254 research outputs found

    Mitochondrial dysfunction in inherited renal disease and acute kidney injury

    No full text
    Mitochondria are increasingly recognized as key players in genetic and acquired renal diseases. Most mitochondrial cytopathies that cause renal symptoms are characterized by tubular defects, but glomerular, tubulointerstitial and cystic diseases have also been described. For example, defects in coenzyme Q10 (CoQ10) biosynthesis and the mitochondrial DNA 3243 A>G mutation are important causes of focal segmental glomerulosclerosis in children and in adults, respectively. Although they sometimes present with isolated renal findings, mitochondrial diseases are frequently associated with symptoms related to central nervous system and neuromuscular involvement. They can result from mutations in nuclear genes that are inherited according to classic Mendelian rules or from mutations in mitochondrial DNA, which are transmitted according to more complex rules of mitochondrial genetics. Diagnosis of mitochondrial disorders involves clinical characterization of patients in combination with biochemical and genetic analyses. In particular, prompt diagnosis of CoQ10 biosynthesis defects is imperative because of their potentially reversible nature. In acute kidney injury (AKI), mitochondrial dysfunction contributes to the physiopathology of tissue injury, whereas mitochondrial biogenesis has an important role in the recovery of renal function. Potential therapies that target mitochondrial dysfunction or promote mitochondrial regeneration are being developed to limit renal damage during AKI and promote repair of injured tissue

    sj-pdf-1-jcb-10.1177_0271678X231156500 - Supplemental material for NAD<sup><b>+</b></sup> precursor nutritional supplements sensitize the brain to future ischemic events

    No full text
    Supplemental material, sj-pdf-1-jcb-10.1177_0271678X231156500 for NAD+ precursor nutritional supplements sensitize the brain to future ischemic events by Wensheng Qu, Kenneth M Ralto, Tao Qin, Yinhong Cheng, Weifeng Zong, Xiang Luo, Miguel Perez-Pinzon, Samir M Parikh and Cenk Ayata in Journal of Cerebral Blood Flow & Metabolism</p

    sj-pdf-2-jcb-10.1177_0271678X231156500 - Supplemental material for NAD<sup><b>+</b></sup> precursor nutritional supplements sensitize the brain to future ischemic events

    No full text
    Supplemental material, sj-pdf-2-jcb-10.1177_0271678X231156500 for NAD+ precursor nutritional supplements sensitize the brain to future ischemic events by Wensheng Qu, Kenneth M Ralto, Tao Qin, Yinhong Cheng, Weifeng Zong, Xiang Luo, Miguel Perez-Pinzon, Samir M Parikh and Cenk Ayata in Journal of Cerebral Blood Flow & Metabolism</p

    The Neuropeptide VGF is Reduced in Human Bipolar Postmortem Brain and Contributes to Some of the Behavioral and Molecular Effects of Lithium

    No full text
    Recent studies demonstrate that the neuropeptide VGF (non-acronymic) is regulated in the hippocampus by antidepressant therapies and animal models of depression and that acute VGF treatment has antidepressant-like activity in animal paradigms. However, the role of VGF in human psychiatric disorders is unknown. We now demonstrate using in situ hybridization that VGF is downregulated in bipolar disorder in the CA region of the hippocampus and Brodmann’s Area 9 (BA9) of the prefrontal cortex. The mechanism of VGF in relation to LiCl was explored. Both LiCl intraperitoneally (IP) and VGF intracerebroventricularly (ICV) reduced latency to drink in novelty-induced hypophagia and LiCl was not effective in VGF+/- mice suggesting that VGF may contribute to the effects of LiCl in this behavioral procedure that responds to chronic antidepressant treatment. VGF by intrahippocampal injection also had novel activity in an amphetamineinduced hyperlocomotion assay thus mimicking the actions of LiCl injected IP in a system that phenocopies manic-like behavior. Moreover, VGF+/- mice exhibited increased locomotion following amphetamine and did not respond to LiCl, suggesting that VGF is required for the effects of LiCl in curbing the response to amphetamine. Finally, VGF by ICV in vivo activated the same signaling pathways as LiCl and is necessary for the induction of MAPK and AKT by LiCl thus lending insight into the molecular mechanisms underlying the actions of VGF. The dysregulation of VGF in bipolar disorder as well as the behavioral effects of the neuropeptide similar to LiCl suggests that VGF may underlie the pathophysiology of bipolar disorder.Peer reviewe

    Examining mechanical properties of single acetaminophen crystal using nanoindentation methods

    No full text
    The pharmaceutical industry incurs substantial loss in revenue and consumer confidence with inefficient manufacturing practices. Large scale processing of organic compounds is challenging due to its sensitivity to environmental conditions and the unpredictable breakage behavior of tablets under applied stress. Tablet compaction and particle size reduction through milling induces variability in the end product. Variability in powder flow, stress induced transformation in polymorphic compounds, re-crystallization after compaction, and lack of content uniformity are some factors that translate into poor product quality. These challenges can be partially resolved by a better understanding of mechanical properties of crystalline pharmaceutical materials at single particle level. The endeavor of this study was to understand the breakage behavior of various planes of a single Acetaminophen crystal using nanoindentation instrumentation. The results of the study indicated that the Acetaminophen crystal is anisotropic with respect to hardness and Young’s modulus values. Analysis of the load-depth curve, discontinuities on the loading and unloading cycle were observed, as well as pop-in events during constant load intervals. Furthermore, the frequency of pop-in events on the loading depth curve was found to correlate with the elasticity of the planes in question. It was also apparent that the organic compound was sensitive to environmental conditions. Varying strain rates effects different planes of the same crystal and also in adhesion reflected sensitivity to environmental conditions. The exact mechanism by which the crystal deforms is still unknown. However it is theorized that it could be through partial dislocations and crack propagations.M.S.Includes bibliographical referencesby Hiral Parik

    Proposal for a Community "Solidarity" Refrigerator that Would Both Feed the Hungry and Lessen Food Waste

    No full text
    Approximately 40% of the food produced in America is wasted with much of this waste produced by homeowners and restaurants. A “solidarity” refrigerator in Spain enables restaurants and residents to bring leftover food to a community refrigerator instead of throwing it out. Individuals in need of food can then take the food. Starting a “solidarity” refrigerator in communities throughout the US would keep waste out of the landfill and feed the hungry.Fall 2015Accompanied by video fil

    Angiopoietins and Tie2 in vascular inflammation

    No full text

    Aging and the kidney: lessons for health?

    No full text
    Detailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin

    Sex‐Associated Disparities in Industry Payments to US Authors in High‐Impact Rheumatology Journals: Correlation with Author Impact

    No full text
    Objective The aim of this study was to assess sex‐associated disparities in the frequency and magnitude of industry payments to US physician authors in high‐impact rheumatology journals and their correlation with author impact. Methods US authors of publications in four high‐impact rheumatology journals were vetted on Open Payments Database (OPD) for industry payments. The h‐index (an accepted metric of author impact), physician type, and dollar amounts for each OPD category were recorded. Differences in the percentages of male versus female US authors with or without OPD entries, differences in research‐associated and non–research‐associated payments, and differences in h‐indexes were determined. Two hematology, two surgery, and two obstetrics/gynecology high‐impact journals were similarly vetted. Results The h‐indexes of, and industry payments to, US male physician authors were greater than those of and to US female physician authors across all four vetted journal disciplines, with the male‐to‐female ratio of median dollar payments being greatest for rheumatology. Whereas payments to male US physician authors tended to be larger than those to female US physician authors at low h‐indexes, payments to female US physician authors, especially for rheumatology, tended to match and surpass those to male US physician authors as the h‐indexes rose. Conclusion Significant differences exist in industry payments and h‐indexes between male and female US physician authors of publications in high‐impact journals, especially high‐impact rheumatology journals. Sex‐associated differences in industry payments can be attributed, at least in part, to sex‐associated differences in author impact
    corecore