Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116326/1/feb2s0014579398000313.pd

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock

Methylene blue increases blood pressure and myocardial function in septic shock mainly by inhibiting nitric oxide (NO) actions. However, a dose-dependency of methylene blue has not been established. Therefore, the compound is currently used as rescue treatment only. To evaluate dose-dependency, a prospective, randomized, double blind, single centre study was performed in 15 consecutive, mechanically ventilated patients with septic shock admitted to the intensive care unit, in whom methylene blue was infused at 1 mg/kg (n = 4), 3 mg/kg (n = 6) or 7 mg/kg (n = 5) over 20 min. Hemodynamic parameters were measured before and after the infusion. Gastric tonometry was performed. Methylene blue treatment increased heart rate, cardiac index, mean arterial, pulmonary artery, pulmonary artery occlusion and central venous pressures, systemic vascular resistance, ventricular stroke work indices and O-2 delivery and uptake, and decreased lactate levels. Methylene blue had a dose-dependent effect on cardiac index, mean arterial, mean pulmonary artery and pulmonary artery occlusion pressures, left ventricular function, O-2 delivery and consumption and lactate levels. The drug dose-dependently increased the gastric-arterial blood PCO2 gap. The data suggest that in human septic shock, methylene blue increases mean arterial blood pressure by an increase in cardiac index and systemic vascular resistance. The rise in cardiac index is caused by an increase in left ventricular filling and function, increasing tissue oxygenation, even at a dose of 1 mg/kg. High doses of methylene blue may compromise splanchnic perfusion, even though further enhancing global hemodynamics, and should therefore, be avoided in future studies. (C) 2010 Elsevier Inc. All rights reserve