Generation of peroxynitrite in localised, moderate temperature burns

Simultaneous generation of nitric oxide (NO.) and superoxide (O-2(-)) can lead to the formation of peroxynitrite (ONOO-); a potent oxidant that has been implicated in the pathogenesis of a number of disease states. This study was designed to investigate the possible generation of ONOO- in local cutaneous tissues following thermal injury. Male Wistar rats were anaesthetised in a nonrecovery procedure and subjected to a small (1 cm diameter). abdominal burn of moderate temperature (50 degrees C, 5-15 min). Al either the 60 or 180 min time point postburn the animals were killed, and skin sites were removed and homogenised. An ELISA was used to quantify protein bound 3-nitrotyrosine (3NT), a biomarker for ONOO- in the rat skin. In separate experiments the accumulation of [I-125]-albumin in thermally injured skin was used to calculate plasma extravasation. Thermal injury (50 degrees C, 10 min) to rat abdominal skin caused a significant increase in both 3NT (p <0.05) and oedema formation (p <0.001) when compared to unheated control sites at the 180 min time point postburn. This data is the first to show protein nitration in thermally injured, oedematous skin and strongly suggests that ONOO- is generated in thermally damaged cutaneous tissue. (C) 2000 Published by Elsevier Science Ltd. All rights reserved

Urine C-peptide creatinine ratio can be used to assess insulin resistance and insulin production in people without diabetes: an observational study.

The current assessment of insulin resistance (IR) in epidemiology studies relies on the blood measurement of C-peptide or insulin. A urine C-peptide creatinine ratio (UCPCR) can be posted from home unaided. It is validated against serum measures of the insulin in people with diabetes. We tested whether UCPCR could be a surrogate measure of IR by examining the correlation of UCPCR with serum insulin, C-peptide and HOMA2 (Homeostasis Model Assessment 2)-IR in participants without diabetes and with chronic kidney disease (CKD).This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text from the publisher's site.11/0004171/Diabetes UK/United Kingdo

Functional Significance of Inducible Nitric Oxide Synthase Induction and Protein Nitration in the Thermally Injured Cutaneous Microvasculature

Increased nitric oxide (NO) production after burn injury is well established. However, there is little information relating to the reactions that occur as a consequence of NO generation under such circumstances. We have investigated the synthesis and function of NO in a rat model of local cutaneous thermal injury. We show that NO levels are elevated from 3 hours after injury with a concomitant increase in protein nitration. A selective inducible nitric oxide synthase (iNOS) inhibitor (1400W) significantly attenuated NO synthesis, protein nitration, and neutrophil accumulation in this model, but had no effect on edema formation. The results also indicate that NO synthesis and protein nitration occurred independently of neutrophil accumulation because these parameters were unaffected by depletion of circulating neutrophils. 3-Chlorotyrosine, a marker of neutrophil/myeloperoxidase-mediated protein damage was significantly increased from 1 hour after burn. Our observations provide evidence for the involvement of reactive species in the inflammatory response after burn. The use of selective iNOS inhibitors may represent a novel approach for the management of human burn injuries

The impact of gender on urine C-peptide creatinine ratio interpretation.

Urinary C-peptide creatinine ratio (UCPCR) is a non-invasive and convenient way of assessing endogenous insulin production. Adjusting for urine creatinine levels allows for differences in urine concentration. Creatinine excretion is known to be higher in men due to gender differences in muscle mass. We investigated the impact of gender on UCPCR.This article is freely available via Open Access. Click on the ‘Additional Link’ above to access the full-text from the publisher’s site.PDA/02/06/098/Department of Health/United Kingdo