.

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 …

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 …

Safety Of Infliximab In Children With Ibd: The Experience Of An Academic Center In Wv, Michael Northcutt Md, Awni Al-Subu Md, Brooke Bella Rn, Yoram Elitsur Md

Biochemistry and Microbiology

BACKGROUND: The immune-modulating drug, infliximab, is approved for Inflammatory Bowel Disease (IBD) treatment in children. Chronic therapy with infliximab is associated with the development of early and delayed infusion reactions. We reviewed our experience with infliximab treatment and its side effects in a cohort of children diagnosed with IBD who were treated in our clinic.

METHODS: A retrospective analysis of all IBD children treated with infliximab in our center from 2006-2011 was performed. The demographic, chronological and clinical data were recorded. The infliximab infusion was given at 5mg/ kg according to a standard protocol after pre-treatment with low dose …

Dysglycemia Induces Abnormal Circadian Blood Pressure Variability, Sivarajan Kumarasamy, Kathirvel Gopalakrishnan, Dong Hyun Kim, Nader G. Abraham, William D. Johnson, Bina Joe, Alok K. Gupta

Biochemistry and Microbiology

Background: Prediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).

Hypothesis: Systemic inflammation and glycemia influence circadian blood pressure variability.

Methods: Dahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) …

Epocrates….Is It Useful At The Neonatal Bedside?, Bobby L. Miller Md

Biochemistry and Microbiology

Most physicians, including residents and medical students have heard of, and many use, a mobile drug database called Epocrates. The purpose of this review is to evaluate Epocrates as a bedside tool from the perspective of a neonatologist on a busy teaching service.

The Cell Surface Receptor Slam Controls T Cell And Macrophage Functions, Ninghai Wang, Abhay Satoskar, William Faubion, Susumu Okamoto, Stefan Feske, Charles A. Gullo Phd, Kareem Clarke, Miriam Rodriguez Sosa, Arlene H. Sharpe, Cox Terhorst

Biochemistry and Microbiology

Signaling lymphocyte activation molecule (SLAM), a glycoprotein expressed on activated lymphocytes and antigen-presenting cells, has been shown to be a coregulator of antigen-driven T cell responses and is one of the two receptors for measles virus. Here we show that T cell receptor–induced interleukin (IL)-4 secretion by SLAM−/− CD4+ cells is down-regulated, whereas interferon γ production by CD4+ T cells is only slightly up-regulated. Although SLAM controls production of IL-12, tumor necrosis factor, and nitric oxide in response to lipopolysaccharide (LPS) by macrophages, SLAM does not regulate phagocytosis and responses to peptidoglycan or CpG. Thus, SLAM acts as a coreceptor …