Effects on plasma noradrenaline may explain some of the improved insulin sensitivity seen by AT-1 receptor blockade.

AIMS: We have previously found improved insulin sensitivity in hypertensives after additional treatment with angiotensin II-receptor blocker (ARB) compared with calcium-channel blocker (CCB) alone, despite similar blood pressure lowering effects. In this study, we compare the effect of these two principal different vasodilating agents on the autonomic nervous system in the same patients, and test whether potential differences in these variables might explain the difference seen in insulin sensitivity. METHODS: In a double-blind crossover study, 21 hypertensive patients were randomized to receive either 100 mg losartan (ARB) or 5 mg amlodipine (CCB) in addition to an open-labelled treatment of amlodipine 5 mg. The patients were treated for 8 weeks with either treatment regimens after a 4-week run-in and a 4-week washout period. Plasma catecholamines were measured using radioenzymatic technique and baroreflex sensitivity and heart rate variability was tested at rest and during 24-h ECG registration. RESULTS: Plasma noradrenaline was significantly lower after additional treatment with ARB compared with CCB alone (304+/-29 pg/ml vs 373+/-43 pg/ml, p = 0.022). Heart rate variability, baroreflex sensitivity or plasma adrenaline did not differ significantly between the two treatment regimens. CONCLUSION: The results may suggest that improvement of insulin sensitivity by ARB is related to decreased plasma noradrenaline and potential sympatholytic effects.

Extremely slow formate elimination in severe methanol poisoning: a fatal case report.

UNLABELLED: Methanol poisoning is a potentially fatal medical emergency because of its metabolism to formic acid. The half-life of formate has been reported in the range of 2.5-12.5 hours, but the degree of inter-individual variation is not known. We studied methanol and formate kinetics in a case of late diagnosed methanol poisoning with persisting metabolic acidosis and circulatory failure. CASE REPORT: A 63-year-old man was referred to our hospital with a tentative diagnosis of stroke. He was awake on admission, but he soon deteriorated in the emergency department and a metabolic acidosis was revealed. Methanol poisoning was then suspected approximately five hours after admission but in spite of intensive treatment he died after six days. RESULTS: The S-methanol half-lives during treatment with fomepizole before and during hemodialysis were 49.5 and 4.1 hours, respectively, while the similar half-lives of S-formate were 77.0 and 2.9 hours. S-fomepizole was measured and found to be within the therapeutic range during treatment. DISCUSSION: The patient was treated with the established dosing regimen for fomepizole and the measured S-fomepizole levels throughout the treatment were adequate; the S-methanol elimination also suggests that methanol metabolism was blocked. Hence, other explanations for this exceptionally long formate half-life include slow formate metabolism, due to small hepatic folate stores or to genetic deficiencies in formate-metabolizing enzymes, or slow formate excretion, due to renal tubular acidosis, to a non-oliguric renal failure, or to genetic deficiencies in the renal formate transporters. CONCLUSION: This case report indicates that the half-life of S-formate may have greater inter-individual variation than earlier expected, being by far the longest half-life reported in the medical literature. These results support the use of hemodialysis in the treatment of such patients.