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clinical Efficacy of Inhaled Nitric Oxide in Preventing the Progression of Moderate to Severe cOVID-19 and Its correlation to Viral clearance:Results of a Pilot Study

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Infectious Microbes & Diseases 2022年第1期4卷 26-33页

作者： Merlin Moni Thushara Madathil Dipu T.Sathyapalan Veena Menon Georg Gutjahr Fabia Edathadathil Deepthi Sureshkumar Preetha Prasanna Soumya Jose Roshni Jerome Ajai Krishnan indulekha c.l.pillai Geetha Kumar Bipin Nair Victor Nizet Aveek Jayant Department of Medicine Division of Infectious DiseasesAmrita Institute of Medical ScienceAmrita Vishwa VidyapeethamKochiKeralaIndia Department of cardiac Anaesthesiology Amrita Institute of Medical ScienceAmrita Vishwa VidyapeethamKochiKeralaIndia clinical Virology laboratory Amrita Institute of Medical SciencesAmrita Vishwa VidyapeethamKochiKeralaIndia center for Research in Analytics and Technologies for Education(cREATE) Amrita Vishwa VidyapeethamAmritapuriKollamKeralaIndia Department of Infection control and Epidemiology Amrita Institute of Medical ScienceAmrita Vishwa VidyapeethamKochiKeralaIndia School of Medicine Amrita Institute of Medical ScienceAmrita Vishwa VidyapeethamKochiKeralaIndia School of Biotechnology Amrita Vishwa VidyapeethamAmritapuriKollamKeralaIndia Skaggs School of Pharmacy and Pharmaceutical Sciences University of CaliforniaSan DiegoLa JollaCaliforniaUSA Department of Pediatrics University of CaliforniaSan DiegoLa JollaCaliforniaUSA

Hypoxic patients with coronavirus disease 2019(cOVID-19)are at high risk of adverse *** nitric oxide(iNO)has shown anti-viral and immunomodulatory effects in ***,in vivo evidence of efficacy in hypoxic cOVID-19 is *** open label feasibility study was conducted at a single referral center in South India and evaluated the effectiveness of repurposed iNO in improving clinical outcomes in cOVID-19 and its correlation with viral *** recruited hypoxemic cOVID-19 patients and allocated them into treatment(iNO)and control groups(1:1).Viral clearance on day 5 favored the treatment group(100%vs 72%,Pl clearance as adjudged by normalized longitudinal cycle threshold(ct)values was positively impacted in the treatment *** proportion of patients who attained clinical improvement,defined as a≥2-point change on the World Health Organization ordinal scale,was higher in the iNO cohort(n=11,79%)as compared to the control group(n=4,36%)(odds ratio 6.42,95%confidence interval 1.09–37.73,P=0.032).The proportion of patients progressing to mechanical ventilation in the control group(4/11)was significantly higher than in the treatment group(0/14).The all-cause 28-day mortality was significantly different among the study arms,with 36%(4/11)of the patients dying in the control group while none died in the treatment *** numbers needed to treat to prevent an additional poor outcome of death was estimated to be *** study demonstrates the putative role of repurposed iNO in hypoxemic cOVID-19 patients and calls for extended validation.

关键词： nitric oxide cOVID-19 antiviral activity WHO ordinal scale

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Synchronous Dosing of levodopa with Quercetin Enhances Therapeutic Efficacy and Mitigates Apoptotic Events in Experimental Parkinsonism

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生物组学研究杂志(英文) 2024年第3期7卷 105-113页

作者： Sureshkumar Arya indulekha latha chempakam Biju Pradeep Akshara Padmanabhan Renjini Ambika Ramachandran Rajesh Department of cell and Molecular Biology Center for Research on Molecular and Applied Sciences (P) Ltd. Thiruvananthapuram Kerala India Sree Narayana college of Technology Vadakkevila Kerala India

Parkinson’s disease (PD) affects millions of people annually across the globe and is primarily managed through dopamine replacement therapy employing levodopa (l-DOPA), which is still the preferred gold standard. Prolonged use of l-DOPA leads to severe adverse effects, including motor complications such as l-DOPA-induced dyskinesia, which considerably compromise treatment outcomes and patients'' quality of life. Potentiating l-DOPA with natural or synthetic compounds with less toxicity and neuroprotective activity is an area of emerging significance, and many studies in this area have gained widespread research attention. Phytochemicals, essentially compounds with antioxidant and neuroprotective activity, may be potent candidates to potentiate l-DOPA, and in this context, we explored the potential of combining quercetin with l-DOPA to mitigate rotenone-induced PD using human neuroblastoma cells. The optimal nontoxic concentrations of l-DOPA and quercetin were determined via the MTT [3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide] assay. The combination treatment notably increased cell viability to 95% at a concentration of 6.25 μg/ml, whereas the viability of the rotenone-treated group was 46.8%. lactate dehydrogenase leakage assays further confirmed that membrane integrity was significantly preserved in the combination-treated groups compared with those treated with l-DOPA or quercetin alone. Morphological improvements were evident under microscopic observation. compared with the individual treatments, the combination treatment also resulted in increased inhibition of acetylcholinesterase activity. Additionally, apoptosis induction was significantly reduced in the combination group, as shown by EtBr/acridine orange fluorescence staining. cellular calcium levels, which were elevated by rotenone exposure, were effectively normalized by the combination treatment. Moreover, the combination therapy promoted neurite outgrowth more effectively than l-DOPA or

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