Influence of adiposity on cooling efficiency in hyperthermic individuals

This study evaluated the effect of body adiposity on core cooling rates, as measured by decreases in rectal (T (re)), esophageal (T (es)) and aural canal (T (ac)) temperatures, of individuals rendered hyperthermic by dynamic exercise in the heat. Seventeen male participants were divided into two groups; low body fat (LF, 12.9 +/- 1.9%) and high body fat (HF, 22.3 +/- 4.3%). Participants exercised at 65% of their maximal oxygen uptake at an ambient air temperature of 40 degrees C until T (re) increased to 40 degrees C or until volitional fatigue. Following exercise, participants were immersed up to the clavicles in an 8 degrees C circulated water bath until T (re) returned to 37.5 degrees C. No significant differences were found between the LF and HF in the time to reach a T (re) of 39.5 degrees C (P = 0.205), 38.5 degrees C (P = 0.343) and 37.5 degrees C (P = 0.923) during the immersion. Overall cooling rate for T (re) was also similar between groups (0.23 +/- 0.09 degrees C/min (LF) vs. 0.20 +/- 0.09 degrees C/min (HF), P = 0.647) as well as those for T (es) (P = 0.502) and T (ac) (P = 0.940). Furthermore, mean rate of non-evaporative heat loss (702 +/- 217 W/m(2) (LF) vs. 612 +/- 141 W/m(2) (HF), P = 0.239) was not different between groups. These results suggest that a difference of approximately 10% of body adiposity does not affect core cooling rates in active individuals under 25% body fat rendered hyperthermic by exercise.     

Effects of caffeine and high ambient temperature on haemodynamic and body temperature responses to dynamic exercise.

Caffeine can enhance mean arterial blood pressure (MAP) and attenuate forearm blood flow (FBF) and forearm vascular conductance (FVC) during exercise in thermal neutral conditions without altering body temperature. During exercise at higher ambient temperatures, where a greater transfer of heat from the body core to skin would be expected, caffeine-induced attenuation of FBF (i.e. cutaneous blood flow) could attenuate heat dissipation and increase body temperature (T(re)). We hypothesized that during exercise at an ambient temperature of 38 degrees C, caffeine increases MAP, and attenuates FBF and FVC such that T(re) is increased. Eleven caffeine-naive, active men, were studied at rest and during exercise after ingestion of a placebo or 6 mg kg(-1) of caffeine. MAP, heart rate (HR), FBF, FVC, T(re) skin temperature (T(sk)) and venous lactate concentrations (lactate) were assessed sequentially during rest at room temperature, after 45 min of exposure to an ambient temperature of 38 degrees C, and during 35 min of submaximal cycling. Heat exposure caused increases in MAP, FBF, FVC and T(sk) that were not altered by caffeine. HR, T(re), and lactate were unaffected. During exercise, only MAP (95 +/- 2 vs. 102 +/- 2 mmHg), HR (155 +/- 10 vs. 165 +/- 10 beats min(-1)), and lactate (2.0 +/- 0.4 vs. 2.3 +/- 0.4 mmol l(-1)) were increased by caffeine. These data indicate that increases in cutaneous blood flow during exercise in the heat are not reduced by caffeine. This may be because of activation of thermal reflexes that cause cutaneous vasodilation capable of offsetting caffeine-induced reductions in blood flow. Caffeine-induced increases in lactate, MAP and HR during exercise suggest that this drug and high ambient temperatures increase production of muscle metabolites that cause reflex cardiovascular responses.     

Ambient temperature and the pituitary hormone responses to exercise in humans

Pituitary hormones have an important role during exercise yet relatively little is known about the stimulus for their release. Body temperature progressively increases during prolonged steady-state exercise in the heat and we have investigated the role that this may play in the release of prolactin, growth hormone and cortisol (as an indicator of adrenocorticotropic hormone) into the circulation. Fit young male subjects exercised at 73% V(O2,max) until volitional fatigue at 20 degrees C and at 35 degrees C (30% relative humidity at both temperatures). Rectal temperature and mean skin temperature were monitored and blood samples analysed for lactate, glucose, cortisol, growth hormone and prolactin concentrations. During the first 20 min, core temperature rose continuously and to a similar extent at both temperatures, while mean skin temperature was approximately 4 degrees C lower during exercise in the cool. Blood glucose concentration was essentially constant throughout the period of exercise while lactate concentration increased in the first 10 min and then remained constant with very similar changes in the two exercise conditions. Prolactin and growth hormone concentrations both increased during the exercise period while the concentration of cortisol declined slightly before rising slightly over the 40 min period. Prolactin release was significantly greater when exercise was carried out in the heat while there was no difference in the release of growth hormone or cortisol in the two conditions. When plotted as a function of rectal temperature, growth hormone concentration showed a linear relationship which was the same at ambient temperatures of 35 degrees C and 20 degrees C. Prolactin concentration had a curvilinear relationship with rectal temperature and this differed markedly at the two ambient temperatures. Cortisol concentration showed no dependence on any measure of body temperature. Our results are consistent with some aspect of body temperature being a stimulus for growth hormone and prolactin secretion; however, the precise mechanism clearly differs between the two hormones and we suggest that skin temperature modulates prolactin release, but does not affect the release of growth hormone.     

Effect of a personal ambient ventilation system on physiological strain during heat stress wearing a ballistic vest

The present study was conducted in order to evaluate whether physiological strain is alleviated by a new personal cooling system (CS) consisting of a layered vest and integrated blower that generate a flow of air. Twelve male volunteers were exposed to climatic conditions of 40 degrees C, 40%RH (40/40), and 35 degrees C, 60%RH (35/60) during a 115 min exercise routine, followed by 70 min resting recovery, while wearing a battle dress uniform (BDU) and a ballistic vest, with (COOL) or without (NOCOOL) CS. The CS was able to attenuate the physiological strain levels during exercise, when compared to identical exposures without the CS. Temperature elevation, (DeltaT (re)) after 100 min of exercise, was lower by 0.26 +/- 0.20 and 0.34 +/- 0.21 degrees C in 40/40 and 35/60, respectively, (p < 0.05). Mean skin temperature [Formula: see text] was lower by 0.9 +/- 0.4 and 0.6 +/- 0.5 degrees C for 40/40 and 35/60, respectively. Heart rate (HR) was not significantly different for COOL versus NOCOOL for 40/40. At 35/60, HR was lower by 10 beats per min (bpm) (p < 0.05). Physiological strain index (PSI) was 9 and 21% lower for the 40/40 and 35/60, respectively, for COOL versus NOCOOL (p < 0.05). Heat storage (S) rates were 19 and 24% lower and sweat rates were 21 and 25% lower for the 40/40 and 35/60, respectively, for COOL versus NOCOOL (p < 0.05). However, the CS was not effective in alleviating physiological strain during resting recovery with no difference in T (re) cooling rate, S, or HR drop rate between groups over resting recovery periods. The CS tested in this study was found to be an effective tool for lowering physiological strain while exercising but not during resting recovery. Therefore, the CS should be further developed in order to achieve greater attenuation of the thermal strain during exercise and improve effectiveness during rest. Overall, it has the potential to be useful for both military and sports personnel.     

Diurnal cycle of core temperature in huddling, week-old rat pups

Lean Zucker rat pups were reared at 25 degrees C on four staggered 12:12 light:dark cycles with lights on at 0100, 0700, 1300 or 1900 hr. Core temperature (Tc) of 5- to 8-day-old pups was measured repeatedly at the rearing temperature of 25 degrees C between 0700 and 1900 hr using a procedure that minimally interfered with spontaneous nursing cycles and huddling of the pups. Tc of litters measured 30 to 60 min after the mother spontaneously left the nest was low and variable (32.2-35.4 degrees C) during the first few hours after lights-on, but was uniformly high and much less variable (35.5-36.5 degrees C) around the time of lights-off. Pup Tc was phase-advanced to the nocturnal elevation of maternal Tc, and lagged several hours behind the diurnal elevation of nursing activity. Cyclic variations in Tc of pups huddling in the nest thus reflect a diurnal rhythm in the ability and/or drive for body temperature defense that is independent of heat derived from the mother during nursing.     

Cytotoxicity and weak CD40 ligand expression of CD8+ type 2 cytotoxic T cells restricts their potential B cell helper activity

Naive CD8⁺ T cells differentiate into distinct cytokine-secreting subsets: T helper (Th)1-like cytotoxic T cells (Tc1) and Th2-like Tc2. Although Th2 cells provide strong B cell help, we show that Tc2 cells secreting the same cytokines provide only modest B cell help for IgM production, and only when large numbers of B cells were stimulated with small numbers of Tc2 cells. Lack of effective B cell help by Tc2 cells was attributable partly to their cytotoxicity towards B cells. Both Tc1 and Tc2 cells killed small resting B cells mainly by a perforin-dependent mechanism. In contrast to normal Tc2 cells, perforin-deficient Tc2 cells failed to kill small resting B cells and induced IgM and IgG1 production, although their B cell help was significantly lower than that mediated by Th2 cells. This may be partly attributable to the ability of Tc2 but not Th2 cells to kill activated B cells even in the absence of perforin. Plate-bound anti-CD3 antibodies inhibited Tc2 killing of B cells and induced substantial immunoglobulin production. Additionally, Tc1 and Tc2 cells failed to express CD40 ligand (CD40L), whereas Th1 and Th2 cells expressed high levels of CD40L. Stimulation of Tc1 and Tc2 cells with plate-bound anti-CD3 antibodies for extended periods resulted in low-level expression of CD40L. Proliferation of small resting B cells correlated with immunoglobulin production: proliferation was promoted strongly by Th1 and Th2, weakly by normal Tc1 and Tc2, and moderately by perforin-deficient Tc1 and Tc2 cells. Thus, Tc2 cells may not contribute significantly to cognate B cell help during normal responses.     

Comparison of thermal responses between young children (1- to 3-year-old) and mothers during cold exposure

To investigate thermal responses of children during cold exposure, children and their mothers were exposed to identical environmental conditions in climatic chambers. Subjects comprised 14 mothers (age, 29-40 years) and 15 children (age, 15 months-3 years; 9 boys, 6 girls). Each mother and child wore a t-shirt and short pants over underwear. Subjects were initially seated in a chamber at 25 degrees C for 60 min, then moved to a chamber at 15 degrees C where they were seated for 30 min. During the recovery period, they were returned to the 25 degrees C chamber and kept there for an additional 30 min. During exposure to 15 degrees C, declines in skin temperature (T (s)) of the hand and foot were significantly greater in children than in mothers. Rectal temperatures (T (re)) of children increased during cold exposure, whereas T (re) of mothers decreased. This variation in T (re) in children might be linked to homodynamic alterations accompanied by greater decreases in T (s) of the extremities due to a greater degree of vasoconstriction in distal regions during cold exposure. Increases in T (re) during cold exposure for children correlated with body surface area to mass (Ab/mass), mass and decreases in T (s) of the abdomen, thigh and leg. During the rewarming period, children exhibited a greater increase in T (s) of the arm, hand and foot than mothers, and this was attributed to greater relaxation of vasoconstriction in distal regions of children during exposure to the thermoneutral environment. T (re) in children and mothers decreased during the rewarming period. A gender difference was found only with regard to T (re) and heart rate (HR) responses in children during cold exposure, and neither physical characteristics nor any T (s) differed between genders. Furthermore, no significant differences were observed in resting HR of mothers and girls, whereas boys showed significantly lower heart rates at 15 degrees C than at 25 degrees C.     

Enhanced heat loss responses induced by short-term endurance training in exercising women

We investigated the effects of short-term endurance training and detraining on sweating and cutaneous vasodilatation during exercise in young women, taking into account changes in maximal oxygen uptake (VO2max) and the phase of the menstrual cycle. Eleven untrained women participated in endurance training; cycle exercise at approximately 60% VO2max for 60 min day(-1), 4-5 days week(-1) (30 degrees C, 45% relative humidity) for three complete menstrual cycles. The standard exercise test consisted of exercise at 50% VO2max for 30 min (25 degrees C, 45% relative humidity), and was conducted before training (Pre), during training sessions (T1, T2 and T3) and after cessation of training (D1 and D2). Values of VO2max increased significantly from 32.7 +/- 1.2 to 37.8 +/- 1.2 ml min(-1) kg(-1) at the end of the training. Local sweat rate in the chest and thigh, but not in the back and forearm, were significantly greater during T1 and T2 only in women who started training from the midfollicular phase. Cutaneous blood flow did not change with training. The threshold oesophageal temperatures for heat loss responses were significantly decreased during T1 versus Pre (averaged values for each body site: sweating, 37.49 +/- 0.08 versus 37.22 +/- 0.12 degrees C; and cutaneous vasodilatation, 37.40 +/- 0.07 versus 37.17 +/- 0.10 degrees C) and maintained through T3; the sensitivities of heat loss responses were not altered. These changes returned to the Pre level by D1. Our data indicate that physical training improves heat loss responses by decreasing the threshold temperatures and that these effects occur within a month of training and disappear within a month after cessation of training. The degree of increase in sweating with training differs among body sites and might be affected by the phase of the menstrual cycle.     

Diel changes in adult mosquito microhabitat temperatures and their relationship to the extrinsic incubation of arboviruses in mosquitoes in Kern County, California

Microhabitat temperatures experienced by nocturnally active Culex tarsalis Coquillett mosquitoes were measured in the southern San Joaquin Valley of California. Temperatures of the diurnal resting shelter and nocturnal activity air space were measured by digital recorder at three Cx. tarsalis habitats in Kern County. Temperatures measured by digital recorders agreed well with temperatures recorded concurrently at nearby California Irrigation Management and Inspection System weather stations. Monthly temperatures among habitats were combined to depict the diel temperature regimen experienced by female Cx. tarsalis as a consequence of daily movement between the diurnal resting shelter and nocturnal air space. Transitions between the two microhabitats corresponded to the times of mosquito ingress and egress (i.e., sunrise and sunset). The composite daily temperature mean ranged from 7.4 degrees C in December to 21.5 degrees C in July, and temperature extremes seldom exceeded a daily maximum of 25.0 degrees C during the summer or dropped below a daily minimum of 5.0 degrees C during the winter. Overall, mosquitoes occupied a composite thermal environment where the extrinsic incubation of an arbovirus would have occurred at ambient temperatures that were cooler than either the diurnal resting shelter or activity air space.     

The effect of water temperature on the hormonal response to prolonged swimming.

The relationship between thermoreception, hormonal secretion and muscular activity was studied. 6 men swam 60 min in 21, 27 and 33 degrees C water at a speed requiring 68% of VO2 max (determined in 27 degrees C water). Rectal temperature increased in 33 degrees C (1.3 +/- 0.2 degrees C, mean and S.E.) and 27 degrees C (0.7+/- 0.1 degrees C) expts. but decreased in 21 degrees C expts. (0.8 +/- 0.3 degrees C). Changes in esophageal and muscle temperatures parallelled changes in rectal temperature. Plasma noradrenaline was higher in 33 degrees C than in 27 degrees C expts. and growth hormone, cortisol and glucagon concentrations increased in 27 degrees C and 33 degrees C expts. only. Insulin concentrations were uniformly depressed during swimming at the different water temperatures. In 21 degrees C expts. noradrenaline and adrenaline concentrations were higher than in 27 degrees C expts. VO2, carbohydrate combustion and peak lactate were slightly lower in 33 degrees C expts. Plasma glucose decreased slightly and FFA and glycerol concentrations increased identically in all expts. Heart rate increased continuously during swimming in 27 degrees C and 33 degrees C expts., but not in 21 degrees C expts. In conclusion the rise in body temperatures normally observed during exercise enhances the exercise induced increases in the plasma concentrations of noradrenaline, cortisol, growth hormone and glucagon. Decreased body temperatures may elicit catecholamine secretion as a direct consequence of thermoreception. Shivering may account for previously observed decreases in insulin secretion during cold stress but not for increases in cortisol and growth hormone.     

Effect of skin temperature on the cholinergic sensitivity of the human eccrine sweat gland

Although sweat gland activity is directly controlled by the central nervous system, which detects changes in core body temperature, sweat glands can also be influenced by local cutaneous thermal conditions. OBJECTIVE: The present study sought to determine the effect of local skin temperature on pilocarpine-induced sweating within a range of typical skin temperatures. METHODS: Thirteen subjects (30 +/- 6 years; 172 +/- 11 cm; 72.8 +/- 11.0 kg) had forearm sweat rates measured at rest following pilocarpine iontophoresis at each of three skin temperatures in randomized order: warm (T(warm) = 37.1 +/- 0.9 degrees C), control (T(con) = 32.3 +/- 1.4 degrees C), and cool (T(cool) = 26.6 +/- 1.3 degrees C). T(skin) was raised and lowered with an electric heating pad and gel ice pack, respectively. Forearm T(skin) was measured with a skin temperature probe. Pilocarpine iontophoresis was used on an approximately 7 cm(2) area of the anterior forearm to stimulate localized sweating. Following stimulation, sweat was collected from the area for 15 min with a Macroduct Sweat Collection System. RESULTS: There was a higher sweat rate at T(warm) (p = 0.001) and T(con) (p = 0.006) compared to that at T(cool). However, there was no difference between the sweat rate at T(warm) and that at T(con) (p = 0.127). CONCLUSION: These results indicated that skin temperatures below approximately 32 degrees C affect local sweat production primarily by altering glandular sensitivity to the neurotransmitter, whereas skin temperatures above approximately 32 degrees C predominantly affect neurotransmitter release. Furthermore, sweat glands display maximal or near maximal cholinergic sensitivity at resting skin temperature in a thermoneutral environment.     

Behavioral thermoregulation in the squirrel monkey: adaptation processes during prolonged microwave exposure

During 10-min exposures to 2450-MHz microwaves at a power density of 6-8 m W/cm2, squirrel monkeys reliably select a cooler environment. Exposure duration, at power densities above and below this threshold, was the parameter investigated in these experiments. Monkeys were restrained in the far field of a horn antenna inside a 1.8 x 1.8 x 2.5 m anechoic chamber which was heated and cooled by forced convection. The animals learned to control the temperature of the circulating chamber air by selecting between cold (10-15 degrees C) and warm (50-55 degrees C) air sources. During the experiments, they were exposed to 12.4-cm (2450-MHz) continuous-wave microwaves for periods from 5 to 150 min. Microwave power densities explored were 4, 10, and 20 mW/cm2 which represent rates of whole-body energy absorption that range from approximately, .6 to 3.0 W/kg. No microwaves were present during 4-hr control experiments. The 4 mW/cm2 microwave exposure did not modify thermoregulatory behavior, no matter how long it lasted. The 10 and 20 mW/cm2 exposures stimulated the monkeys to select ambient temperatures 1.5 and 3.0 degrees C cooler than control levels, respectively. Except during the first microwave presentation of a series, or during the early minutes of a single long exposure, duration had no significant effect on selection of air temperature or on the body temperatures achieved thereby.     

Thermal preference behavior following clonidine, norepinephrine, isoproterenol, and ephedrine.

A thermal gradient (temperature range 7-45 degrees C) was used to assess ambient temperature (Ta) preferences of rats following treatment with clonidine (25 microg/kg), norepinephrine (NE, 250 microg/kg), isoproterenol (ISO, 50 microg/kg), and ephedrine (EPH, 10 mg/kg). Clonidine produced a preference for a temperature (31.5 degrees C) slightly warmer than that preferred after saline (28.3 degrees C), but this resulted in no significant change in posttest colonic temperature (Tc). NE, ISO and EPH produced a preference for a colder region of the gradient (20-22 degrees C) compared to saline (24.5-28.9 degrees C). Posttest Tc was reduced significantly from 37.7-37.9 degrees C after saline to 37.2 degrees C (NE), 37.3 degrees C (ISO), and 36.8 degrees C (EPH). Thus, given the opportunity to select an environmental temperature, the animals selected a Ta that resulted in significantly lower body temperatures after NE, ISO, and EPH. This suggests that paradoxical thermoregulatory effects of these thermogenic adrenergic agonists are due, at least in part, to a preference for a lower body temperature.     

Effects of chemoreflexes on hyperthermic hyperventilation and cerebral blood velocity in resting heated humans

We tested the hypothesis that hyperthermic hyperventilation in part reflects enhanced chemoreceptor ventilatory O(2) drive, and that the resultant hypocapnia attenuates ventilatory responses and/or middle cerebral artery mean blood velocity (MCAV(mean)) in resting humans. Eleven healthy subjects were passively heated for 50-80 min, causing oesophageal temperature (T(oes)) to increase by 1.6 degrees C. During heating, minute ventilation increased (P < 0.05), while end-tidal CO(2) pressure (P(ET,CO(2))) and MCAV(mean) declined. A hyperoxia test in which three breaths of hyperoxic air were inspired was performed once before heating and three times during the heating. When we observed hypocapnia (P(ET,CO(2)) below 40 mmHg), P(ET,CO(2)) was restored to the eucapnic level by adding 100% CO(2) to the inspired air immediately before the last two tests. Minute ventilation was significantly reduced by hyperoxia, and that reduction gradually increased with increasing T(oes). However, the percentage decrease in from the normoxic level was small (20-29%) and unchanged during heating. When P(ET,CO(2)) was restored to eucapnic levels, was unchanged, but MCAV(mean) was partly restored to the level seen prior to heating (28.1% restoration at T(oes) 37.6 degrees C and 38.1% restoration at T(oes) 38.0 degrees C). These findings suggest that although hyperthermia increases chemoreceptor ventilatory O(2) drive in resting humans, the relative contribution of the chemoreceptor ventilatory O(2) drive to hyperthermic hyperventilation is small ( approximately 20%) and unaffected by increasing core temperature. Moreover, hypocapnia induced by hyperthermic hyperventilation reduces cerebral blood flow but not ventilatory responses.     

Temperature regulation during intermittent exercise with progressive dehydration

Effects of dehydration (3% of initial body weight) on temperature regulation were investigated in 5 men during intermittent exercise of 4 h duration at a dry air temperature of 34 degrees C. Relative mechanical work load was 50% of the subject's steady state heart rate, which was 170 beats . min-1. During rehydration from the 70th min to the end of the exercise, the subjects drank, every 10 min in equal portions, an amount of water (20 degrees C) totaling up to 80% of the body weight loss recorded during dehydration runs. Continuous measurements were made of rectal (Tre) and mean skin (Tsk) temperatures and of whole body weight loss. Chest sweating rate (msw) was measured from a capsule located under a local thermal clamp (36 degrees C). Blood samples were obtained during rest periods and after the 1st and the 4th hour of exercise. Compared to dehydration runs, water intake did not always cause an increase of msw while body temperatures always decreased. Dehydration resulted in a decrease in plasma volume and in increases of plasma osmolality, [Na+] and [K+]. Water intake induced a thermoregulatory response whose intensity largely differs from one body area to another. The change in the slope of the relation of msw to Tre features a decrease in the sensitivity of the thermoregulatory system with dehydration. The whole body water loss is significantly correlated with the change in plasma volume and body temperatures (Tre, Tsk). This suggests that the reduced sweating response observed during dehydration can be related to plasma hypovolemia.     

Cerebrospinal fluid [Ca2+] and rectal temperature response during exercise in dogs.

Rectal temperature (Tre) was measured in five dogs during 1 h of rest and 1 h of moderate treadmill exercise (1.2 m/s up a 12 degree slope), with no infusion and with continuous infusion (40 mul/min) of normocalcic (1.3 mM Ca2+, 151.5 mM Na+) and hypercalcic (2.6 mM Ca2+, 149.6 mM Na+) concentrations of artificial cerebrospinal fluids into the left lateral cerebral ventricle. There was no effect of the normo- or hypercalcic infusions on resting Tre. In comparison with the postexercise Tre level of 39.9 degrees C (deltaTre= +1.4 degrees C) with no infusion, Tre rose to 40.0 degrees C (delta Tre = +1.4 degrees C) with normocalcic infusion (NS); there was a significantly smaller (P less than 0.01) rise in Tre to 39.2 degrees C (delta Tre = +0.8 degrees C) with hypercalcic infusion. The smaller rise in Tre in response to excess Ca2+ in cerebrospinal fluid was not due to plasma fluid or electrolyte shifts. During exercise the mean body weight loss was greater with hypercalcic infusion (-2.7%) compared with normocalcic (-1.0%) and no infusion (-1.4%) values. The results suggest that Ca2+ ions affect the sensitivity of the central thermoreceptor to thermal stimuli and cause an increased heat loss during physical exercise in dogs.     

Melatonin and zopiclone: the relationship between sleep propensity and body temperature

STUDY OBJECTIVES: The sleep promoting effects of the sedative-hypnotics, melatonin and temazepam, have been associated with a decline in core body temperature (Tc). To determine whether changes in body temperature are a general feature of sedative-hypnotics, the present study compared the sleep inducing, core and peripheral temperature effects of melatonin, with those of zopiclone. DESIGN: Subjects were supine from 08:00-21:30 h and received melatonin, zopiclone or placebo at 14:00 h. SETTING: Individual, light and temperature controlled bedrooms. PARTICIPANTS: 12 healthy, young, adults (7m, 5f; 20.3 +/- 0.6 years). INTERVENTIONS: Melatonin (5mg), zopiclone (Imovane; 7.5 mg) and placebo were administered in a double-blind, crossover design. MEASUREMENTS AND RESULTS: From 11:00-20:00 h, modified hourly multiple sleep onset latency tests (MSLT) of a 20-min duration were conducted and heart rate (HR) was recorded. Tc and foot temperature (T(Ft)) were recorded continuously using thermistors. Compared with placebo, melatonin and zopiclone significantly reduced sleep onset latency (SOL) to stage 1 (by 3.50 +/- 0.73 min and 6.80 +/- 0.61 min, respectively) and reduced Tc (by 0.22 +/- 0.02C and 0.14 +/- 0.02C, respectively). For melatonin, Tc declined as the result of an increase in peripheral heat loss (increase in T(Ft) of 1.65 +/- 0.43 degrees C), and possibly a reduction in heat production as indicated by a decrease in HR (4.56 +/- 0.94 bpm). Zopiclone increased heat loss (increase in T(Ft) of 1.43 +/- 0.68C) and had no cardiac effects. For melatonin, a negative association was found between Tc (mean r=-0.43), however, this association was only weak for zopiclone (mean r=-0.23). CONCLUSIONS: These results suggest that body temperature changes may be a general feature of sedative-hypnotics. The potential role of this effect in the promotion of sleep appears to vary between agents.     

Ex vivo rapamycin generates Th1/Tc1 or Th2/Tc2 Effector T cells with enhanced in vivo function and differential sensitivity to post-transplant rapamycin therapy.

Rapamycin prevention of murine graft-versus-host disease (GVHD) is associated with a shift toward Th2- and Tc2-type cytokines. Recently, we found that use of rapamycin during ex vivo donor Th2 cell generation enhances the ability of adoptively transferred Th2 cells to prevent murine GVHD. In this study, using a method, without antigen-presenting cells, of T-cell expansion based on CD3,CD28 costimulation, we evaluated whether (1) rapamycin preferentially promotes the generation of Th2/Tc2 cells relative to Th1/Tc1 cells, (2) rapamycin-generated T-cell subsets induce cytokine skewing after allogeneic bone marrow transplantation (BMT), and (3) such in vivo cytokine skewing is sensitive to post-BMT rapamycin therapy. Contrary to our hypothesis, rapamycin did not preferentially promote Th2/Tc2 cell polarity, because rapamycin-generated Th1/Tc1 cells secreted type I cytokines (interleukin [IL]-2 and interferon-gamma) did not secrete type II cytokines (IL-4, IL-5, IL-10, or IL-13) and mediated fasL-based cytolysis. Rapamycin influenced T-cell differentiation, because each of the Th1, Th2, Tc1, and Tc2 subsets generated in rapamycin had increased expression of the central-memory T-cell marker, L-selectin (CD62L). Rapamycin-generated Th1/Tc1 and Th2/Tc2 cells were not anergic but instead had increased expansion after costimulation in vitro, increased expansion in vivo after BMT, and maintained full capacity to skew toward type I or II cytokines after BMT, respectively; further, rapamycin-generated Th1/Tc1 cells mediated increased lethal GVHD relative to control Th1/Tc1 cells. Rapamycin therapy after BMT in recipients of rapamycin-generated Th1/Tc1 cells greatly reduced Th1/Tc1 cell number, greatly reduced type I cytokines, and reduced lethal GVHD; in marked contrast, rapamycin therapy in recipients of rapamycin-generated Th2/Tc2 cells nominally influenced the number of Th2/Tc2 cells in vivo and did not abrogate post-BMT type II cytokine skewing. In conclusion, ex vivo and in vivo usage of rapamycin may be used to modulate the post-BMT balance of Th1/Tc1 and Th2/Tc2 cell subsets.     

Relationship between behavioral and autonomic thermoregulation in the guinea pig

This study was conducted to correlate the preferred thermal environment of the unrestrained guinea pig with the activity of its thermoregulatory effectors when maintained under a wide range of ambient temperatures (Ta). Eight male guinea pigs were used in a series of experiments on behavioral and autonomic thermoregulatory function. In the behavioral experiment, individual guinea pigs were placed in a temperature gradient for 90 min while their position in the gradient was noted at 5 min intervals during the last 30 min of treatment. Their position in the gradient corresponded to a preferred Ta of 30.6 +/- 3.8 (S.D.) degrees C. In the experiments to determine autonomic function, individual guinea pigs were placed in an environmental chamber thermostabilized to Ta's of 16 to 34 degrees C. Metabolic rate (MR) and evaporative water loss (EWL) were continuously monitored for 90 min. After the guinea pigs were in the chamber for 90 min their colonic temperature was measured. MR was relatively stable between Ta's of 20 to 34 degrees C. The lower critical Ta, or the Ta below which MR increased above the resting level, was 20 degrees C for the guinea pig. EWL was minimal between Ta's of 14 and 28 degrees C. Increasing Ta above 28 degrees C led to a gradual increase in EWL. Thermal conductance was minimal and stable between Ta's of 14 and 26 degrees C and increased sharply as Ta increased above 26 degrees C. Colonic temperature was maintained at 38 degrees C between Ta's of 22 to 30 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Face temperature and cardiorespiratory responses to wind in thermoneutral and cool subjects exposed to -10 degrees C

The effects of the thermal state of the body (slightly cool and neutral) and moderate wind speeds on face temperature, blood pressure, respiratory function and pain sensation during cold exposure were studied on eight healthy male subjects. They were dressed in cold-protective clothing and preconditioned at + 20 degrees C (TN) and -5 degrees C (CO) for 60 min, then exposed to -10 degrees C and 0 m x s(-1) (NoW), 1 (W1) and 5 (W5) m x s(-1) wind for 30 min. Thus, each individual was exposed six times. The exposure to wind entailed a combination of strong cooling of the bare face and mild body cooling. The forehead, cheek and nose temperatures decreased during cold exposure, and the decrease was greater at higher air velocities (P < 0.0001). All subjects reported pain sensations at 5 m x s(-1). At the end of exposure only the nose temperature was significantly lower in CO than in TN subjects; it was about 2 degrees C and reached 0 degrees C in two experiments. The systolic and diastolic blood pressure (SBP and DBP, respectively) increased significantly by 7.7 and 5.9 mmHg, respectively, during preconditioning at -5 degrees C, but did not change at + 20 degrees C. SBP and DBP increased during exposure to -10 degrees C in TN by approximately 9 mmHg. However, the total average increase of blood pressure (1-90 min) was similar in TN and CO (SBP 15 mmHg and DBP 13 mmHg). SBP and DBP increased more during exposure to 5 m x s(-1) at -10 degrees C than NoW. Blood pressure responses as observed in this study (SBP and DBP up to 51 and 45 mmHg, respectively) are potential health risks for hypertensive individuals and angina patients. Respiratory functions (FVC, FEV1) were reduced by about 3% by the cold (-5 and -10 degrees C) compared to pre-experiment values. Furthermore, the Wind Chill Index seems to underestimate the cooling power of 5 m x s(-1) at -10 degrees C of bare skin (e.g. face). Therefore it needs to be revised and we suggest that it is expanded to include risk levels for pain sensation.