[Tick-borne encephalitis in the North part of the canton de Vaud]. / Méningo-encéphalite verno-estivate dans le Nord vaudois.

Tick-borne encephalitis (TBE) is described in Switzerland since 1969. More than 200 cases are reported every year to the Federal office of public health (FOPH) and new sites of endemic disease have been documented recently, in particular in the North part of the canton de Vaud. The aim of this article is to review the clinical pictures of 11 patients hospitalised in Yverdon-les-Bains with a diagnosis of TBE between 2003 and August 2007. The occurrence of 5 new cases exposed in the North part of the canton de Vaud over these last 18 months confirms the presence of endemic foci in this area and should prompt the vaccination against the MEVE which is recommended by the FOPH in endemic zones. The sequels of MEVE being observed mainly in the elderly, vaccination should be afforded also to this group of patients.

Suppression of alcohol-induced hypertension by dexamethasone.

BACKGROUND: Alcohol consumption is associated with an increased incidence of hypertension and stroke, but the triggering mechanisms are unclear. In animals, alcohol causes activation of the sympathetic nervous system and also stimulates the release of corticotropin-releasing hormone (CRH), which has sympatho-excitatory effects when administered centrally. METHODS: To determine whether alcohol evokes sympathetic activation and whether such activation is attenuated by the inhibition of CRH release, we measured blood pressure, heart rate, and sympathetic-nerve action potentials (using intraneural microelectrodes) in nine normal subjects before and during an intravenous infusion of alcohol (0.5 g per kilogram of body weight over a period of 45 minutes) and for 75 minutes after the infusion. Each subject received two infusions, one after the administration of dexamethasone (2 mg per day) and one after the administration of a placebo for 48 hours. RESULTS: The infusion of alcohol alone evoked a marked (P < 0.001) and progressive increase in the mean (+/- SD) rate of sympathetic discharge, from 16 +/- 3 bursts per minute at base line to 30 +/- 8 bursts per minute at the end of the two-hour period. This sympathetic activation was accompanied during the second hour by an increase in mean arterial pressure of 10 +/- 5 mm Hg (P < 0.001). After the administration of dexamethasone, the alcohol infusion had no detectable sympathetic effect. The dexamethasone-induced suppression of sympathetic activation was associated with a decrease in mean arterial pressure of 7 +/- 6 mm Hg (P < 0.001) during the alcohol infusion and with suppression of the pressor effect during the second hour. CONCLUSIONS: Alcohol induces pressor effects by sympathetic activation that appear to be centrally mediated. It is possible that these alcohol-induced hemodynamic and sympathetic actions could participate in triggering cardiovascular events.

Nitric oxide release accounts for insulin's vascular effects in humans.

Insulin exerts effects on the vasculature that (a) may play a role in the regulation of blood pressure; and (b) by boosting its own delivery to target tissues, also have been proposed to play an integral part in its main action, the promotion of glucose disposal. To study the role of nitric oxide (NO) in the mediation of insulin's effects on the peripheral vasculature, NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of the synthesis of endothelium-derived NO, was infused into the brachial arteries of healthy volunteers both before, and at the end of a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp. L-NMMA (but not norepinephrine, an NO-independent vasoconstrictor) caused larger reductions in forearm blood flow during hyperinsulinemia than at baseline. Moreover, L-NMMA prevented insulin-induced vasodilation throughout the clamp. Prevention of vasodilation by L-NMMA led to significant increases in arterial pressure during insulin/glucose infusion but did not alter glucose uptake. These findings indicate that insulin's vasodilatory effects are mediated by stimulation of NO release, and that they play a role in the regulation of arterial pressure during physiologic hyperinsulinemia. Abnormalities in insulin-induced NO release could contribute to altered vascular function and hypertension in insulin-resistant states.

Mechanisms of dexamethasone-induced insulin resistance in healthy humans.

Insulin resistance may result from decreased muscle blood flow, impaired cellular glucose transport, or intracellular deficits of glucose metabolism. The mechanisms responsible for dexamethasone-induced insulin resistance were investigated in healthy human subjects. During a 2-h hyperinsulinemic clamp, dexamethasone decreased glucose uptake, oxidation, and nonoxidative glucose disposal during the first hour. During the second hour, glucose uptake was normalized by means of hyperglycemia; glucose oxidation, however, remained suppressed by dexamethasone. Dexamethasone also abolished the insulin-mediated increase in calf blood flow. When acipimox was administered during the clamps to correct glucocorticoid-induced inhibition of glucose oxidation, dexamethasone decreased whole body glucose uptake and nonoxidative glucose disposal in the same proportion as when no acipimox was administered. However, glucose oxidation and insulin-mediated calf blood flow were normalized after acipimox. During the second hour, exogenous glucose infusion was matched to that used in the control clamp and normalized whole body glucose uptake. However, hyperglycemia developed, indicating insulin resistance. It is concluded that dexamethasone 1) decreases glucose oxidation independently of glucose transport; this inhibition is reversed by acipimox; and 2) decreases whole body glucose uptake independently of increased lipolysis, decreased glucose oxidation, or an altered muscle blood flow.

Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans.

The sympathetic nervous system is an important regulatory mechanism of both metabolic and cardiovascular function, and altered sympathetic activity may play a role in the etiology and/or complications of obesity. In lean subjects, insulin evokes sympathetic activation and vasodilation in skeletal muscle. In obese subjects such vasodilation is impaired and, in turn, may contribute to insulin resistance. To examine the relationship between sympathetic and vasodilatory responses in skeletal muscle to hyperinsulinemia, we simultaneously measured muscle sympathetic nerve activity (MSNA) and calf blood flow at basal and during a 2-h hyperinsulinemic (6 pmol/kg per min) euglycemic clamp in eight lean and eight obese subjects. The major findings of this study are twofold: obese subjects had a 2.2 times higher fasting rate of MSNA, and euglycemic hyperinsulinemia, which more than doubled MSNA and increased calf blood flow by roughly 30% in lean subjects, had only a minor vasodilatory and sympathoexcitatory effect in obese subjects. In contrast, two non-insulin-sympathetic stimuli evoked comparably large increases in MSNA in lean and obese subjects. We conclude that insulin resistance in obese subjects is associated with increased fasting MSNA and a specific impairment of sympathetic neural responsiveness to physiological hyperinsulinemia in skeletal muscle tissue.

Body fat and sympathetic nerve activity in healthy subjects.

BACKGROUND: Obesity is associated with an increased incidence of cardiovascular complications, but the underlying mechanism is unknown. In experimental animals, overfeeding is associated with sympathetic activation, and there is evidence that adrenergic mechanisms contribute to cardiovascular complications. METHODS AND RESULTS: We recorded resting postganglionic sympathetic nerve discharge (using intraneural microelectrodes) to skeletal muscle blood vessels in 37 healthy subjects covering a broad spectrum of percent body fat. To assess potential functional consequences of sympathetic nerve discharge, we simultaneously measured calf vascular resistance and energy expenditure. The resting rate of sympathetic nerve discharge to skeletal muscle was directly correlated with body mass index (r = .67, P < .0001) and percent body fat (r = .64, P < .0001). In addition to body fat, muscle sympathetic nerve activity was correlated with age (r = .40, P < .02), plasma insulin concentration (r = .34, P < .04), and plasma lactate concentration (r = .35, P < .04). Together, these four covariates accounted for 58% of the variance of muscle sympathetic nerve activity (P < .0001). The rate of sympathetic nerve discharge to calf blood vessels was directly correlated with calf vascular resistance (r = .40, P < .02) but did not predict energy expenditure (r = .22, P = .19). CONCLUSIONS: In healthy humans, body fat is a major determinant of the resting rate of muscle sympathetic nerve discharge. Overweight-associated sympathetic activation could represent one potential mechanism contributing to the increased incidence of cardiovascular complications in overweight subjects.

Effects of adrenergic and cholinergic blockade on insulin-induced stimulation of calf blood flow in humans.

Euglycemic hyperinsulinemia stimulates both sympathetic nerve activity and blood flow to skeletal muscle, but the mechanism is unknown. Possible mechanisms that may stimulate muscle blood flow include neural, humoral, or metabolic effects of insulin. To determine whether such insulin-induced vasodilation is modulated by stimulation of adrenergic or cholinergic mechanisms, we obtained, in eight healthy lean subjects, plethysmographic measurements of calf blood flow during 3 h of hyperinsulinemic (1 mU.kg-1.min-1) euglycemic clamp performed alone or during concomitant beta-adrenergic (propranolol infusion), cholinergic (atropine infusion), or alpha-adrenergic (prazosin administration) blockade. Euglycemic hyperinsulinemia alone increased calf blood flow by 38 +/- 10% (means +/- SE) and decreased vascular resistance by 27 +/- 4% (P < 0.01). The principal new observation is that these insulin-induced vasodilatory responses were not attenuated by concomitant propranolol or atropine infusion, nor were they potentiated by prazosin administration. In conclusion, these findings provide evidence that during euglycemic hyperinsulinemia in lean healthy humans stimulation of muscle blood flow is not mediated primarily by beta-adrenergic or cholinergic mechanisms. Furthermore, alpha-adrenergic mechanisms do not markedly limit insulin-induced stimulation of muscle blood flow.

Suppression of insulin-induced sympathetic activation and vasodilation by dexamethasone in humans.

BACKGROUND: Physiological hyperinsulinemia in lean human subjects stimulates sympathetic nerve activity and blood flow in skeletal muscle, but the underlying mechanism is unknown. Potential mechanisms include central neural or peripheral actions of insulin. Glucocorticoids may potentially interfere with both such actions and thereby may attenuate sympathoexcitatory and vasodilatory effects of insulin in skeletal muscle. METHODS AND RESULTS: To determine whether insulin-induced sympathetic activation and vasodilation are attenuated by dexamethasone, we measured muscle sympathetic nerve activity and muscle blood flow during euglycemic hyperinsulinemia before and after short-term administration of this pharmacological agent. Insulin concentrations, which normally doubled sympathetic activity and markedly increased blood flow, had no such stimulatory effect after short-term dexamethasone administration. In contrast, responses to two noninsulin sympathetic stimuli, the Valsalva maneuver and immersion of the hand in ice water, and the vasodilatory response to calf vascular occlusion were not altered by dexamethasone. CONCLUSIONS: These results demonstrate a dramatic impairment of insulin-induced sympathetic activation and vasodilation by dexamethasone in lean, healthy humans. This study suggests that dexamethasone administration to lean subjects may offer an experimental model to examine underlying mechanisms that regulate the interplay between cardiovascular, sympathetic, and metabolic effects of insulin.

Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans.

Euglycemic hyperinsulinemia evokes both sympathetic activation and vasodilation in skeletal muscle, but the mechanism remains unknown. To determine whether insulin per se or insulin-induced stimulation of carbohydrate metabolism is the main excitatory stimulus, we performed, in six healthy lean subjects, simultaneous microneurographic recordings of muscle sympathetic nerve activity, plethysmographic measurements of calf blood flow, and calorimetric determinations of carbohydrate oxidation rate. Measurements were made during 2 h of: (a) insulin/glucose infusion (hyperinsulinemic [6 pmol/kg per min] euglycemic clamp), (b) exogenous glucose infusion at a rate matched to that attained during protocol a, and (c) exogenous fructose infusion at the same rate as for glucose infusion in protocol b. For a comparable rise in carbohydrate oxidation, insulin/glucose infusion that resulted in twofold greater increases in plasma insulin concentrations than did glucose infusion alone, evoked twofold greater increases in both muscle sympathetic nerve activity and calf blood flow. Fructose infusion, which increased carbohydrate oxidation comparably, but had only a minor effect on insulinemia, did not stimulate either muscle sympathetic nerve activity or calf blood flow. These observations suggest that in humans hyperinsulinemia per se, rather than insulin-induced stimulation of carbohydrate metabolism, is the main mechanism that triggers both sympathetic activation and vasodilation in skeletal muscle.