Manipulation of nitric oxide in an animal model of acute liver injury: The impact on liver and intestinal function

Background: Nitric oxide may have a protective effect on the liver during endotoxemia and chronic inflammation. There is evidence that it maintains liver and intestinal tissue integrity during inflammatory processes. We evaluated the impact of altering nitric oxide release on acute liver injury, the associated gut injury and bacterial translocation, at different time intervals.Methods: An acute rat liver injury model induced by D-galactosamine was used. Sprague Dawley rats were divided into four main groups: normal control, acute liver injury control, acute liver injury + N-nitro-L-arginine methyl ester (L-NAME), acute liver injury + L-NAME + L-arginine. Each group was divided into three subgroups according to the different time intervals (6, 12, 24 hours) after the induction of the liver injury. Liver enzymes and bilirubin were evaluated, as well as bacterial translocation, cecal and colonic microflora, and histological study of liver, ileum and cecum.Results: Liver enzymes increased significantly at all time intervals in acute liver injury + L-NAME compared to liver injury control groups. Bacterial translocation increased significantly in liver injury + L-NAME groups; at 6 hours to the liver, at 12 hours to the liver and mesenteric lymph nodes (MLNs), and at 24 hours to arterial and portal blood, liver and MLNS. Inhibition of nitric oxide increased significantly the Enterobacteriaceae count in cecum compared to normal and liver injury control groups. The G-negative anaerobes increased significantly in the colon compared to the liver injury control group.Conclusion: Inhibition of nitric oxide in an acute liver injury model potentiates the liver injury as evidenced by increased appearance of hepatocellular necrosis and elevated liver enzymes and bilirubin. It increases the Enterobacteriaceae in both cecum and colon and G-negative anaerobes in the colon. It also increases bacterial translocation to extra-intestinal sites. The increased bacterial translocation could be one of the mechanisms potentiating liver injury and nitric oxide may be pathophysiologically involved. Further studies are required to confirm this hypothesis. Keywords: Acute liver injury, Arginine, Bacterial translocation, Intestinal microflora, L-NAME, Nitric oxid

Prophylactic use of vancomycin in adult cardiology and cardiac surgery

The recent appearance of Staphylococcus aureus and Staphylococcus epidermidis strains that have reduced susceptibility to vancomycin, and the spread of vancomycin-resistant enterococci, raise the specter of endovascular infections that will be difficult or impossible to cure with available drugs. We review issues concerning the prophylactic use of vancomycin in adult cardiology and cardiac surgery with special attention to dosing and indications. There is no indication for the routine use of prophylactic vancomycin in pacemaker implantations, cardiac catheterization, and transesophageal echocardiography. In institutions with a high incidence of methicillin-resistant S. aureus and S. epidermidis, vancomycin may be used for antibiotic prophylaxis in place of cephalosporins for pacemaker or defibrillator implantation. The strongest evidence in support of the prophylactic use of vancomycin is during cardiac surgeries, particularly valvular surgeries in institutions with a high prevalence of methicillin-resistant S. aureus and S. epidermidis. When vancomycin is used prior to open heart surgery, the dose should be 15 mg/kg rather than the standard I g dose that is often recommended in the literature and used by 85% of institutional pharmacists who responded to our survey. Cardiologists and cardiac surgeons should assume leadership roles in promoting its responsible use

Exploring the interaction of quercetin-3-O-sophoroside with SARS-CoV-2 main proteins by theoretical studies: A probable prelude to control some variants of coronavirus including Delta

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2?s proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variantsScopu