The Experts below are selected from a list of 5007 Experts worldwide ranked by ideXlab platform
Kevin K M Yue - One of the best experts on this subject based on the ideXlab platform.
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ginsenoside re of panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin induced diabetic rats
European Journal of Pharmacology, 2006Co-Authors: William C S Cho, Waishing Chung, Sally Kinwah Lee, Albert Wingnang Leung, Christopher H K Cheng, Kevin K M YueAbstract:Diabetes mellitus is characterized by hyperglycemia and complications affecting the eye, Kidney, Nerve and blood vessel. We have previously demonstrated the occurrence of oxidative stress of streptozotocin-induced diabetic rats, preceded by a depletion in the tissue level of glutathione. In this study, when diabetic rats were treated with ginsenoside Re of Panax ginseng C.A. Meyer, there was a significant reduction in blood glucose, total cholesterol and triglyceride levels. On the other hand, oxidative stress has been implicated in the pathogenesis of diabetes and its complications. It was found that treatment by ginsenoside Re restored the levels of both glutathione and malondialdehyde in the eye and Kidney to those found in the control rats. This is the first report demonstrating ginsenoside Re has significant antioxidant efficacy in diabetes, and prevents the onset of oxidative stress in some vascular tissues. Our results demonstrated that ginsenoside Re could lower blood glucose and lipid levels, and exerts protective actions against the occurrence of oxidative stress in the eye and Kidney of diabetic rats. Our data also provide evidence that ginsenoside Re could be used as an effective antidiabetic agent particularly in the prevention of diabetic microvasculopathy.
Frank C. Brosius - One of the best experts on this subject based on the ideXlab platform.
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Shared and distinct lipid-lipid interactions in plasma and affected tissues in a diabetic mouse model
Journal of Lipid Research, 2017Co-Authors: Kelli M. Sas, Jiahe Lin, Thekkelnaycke M. Rajendiran, Tanu Soni, Viji Nair, Lucy M. Hinder, Hosagrahar V. Jagadish, Thomas W. Gardner, Steven F. Abcouwer, Frank C. BrosiusAbstract:Lipids are ubiquitous metabolites with diverse functions; abnormalities in lipid metabolism appear to be related to complications from multiple diseases, including type 2 diabetes. Through technological advances, the entire lipidome has been characterized and researchers now need computational approaches to better understand lipid network perturbations in different diseases. Using a mouse model of type 2 diabetes with microvascular complications, we examined lipid levels in plasma and in renal, neural, and retinal tissues to identify shared and distinct lipid abnormalities. We used correlation analysis to construct interaction networks in each tissue, to associate changes in lipids with changes in enzymes of lipid metabolism, and to identify overlap of coregulated lipid subclasses between plasma and each tissue to define subclasses of plasma lipids to use as surrogates of tissue lipid metabolism. Lipid metabolism alterations were mostly tissue specific in the Kidney, Nerve, and retina; no lipid changes correlated between the plasma and all three tissue types. However, alterations in diacylglycerol and in lipids containing arachidonic acid, an inflammatory mediator, were shared among the tissue types, and the highly saturated cholesterol esters were similarly coregulated between plasma and each tissue type in the diabetic mouse. Our results identified several patterns of altered lipid metabolism that may help to identify pathogenic alterations in different tissues and could be used as biomarkers in future research into diabetic microvascular tissue damage.
Christopher P Austin - One of the best experts on this subject based on the ideXlab platform.
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compound cytotoxicity profiling using quantitative high throughput screening
Environmental Health Perspectives, 2007Co-Authors: Ruili Huang, Cynthia S Smith, Christopher J Portier, Kristine L. Witt, Jennifer Fostel, Ajit Jadhav, Noel Southall, Raymond R Tice, James Inglese, Christopher P AustinAbstract:Animal toxicity data is used to predict human toxicity, based on the assumption that adverse effects in laboratory animals indicate the potential for adverse effects in humans. Various animal models have been developed to evaluate a broad range of toxicologic responses in order to classify compounds by their potential for causing adverse health effects in humans. These animal models include acute, subchronic, and/or chronic tests for end points such as oral, dermal, and ocular toxicity; immunotoxicity; genotoxicity; reproductive and developmental toxicity; and carcinogenicity (Chhabra et al. 2003). Animal tests, while clearly useful, can be relatively expensive and low throughput. Furthermore, intrinsic differences in species sensitivity can confound the extrapolation of certain test results to human health effects. Also, there is increasing societal concern about the use of animals in testing, especially in test methods that might induce pain and suffering in the treated animals (e.g., ocular toxicity). Thus, there is increased interest among the international scientific community in the development, translation, validation, and use of nonanimal alternative test methods for making regulatory decisions [European Center for the Validation of Alternative Methods (ECVAM) 2007; Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) 2007; National Research Council 2007; Tweats et al. 2007]. Given these scientific and societal issues, and the increasing number of new compounds requiring toxicity testing, the National Toxicology Program (NTP) recently began a major initiative to develop a high-throughput screening (HTS) program to prioritize compounds for further in-depth toxicologic evaluation, identify mechanisms of action for further investigation, and develop predictive models for in vivo biological response (NTP 2004a; Tice et al. 2007). In support of this initiative, the NTP and the National Institutes of Health (NIH) Chemical Genomics Center (NCGC) formed a partnership in 2005 to a) develop a library of compounds suitable for HTS that had been characterized to some degree by traditional toxicologic testing methods, b) identify and/or develop cell-based or biochemical HTS assays potentially informative for in vivo toxicologic effects, and c ) profile the compound library in these HTS assays. The ultimate goal of this collaboration is to establish in vitro “signatures” of in vivo rodent and human toxicity by comparing the data generated in HTS assays with the rich historical database generated by the NTP using traditional in vivo and in vitro toxicologic assays. The U.S. Environmental Protection Agency (EPA) has also recognized the potential of high-throughput screening in toxicology testing and has initiated the ToxCast program for prioritizing the toxicity testing of environmental chemicals (Dix et al. 2007). HTS was developed by the pharmaceutical industry to evaluate the biological activity of thousands of chemicals to identify potential drug candidates. Because HTS for this purpose is generally performed at a single concentration only (typically 10 μM), the approach is characterized by a high prevalence of false positives and negatives. To address these limitations and make HTS useful for toxicology and chemical genomics, the NCGC developed the quantitative high-throughput screening (qHTS) paradigm (Inglese et al. 2006). With this approach, all compounds are screened for a concentration-dependent response, which allows for a more accurate assessment of biological activity. Here, we report on the use of qHTS to profile the cytotoxicity (the term “cytotoxicity” is used to describe the cumulative effect of a compound over a given period of time on cell number, whether due to apoptosis, necrosis, or a reduction in the rate of cell proliferation) of 1,408 compounds in 13 cell types using a homogeneous, luminescent cell viability assay that measures the intracellular levels of adenosine triphosphate (ATP) as an indicator of the number of metabolically active cells. Selection of the 1,408 compounds was based in part on the availability of toxicologic data from standard tests for carcinogenicity, genotoxicity, immunotoxicity, and/or reproductive and developmental toxicity; all compounds were tested at 14 concentrations from 0.59 nM to 92 μM. The cell types used in this evaluation include corresponding human and rodent cells derived from six tissues (liver, blood, Kidney, Nerve, lung, skin) that are common targets of xenobiotic toxicity. Using this approach, we developed species- and cell type–specific cytotoxicity profiles for each compound. Furthermore, we demonstrate that compounds with similar end point toxicity may exhibit different cytotoxicity kinetics, suggestive of different mechanisms of action. In vitro profiling of compounds promises to provide information on molecular mechanisms of toxicity, and may allow the creation of algorithms for predictive in vivo toxicology.
Michael J. Fowler - One of the best experts on this subject based on the ideXlab platform.
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The Diabetes Treatment Trap: Hypoglycemia
Clinical Diabetes, 2011Co-Authors: Michael J. FowlerAbstract:O ne of the ethical pillars of medical treatment has always been to “do no harm.” Treating patients with diabetes medications, however, carries a significant risk of inflicting harm and injury by causing hypoglycemia. Were it not for this potential adverse reaction, diabetes treatment would be considerably easier for both patients and providers. Such treatments frequently involve augmenting insulin effects directly (injected insulin) or indirectly (increasing insulin release from the pancreatic β-cells, increasing insulin sensitivity, and/or inhibiting hepatic glucose production). Whenever glucose homeostasis is altered, hypoglycemia is always a potential side effect to therapy and, in fact, is one of the most common adverse reactions in diabetes treatment. It is important, therefore, to be able to identify, treat, and also avoid the hypoglycemic complications of diabetes therapy. Such complications may even be life-threatening and resistant to initial therapy. Therefore, physicians who prescribe potent diabetes medications such as insulin must be able to identify the causes of such adverse reactions and arrest such complications before they progress. Hypoglycemia is in many ways the Achilles heel of diabetes treatment. Medical authors have astutely noted that hypoglycemia is the “limiting factor” in the treatment of diabetes.1–3 Reduction of glucose levels in patients with either type 1 or type 2 diabetes has been shown to decrease the risks of Kidney, Nerve, and retinal injury. Lower glucose levels are also associated with a reduction in cardiovascular disease in patients with type 1 diabetes. Were it not for the development of hypoglycemia, all patients with diabetes could conceivably control their diabetes with ease using high doses of oral medications or insulin. Such is not the case, however. Treatment of diabetes, especially intensive treatment, carries a significant risk of lowering blood glucose levels excessively and causing hypoglycemia. Severe hypoglycemia is usually considered to be …
Jayadev Raju - One of the best experts on this subject based on the ideXlab platform.
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Regulation of metabolic pathways in liver and Kidney during experimental diabetes: Effects of antidiabetic compounds
Indian Journal of Clinical Biochemistry, 1998Co-Authors: Najma Zaheer Baquer, Dhananjay Gupta, Jayadev RajuAbstract:Diabetes has been classified as a disease of glucose overproduction by tissues, mainly liver and glucose underutilization by insulin requiring tissues like liver, adipose and muscle due to lack of insulin. There is, however, glucose over utilization in tissues not dependent on insulin for glucose transport like Kidney, Nerve and brain. There are serious complications due to this excess glucose in these tissues and their reversal is important for a good metabolic control and normalisation of other parameters. Insulin, trace metals and some plant extracts have been used to see the reversal effects of the complications of diabetes in liver and Kidney in experimental diabetes. Almost complete reversal of the metabolic changes has been achieved in the activities of key enzymes of metabolic pathways in liver and Kidney and an effective glucose control has been achieved suggesting a combination of therapies in the treatment of metabolic disturbance of the diabetic state.
