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PubMed1993

Effects of terbutaline on basal thermogenesis of human skeletal muscle and Na-K pump after 1 week of oral use--a placebo controlled comparison with propranolol.

1. A double-blind placebo-controlled study was conducted on the effects of oral terbutaline (beta 2-adrenoceptor agonist) and propranolol (beta 1 beta 2-adrenoceptor antagonist) on basal heat production of skeletal muscle, measured ex vivo by direct microcalorimetry. Terbutaline slow-release 7.5 mg, propranolol 80 mg, and matching placebo were randomly administered twice daily for 1 week to 15 healthy males, using a cross-over design. 2. Resting heat production in biopsied vastus lateralis was lowered by median 27% (P < 0.01) after terbutaline medication as compared with placebo. The cause of this hypometabolism at the cellular level is obscure but may possibly be explained by desensitization of beta 2-receptors. 3. Propranolol decreased the metabolic rate by 17% (P > 0.3); this might imply that the sympathetic nervous system is playing only a minor role in the regulation of basal metabolic rate in muscle, or that up-regulation of beta-receptors had influenced the decline. 4. The muscle utilized about 6% of its total energy for the Na-K pump as assessed after inhibition by ouabain. 5. Serum potassium was significantly lowered by terbutaline and slightly increased by propranolol with no relationship between changes in extracellular levels and muscle content of potassium under resting conditions. Energy values for the Na-K pump in muscle after 1 week of terbutaline or propranolol medication were similar to placebo. The results are not consistent with the hypothesis that decreased serum potassium during continuous beta 2-adrenoceptor agonist treatment is due to a chronically activated Na-K pump, at least not in resting muscle.

Adult↗
PubMed2004

Differential effects of (R)-, (R, S)- and (S)-8-hydroxy-2-(di-n-propylamino)tetralin on hippocampal serotonin release and induction of hypothermia in awake rats.

The effects of (R)- and (S)-optical isomers of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and of the racemate (R,S)-8-OH-DPAT on serotonin (5-HT) release in the ventral hippocampus of awake rats and on induction of the whole-body hypothermia were studied. Extracellular 5-HT levels were determined by a newly developed high-sensitive HPLC method based on derivatization with benzylamine and fluorescence detection. The basal levels of 5-HT in 20 min microdialysates from rats perfused with Ringer solution or with Ringer solution containing 1 microM citalopram were 6.3 +/- 1.3 fmol/20 microl and 36.1 +/- 4.2 fmol/20 microl (n=20), respectively. The reduction of hippocampal 5-HT levels induced by subcutaneous (s.c.) administration of (R,S)-8-OH-DPAT (0.3 mg/kg) was significantly attenuated by the presence of 5-HT reuptake inhibitor citalopram in Ringer solution only at its peak value at 40 min (maximal reduction to 60% compared to 46% of control values in Ringer-perfused rats), whereas the overall effects were comparable at both experimental conditions. Injection of (R)-8-OH-DPAT (0.3 mg/kg s.c.) caused further reduction of 5-HT levels, to 49% and 41%, respectively, whereas (S)-8-OH-DPAT (0.3 mg/kg s.c.) caused maximal reduction of 5-HT levels only to 74% of controls in both perfusion groups. Similar pattern and time-courses were observed in rats with hypothermia induced by injection of 8-OH-DPAT enantiomers, where (R,S), (R)-forms were about two-times more potent than the (S)-isomer. It is concluded that the acute systemic dose of (R)-, (S)- and (R,S)-8-OH-DPAT enantiomers exerted enantiomer-specific effects on 5-HT(1A) receptor-mediated function both at the presynaptic and postsynaptic sites as revealed by monitoring hippocampal 5-HT levels and body temperature.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

Inaccuracy of basal body temperature charts in predicting urinary luteinizing hormone surges.

Sixty basal body temperature (BBT) charts were reviewed by three reproductive endocrinologists in an attempt retrospectively to predict the urinary luteinizing hormone (LH) surge. LH surges had been previously detected in all cycles with the use of a commercially available monoclonal antibody kit, Ovustick (Monoclonal Antibodies, Inc., Mountain View, CA). Surges were correctly predicted to the day (day 0) 18.3% to 30.0% of the time, to within 1 day on either side of day 0 56.7% to 70.0% of the time, to within 2 days 83.3% to 98.3% of the time, and to within 3 days 96.7% to 98.3% of the time. The BBT remains an inaccurate predictor of the day of the LH surge but does provide a reasonably accurate guide to the 2- to 3-day period on either side of the surge.

Body Temperature↗
PubMed1998

Simulation of a cold-stressed finger including the effects of wind, gloves, and cold-induced vasodilatation.

The thermal response of fingers exposed to cold weather conditions has been simulated. Energy balance equations were formulated, in a former study, for the tissue layers and the arterial, venous, and capillary blood vessels. The equations were solved by a finite difference scheme using the Thomas algorithm and the method of alternating directions. At this stage of development the model does not include any autonomic control functions. Model simulations assumed an electrical heating element to be embedded in the glove layers applied on the finger. A 1.3 W power input was calculated for maintaining finger temperatures at their pre-cold exposure level in a 0 degree C environment. Alternate assumptions of nutritional (low) and basal (high) blood flows in the finger demonstrated the dominance of this factor in maintaining finger temperatures at comfortable levels. Simulated exposures to still and windy air, at 4.17 m/s (15 km/h), indicated the profound chilling effects of wind on fingers in cold environments. Finally, the effects of variable blood flow in the finger, known as "cold-induced vasodilatation," were also investigated. Blood flow variations were assumed to be represented by periodic, symmetric triangular waves allowing for gradual opening-closing cycles of blood supply to the tip of the finger. Results of this part of the simulation were compared with measured records of bare finger temperatures. Good conformity was obtained for a plausible pattern of change in blood flow, which was assumed to be provided in its entirety to the tip of the finger alone.

Algorithms↗
PubMed1980

Micropipette measurement of airway submucosal gland secretion. Autonomic effects.

We describe a micropipette method for obtaining secretions from single submucosal gland ducts in vivo in cat tracheas. The secretory rate of 65 glands sampled under basal conditions in 16 animals varied from 3 to 30 nl/min (mean +/- SE, 9.05 +/- 0.60 nl/min) and varied 2 to 3-fold among glands sampled within an animal. Sequential samples collected from individual ducts during a 10-min period were highly repeatable (correlation coefficient, 0.96) and were remarkably constant for as long as 4 h. Vagal cooling decreased the secretory rate by a mean of 39% (n = 11, p less than 0.05). Stimulation of the cervical vagus nerves increased flow from 8.3 +/- 0.7 to 16.4 +/- 0.8 nl/min (n = 15, p less than 0.01), an effect that was abolished by intravenous injection of 0.5 mg of atropine sulfate/kg of body weight or by cooling of the vagus nerves, but not by 0.08 mg of phentolamine/kg given intravenously. Intravenous injection of 0.3 mg of phenylephrine/kg of body weight increased flow from 8.6 +/- 0.6 to 18.9 +/- 1.1 nl/min (n = 20, p less than 0.001), an effect that was prevented by phentolamine, but not by atropine. We conclude that cholinergic and alpha-adrenergic stimulation increases fluid secretion from feline submucosal glands.

Animals↗
PubMed2001

The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice.

OBJECTIVE: To directly ascertain the physiological roles in adipocytes of hormone-sensitive lipase (HSL; E.C. 3.1.1.3), a multifunctional hydrolase that can mediate triacylglycerol cleavage in adipocytes. RESEARCH METHODS AND PROCEDURES: We performed constitutive gene targeting of the mouse HSL gene (Lipe), subsequently studied the adipose tissue phenotype clinically and histologically, and measured lipolysis in isolated adipocytes. RESULTS: Homozygous HSL-/- mice have no detectable HSL peptide or cholesteryl esterase activity in adipose tissue, and heterozygous mice have intermediate levels with respect to wild-type and deficient littermates. HSL-deficient mice have normal body weight but reduced abdominal fat mass compared with normal littermates. Histologically, both white and brown adipose tissues in HSL-/- mice show marked heterogeneity in cell size, with markedly enlarged adipocytes juxtaposed to cells of normal morphology. In isolated HSL-/- adipocytes, lipolysis is not significantly increased by beta3-adrenergic stimulation, but under basal conditions in the absence of added catecholamines, the lipolytic rate of isolated HSL-/- adipocytes is at least as high as that of cells from normal controls. Cold tolerance during a 48-hour period at 4 degrees C was similar in HSL-/- mice and controls. Overnight fasting was well-tolerated clinically by HSL-/- mice, but after fasting, liver triglyceride content was significantly lower in HSL-/- mice compared with wild-type controls. CONCLUSIONS: In isolated fat cells, the lipolytic rate after beta-adrenergic stimulation is mainly dependent on HSL. However, the observation of a normal rate of lipolysis in unstimulated HSL-/- adipocytes suggests that HSL-independent lipolytic pathway(s) exist in fat. Physiologically, HSL deficiency in mice has a modest effect under normal fed conditions and is compatible with normal maintenance of core body temperature during cold stress. However, the lipolytic response to overnight fasting is subnormal.

Adipocytes↗
PubMed1993

The impact of a pure anti-androgen (flutamide) on LH, FSH, androgens and clinical status in idiopathic hirsutism.

OBJECTIVES: We assessed in women the effects of androgen suppression on gonadotrophin secretion and the therapeutic efficacy of the pure anti-androgen flutamide (2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-propanamide). DESIGN AND SUBJECTS: Ten women, aged 28-35 years, using an intrauterine device for contraception, were selected for this study. All women had idiopathic hirsutism with or without acne and seborrhoea. Flutamide was administered orally in a dose of 250 mg twice daily for 1 year. Basal body temperature was recorded and pelvic ultrasonography performed before and every 3 months during treatment. LH pulse frequency and amplitude (Cluster analysis) and basal and GnRH-stimulated plasma LH and FSH levels were determined on day 5 of the cycle prior to flutamide treatment, and after 6 and 12 months of therapy. Plasma total testosterone (T), non-SHBG bound T, androstenedione (A), dehydroepiandrosterone sulphate (DHEAS), androstanediol glucuronide (3 alpha-diol G) and sex hormone binding globulin (SHBG) levels were measured before and every 3 months during therapy, on day 5 of the cycle. Plasma oestradiol and progesterone levels were determined on day 22 of the studied cycles. RESULTS: Disappearance of acne and seborrhoea occurred after 2 months with a marked improvement of hirsutism at 6 months. At 12 months, hirsutism had disappeared with a Ferriman and Gallwey score < 7. No adverse side-effects, apart from transient diarrhoea in two patients, were reported with this flutamide dose. None of the patients had any disturbance of menstrual cycles which remained ovulatory. The pure anti-androgen flutamide induced no significant change in LH pulsatile profile, nor in LH and FSH responsiveness to GnRH. Plasma concentrations of steroids were not altered. Plasma SHBG and 3 alpha-diol G levels did not change during flutamide treatment. CONCLUSION: Flutamide, which interacts only with the androgen receptor, is effective for hirsutism, acne and seborrhoea, and does not disturb menstrual cyclicity or ovulation. It may represent a treatment of choice for essential hirsutism in women using safe contraceptive methods.

Acne Vulgaris↗
PubMed2006

Basal heat pain thresholds predict opioid analgesia in patients with postherpetic neuralgia.

BACKGROUND: A variety of analgesics have been studied in the treatment of postherpetic neuralgia, with several medications demonstrating some degree of efficacy. However, existing trials have documented large individual differences in treatment responses, and it is important to identify patient characteristics that predict the analgesic effectiveness of particular interventions. Several animal studies have indicated that reduced basal nociceptive sensitivity, in the form of relatively high heat pain thresholds, is associated with greater opioid analgesia, but this finding has not been applied to human studies of opioid treatment for chronic pain. METHODS: Using data from a previously published crossover trial of opioids and tricyclics in postherpetic neuralgia, the authors evaluated baseline thermal pain thresholds, assessed at a body site contralateral to the affected area, as a predictor of treatment responses. RESULTS: During opioid treatment, a greater reduction in pain and higher ratings of pain relief were observed in patients with relatively higher heat pain thresholds at baseline. Baseline pain thresholds did not predict responses to tricyclics or placebo. Interestingly, other individual-difference variables such as age and baseline pain intensity also significantly predicted opioid responses (i.e., higher baseline pain and younger age were related to greater opioid-associated pain reduction, with nearly 20% of the variance in opioid analgesia explained by these two factors). CONCLUSIONS: These findings, which will require replication, suggest that pretreatment assessment of heat pain sensitivity might prove useful in identifying those patients most likely to respond to opioids.

Aged↗
PubMed2006

Mitochondrial proton leak rates in the slow, oxidative myotomal muscle and liver of the endothermic shortfin mako shark (Isurus oxyrinchus) and the ectothermic blue shark (Prionace glauca) and leopard shark (Triakis semifasciata).

Mitochondrial proton leak was assessed as a potential heat source in the slow, oxidative (red) locomotor muscle and liver of the shortfin mako shark (Isurus oxyrinchus), a regional endotherm that maintains the temperature of both tissues elevated above ambient seawater temperature. We hypothesized that basal proton leak rates in red muscle and liver mitochondria of the endothermic shortfin mako shark would be greater than those of the ectothermic blue shark (Prionace glauca) and leopard shark (Triakis semifasciata). Respiration rate and membrane potential in isolated mitochondria were measured simultaneously at 20 degrees C using a Clark-type oxygen electrode and a lipophilic probe (triphenylmethylphosphonium, TPMP(+)). Succinate-stimulated respiration was titrated with inhibitors of the electron transport chain, and the non-linear relationship between respiration rate and membrane potential was quantified. Mitochondrial densities of both tissues were measured by applying the point-contact method to electron micrographs so that proton leak activity of the entire tissue could be assessed. In all three shark species, proton leak occurred at a higher rate in red muscle mitochondria than in liver mitochondria. For each tissue, the proton leak curves of the three species overlapped and, at a membrane potential of 160 mV, mitochondrial proton leak rate (nmol H(+) min(-1) mg(-1) protein) did not differ significantly between the endothermic and ectothermic sharks. This finding indicates that red muscle and liver mitochondria of the shortfin mako shark are not specialized for thermogenesis by having a higher proton conductance. However, mako mitochondria did have higher succinate-stimulated respiration rates and membrane potentials than those of the two ectothermic sharks. This means that under in vivo conditions mitochondrial proton leak rates may be higher in the mako than in the ectothermic species, due to greater electron transport activity and a larger proton gradient driving proton leak. We also estimated each tissue's total proton leak by combining mitochondrial proton leak rates at 160 mV and tissue mitochondrial density data with published values of relative liver or red muscle mass for each of the three species. In red muscle, total proton leak was not elevated in the mako shark relative to the two ectothermic species. In the liver, total proton leak would be higher in the mako shark than in both ectothermic species, due to a lower proton conductance in the blue shark and a lower liver mitochondrial content in the leopard shark, and thus may contribute to endothermy.

Animals↗
PubMed1985

Visceral predictors of cardiovascular deconditioning in late middle-aged men.

A major task for space biologists is to try to delineate methods which can be used to predict the degree of cardiovascular deconditioning that given individuals might develop while in space. Toward that end, we have studied a number of different visceral and behavioral variables in a group of late middle-aged men (55-65 years) on day 1 and day 5 of a bedrest regimen. During each 8-h study period, data were collected every 15 min. Mean arterial blood pressure and plasma cortisol and norepinephrine concentrations were significantly higher on the day 5 than on the day 1 of bedrest; heart rate, core temperature, plasma epinephrine and subjective arousal were unchanged. Pair-wise correlations between each of these variables and the time to blackout on a +3-Gz test of acceleration tolerance administered on day 9 of bedrest (mean decrease in latencies from prebedrest was 52%) revealed a significant correlation for the mean arterial blood pressure variable. Thus, these data indicate that men in this age span with relatively low resting blood pressures are at greater risk for developing clinical signs relating to their cardiovascular deconditioning than other men with higher basal blood pressures.

Acceleration↗
PubMed1968

Shivering and non-shivering therogenesis during summit metabolism in young lambs.

1. Summit metabolism of lambs declined steadily from about 3.5 l. O(2)/kg.hr during the first day of life, to about 2.0 l. O(2)/kg.hr at 2 months of age.2. The contributions of shivering and non-shivering thermogenesis to these changes were estimated by three independent methods; non-shivering thermogenesis was stimulated by catecholamines in a thermoneutral environment, shivering was suppressed by curariform drugs during summit metabolism, and an attempt was made to suppress non-shivering thermogenesis during summit metabolism by use of the sympatholytic drugs phentolamine and propranolol. Drugs were given by intravenous infusion during measurement of oxygen consumption in a closed circuit respiration chamber.3. ;Resting' metabolic rate of lambs during the first day of life was increased two to three-fold, from 1 l. O(2)/kg.hr, by either adrenaline or noradrenaline infused at 1-10 mug/kg.min. The increase declined with increasing age of lamb and was virtually absent by 3 weeks. The response to catecholamines appeared maximal at the dose levels used.4. Muscular paralysis induced by suxamethonium or gallamine reduced summit metabolism by about 2 l. O(2)/kg.hr in all lambs examined within the first 2 months of life. The residual metabolic rate, and the metabolic response to catecholamines under thermoneutral conditions, declined with age in the same manner, and their magnitudes were similar.5. Summit metabolism in lambs aged up to 2 months was depressed to varying degrees by the sympathetic inhibitors phentolamine, propranolol and hexamethonium. The depression with propranolol was greater, and the decline with age clearer, than with phentolamine. Hexamethonium and phentolamine depressed blood pressure, propranolol decreased heart rate and phentolamine and propranolol each suppressed shivering in some experiments.6. In 1 day-old lambs estimates of non-shivering thermogenesis, by the various methods, ranged from 0.8 to 1.4 l. O(2)/kg.hr (mean 1.1 l. or 31% of summit metabolism), and the estimates of shivering ranged from 1.3 to 1.9 l. O(2)/kg.hr (mean 1.6 l. or 46% of summit metabolism). However, in lambs 1-month old, estimates of non-shivering thermogenesis from sympathetic inhibition (0.6 and 0.8 l. O(2)/kg.hr) were considerably higher than estimates from muscular paralysis or stimulation by catecholamines (0.2 and 0.1 l. O(2)/kg.hr). It is suggested that the depression of summit metabolism by the sympathetic inhibitors is not solely due to specific inhibition of non-shivering thermogenesis, at least in the older lambs.7. The possession of a non-shivering thermogenic mechanism in addition to shivering is of clear survival value to new-born lambs.

Age Factors↗
PubMed1995

Effects of lactate infusion on hepatic gluconeogenesis and glycogenolysis.

Endogenous glucose production rate (EGPR) remains constant when lactate is infused in healthy humans. A decrease of glycogenolysis or of gluconeogenesis from endogenous precursors or a stimulation of glycogen synthesis, may all be involved; This autoregulation does not depend on changes in glucoregulatory hormones. It may be speculated that alterations in basal sympathetic tone may be involved. To gain insights into the mechanisms responsible for autoregulation of EGPR, glycogenolysis and gluconeogenesis were measured, with a novel method (based on the prelabelling of endogenous glycogen with 13C glucose, and determination of hepatic 13C glycogen enrichment from breath 13CO2 and respiratory gas exchanges) in healthy humans infused with lactate or saline. These measurements were performed with or without beta-adrenergic receptor blockade (propranolol). Infusion of lactate increased energy expenditure, but did not increase EGPR; the relative contributions of gluconeogenesis and glycogenolysis to EGPR were also unaltered. This indicates that autoregulation is attained, at least in part, by inhibition of gluconeogenesis from endogenous precursors. beta-adrenergic receptor blockade alone (with propranolol) did not alter EGPR, glycogenolysis or gluconeogenesis. During infusion of lactate, propranolol decreased the thermic effect of lactate but EGPR remained constant. This indicates that alterations of beta-adrenergic activity is not required for autoregulation of EGPR.

Adrenergic beta-Antagonists↗
PubMed1995

Effects of bromocriptine on cardiovascular regulation in healthy humans.

Bromocriptine, a dopamine agonist with central nervous system actions, may reduce sympathetic nervous system activity. We tested this hypothesis by measuring arterial blood pressure, central venous pressure, heart rate, muscle sympathetic nerve activity, and forearm blood flow before and after unloading the arterial baroreceptors with sodium nitroprusside (0.5 to 1.5 mcg/kg per minute IV), before and after unloading the cardiopulmonary baroreceptors with incremental lower body negative pressure (0 to -15 mm Hg), and before and after immersion of the hand in ice-cold water for 2 minutes (cold pressor test). After obtaining basal responses to provocative maneuvers, we gave 20 healthy subjects either 5 mg oral bromocriptine (n = 10) or placebo (n = 10) in a randomized, double-blind fashion. Bromocriptine did not affect resting mean arterial pressure, heart rate, or forearm blood flow. Bromocriptine decreased resting central venous pressure by 1.2 mm Hg (P < .05) and tended to increase total integrated muscle sympathetic nerve activity (from 151 +/- 44 to 212 +/- 82 U/min, P = NS). The reflex increases in muscle sympathetic nerve activity to nitroprusside infusion and lower body negative pressure were unchanged by bromocriptine; however, vascular responsiveness to both maneuvers was impaired after bromocriptine administration compared with control. Without bromocriptine, the reflex increase in muscle sympathetic nerve activity after nitroprusside-induced hypotension maintained forearm blood flow at a constant level, whereas with bromocriptine the forearm blood flow increased from 1.9 +/- 0.3 to 2.8 +/- 0.6 mL/min per 100 mL (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Methiothepin reduces glucose utilization in forebrain regions of awake rats.

Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic [14C]2-deoxy-D-glucose method, in 92 discrete brain regions of awake rats, at 1, 2, 3, or 4 h after administration of the serotonergic antagonist methiothepin 0.1 mg/kg IP. The drug produced a cataleptic behavior that peaked in intensity at 3 h after its administration. LCGU declined significantly in 35% of the 92 regions at one or more time points after methiothepin administration. No area of increased metabolism was found. The time-course of the decline in LCGU closely paralleled the intensity of catalepsy; the peak effect was at 3 h, when LCGU was significantly reduced in 32% of the regions examined (mean decline for all regions was 15%). Metabolic depression after methiothepin was most notable in the forebrain, where LCGU declined in many regions of the cerebral cortex, basal ganglia, and thalamus. Most of the regions affected by methiothepin possess a substantial number of serotonin receptors, although LCGU was also reduced in a few regions not primarily involved in serotonergic neurotransmission.

Animals↗
PubMed2005

Baker yeast-induced fever in young rats: characterization and validation of an animal model for antipyretics screening.

In this study we describe a low-cost and reliable method for inducing fever in young male rats (28-30 days of age, 75-90 g), which seems suitable for the screening of new antipyretics. The effects of temperature measuring procedure-induced stress on the basal rectal temperature and on Baker yeast-induced hyperthermia was assessed. Rectal temperature (T) was recorded every hour for 12 h (07:00-19:00 h) with a lubricated thermistor probe. The animals were injected intraperitoneally with baker yeast (0.25, 0.135, 0.05 g/kg) or the equivalent volume of saline at 7:00 h. The administration of 0.135 g/kg baker yeast induced a sustained increase in rectal temperature for 4 h. Classical (dipyrone and acetaminophen) and novel (MPCA and FPCA) antipyretics, at doses that had no effect per se, reverted baker yeast-induced fever. The method presented induces a clear-cut fever, which is reverted by antipyretics commonly used in human beings and selected novel antipyretics in small animals. The method also allows antipyretic evaluation with low amount of drugs, due to the use of small animals and to the small variability of the pyretic response, which ultimately causes a significant reduction in the number of animals necessary for antipyretic evaluation. Therefore, this study describes an animal model of fever that is not only advantageous from the economical and technical point of view, but that also bears ethical concerns.

Analgesics, Non-Narcotic↗
PubMed2004

Comparison of the acute pharmacodynamic responses after single doses of ephedrine or sibutramine in healthy, overweight volunteers.

OBJECTIVE: With an increase in the incidence of obesity, tremendous effort has been devoted to the development of weight loss agents and the prospective surrogate markers of both a product's efficacy and safety. The objective of the present study was to compare the pharmacodynamic responses of ephedrine and sibutramine using surrogate markers of weight loss potential and potential adverse events. DESIGN AND SUBJECTS: The study was designed as a 5-way, randomized, double-blinded, placebo-controlled trial with 3 single doses of ephedrine sulfate (0.25, 0.5 and 1 mg x kg(-1)) followed by an open-labeled sibutramine (10 mg) treatment. Healthy, mildly overweight (BMI = 25) subjects were administered the respective treatment and pharmacokinetic and pharmacodynamic measurements (body surface temperature, resting metabolic rate, blood pressure, heart rate, glucose, glycerol, nonesterified fatty acids, triglycerides) were obtained for 8 hours post dose and for an additional 4 measurements during the sibutramine treatment period. RESULTS: Sibutramine treatment significantly increased resting metabolic rate compared to the placebo condition. Ephedrine significantly increased heart rate, systolic blood pressure and glucose but did not significantly affect other measurements. CONCLUSION: Both sibutramine and ephedrine have been shown to have weight loss potential, however, they elicit different metabolic and biochemical responses after a single dose. The nontherapeutic responses from these types of compounds may serve as a screening tool for the development of agents in the treatment of obesity.

Adult↗
PubMed2005

Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism.

BACKGROUND: Prolonged dietary restriction increases the life span in rodents. Some evidence suggests that alternate-day fasting may also prolong the life span. OBJECTIVE: Our goal was to determine whether alternate-day fasting is a feasible method of dietary restriction in nonobese humans and whether it improves known biomarkers of longevity. DESIGN: Nonobese subjects (8 men and 8 women) fasted every other day for 22 d. Body weight, body composition, resting metabolic rate (RMR), respiratory quotient (RQ), temperature, fasting serum glucose, insulin, free fatty acids, and ghrelin were assessed at baseline and after 21 d (12-h fast) and 22 d (36-h fast) of alternate-day fasting. Visual analogue scales were used to assess hunger weekly. RESULTS: Subjects lost 2.5 +/- 0.5% of their initial body weight (P < 0.001) and 4 +/- 1% of their initial fat mass (P < 0.001). Hunger increased on the first day of fasting and remained elevated (P < 0.001). RMR and RQ did not change significantly from baseline to day 21, but RQ decreased on day 22 (P < 0.001), which resulted in an average daily increase in fat oxidation of > or =15 g. Glucose and ghrelin did not change significantly from baseline with alternate-day fasting, whereas fasting insulin decreased 57 +/- 4% (P < 0.001). CONCLUSIONS: Alternate-day fasting was feasible in nonobese subjects, and fat oxidation increased. However, hunger on fasting days did not decrease, perhaps indicating the unlikelihood of continuing this diet for extended periods of time. Adding one small meal on a fasting day may make this approach to dietary restriction more acceptable.

Adult↗
PubMed1998

Neonatal pig brain: lack of heating during Doppler US.

PURPOSE: To evaluate potential local brain-heating effects of Doppler ultrasound (US) at high power output settings. MATERIALS AND METHODS: After craniotomy, a temperature probe was inserted into deep white matter or basal ganglia in 12 anesthetized newborn piglets. The range gate and focal zone were placed directly over the temperature sensor. Brain and core (rectal) temperatures were measured before and during 5 minutes of continuous transdural duplex or color Doppler US, with transmitter power output settings of less than 500 mW in situ spatial peak temporal average or less than 800 mW in situ spatial peak temporal average. Temperature also was measured during administration of a US contrast agent with duplex US at less than 500 mW in situ spatial peak temporal average and after death at the same output setting. RESULTS: Maximal differences between the baseline and the post-US temperatures were, on average, less than 0.3 degree C (P > .5) and were highly correlated with changes in core temperature (r = .9, P < .001). Addition of the contrast agent did not result in focal brain heating during pulsed Doppler US (P > .6). There was no association between an increase in estimated power output and brain temperature change (P = .9). In addition, brain ischemia (postmortem exposure) was not associated with focal brain heating during pulsed Doppler US. CONCLUSION: Transfontanellar Doppler US alone or with administration of a contrast agent does not produce statistically significant focal brain heating at high transmitter power levels.

Analysis of Variance↗