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Impaired Activity of Ryanodine Receptors Contributes to Calcium Mishandling in Cardiomyocytes of Metabolic Syndrome Rats
Conclusion Principal findings of this work are that abnormal Ca2+ transient amplitude, contractile dysfunction; and impaired relaxation of MetS cardiomyocytes underlies intrinsic dysfunctional RyR2 and SERCA pump. Abnormal activity of RyRs was evidenced by its decreased ability to bind [3H]-ryanodine. Although the MetS condition does not modify RyR2 protein expression, its phosphorylation at Ser2814 is decreased, which impairs its capacity for activation during ECC. The dysfunctional RyRs, together with a decreased activity of SERCA pump due to decreased Thr17-PLN phosphorylation suggest a downregulation of CaMKII in MetS...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research

Development, Validation of LC-MS/MS Method and Determination of Pharmacokinetic Parameters of the Stroke Neuroprotectant Neurounina-1 in Beagle Dog Plasma After Intravenous Administration
Conclusion The developed and validated method to quantify neurounina-1 in beagle dog plasma using LC-MS/MS presented sensitivity and selectivity, thus allowing the rapid and precise determination of the pharmacokinetics of this neuroprotective compound working in the low nanomolar range. Ethics Statement This study was carried out in accordance with the recommendations of the general ethical guidelines established by the Brazilian Society for Laboratory Animal Science (SBCAL). The protocol was approved by the Committee for Ethics in Animal Use – State University of Campinas (CEUA/UNICAMP, protocol n° 3340-...
Source: Frontiers in Pharmacology - April 24, 2019 Category: Drugs & Pharmacology Source Type: research

CNS Summit 2017 Abstracts of Poster Presentations
Conclusion: This novel technology discriminates and quantifies subtle differences in behavior and neurological impairments in subjects afflicted with neurological injury/disease. KINARM assessments can be incorporated into multi-center trials (e.g., monitoring stroke motor recovery: NCT02928393). Further studies will determine if KINARM Labs can demonstrate a clinical effect with fewer subjects over a shorter trial period. Disclosures/funding: Dr. Stephen Scott is the inventor of KINARM and CSO of BKIN Technologies.   Multiplexed mass spectrometry assay identifies neurodegeneration biomarkers in CSF Presenter: Chelsky...
Source: Innovations in Clinical Neuroscience - November 1, 2017 Category: Neuroscience Authors: ICNS Online Editor Tags: Assessment Tools biomarkers Cognition Current Issue Drug Development General Genetics Medical Issues Neurology Patient Assessment Psychopharmacology Scales Special Issues Supplements Trial Methodology clinical trials CNS Su Source Type: research

The Association of Arsenic Metabolism with Cancer, Cardiovascular Disease, and Diabetes: A Systematic Review of the Epidemiological Evidence
Conclusions: Population level of iAs% and DMA%, but not MMA%, were associated with arsenic exposure levels. Overall, study findings suggest that higher MMA% was associated with an increased risk of cancer and cardiovascular disease, while lower MMA% was associated with an increased risk of diabetes and metabolic syndrome. Additional population-based studies and experimental studies are needed to further evaluate and understand the role of arsenic exposure in arsenic metabolism and the role of arsenic metabolism in disease development. https://doi.org/10.1289/EHP577 Received: 01 June 2016 Revised: 26 February 2017 Acce...
Source: EHP Research - August 2, 2017 Category: Environmental Health Authors: Daniil Lyalko Tags: Research Source Type: research