Local methacholine but not bradykinin potentiates insulin-mediated glucose uptake in muscle in vivo by augmenting capillary recruitment

Aims/hypothesis Insulin has nitric-oxide-dependent vasodilatory effects in muscle, including capillary recruitment, that enhance access for itself and glucose. However, nitric-oxide-dependent vasodilators other than methacholine do not enhance insulin action. Our hypothesis is that methacholine, unlike bradykinin, enhances insulin-mediated glucose uptake in muscle by augmenting capillary recruitment.Methods Local infusion of either methacholine or bradykinin into one leg of the anaesthetised rat was made during physiological insulin (3 mU·kg^–1·min^–1) infusion under euglycaemic conditions and without affecting systemic blood pressure. Whole-body glucose infusion was determined, as was femoral blood flow, 2-deoxyglucose uptake into calf muscles and the metabolism of infused 1-methylxanthine, a measure of capillary recruitment for each leg.Results Methacholine alone (0.3 µmol·l^–1) increased femoral arterial blood flow, increased capillary recruitment but had no effect on 2-deoxyglucose uptake of the test leg relative to the contra-lateral control leg. Insulin alone (systemically) required a glucose infusion rate of 8.7 mg·kg^–1·min^–1 to maintain euglycaemia, increased 2-deoxyglucose uptake and capillary recruitment, but was without effect on femoral blood flow in either leg. Local methacholine with systemic insulin infusion increased femoral blood flow, 2-deoxyglucose uptake and capillary recruitment in the test leg only. Bradykinin (0.07 µmol·l^–1), alone or with insulin, administered in a manner that increased femoral blood flow similarly to methacholine, did not affect 2-deoxyglucose uptake or capillary recruitment.Conclusions/interpretation Methacholine but not bradykinin enhances insulin-mediated muscle glucose uptake in vivo. We conclude that methacholine acts at specific sites in the vasculature of muscle to stimulate capillary recruitment and thereby enhance insulin access.     

Relative values of the interventions of diversion and improved donor-arm disinfection to reduce the bacterial risk from blood transfusion

BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate the efficiency of diverting the initial 20-ml donation from the collection bag and of an improved donor-arm disinfection procedure in reducing bacterial contamination in blood. MATERIALS AND METHODS: Donations were collected in bags specially manufactured for the study. These bags incorporated two satellite pouches into each of which 20 ml of blood was collected. Blood initially flowed into sample pouch P1, representing a diversion pouch. Pouch P2 was then filled with 20 ml of blood, which allowed us to sample the collection bag after diversion was complete. Blood then flowed into the standard collection bag. The contents of the pouches were aerobically and anaerobically cultured on the BacT/ALERT automated culture system for 7 days. Two procedures were investigated in the study (each involving 1409 blood donations): one analysed the current disinfection procedure; and the other analysed an improved donor-arm disinfection procedure. RESULTS: The use of diversion alone resulted in a 47% reduction in contamination, and improved donor-arm disinfection alone resulted in a 57% reduction in contamination. Diversion plus improved donor-arm disinfection produced a predicted 77% reduction in contamination. CONCLUSIONS: The study validates diversion and an improved donor-arm disinfection procedure. In combination, these two interventions produced a substantial reduction in contamination. These procedures are to be introduced by the English National Blood Service to enhance the safety of the blood supply.     

A case of successful ablation of a gastrophrenic fistula with n-Butyl-2-Cyanocrylate.

A 79-year-old woman with a fistula between a subphrenic abscess and the fundus of the stomach was successfully treated with n-Butyl-2-Cyanoacrylate. Conservative management had failed. Clinical presentation, treatment progress and imaging findings by computed tomography scan, ultrasound, gastroscopy and fluoroscopy are presented, along with a brief review of the relevant literature.     

Proteomic Analyses of the Effects of Drugs of Abuse on Monocyte-Derived Mature Dendritic Cells

Drug abuse has become a global health concern. Understanding how drug abuse modulates the immune system and how the immune system responds to pathogens associated with drug abuse, such hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1), can be assessed by an integrated approach comparing proteomic analyses and quantitation of gene expression. Two-dimensional (2D) difference gel electrophoresis was used to determine the molecular mechanisms underlying the proteomic changes that alter normal biological processes when monocyte-derived mature dendritic cells were treated with cocaine or methamphetamine. Both drugs differentially regulated the expression of several functional classes of proteins including those that modulate apoptosis, protein folding, protein kinase activity, and metabolism and proteins that function as intracellular signal transduction molecules. Proteomic data were validated using a combination of quantitative, real-time PCR and Western blot analyses. These studies will help to identify the molecular mechanisms, including the expression of several functionally important classes of proteins that have emerged as potential mediators of pathogenesis. These proteins may predispose immunocompetent cells, including dendritic cells, to infection with viruses such as HCV and HIV-1, which are associated with drug abuse.     

Assessing Coronavirus Fear in Indian Population Using the Fear of COVID-19 Scale

International Journal of Mental Health and Addiction - The current study aimed to determine the level of fear of COVID-19 among Indian residents using the Fear of COVID-19 Scale (FCV-19S) and...