Basal and cold-induced fatty acid uptake of human brown adipose tissue is impaired in obesity.

Fatty acids (FA) are important substrates for brown adipose tissue (BAT) metabolism, however, it remains unclear whether there exists a difference in FA metabolism of BAT between lean and obese healthy humans. In this study we evaluated supraclavicular BAT fatty acid uptake (FAU) along with blood perfusion in lean and obese subjects during cold exposure and at room temperature using positron emission tomography (PET)/computed tomography (CT). Additionally, tissue samples were taken from supraclavicular region (typical BAT region) from a subset of subjects to evaluate histological presence of BAT. Non-shivering cold stress elevated FAU and perfusion of BAT in lean, but not in obese subjects. Lean subjects had greater FAU in BAT compared to obese subjects during cold exposure and interestingly also at room temperature. The higher BAT FAU was related to younger age and several indicators of superior systemic metabolic health. The subjects who manifested BAT histologically had several folds higher BAT FAU compared to subjects with no such histological manifestation. Together, obese subjects have less active tissue in supraclavicular region both in basal and cold-activated state and the FA metabolism of BAT is blunted in obesity.

Brown adipose tissue triglyceride content is associated with decreased insulin sensitivity, independently of age and obesity.

The aim of the present study was to determine whether single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) can non-invasively assess triglyceride content in both supraclavicular fat depots and subcutaneous white adipose tissue (WAT) to determine whether these measurements correlate to metabolic variables. A total of 25 healthy volunteers were studied using (18)F-fluorodeoxyglucose positron emission tomography (PET) and (15)O-H2O PET perfusion during cold exposure, and (1)H-MRS at ambient temperature. Image-guided biopsies were collected from nine volunteers. The supraclavicular triglyceride content determined by (1)H-MRS varied between 60 and 91% [mean ± standard deviation (s.d.) 77 ± 10%]. It correlated positively with body mass index, waist circumference, subcutaneous and visceral fat masses and 8-year diabetes risk based on the Framingham risk score and inversely with HDL cholesterol and insulin sensitivity (M-value; euglycaemic-hyperinsulinaemic clamp). Subcutaneous WAT had a significantly higher triglyceride content, 76-95% (mean ± s.d. 87 ± 5%; p = 0.0002). In conclusion, the triglyceride content in supraclavicular fat deposits measured by (1)H-MRS may be an independent marker of whole-body insulin sensitivity, independent of brown adipose tissue metabolic activation.

Amino-acid-based peritoneal dialysis solution improves amino-acid transport into skeletal muscle.

Abnormalities of amino-acid (AA) and protein metabolism are known to occur in chronic kidney disease (CKD). Protein malnutrition may contribute to impaired prognosis of dialysis patients. A crucial step in protein metabolism is AA transport into the cells. We compared the effects of an AA-containing peritoneal dialysis (PD) solution to glucose-based solutions on skeletal muscle AA uptake. Thirteen nondiabetic PD patients were studied twice in a random order and in a crossover manner both in the fasting state and during euglycemic insulin stimulation using [(11)C]methylaminoisobutyrate ([(11)C]MeAIB) and positron emission tomography (PET). Before both PET study days, patients had been using either glucose-based PD solutions only or one daily bag of AA solution in addition to glucose-based PD solutions for at least 6 weeks. Skeletal muscle AA uptake was calculated with graphical analysis. AA-containing PD solution increased plasma AA concentrations from 2.18+/-0.34 to 3.08+/-0.55 mmol l(-1) in the fasting state (P=0.0002) and from 1.88+/-0.15 to 2.42+/-0.30 mmol l(-1) during insulin stimulation (P<0.0001). As compared to PD treatment using glucose-based solutions only, skeletal muscle AA uptake was significantly higher during treatment containing AA solution both in the fasting state (15.2+/-5.8 vs 20.0+/-5.6 micromol kg(-1) min(-1), respectively, P=0.0057) and during insulin stimulation (16.8+/-4.5 vs 21.1+/-4.9 micromol kg(-1) min(-1), respectively, P=0.0046). In conclusion, PD treatment with an AA-containing PD solution is associated with a significant increase in skeletal muscle AA uptake both in the fasting state and during insulin stimulation.

Vipera berus adder bite in the water, complicated by rapid shock. A case history.

A case of a child who presented with severe and rapid shock after receiving a common adder (vipera berus berus) bite in sea water is presented. Although most poisonous snakebites in Europe tend to be relatively minor and uncomplicated, the present case highlights the need to regard all viper bites as life-threatening accidents, before proved otherwise by a medical professional.

Effect of clonidine on changes in plasma catecholamine concentrations and oxygen consumption caused by the cold pressor test.

This study was designed to investigate whether clonidine could attenuate the increase in oxygen consumption (VO2), arterial pressure (AP) and plasma catecholamines in response to the cold pressor test (CPT), an intense stimulation of the sympathetic nervous system. Six volunteers were given clonidine (2 micrograms kg-1 and 4 micrograms kg-1) and placebo i.m. in a random, double-blind, cross-over manner. Both clonidine doses decreased plasma catecholamine concentrations (P < 0.01), but only the higher dose of clonidine attenuated the CPT-induced absolute increase in plasma catecholamine concentration compared with the placebo group (P < 0.01). VO2 and AP decreased and were less after clonidine 4 micrograms kg-1 when compared with clonidine 2 micrograms kg-1 and placebo (P < 0.05) throughout the observation period. Thus, although clonidine 4 micrograms kg-1 attenuated the catecholamine response, the increases in VO2 and AP in response to CPT were similar in all groups.

The effect of clonidine or midazolam premedication on perioperative responses during ketamine anesthesia.

UNLABELLED: The use of ketamine as a sole anesthetic induces marked central sympathetic stimulation, causing increased heart rate, blood pressure (BP), and oxygen consumption (VO2). Both alpha 2-agonists and benzodiazepines have been used to attenuate these potentially harmful ketamine-induced responses. This double-blind, randomized, placebo-controlled study was designed to compare the perioperative metabolic, hemodynamic, and sympathoadrenal responses to IM clonidine (2 micrograms/kg) and midazolam (70 micrograms/kg) premedication during ketamine anesthesia. VO2 was measured continuously using indirect calorimetry in 30 ASA physical status I patients. The patients received ketamine, mivacurium, and fentanyl for the induction of anesthesia. Anesthesia was maintained using a ketamine infusion and fentanyl boluses i.v. Preoperatively, both VO2 and BP decreased significantly after the administration clonidine and midazolam compared with placebo (P < 0.01). Intraoperatively, VO2 was higher in the midazolam group than in the placebo and clonidine groups (P < 0.05). Postoperatively, there were no significant differences in BP and VO2, although they stayed at lower level in the clonidine group during the whole postoperative period. Clonidine decreased pre- and postoperative plasma catecholamine concentrations (P < 0.05). Our results indicate that a midazolam-ketamine combination may induce potentially harmful metabolic stimulation, whereas the sympatholytic effects of clonidine on ketamine-anesthetized patients may be beneficial, as perioperative VO2 was decreased. IMPLICATIONS: Ketamine causes sympathetic stimulation with an ensuing increase in oxygen consumption. Anticipating that clonidine might attenuate this response, we measured oxygen consumption in patients undergoing surgery during ketamine anesthesia. Patients treated with a clonidine-ketamine combination had lower intra- and postoperative oxygen consumption than those treated with a midazolam-ketamine combination.

The effect of low-dose ketamine on fentanyl-induced respiratory depression.

This study evaluated if adding low-dose ketamine to fentanyl could offer a haemodynamically stable drug combination with little respiratory side-effects. Eight healthy, consenting male volunteers received in a random, cross-over and double-blind fashion both fentanyl 2 micrograms.kg-1 + ketamine 0.25 mg.kg-1 and fentanyl 2 micrograms.kg-1 + placebo. The fentanyl and placebo reduced minute ventilation, alveolar ventilation and oxygen consumption (p < 0.05), with little effect on haemodynamics. After fentanyl and ketamine, the decrease in minute ventilation and alveolar ventilation was attenuated compared to the placebo-containing combination (p < 0.05), but with a simultaneous increase in oxygen consumption (p < 0.05) and stimulation of haemodynamics (p < 0.05). Both treatments decreased oxygen saturation and arterial oxygen pressure similarly. Ketamine thus attenuated the fentanyl-induced reduction in ventilation without preventing the decrease in blood oxygenation. In conclusion, combining low-dose ketamine to fentanyl offers no benefits in terms of preventing respiratory depression.

Effect of clonidine and dexmedetomidine premedication on perioperative oxygen consumption and haemodynamic state.

Premedication has been shown to affect both oxygen consumption and metabolic rate. We have compared the perioperative metabolic and haemodynamic effects of two alpha 2-agonists, clonidine and the more selective dexmedetomidine, in 30 ASA I patients undergoing plastic surgical procedures under general anaesthesia. Patients were premedicated with clonidine 4 micrograms kg-1 (n = 10), dexmedetomidine 2.5 micrograms kg-1 (n = 10) or saline (n = 10) i.m. The doses of clonidine and dexmedetomidine were intended to be equipotent. The maximum decrease in preoperative oxygen consumption was 8% and decreases in systolic and diastolic arterial pressures were 11% from baseline after clonidine and dexmedetomidine. During operation, the maximum reduction in heart rate was 18% in the clonidine and dexmedetomidine groups compared with the placebo group. After operation, the maximum decrease in systolic arterial pressure was 11%, diastolic arterial pressure 15% and oxygen consumption 17% in the clonidine and dexmedetomidine groups compared with placebo. In summary, both clonidine 4 micrograms kg-1 and dexmedetomidine 2.5 micrograms kg-1 decreased perioperative oxygen consumption effectively, with a similar haemodynamic profile.

Cardiovascular and metabolic responses to clonidine and midazolam premedication.

In this double-blind placebo controlled study the preoperative cardiovascular and metabolic effects of intramuscular (i.m.) clonidine and midazolam are assessed. Forty-five ASA Grade I patients (n = 15 per group) undergoing plastic surgical procedures were randomly allocated to receive either placebo, clonidine 4 micrograms kg-1 or midazolam 70 micrograms kg-1. Drugs were administered into the deltoid muscle approximately 90 min prior to the scheduled induction of anaesthesia. The metabolic measurements were performed using an indirect calorimetry device. Heart rate and blood pressure were measured noninvasively. Pre-operative subjective anxiety, dryness of mouth and tiredness were assessed using visual analogue scales (VAS). Clonidine increased subjective tiredness significantly more than placebo. Clonidine also induced moderate decreases in blood pressure and heart rate. Oxygen consumption (VO2), CO2 production and energy expenditure (EE) decreased significantly after clonidine and midazolam. The decrease in VO2 and EE was maximally 11-14% on average from the base-lines after clonidine and midazolam. These effects were of longer duration after clonidine and lasted until the end of the 90 min study period. In conclusion, both clonidine and midazolam are effective as a means of decreasing pre-operative VO2 and EE.

The metabolic effects of oral tizanidine in healthy volunteers.

This pilot study compared the metabolic effects of placebo and 6 mg and 12 mg of oral tizanidine in random double-blind cross-over fashion in five healthy volunteers. The metabolic measurements were made with a portable metabolic chart (Deltatrac, Datex/Instrumentarium, Helsinki, Finland). Heart rate (HR), systolic (BPS), mean (BPM) and diastolic (BPD) blood pressure were measured noninvasively. Subjective assessment of tiredness and dryness of mouth were measured by using visual analogue scales (VAS). There were no statistically significant differences in tiredness or dryness of mouth between the groups. BPD decreased significantly after both doses of tizanidine when compared to placebo (by an average of 12% after 6 mg of tizanidine and 15% after 12 mg of tizanidine from the baseline). Oxygen consumption and energy expenditure decreased significantly after 6 and 12 mg of tizanidine when compared to placebo. The average decrease in oxygen consumption was 3% after 6 mg of tizanidine and 8% after 12 mg of tizanidine, when compared to the baseline. Energy expenditure decreased by an average of 5% after 6 mg of tizanidine and 9% after 12 mg of tizanidine, when compared to the baseline. There were no other statistically significant differences between the groups. This study indicates that 6 and 12 mg of oral tizanidine can be useful for reducing energy expenditure and oxygen consumption without prominent cardiovascular effects.