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PubMed2005

Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans.

RATIONALE: Although 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) has been reported to cause fatal hyperthermia, few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature. In rats, MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones. OBJECTIVES: In this study, the physiological and subjective effects of MDMA in humans were determined at cold (18 degrees C) and warm (30 degrees C) ambient temperatures in a temperature and humidity-controlled laboratory. METHODS: Ten healthy volunteers who were recreational users of MDMA were recruited. Four laboratory sessions were conducted in a 2x2 design [i.e., two sessions at 30 degrees C and two at 18 degrees C, two during MDMA (2 mg/kg, p.o.) and two during placebo, in double-blind fashion]. Core body temperature (ingested radiotelemetry pill), skin temperature (four weighted sites), heart rate, blood pressure, metabolic rate (indirect calorimetry), shivering (electromyogram levels), and sweat rate (capacitance hygrometry) were measured as well as subjective effects for several time periods following capsule ingestion. RESULTS: MDMA produced significant elevations in core body temperature and metabolic rate in both warm and cold conditions. MDMA also produced significant elevations in blood pressure and heart rate and significantly increased several ratings of subjective effects similar to those previously reported. There were no differences related to ambient temperature for any of the subjective effects, except that ratings of cold and warm were appropriate to the ambient temperature and were not influenced by MDMA. CONCLUSIONS: Unlike findings in rats, MDMA increased core body temperature regardless of ambient temperature in humans. These increases appeared related to increases in metabolic rate, which were substantial. These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis.

Adolescent↗
PubMed2005

Seasonal thermoregulatory responses in mammals.

This study examined the proportional seasonal winter adjustments of total and mass-specific basal power (watts and watts g-1, respectively), thermal conductance (watts g-1 degrees C-1), non-shivering thermogenesis capacity (ratio of NST/basal power), body temperature ( degrees C), and body mass (g) of mammals. The responses are best summarized for three different body size classes; small mammals (<100 g), intermediate-sized mammals (0.1-10 kg), and large mammals (>10 kg). The principal adjustments of the small mammals center on energy conservation, especially the Dehnel Effect, the winter reduction in body size of as much as 50%, accompanied by reductions in mass-specific basal power. On average, these reductions reduce the total basal power approximately in direct proportion to the mass reductions. Reductions in mass-specific basal power are matched by concomitant reductions in conductance to maintain the setpoint body temperature during winter. The overall thermoregulatory adjustments in small mammals serve to (a) lower overall winter power consumption, (b) maintain the setpoint body temperature, and (c) lower the lower critical limit of thermoneutrality and hence thermoregulatory costs. In intermediate-size mammals, the seasonal response is centered more on increasing thermogenic capacity by increasing basal power and NST capacity, accompanied by predictable and large reductions in conductance. The Dehnel effect is negligible. Very large mammals undergo the largest reductions in total and mass-specific basal power and conductance. However, there are too few data to resolve whether the reductions in total basal power can be attributed to the Dehnel effect, because the moderate decreases in body mass may also be caused by nutritional stress. Apart from the seasonal changes in basal power, these observations are consistent with the predictions of Heldmaier's seasonal acclimatization model.

Acclimatization↗
PubMed1997

Ontogeny of cardiac rate regulation and brown fat thermogenesis in golden hamsters (Mesocricetus auratus).

It was shown previously in infant rats (Rattus norvegicus) that the ability to produce heat in the cold using brown adipose tissue (BAT) is closely related to the ability to maintain cardiac rate. When the limits of BAT thermogenesis were exceeded, interscapular temperature (which reflects the temperature of the interscapular BAT depot) and cardiac rate fell together. As an extension of this earlier study, the relation between BAT thermogenesis and cardiac rate was examined here in the golden hamster (Mesocricetus auratus), a species whose young do not exhibit BAT thermogenesis until the end of the 2nd week postpartum. It was found that 3 to 12-day-old hamsters were unable to increase shivering or nonshivering thermogenesis in the cold and exhibited decreases in cardiac rate that proceeded in lock-step with decreases in interscapular temperature. In contrast, as the thermogenic capability of hamsters increased after 12 days of age, cardiac rate was maintained within narrow limits across a wide range of air temperatures. These results support the hypothesis that heat produced by BAT helps to warm the heart and thus aids in the maintenance of cardiac rate during cold exposure.

Adipose Tissue, Brown↗
PubMed1998

Thermogenic responses to body cooling during fever induced by Staphylococcus aureus cell walls in rabbits.

Hypothalamic temperature (Thypo) and metabolic heat production (M) were measured in seven conscious rabbits injected intravenously with either saline or with Staphylococcus aureus, (8.10(7) cell walls.kg-1) while being subjected to a 3-h period of ramp-like total body cooling using a chronically implanted intravascular heat exchanger. In pyrogen-injected animals cooling started (1) at the time of injection or (2) 70 min after injection. In (1) the fall in Thypo induced by heat extraction was similar (1.0 degree C) in afebrile and febrile animals. In (2) there was a transient increase in Thypo of about 0.5 degree C at a time corresponding to the start of fever resulting in a significantly smaller fall in Thypo at the end of the 3-h cooling period (0.5 degree C vs 0.9 degree C, P < 0.05, n = 5). At this time in both (1) and (2) M was lower than theoretically expected from the increase in shivering threshold during fever. However, most of this effect can be explained when available data showing a decrease in thermosensitivity during S. aureus-induced fever are taken into account. After cessation of cooling in both groups of febrile animals Thypo rose to about 1 degree C higher than the precooling level, which is comparable to the fever level in a separate series of experiments with S. aureus injection without cooling (1.2 degrees C).

Animals↗
PubMed1998

Development of endothermy in a Tasmanian marsupial, Bettongia gaimardi and its response to cold and noradrenaline.

Marsupials at birth are ectothermic and gradually attain the ability to change their metabolic heat production during pouch life. How this process occurs in the bettong has been measured on 13 pouch young from week 1 until 3 weeks after pouch vacation (week 18). Oxygen consumption was measured at 35 degrees C (pouch temperature) and at 22 degrees C. The results at 35 degrees C showed an increase in metabolic rate from week 1 until week 12 when there was a decrease to near adult levels after pouch vacation. At 22 degrees C young bettongs had a lower metabolic rate (compared with measurements made at 35 degrees C) until week 9 after which there was an increase above measurements made at 35 degrees C. Noradrenaline had little effect until week 10 after which the metabolic rate (although measured at 35 degrees C) paralleled the levels measured at 22 degrees C. The free thyroxine level was low in early pouch life, increased to a peak at week 12 then decreased. Thermal conductance increased until week 10 after which it decreased, reaching values similar to those of adult bettongs by week 20. The results indicate that non-shivering thermogenesis occurs in this macropodoid marsupial. This phenomenon may be a phylogenetic difference between macropodid and non-macropodid marsupials as also suggested by Nicol et al. (1997).

Age Factors↗
PubMed2001

Ontogeny of catabolic and morphological properties of skeletal muscle of the red-winged blackbird (Agelaius phoeniceus).

Thermogenic capabilities of red-winged blackbirds improve markedly during their 10-12-day nestling period, especially between day 5 and day 8. The time course of improvements may be determined by the maturation of skeletal muscles involved in shivering thermogenesis, particularly the pectoralis muscles. To test this hypothesis, morphological and biochemical changes in pectoral and leg muscles were measured in young and adult blackbirds. Both muscles grew disproportionately relative to body mass. The pectoralis consisted entirely of fast-twitch fibers, predominantly fast oxidative glycolytic. In contrast, the gastrocnemius muscle consisted of a mixture of slow and fast fibers (predominantly fast glycolytic). Although fiber composition was constant, both cross-sectional area and density of fibers increased with age in both muscles. Catabolic capacities of the pectoralis increased significantly (approximately 7-8-fold) throughout the nestling period, most abruptly after day 3 (citrate synthase, CS) or day 4 (3-hydroxacyl-CoA-dehydrogenase, HOAD). Myofibrillar ATPase activities in the pectoralis were initially low, but increased after day 5. Further increases in CS and myofibrillar ATPase activities occurred in the pectoralis after fledging. CS and HOAD activities in the leg were much lower, but myofibrillar ATPase activities were remarkably similar in the two muscles, differing only in adults. These results are consistent with the hypothesis that the development of endothermy is dependent on the morphological and biochemical maturation of skeletal muscles important in thermogenesis.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1996

Myelination by transplanted human and mouse central nervous system tissue after long-term cryopreservation.

Human and mouse oligodendrocytes were transplanted, after a long period of cryostorage, into newborn mouse brain. Tissue fragments were obtained from brain and spinal cord of 10-week-old human fetuses and from the periventricular zone of embryonic and newborn mouse brains. Samples were stored at -180 degrees C for periods of 3 days to over 5 years. Frozen or fresh fragments were transplanted into the brains of newborn shiverer mutant mice, which are deficient in myelin basic protein (MBP). Normal myelin, produced by grafted oligodendrocytes, was detected by immunohistochemistry with an anti-MBP antiserum. The best results were obtained with isospecific grafts. The timing of myelin appearance did not depend significantly on the species or age of the donor. Myelination obtained with mouse grafts was more profuse when the donor was younger (embryonic versus newborn). Cryopreservation over 5 years did not impede the graft's ability to produce myelin and can be considered for long-term storage of oligodendrocytes in view of cell therapy.

Animals↗
PubMed2001

Use of misoprostol for the termination of second trimester pregnancies.

Surgical termination of pregnancy is of high risk for the woman's health and safe medical ways are required. The use of prostaglandins may substantially reduce this risk. The efficacy and safety of misoprostol as a medication for the termination of the second trimester pregnancies were studied. During a 15-month period ninety-eight healthy pregnant women (13-24 weeks) wishing to terminate their pregnancy due to medical reasons participated voluntarily in this study. Misoprostol was administered 400 microg per os and 400 microg vaginally. Dose was repeated every 6 hours until adequate contractions and cervical ripening were achieved. Outcome measures included successful termination rates, mean expulsion time and side effects of the medication. The efficacy of the method was as high as 91.8% (90/98 cases 95%, CI 86-97%). Mean expulsion time was 10.2 h (range 3-23.4 h) for primigravida and 9.2 h (range 2.5-22.2 h) for multigravida. In 9 cases (9.2%) placenta remnants and in 8 (8.2%) placenta retention were found. Most common side effect was shivering in 17.3% of cases, vomiting and nausea (10.2%), headache and dizziness (7.1%), abdominal pain (79.6%), while diarrhea was noticed in 4.1%. The high efficacy and low incidence of side effects make misoprostol a useful alternative method for medical termination of second trimester pregnancies.

Abortifacient Agents, Nonsteroidal↗
PubMed1998

Thermoregulatory changes in the cold induced by physical training in humans.

It has previously been demonstrated that metabolic heat production (M) during cold exposure at rest was related to maximal oxygen uptake (VO2max). Consequently, an increase in VO2max could allow an increase M in the cold. The aim of the present study was therefore to test this hypothesis. Eight male volunteers undertook interval training (periods of 25% VO2max of 30-s duration and 110% VO2max of 60-s duration until exhaustion, five times a week over 8 weeks) to increase VO2max. Both before and after this physical training, they were subjected to a 10 degrees, 5 degrees and 1 degrees C 2-h cold air test in a climatic chamber. During the cold exposure, rectal temperature (Tre), tympanic temperature (Tty) mean skin temperature (Tsk) and M were measured as well as the time to onset of shivering (t) and body temperatures (Tre, Try and Tsk) at t. The results showed that physical training involved an increase in VO2max (14%-15%, P < 0.05). During the cold exposure, Tre was higher after training both at 10 degrees, 5 degrees and 1 degree C (P < 0.05) whereas Tty, TSk and M were not significantly changed. However, an increase in the sensitivity of the thermoregulatory system was attested by a decreased t at higher Tsk. These slight physiological changes found after training were not related to the increases in VO2max. In conclusion, this study demonstrated that interval training induced slight thermoregulatory changes unrelated to changes in VO2max and it suggested that M during cold exposure could be related mainly to the level of VO2max observed before training, since increases in VO2max did not modify M.

Adult↗
PubMed1998

Human thermoregulatory responses during prolonged walking in water at 25, 30 and 35 degrees C.

Eight healthy and physically well-trained male students exercised on a treadmill for 60 min while being immersed in water to the middle of the chest in a laboratory flowmill. The water velocity was adjusted so that the intensity of exercise correspond to 50% maximal oxygen uptake of each subject, and experiments were performed once at each of three water temperatures: 25, 30, 35 degrees C, following a 30-min control period in air at 25 degrees C, and on a treadmill in air at an ambient temperature of 25 degrees C. Thermal states during rest and exercise were determined by measuring rectal and skin temperatures at various points, and mean skin temperatures were calculated. The intensity of exercise was monitored by measuring oxygen consumption, and heart rate was monitored as an indicator for cardiovascular function. At each water temperature, identical oxygen consumption levels were attained during exercise, indicating that no extra heat was produced by shivering at the lowest water temperature. The slight rise in rectal temperature during exercise was not influenced by the water temperature. The temperatures of skin exposed to air rose slightly during exercise at 25 degrees C and 30 degrees C water temperature and markedly at 35 degrees C. The loss of body mass increased with water temperature indicating that both skin blood flow and sweating during exercise increased with the rise in water temperature. The rise in body temperature provided the thermoregulatory drive for the loss of the heat generated during exercise. Heart rate increased most during exercise in water at 35 degrees C, most likely due to enhanced requirements for skin blood flow. Although such requirements were certainly smallest at 25 degrees C water temperature, heart rate at this temperature was slightly higher than at 30 degrees C suggesting reflex activation of sympathetic control by cold signals from the skin. There was a significantly greater increase in mean skin and rectal temperatures in subjects exercising on the treadmill in air, compared to those exercising in water at 25 degrees C.

Adolescent↗
PubMed2004

The steroid RU486 induces UCP1 expression in brown adipocytes.

RU486 (mifepristone), a potent antagonist at progesterone and glucocorticoid receptors (PR and GR), is well known for its use in the termination of unwanted pregnancies, the potential development of oral contraceptives, treatment of certain cancers and other activities. Potentially, it could also play a role in obesity control, although the few studies that have addressed this aspect have focused mainly on its central and anti-glucocorticoid effects. We have shown previously that it could have a direct effect on brown adipocytes in culture when administered together with progesterone. The aim of the present work was to analyse the effects of RU486 on the expression of uncoupling proteins (UCPs) in brown adipocytes. In culture-grown, differentiated brown adipocytes, placed in a serum-free medium to exclude the presence of progesterone or glucocorticoids, RU486 stimulated UCP1 expression at both the mRNA and protein levels. These effects could be mediated by PR, GR or other unknown mechanisms but do not seem to be due to its anti-progestin or anti-glucocorticoid actions. The results suggest that the steroid RU486 has a direct action on adipocytes which could be useful for stimulating non-shivering BAT thermogenesis and therefore is of interest in obesity studies.

Adipocytes↗
PubMed1999

Blood flow to the brown adipose tissue of conscious young rabbits during hypoxia in cold and warm conditions.

Brown adipose tissue (BAT) non-shivering thermogenesis is stimulated by cold temperature and depressed by hypoxia. We investigated the extent to which changes in metabolic rate during cold and hypoxia, singly or combined, were accompanied by changes in BAT perfusion. One-month-old rabbits were instrumented for measurements of regional blood flow by the coloured microsphere technique. One group of rabbits was tested in warm (24 degrees C, n=17), and the other in cold (13 degrees C, n=9) conditions, first in normoxia (inspired oxygen concentration FIO2 about 21%, arterial oxygen saturation SaO2 approximately 88%) followed by hypoxia (FIO2 approximately 10%, SaO2 approximately 54%). In warm conditions, oxygen consumption (VO2, measured by an open-flow method) averaged 22 ml.kg-1.min-1 (STPD), and BAT blood flow 98 ml.100g-1.min-1. In hypoxia, VO2 dropped on average to 87%, whereas BAT flow dropped to 43% of the normoxic values. In the cold during normoxia, VO2 averaged 31 ml.kg-1.min-1 (STPD), and BAT blood flow was 155 ml.100g-1.min-1. In cold and hypoxia VO2 dropped to 19 ml.kg-1.min-1 (STPD) (i.e. 60% of the normoxic value), whereas BAT blood flow was not altered significantly (148 ml.100g-1.min-1). Hence, BAT blood flow decreased in hypoxia in absence of cold stimuli, whereas it remained high when hypoxia occurred during cold, despite the major drop in VO2. We conclude that cold is more important than hypoxia in determining BAT perfusion, and that changes in BAT blood flow are not a mechanism for the hypoxic control of V.O2.

Adipose Tissue, Brown↗
PubMed1997

Functional analysis in vivo of the double mutant mouse deficient in both proteolipid protein (PLP) and myelin basic protein (MBP) in the central nervous system.

Myelination is an important developmental process of the central (CNS) and peripheral nervous system (PNS). To unravel the functions of the two dominant myelin proteins in the CNS, proteolipid protein (PLP) and myelin basic protein (MBP), we generated and characterized the homozygous double mutant mouse line (plp-/-, mbp-/-), which is viable and fertile. Plasma membrane processes of oligodendrocytes deficient in PLP and MBP, but not in myelin-associated glycoprotein (MAG), spirally wrap large diameter axons, tightly adhering at their extracytosolic surfaces and forming a pseudo-compacted myelin. Neuromotor activity and coordination are considerably improved compared to the shiverer trait.

Animals↗
PubMed1998

An immunohistochemical and in situ hybridisation study of the postnatal development of uncoupling protein-1 and uncoupling protein-1 mRNA in lamb perirenal adipose tissue.

In the lamb, the uncoupling protein-1 (UCP1) content of perirenal adipose tissue at birth is an important factor in heat production by non-shivering thermogenesis and the prevention of hypothermia. This study examines UCP1 gene expression and protein content in perirenal adipose tissue over the first 15 days of life by in situ hybridisation and immunohistochemistry. UCP1 mRNA was detected at birth in 30% of adipocytes, and in approximately 24% of fat cells at 2 days of life. However, by 5 days of age and thereafter UCP1 mRNA was undetectable. Immunoreactive UCP1 was present in all adipocytes at birth and at 2 days of age, and remained detectable in a decreasing proportion of cells until day 10 of life. By 15 days of age no immunoreactive UCP1 was detected and the perirenal adipose tissue had the appearance of white fat. It is concluded that UCP1 gene expression is suppressed in most adipocytes in perirenal adipose tissue of newborn lambs, and gene expression rapidly falls in the remaining adipocytes over the first 5 days of postnatal life. In contrast, immunoreactive UCP1, a characteristic of brown adipose tissue, was present in many adipocytes for up to 10 days of age, suggesting that UCP1 has a long half-life in lambs. All adipocytes in perirenal adipose tissue of newborn lambs appear to be functionally brown, but over the first 2 weeks of postnatal life there is a complete transformation to white adipocytes.

Adipose Tissue↗
PubMed2001

Fatty acid composition of brown adipose tissue in genetically heat-tolerant FOK rats.

The phospholipid fatty acid composition of brown adipose tissue (BAT) was examined in inbred heat-tolerant FOK rats and compared with that in conventional Wistar rats not previously exposed to heat. The FOK rats showed higher unsaturation states, as indicated by higher levels of polyunsaturated fatty acids and a higher unsaturation index and polyunsaturated fatty acids/saturated fatty acids ratio. This higher level of unsaturation was characterized by the higher amount of polyunsaturated fatty acids such as linoleic acid, arachidonic acid and docosahexaenoic acid. It may be concluded that the increased docosahexaenoic acid level in BAT phospholipids brings about the hyperplasia of BAT, causing an enhancement of its in vivo thermogenic activity as well as the systemic non-shivering thermogenesis observed in heat-tolerant FOK rats.

Adipose Tissue, Brown↗
PubMed2001

Computer prediction of human thermoregulatory and temperature responses to a wide range of environmental conditions.

A mathematical model for predicting human thermal and regulatory responses in cold, cool, neutral, warm, and hot environments has been developed and validated. The multi-segmental passive system, which models the dynamic heat transport within the body and the heat exchange between body parts and the environment, is discussed elsewhere. This paper is concerned with the development of the active system, which simulates the regulatory responses of shivering, sweating, and peripheral vasomotion of unacclimatised subjects. Following a comprehensive literature review, 26 independent experiments were selected that were designed to provoke each of these responses in different circumstances. Regression analysis revealed that skin and head core temperature affect regulatory responses in a nonlinear fashion. A further signal, i.e. the rate of change of the mean skin temperature weighted by the skin temperature error signal, was identified as governing the dynamics of thermoregulatory processes in the cold. Verification and validation work was carried out using experimental data obtained from 90 exposures covering a range of steady and transient ambient temperatures between 5 degrees C and 50 degrees C and exercise intensities between 46 W/m2 and 600 W/m2. Good general agreement with measured data was obtained for regulatory responses, internal temperatures, and the mean and local skin temperatures of unacclimatised humans for the whole spectrum of climatic conditions and for different activity levels.

Acclimatization↗
PubMed2000

Delayed infection of a lymphocele following mastectomy with immediate breast reconstruction: report of a case.

We report herein a rare case of delayed infection of a lymphocele following mastectomy with immediate breast reconstruction. A 38-year-old woman presented to our hospital 7 months after undergoing a left-modified radical mastectomy with an immediate breast reconstruction, following the sudden development of a giant mass in the left thoracoabdominal region as well as a high fever and shivering. Ultrasonography and a computed tomographic scan revealed massive fluid retention extending from the left axilla to the lower abdominal region. Puncture drainage was performed three times and the injection of an antibiotic directly into the cyst resulted in resolution of the fluid. This massive retraction of fluid was considered to have resulted from a delayed infection of an axillary lymphocele.

Adenocarcinoma↗
PubMed2001

Responsiveness of plasma catecholamines to intracerebroventricular injection of glucagon in Muscovy ducklings.

Recent investigations have demonstrated a modulatory action of glucagon on shivering via the central nervous system in ducklings. The aim of this study was to investigate the effects of intracerebroventricular injection (i.c.v.) of glucagon on metabolic rates (MR) and plasma catecholamines in control ducklings (TN) and in ducklings exhibiting nonshivering thermogenesis after chronic glucagon treatment: (GT). At thermoneutrality (25 degrees C, Ta), i.c.v. injection of glucagon had no thermogenic effects in TN and GT ducklings. At cold (+4 degrees C, Ta), i.c.v. glucagon injection elicited a concomitant decrease of plasma norepinephrine (NE) and MR in TN ducklings, whereas in GT ducklings, the plasma catecholamines and the MR remained unchanged. These results indicate that glucagon treatment rendered the catecholaminergic system of GT ducklings insensitive to cold or i.c.v. glucagon injection.

Animals↗