Fall In Rectal Temperature Research Articles

A Murine Model of Food Allergy by Epicutaneous Adjuvant-Free Allergen Sensitization Followed by Oral Allergen Challenge Combined with Aspirin for Enhanced Detection of Hypersensitivity Manifestations and Immunotherapy Monitoring.

Food allergy is one of the major existing health problems, but no effective treatment is available. In the current work, a murine model that closely mimics pathogenesis of human food allergy and its quantifiable diagnostic parameter design, even for mild hypersensitivity reactions, were established. BALB/c mice were epicutaneously sensitized with 1 mg chicken egg ovomucoid (OVM) or cow's milk casein, free of adjuvants, five times a week for two consecutive weeks. Eleven days later, allergen-specific IgG1 and IgE in serum were measured by ELISA. On day 25, 20 mg OVM or 12 mg α-casein was administered orally, and allergic reactions such as the fall in rectal temperature, symptom scores during 90-120 min, serum mast cell protease-1 and cytokine levels were monitored. The detection of mild allergic reactions due to adjuvant-free allergen sensitization and oral allergen challenge routes was amplified by the combination of oral allergen and aspirin administration simultaneously or aspirin administration within 15-30 min before an allergen challenge. Quantification of the maximum symptom score and the frequency of symptoms during the monitoring period improved evaluation accuracy of food allergy signals. Based on these results, efficacy of casein oral immunotherapy for cow's milk allergies, which are generally difficult to detect, was monitored adequately.

Acral skin vasoreactivity and thermosensitivity to hand cooling following 5 days of intermittent whole body cold exposure.

We sought to examine whether short-term, whole body cold acclimation would modulate finger vasoreactivity and thermosensitivity to localized cooling. Fourteen men were equally assigned to either the experimental (CA) or the control (CON) group. The CA group was immersed to the chest in 14°C water for ≤120 min daily over a 5-day period while the skin temperature of the right-hand fingers was clamped at ∼35.5°C. The CON group was instructed to avoid any cold exposure during this period. Before and after the intervention, both groups performed, on two different consecutive days, a local cold provocation trial consisting of a 30-min hand immersion in 8°C water while immersed to the chest once in 21°C (mild-hypothermic trial; 0.5°C fall in rectal temperature from individual preimmersion values) and on the other occasion in 35.5°C (normothermic trial). In the CA group, the cold-induced reduction in finger temperature was less (mild-hypothermic trial: P = 0.05; normothermic trial: P = 0.02), and the incidence of the cold-induced vasodilation episodes was greater (in normothermic trials: P = 0.04) in the post- than in the preacclimation trials. The right-hand thermal discomfort was also attenuated (mild-hypothermic trial: P = 0.04; normothermic trial: P = 0.01). The finger temperature responses of the CON group did not vary between testing periods. Our findings suggest that repetitive whole body exposure to severe cold within a week may attenuate finger vasoreactivity and thermosensitivity to localized cooling. These regional thermo-adaptions were ascribed to central neural habituation produced by the iterative, generalized cold stimulation.

Interactions of mild hypothermia and hypoxia on finger vasoreactivity to local cold stress.

We examined the interactive effects of mild hypothermia and hypoxia on finger vasoreactivity to local cold stress. Eight male lowlanders performed, in a counterbalanced order, a normoxic and a hypoxic (partial pressure of oxygen: ~12 kPa) hand cold provocation (consisting of a 30-min immersion in 8°C water), while immersed to the chest either in 21°C [cold trials; 0.5°C fall in rectal temperature (Trec) from individual preimmersion values], or in 35.5°C water, or while exposed to 27°C air. The duration of the trials was kept constant in each breathing condition. Physiological (Trec, skin temperature, cutaneous vascular conductance, oxygen uptake) and perceptual (thermal sensation and comfort, local pain, affective valence) reactions were monitored continually. Hypoxia accelerated the drop in Trec by ~14 min (P = 0.06, d = 0.67). In the air-exposure trials, hypoxia did not alter finger perfusion during the local cooling, whereas it impaired the finger rewarming response following the cooling (P < 0.01). During the 35.5°C immersion, the finger vasomotor tone was enhanced, especially in hypoxia (P = 0.01). Mild hypothermia aggravated finger vasoconstriction instigated by local cooling (P < 0.01), but the response did not differ between the two breathing conditions (P > 0.05). Hypoxia tended to attenuate the sensation of coldness (P = 0.10, r = 0.40) and thermal discomfort (P = 0.09, r = 0.46) in the immersed hand. Both in normoxia and hypoxia, the whole body thermal state dictates the cutaneous vasomotor reactivity to localized cold stimulus.

In Shackleton's trails: Central and local thermoadaptive modifications to cold and hypoxia after a man-hauling expedition on the Antarctic Plateau

Cold and hypoxia constitute the main environmental stressors encountered on the Antarctic Plateau. Hence, we examined whether central and/or peripheral acclimatisation to the combined stressors of cold and hypoxia would be developed in four men following an 11-day man-hauling expedition on this polar region. Before and after the journey, participants performed a static whole-body immersion in 21 °C water, during which they were breathing a hypoxic gas (partial pressure of inspired O2: ~97 mmHg). To evaluate their local responses to cold, participants also immersed the hand into 8 °C water for 30 min, while they were whole-body immersed and mildly hypothermic [i.e. 0.5 °C fall in rectal temperature (Trec) from individual pre-immersion values]. Trec and skin temperature (Tsk), skin blood flux, and oxygen uptake (reflecting shivering thermogenesis) were monitored throughout. The polar expedition accelerated by ~14 min the drop in Trec [final mean (95% confidence interval) changes in Trec: Before = −0.94 (0.15) °C, After: − 1.17 (0.23) °C]. The shivering onset threshold [Before: 19 (22) min, After: 25 (19) min] and gain [Before: − 4.19 (3.95) mL min−1 kg−1, After: − 1.70 (1.21) mL min−1 kg−1] were suppressed by the expedition. Tsk did not differ between trials. The development of a greater post-expedition hypothermic state did not compromise finger circulation during the hand-cooling phase. Present findings indicate therefore that a hypothermic pattern of cold acclimatisation, as investigated in hypoxia, was developed following a short-term expedition on the South Polar Plateau; an adaptive response that is characterised mainly by suppressed shivering thermogenesis, and partly by blunted cutaneous vasoconstriction.

Aerocryothermal training as a method of emergency increase of human resistance to exposure to low ambient temperatures

Objective: testing applications of aerocryothermal training (ACT) to emergency increase the cold resistance of persons exposed to low ambient temperatures. Materials and methods: the study involved 25 men at the age of 20-35 years (mean age of 28.2±2.1 years) who completed the ACT: 10 procedures of 2-5-minute stay in the cryochamber at a temperature of -150 ± 20C, in the process of which were evaluated parameters of thermal status and the reactivity of the indicators of systemic circulation. Results: as a result of ACT took place a gradual increase in stability of the subjects to hypothermia. Th is was evidenced by improved subjective tolerability eff ects, lengthening the time maximum duration of hypothermia (average 40% compared with the 1st procedure), slowing the rate of fall of rectal temperature (average 19%), reducing the reactivity of the indicators of system of blood circulation in hypothermia (average of 23-40%). Conclusion: aerocryothermal training is highly eff ective non-drug means to enhance the person sustainability to exogenic hypothermia.

Paracetamol like antipyretic activity of lyophilized succulent of Aloe vera leaves in rats

Aims: To evaluate the antipyretic activity of lyophilized succulent of Aloe vera (AVS) as well as its interaction with conventional antipyretic drug paracetamol (PCM) against experimentally induced pyrexia in rats. Materials and Methods: Pyrexia was induced experimentally by either Brewer’s yeast or misoprostol injection after recording basal rectal temperature in rats. Animals were treated with lyophilized AVS at the dose of 100, 200, and 300 mg kg and standard drug PCM 150 mg/kg, 18 h after injection of Brewer’s yeast suspension in one set of experiment and combination of sub‑effective dose of AVS with that of PCM 1 h after injecting misoprostol in other set of experiment. Rectal temperature was recorded at different time intervals after drug administration. AVS was also phytochemically screened for the presence of tannins, saponins, flavonoids, coumarins, sterols, reducing sugar, glycosides, starch, alkaloids, and triterpenoids. Results: Pyrexia was observed at 18 h and at 1 h after Brewer’s yeast and misoprostol injection subcutaneous, respectively. AVS (200 and 300 mg/kg) treated groups showed significant fall in rectal temperature (P 0.05) with standard drug PCM at 150 mg/kg. The combination of sub‑effective dose of AVS (100 mg/kg) with that of PCM (50 mg/kg) produced significant (P < 0.05) antipyretic activity against misoprostol‑induced pyrexia at different time intervals as compared with control, AVS 100 mg/kg and PCM 50 mg/kg treated groups when used alone. Phytochemical tests showed the presence of flavonoids, saponins, tannins, reducing sugar, glycoside, starch, and steroids. Conclusion: Lyophilized AVS possesses antipyretic activity. It enhances the antipyretic activity of PCM suggesting its role in inhibition of prostaglandin synthesis.

Effects of Estrogen and Keishibukuryogan on Hot Flash-like Symptoms Induced by Yohimbine in Ovariectomized Rats

Hot flash (HF) is the most common phenomenon in climacteric symptoms which often develop concomitantly with a decrease in estrogen in postmenopausal women. The onset mechanism of the hot flash is complicated and remains unclear. To date, some animal models of postmenopausal HF have been devised, but they are not fully available because of the difficulty in producing them. It is thought that hyperactivity of the central α-adrenergic system with a decrease in estrogen participates in the onset of postmenopausal HF. Therefore, in the present study, we examined whether a HF model could be easily produced by administering yohimbine (YOH), a presynaptic α₂-adrenoceptor antagonist which promotes norepinephrine release, to female rats. HF-like symptoms such as a rise in tail skin temperature and a fall in rectal temperature were shown in the rats who received YOH (3 mg/kg) subcutaneously seven days after the ovariectomy (OVX). Such symptoms following YOH administration were observed in sham rats as well, but were much more clearly noted in OVX rats. We next examined the effects of various drugs, which are clinically effective against postmenopausal HF, on HF-like symptoms in YOH-treated OVX rats: clonidine, a presynaptic α₂-adrenoceptor agonist which inhibits norepinephrine release; β-estradiol as an estrogen; and Keishibukuryogan, a Kampo medicine. These drugs inhibited HF-like symptoms in YOH-treated OVX rats. These results suggest that the activity of the α-adrenergic system is enhanced with a decrease in estrogen in OVX rats whereby YOH causes HF-like symptoms more conspicuously than in sham rats. Therefore, it is thought that YOH-treated OVX rats will be a novel and simple model of postmenopausal HF.

A note on the effect of amantadine on body temperature in mice.

Abstract Amantadine hydrochloride caused a dose-dependent fall in rectal temperature in mice. This response was antagonized by haloperidol, which itself produced some hypothermia, and by pretreatment with α-methyl-p-tyrosine. The mode of action of amantadine and the possible involvement of dopamine in the control of body temperature is discussed.

The mechanism of the hypothermic effect of amantadine in rats and mice.

Amantadine (25--100 mg kg-1, i.p.) given to rats at an ambient temperature of 4 degrees, or mice at 21 degrees, caused a marked fall in rectal temperature. Prior administration of pimozide (1--2 mg kg-1, s.c.) did not block hypothermia due to amantadine in rats or mice; in contrast, hypothermia due to apomorphine (2 mg kg-1, i.p.) and piribedil (10--40 mg kg-1, i.p.) in rats was blocked by pimozide pretreatment. Amphetamine (5 mg kg-1, i.p.) given 2 h after reserpine (2 mg kg-1, i.p.) caused a reversal of the hypothermic effect of reserpine in mice, but a reversal was not obtained with amantadine (50 mg kg-1, i.p.). Direct injection of amantadine (4--8 mg kg-1) into the cerebral ventricles (i.c.v.) of mice caused marked hypothermia which was not blocked by pimozide, but intravenous injection of the same dose of amantadine did not cause hypothermia. Rimantadine, a congener of amantadine but without anti-parkinsonian activity, also caused pimozide insensitive hypothermia in mice at doses of 50 mg kg-1, intraperitoneally or 2--4 mg kg-1, intracerebroventricularly. The main conclusion drawn from these results is that in causing hypothermia amantadine acts in the cns but not on dopamine receptors.

Dopamine Receptor Mediated Hypothermic Action of B-HT 920 in Rats

The hypothermic action of the thiazoloazepine derivative B-HT 920, an alpha 2-adrenoceptor agonist has been investigated in rats. B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)-azepine dihydrochloride) (0.25-1.0 mg kg-1 i.p.) induced a dose-dependent hypothermia. This peak effect was seen within 60-90 min and lasted up to 120 min. Its action was potentiated by the selective D1-dopamine agonist SKF 38393 and inhibited by the D2-antagonists haloperidol (1 mg kg-1) and sulpiride (100 mg kg-1). The hypothermic action of B-HT 920 was centrally mediated; i.c.v. administration of 10 micrograms produced a significant fall in rectal temperature which was sensitive to blockade by haloperidol. B-HT 920 also potentiated the hypothermic action of apomorphine (0.1 and 0.5 mg kg-1) in a haloperidol sensitive manner. Reserpine (5 mg kg-1 i.p.) pretreatment reduced the hypothermic response of B-HT 920 (0.5 mg kg-1) but sensitized the response due to the combination of B-HT 920 (0.5 mg kg-1) and apomorphine (0.1 mg kg-1). Neither the selective alpha 2-adrenoceptor antagonists, yohimbine (1 mg kg-1) or idazoxan (1 mg kg-1), the histamine antagonist mepyramine (10 mg kg-1) nor the 5-HT antagonist cyproheptadine (5 mg kg-1) inhibited B-HT 920-induced hypothermia. Similarly, the selective alpha 1-antagonist prazosin (1 mg kg-1) and the beta-antagonist propranolol (10 mg kg-1) failed to modify the hypothermic action of B-HT 920. These observations demonstrated hypothermia induced by B-HT 920 is mediated by postsynaptic D2-receptors and D1- and D2-receptor interplay is essential for the full expression of hypothermia in rats.

Effects of mild heat exposure on sleep stages and body temperature in older men.

The purpose of this study was to examine the effects of mild heat exposure on sleep stages and body temperature in older men. Ten healthy male volunteers with a mean age of 69.2 +/- 1.35 years served as subjects. The experiments were carried out under two different sets of conditions: 26 degrees C 50% relative humidity (RH) and 32 degrees C 50% RH. The subjects slept from 2200 hours to 0600 hours with a cotton blanket and wearing short-sleeve pajamas and shorts on a bed covered by a sheet. Electroencephalogram, electro-occulogram and mental electromyogram recordings were made through the night. Rectal and skin temperatures were measured continuously. No significant differences were observed in sleep onset latency. In time spent in each sleep stage, wakefulness was significantly increased at 32 degrees C than at 26 degrees C. The total amount of wakefulness increased and rapid eye movement sleep (REM) decreased at 32 degrees C compared to 26 degrees C. The fall in rectal temperature was significantly suppressed and the mean skin temperature was significantly higher at 32 degrees C than at 26 degrees C. These results suggest that, for older men, even mild heat exposure during the nighttime sleep period may increase thermal load, suppress the decrease of rectal temperature, decrease REM, and increase wakefulness and whole-body sweat loss.

Overnight central and peripheral temperature changes in normal infants

To explore the relationship between central and peripheral temperature in normal infants after being put down to sleep. Overnight shin and rectal temperatures of 21 normal infants were continuously recorded at home for three nights at 2 wk, 6 wk, 3 mo and 5 mo of age. Parents documented the start and end of feed/nappy changes during the night. An initial fall in rectal temperature was recorded on 149 out of 161 nights. This was linearly correlated with a rise in shin temperature for 106/149 (71%) nights (median R2 = 0.95, lower quartile 0.92, upper quartile 0.97). It was not possible to rule out a change in thermal insulation over the shins as a confounding variable in this strong association. However, a similar inverse relationship was seen between shin and rectal temperature during 111 of 121 (92%) feed/nappy changes. The fall in rectal temperature after being put down to sleep may be due to redistribution of heat rather than decreased production or heat loss. If causal, the development in early infancy of an inverse relationship between shin and rectal temperature may be important for cardiovascular homeostasis. Further sleep laboratory work is required to distinguish peripheral temperature changes on falling asleep from those associated with changes in thermal insulation.

Central and peripheral temperature change in normal infants.

The purpose was to explore the relationship between the fall in rectal temperature seen in normal infants after being put down to sleep and the concomitant rise in peripheral shin temperature. In this observational study 21 normal infants had continuous overnight peripheral shin and central rectal temperature recorded, for three nights at 2 weeks, 6 weeks, 3 months and 5 months of age. Parents documented the start and end of feed/nappy changing episodes during the night. All recordings were made in the infants' own home. A strong inverse linear correlation (median r2 = 0.95, lower quartile 0.92, upper quartile 0.97) was seen between rectal temperature and shin temperature on falling to sleep when put down on 106 (65%) of 161 nights. On many other nights a significant nonlinear association was present. It was not possible to exclude the process of being put down to sleep as a confounding variable in this strong association. However, a similar inverse relationship between shin and rectal temperature was seen overnight during 111 of 121 (92%) feed/nappy changing episodes. If causal, the development in early infancy of an inverse relationship between shin and rectal temperature may be important for cardiovascular homeostasis. Further sleep laboratory work including video recording is required to separate the peripheral and central temperature changes that take place on falling to sleep from those associated with removal of clothing during a nappy change.

Acute phase proteins, body temperature and urinary melatonin under the influence of bright and dim light intensities during the daytime.

Concentrations of five acute phase proteins: C-reactive protein (CRP), alpha 1-antichymotrypsin (ACT), transferin (Tf), alpha 2-macroglobulin (alpha 2-M) and haptoglobin (Hp) as well as glycosylation profiles of alpha 1-antichymotrypsin (ACT) were studied in sera samples with 7 healthy volunteers under the influence of two different light intensities during the daytime dim (100 lx) and bright (3000 lx) light. Concentration of transferin (negative proteins) under the influence of bright light during the daytime decreased significantly. Other proteins have the tendency to increase (positive proteins) under the influence of daytime bright light. The microheterogeneity of ACT did not change under the influence of different light intensities. Melatonin and rectal temperature were also measured simultaneously. Rectal temperature decreased to be lower during the first half of the night and urinary melatonin secretion rate increased to be higher during the night when the subjects spent time under the bright light during the day. Thus, it is concluded that the diurnal bright light exposure may activate some parameters of acute phase proteins, increase nocturnal melatonin secretion and accelerate a fall of rectal temperature during first half period of night sleep.

Is the Growth of Brown Adipocytes Necessary for Cold Acclimation in Mice?

Chronic exposure to cold increases the growth of brown adipose tissue and the resistance to more severe cold, thus improving thermogenesis. The present study examined the possibility that dietary compounds can modify cold acclimation. Adenosine (ADO) or adenine (ADE) were administered in drinking water (0.05%, w/v) for 5 weeks to male ddY strain mice from 4 weeks of age. At 5 weeks of age, the mice were exposed to 4°C for 4 weeks. After termination of this period, the interscapular brown adipose tissue (IBAT) and rectal temperature on acute exposure to severe cold (–20°C) for 60 min were measured. Chronic exposure to cold increased the weight of IBAT and made mice resistant to a fall in rectal temperature on exposure to severe cold. The growth of IBAT and improvement in thermogenesis can be used as a cold acclimation profile in ddY mice. The growth of IBAT was selectively prevented by ingestion of ADO. The improvement in thermogenesis was reduced, but only a little, by the ingestion of either ADO or ADE. Thus, growth of brown adipocytes might not be necessary for cold acclimation in mice.

Infection with Equine Herpesvirus 1 (EHV-1) Strain HVS25A in Pregnant Mice

The abortigenic effects of equine herpesvirus 1 (EHV-1) strain HVS25A, given intranasally, were assessed in pregnant BALB/c, C57BL/6J and Quakenbush mice at day 16 of pregnancy. All EHV-1-infected BALB/c mice showed clinical signs typical of EHV-1-induced disease, together with evidence of abortion. However, although there were fetal and neonatal deaths in some C57BL/6J and Quakenbush litters, the respiratory and systemic effects of EHV-1 infection in the dams were inconsistent. BALB/c dams were then inoculated at day 15 of pregnancy with either EHV-1 or rabbit kidney (RK) cell lysate (controls) and animals were killed at days 1–5 post-inoculation (pi), i.ebefore the occurrence of abortions. EHV-1-infected mice showed a significant fall in rectal temperature between days 1 and 2 pi and lost weight during the first 4 days pi, demonstrating a significant mean difference in weight gain from the control group at days 2, 3, 4 and 5 pi. Deathin uterowas seen in five of 90 fetuses of EHV-1-infected mice, but in no fetuses from RK-inoculated mice. On days 1, 2, 3, 4 and 5 pi, the fetuses from EHV-1-infected dams were significantly smaller than those from RK-inoculated dams. Congestion and necrosis of the middle layer of trophoblast and chorionic necrosis were observed in the placentae from EHV-1-infected dams and assessed by a scoring system. Virus was isolated rarely from the fetuses (1/73), placentae (3/72) and uteri (1/16) of EHV-1-infected dams, and only from those killed on day 1 or 2 pi. This indicates that, as in the horse, abortion caused by EHV-1 infection in mice is not necessarily a consequence of fetal infection but may be due to fetal compromise due to vascular effects on the placenta.

Improvement in high altitude hypoxic stress tolerance in albino rats on oral glutamate supplementation

Hypoxia results in body weight loss due to anorexia and hypophagia and reduced human performance. The present study was undertaken to evaluate the role of oral glutamate administration with food and water in improvement in hypoxic tolerance, if any. The placebo controlled study revealed that supplementation of optimal dose of glutamate (Glu) promoted hypoxic tolerance in male Sprague Dawley Albino rats fed one dose daily for 5 days and exposed to continuous intermittent hypoxia of 6 hrs per day at 10,668m in an animal exposure chamber. Effect of varying dose of Glu on body weight (bw),food intake and water uptake were studied which revealed the optimal dose of Glu to be 27mgKg bw. Oral feeding of Glu resulted in improved tolerance of combined stress of cold and hypoxia as measured by fall in rectal temperature from 37’C to 23’C and faster rewarming. It enhanced 5.8 times hypoxic tolerance 36% bw gain and 24% food intake in hypoxia possibly by acting as a conditionally essential amino acid under hypoxia.

Effects of two kinds of underwear on metabolic heat production during 60 min recovery after 30 min severe exercise in the cold.

The purpose of this study is to investigate the thermophysiological significance of hydrophilic and hydrophobic properties of underwear materials under the influences of profuse sweating produced during severe exercise in the cold. Two kinds of underwear were used: two layers of cotton underwear with two-piece long-sleeved shirt and full-trousers (C), and two layers of polypropylene underwear with two-piece long-sleeved shirt and full-trousers (P). In addition, the subject put on a two-piece ski suit of 100% polyester including 100% polyester padding. Eight adult females volunteered as subjects in this study. The test was performed in a climatic chamber at an ambient air temperature of 2 degrees C and an air velocity of 0.26 m.s-1. The subject exercised on a cycle ergometer at an intensity of 65% maximal oxygen uptake for 30 min and followed by 60 min recovery. The major findings are summarized as follows: 1) The fall of rectal temperature tended to be greater in P during the recovery. 2) The absolute humidity of innermost layer and middle layer was significantly higher in C than in P during the recovery, but the absolute humidity of middle layer and outermost layer was significantly higher in P than in C during the exercise. 3) Clothing microclimate temperature of innermost at back was significantly higher in C during the exercise and recovery. 4) Metabolic heat production for last 30 min during recovery was significantly higher in P. 5) The degree of skin wettedness sensation and sweating sensation for whole body was significantly higher in P during the exercise. It was concluded that the slower evaporation behavior by absorbing of underwear material in the clothing system has a beneficial influence on thermophysiological responses during severe exercise and its recovery in the cold, although the differences were very small.

Stimulation of 5-HT 1B receptors causes hypothermia in the guinea pig

The selective, brain penetrant, 5-HT 1B/D (formerly 5-HT 1D β/ α ) receptor agonist SKF-99101H (3-(2-dimethylaminoethyl)-4-chloro-5-propoxyindole hemifumarate) (30 mg/kg i.p.) causes a dose related fall in rectal temperature in guinea pigs which previous studies have shown to be blocked by the non-selective 5-HT 1B/D receptor antagonist GR-127935 ( N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1′biphenyl]-4-carboxamide oxalate). The present study shows that the hypothermic response to SKF-99101H is dose-dependently blocked by SB-224289G (1′-methyl-5-(2′-methyl-4′-[(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl)-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4′-piperidone] hemioxalate) (0.3–10.0 mg/kg p.o.) (ED 50 3.62 mg/kg), which is the first compound to be described which is more than 60 fold selective for the 5-HT 1B receptor over the 5-HT 1D receptor. SB-216641A ( N-[3-(2-dimethylamino) ethoxy-4-methoxy-phenyl] 2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1′-biphenyl)-4-carboxamide hydrochloride) (0.6–20.0 mg/kg i.p.), which is somewhat less selective (30 fold) for the 5-HT 1B receptor over the 5-HT 1D receptor had a similar effect (ED 50 4.43 mg/kg). The brain penetrant 5-HT 1D selective receptor antagonist, BRL-15572 (4-(3-chlorophenyl)- α-(diphenylmethyl)-1-piperazineethanol dihydrochloride) (0.3–100.0 mg/kg i.p.) was inactive. When administered alone neither BRL-15572 (0.1–10 mg/kg i.p.) nor SB-224289G (2.2–22 mg/kg p.o.) had an effect on body temperature. These data demonstrate that 5-HT 1B (formerly 5-HT 1D β ) and not 5-HT 1D (formerly 5-HT 1D α ) receptors mediate the hypothermic response to SKF-99101H (30 mg/kg i.p.) in guinea pigs. The compounds described are useful pharmacological tools for distinguishing responses to 5-HT 1B and 5-HT 1D receptors.

Thermal balance of man in water: prediction of deep body temperature change.

Changes in rectal temperature and metabolic rate were continuously monitored in men immersed in water at 15, 20, 25, 30, and 35 degrees C. The subjects (12 healthy male students) wore swimming suits while either resting or doing leg exercise (delta M approximately 60 kcal.h-1.m-2 approximately 70 W.m-2) for 1 h. At all water temperatures below 30 degrees C, the metabolic rate increased but the rectal temperature fell continuously, resulting in hypothermia. The rate of fall in rectal temperature (cooling rate, CR, degrees C.h-1) was inversely proportional to water temperature (Tw, degrees C) according to the equation CR = 3.818-0.109 Tw in resting subjects and CR = 3.434-0.110 Tw in exercising subjects. At a given Tw the cooling rate was greater in resting than in exercising subjects and in lean than in obese subjects. From the relationships between the cooling rate and water temperature the duration of useful activity and the survival time were predicted for resting and exercising subjects of various fatness.