Circulatory and Respiratory Physiology Commons^™

Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough

MIIR Faculty Research

The effects of ageing on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signalling molecules that may be of particular importance in mediating numerous cellular responses, including control of cell growth, differentiation and adaptation, are the proteins associated with the mitogen-activated protein kinase (MAPK) signalling systems. The MAPKs, in conjunction with the p70 S6k signalling cascade, have emerged as critical components for regulating numerous mechanotransduction-related cellular responses. Here we investigate the ability of uniaxial stretch to activate the MAPK and p70 S6k pathways in adult …

Phase I Study Of Medi-534 Of A Live, Attenuated Intranasal Vaccine Against Respiratory Syncytial Virus And Parainfluenza-3 Virus In Seropositive Children, Margarita Gomez, Maurice A. Mufson, Filip Dubovsky, Conor Knightly, Wen Zeng, Genevieve Losonsky

Internal Medicine

A live, attenuated respiratory syncytial virus and parainfluenza virus type 3 vaccine was evaluated in healthy respiratory syncytial virus/parainfluenza virus type 3 seropositive children aged 1 to 9 years. Three cohorts of 40 children were randomized 1:1 to receive 10^4, 10⁵ or 10⁶ median tissue culture infectious dose₅₀ MEDI-534 vaccine of placebo. The vaccine's safety profile was similar to placebo, no viral shedding was detected, and the vaccine was minimally immunogenic.

Aging Influences Multiple Indices Of Oxidative Stress In The Heart Of The Fischer 344/Nnia X Brown Norway/Binia Rat, Shinichi Asano

Theses, Dissertations and Capstones

Here we report the influence of aging on multiple markers of oxidativenitrosative stress in the heart of adult (6-month), aged (30-month) and very aged (36- month) Fischer 344/NNiaHSd X Brown Norway/BiNia (F344/NXBN) rats. Compared to 6 month old rat hearts, indices of oxidative (superoxide anion (–O2 ·), 4-hyrdoxy-2- nonenal (4-HNE)) and nitrosative (protein nitrotyrosylation) stress were 34.1 ± 28.1%, 186 ± 28.1% and 94 ± 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness (r>0.669; r>0.710 and p<0.01, respectively). Regression analysis showed that increases in cardiac oxidative-nitrosative stress with aging were significantly correlated with changes in the expression and/or regulation of proteins involved in transcriptional (NF-κB) activities, signaling (mitogen activated protein kinases along with Src), apoptotic ( Bcl-2, Traf-2), and cellular stress (HSPs). These results suggest that the aging F344/NXBN heart may be highly suited for unraveling the molecular events that lead to age-associated alterations in cardiac oxidative stress.

Age-Related Dgc Structure And Function In The F344/N X Bn Rat Heart, Sunil K. Kakarla

Theses, Dissertations and Capstones

Recent data has suggested that disruption of the dystrophin-glycoprotein complex (DGC) may be involved in mediating the progression of cardiac hypertrophy and failure. Here we examined the regulation of DGC proteins in the hearts of adult (6 months), aged (30 months), and very aged (36 months) F344/N X BN rats . Compared to adult animals, the content of α- and β-dystroglycan were 6.93 ± 5.16% and 58.36 ± 3.64% higher, respectively (P < 0.05) in very aged animals. Immunoblotting and immunhistochemical analysis suggested that aging appeared to diminish alpha-sarcoglycan, beta-sarcoglycan and delta-sarcoglycan content by 13.89 ± 3.1%,15.8 ± 2.8% and 18.63 ± 3.04%, respectively (P < 0.05). These alterations in the DGC occurred coincident with age- associated alterations in cytoplasmic anti-rat IgG immunoreactivity, TUNEL positive nuclei, alpha-fodrin cleavage, indices of caspase-3 activation and diminished AKT phosphoryation (Ser 308). Taken together, these data suggest that aging alters cardiac DGC structure and function.

Whole Genome Expression Profiling Reveals A Significant Role For Immune Function In Human Abdominal Aortic Aneurysms, Guy M. Lenk, Gerard Tromp, Shantel Weinsheimer, Zoran Gatalica, Ramon Berguer, Helena Kuivaniemi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Abdominal aortic aneurysms are a common disorder with an incompletely understood etiology. We used Illumina and Affymetrix microarray platforms to generate global gene expression profiles for both aneurysmal (AAA) and non-aneurysmal abdominal aorta, and identified genes that were significantly differentially expressed between cases and controls.

Results

Affymetrix and Illumina arrays included 18,057 genes in common; 11,542 (64%) of these genes were considered to be expressed in either aneurysmal or normal abdominal aorta. There were 3,274 differentially expressed genes with a false discovery rate (FDR) ≤ 0.05. Many of these genes were not previously known to be involved in …

Comparison Of The Systemic And Pulmonary Inflammatory Response To Endotoxin Of Neutropenic And Non-Neutropenic Rats, Sabrina M. Heidemann, Maria Glibetic

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Neutrophil infiltration commonly occurs in acute lung injury and may be partly responsible for the inflammatory response. However, acute lung injury still occurs in the neutropenic host. The objectives of this study are to determine if inflammation and acute lung injury are worse in neutropenic versus the normal host after endotoxemia.

Methods

Rats were divided into four groups: 1) control, 2) neutropenic, 3) endotoxemic and 4) endotoxemic and neutropenic. Tumor necrosis factor (TNF)-α and macrophage inflammatory protein (MIP-2) were measured in the blood, lung lavage and for mRNA in the lung. Arterial blood gases were measured to determine …

Electrostatic Charge Polarity Effect On Respiratory Deposition In The Glass Bead Tracheobronchial Airways Model, Mohammed Ali, Malay K. Mazumder, Rama N. Reddy, Mariofanna Milanova, Jing Zhang, Alexandru S. Biris

Journal of the Arkansas Academy of Science

The effects of unipolar and bipolar electrostatic charges on the deposition efficiency of therapeutic aerosols in the physical model of human tracheobronchial (TB) airways have been investigated. Respirable size aerosol particles were generated by a commonly prescribed and commercially available nebulizer and charged by a corona charger and then their size and charge distributions were characterized by an Electronic Single Particle Aerodynamic Relaxation Time analyzer to study the drug aerosol particles' deposition pattern. The experiments were performed with a glass bead tracheobronchial model (GBTBM) (physical model) which was designed and developed based upon widely used and adopted dichotomous lung morphometric …