Example of American Way of Life

Enclosed with letter to Dr. Gideonse from James Ayer as an example of American way of life. May 16, 1941

Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

<p>Abstract</p> <p>Background</p> <p>The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM) have not been defined completely. We have shown in conscious dogs with DM that: <it>1</it>) baseline coronary blood flow (CBF) was significantly decreased, <it>2</it>) endothelium-dependent (ACh) coronary vasodilation was impaired, and <it>3</it>) reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes.</p> <p>Methods</p> <p>Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv) over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4).</p> <p>Results</p> <p>The array data revealed that 797 genes were differentially expressed (P < 0.01; fold change of at least ±2). 150 genes were expressed at significantly greater levels in diabetic dogs and 647 were significantly reduced. There was no change in eNOS mRNA. There was up regulation of some components of the NADPH oxidase subunits (gp91 by 2.2 fold, P < 0.03), and down-regulation of SOD1 (3 fold, P < 0.001) and decrease (4 - 40 fold) in a large number of genes encoding mitochondrial enzymes. In addition, there was down-regulation of Ca²⁺cycling genes (ryanodine receptor; SERCA2 Calcium ATPase), structural proteins (actin alpha). Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase), which were markedly down regulated.</p> <p>Conclusion</p> <p>our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.</p

Mitochondrial Function and Dysfunction in Dilated Cardiomyopathy

Cardiac tissue requires a persistent production of energy in order to exert its pumping function. Therefore, the maintenance of this function relies on mitochondria that represent the "powerhouse" of all cardiac activities. Mitochondria being one of the key players for the proper functioning of the mammalian heart suggests continual regulation and organization. Mitochondria adapt to cellular energy demands via fusion-fission events and, as a proof-reading ability, undergo mitophagy in cases of abnormalities. Ca2+ fluxes play a pivotal role in regulating all mitochondrial functions, including ATP production, metabolism, oxidative stress balance and apoptosis. Communication between mitochondria and others organelles, especially the sarcoplasmic reticulum is required for optimal function. Consequently, abnormal mitochondrial activity results in decreased energy production leading to pathological conditions. In this review, we will describe how mitochondrial function or dysfunction impacts cardiac activities and the development of dilated cardiomyopathy

Supercritical Fluid Extraction

In supercritical fluid extraction, many options are available for achieving and controlling the desired selectivity, which is extremely sensitive to variations in pressure, temperature, and choice of solvent. The ability of supercritical fluids to vaporize relatively nonvolatile compounds at moderate temperatures can reduce the energy requirements compared to distillation and liquid extraction

Enhanced permeability transition explains the reduced calcium uptake in cardiac mitochondria from streptozotocin-induced diabetic rats

Cardiac dysfunction is associated with diabetes. It was previously shown that heart mitochondria from diabetic rats have a reduced calcium accumulation capacity. The objective of this work was to determine whether the reduction in calcium accumulation by cardiac mitochondria from diabetic rats is related to an enhanced susceptibility to induction of the mitochondrial permeability transition. Streptozotocin-induced diabetic rats were used as a model to study the alterations caused by diabetes in the permeability transition, 21 days after streptozotocin administration. Heart mitochondria were isolated to evaluate respiratory parameters and susceptibility to the calcium-dependent permeability transition. Our results show that streptozotocin diabetes facilitates the mitochondrial permeability transition in cardiac mitochondria, resulting in decreased mitochondrial calcium accumulation. We also observed that heart mitochondria from diabetic rats had depressed oxygen consumption during the phosphorylative state. The reduced mitochondrial calcium uptake observed in heart mitochondria from diabetic rats is related to an enhanced susceptibility to the permeability transition rather than to damage to the calcium uptake machinery.http://www.sciencedirect.com/science/article/B6T36-49WPBSY-B/1/f91ef5d310996f93c4e23fb3df58562