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Brain stem tonic inhibition of thermoregulation in the rat.

It was shown, by selective levels of decerebration, that a drop in body temperature occurred in a midpontine rat due to impairment in thermoregulatory responses. Lowering the level of decerebration to the lower pons restored a coordinated thermoregulatory response. The response was inadequate to raise the core temperature to normal level, but it was nevertheless an integrated response of vasoconstriction, piloerection, and shivering and was appropriately turned off by warming the skin or core. In intact unanesthetized rats, microinjection of a local anesthetic in the pontine tegmentum resulted in thermoregulatory responses, such as curling of the body, piloerection, tremor in facial muscles, and shivering. Similar injections in the pontine tegmentum of the midpontine decerebrate rat also restored some heat gain responses, including shivering. These experiments suggest that in rats the heat gain responses are powerfully regulated by a tonic inhibitory mechanism located in the midbrain and upper pons that exerts a complete inhibitory effect on the thermoregulatory areas caudal to the midbrain in decerebrate rats and a partial inhibitory effect in intact animals. These experiments also confirm the previous observation in the cat of the presence of a facilitatory area(s) in lower levels of the central nervous system which is responsible for coordinated heat gain responses observed in low-level decerebrate animals. In addition, these experiments suggest that the brain stem thermoregulatory mechanisms are in fact functioning in intact unanesthetized animals.

Animals↗

Effect of total body core cooling during poly I:C-induced fever in rabbits.

At ambient temperature (Ta) 20 and 10 degrees C, metabolic heat production and hypothalamic temperature (Thypo) were measured to determine the fever response in six rabbits injected with polyriboinosinic-polyribocytidylic acid (poly I:C; 5 mg/kg iv). Similar measurements were made in afebrile and febrile animals subjected to 3 h of body cooling, in which heat was extracted with a chronically implanted intravascular heat exchanger in a ramplike manner. The fever time course showed a biphasic pattern. During cooling in the febrile experiments, Thypo remained constant or even slightly increased during the time corresponding to the first phase of fever but rapidly fell during the second phase because of a depressed shivering response. The net effect at the end of the cooling period was that Thypo decreased by 0.4 and 0.6 degree C more than in the afebrile cooling experiments at Ta 20 and 10 degrees C, respectively. The results indicate normal shivering responses during phase I of poly I:C-induced fever and depressed shivering in phase I, possibly because of a reduced thermosensitivity.

Adaptation, Physiological↗

Postnatal development of pyrogenic sensitivity in guinea pigs.

Despite evidence of thermoregulatory ability from birth, neonates generally are unable to develop fever when challenged with endotoxin. This could be due to their small capacity for heat storage. To test this possibility, the pyrogenicity of S. enteritidis endotoxin (2 mug/kg, iv) was measured at both room (Ta = 25 degrees C) and neutral (Tn = 29-33 degrees C, depending on age) temperatures in 0- to 32-day-old unanesthetized guinea pigs, reared from birth at about 24 degrees C. Control guinea pigs received sterile saline injections in concurrent experiments. Shivering, O2 uptake, and colonic (Tre) and subcutaneous [over the interscapular fat pad (Tbat) and the sacrospinalis muscle (Tsc)] temperatures were recorded continuously for 4 h after injection. Endotoxin generally produced no febrile responses at both ambient temperaturess rises in animals aged 8 or more days; Tbat increased before the other sites in the 8- and 16-day-old animals, and shivering did not occur; by 32 days of age, however, Tbat no longer increased first, and there was shivering. In Tn significant febrile rises were not evident until 32 days of age; control temperatures, however, were elevated during this exposure as compared to at Ta. These results showed therefore that pyrogenic sensitivity is not apparent in guinea pigs during the first postnatal week; thereafter fever responses are evocable, but their detection may be masked by environmentally produced changes in body temperature. The data also indicated that the site of the heat production underlying, in part, endotoxic fevers gradually shifts from brown fat so skeletal muscle during the first month of life.

Age Factors↗

Effect of altitude exposure on thermoregulatory response of man to cold.

The thermoregulatory responses to 10 degrees C (for 3 h) were investigated in 1) 12 natives from sea level (lowlanders) at 150 m, and on arrival at 3,350 and 4,340 m; 2) 6 of these during a 6-wk sojourn at 4,360 m, and on return to sea level; and 3) 5 natives from each of the two altitudes (highlanders) in their respective habitat, and after descent to 150 m. The cold-induced increase in the rate of O2 consumption (Vo2) of the lowlanders was significantly smaller at both altitudes than at sea level. It did not recover substantially during the 6 wk at altitude, but was restored to its initial rate on return to sea level. By contrast, visible shivering activity was augmented on arrival at altitude. It persisted throughout the 6 wk there, but was greatly depressed on return to sea level, despite the increased Vo2. Mean skin temperatures (Tsk) stabilized in the cold at significantly higher values at altitude. Rectal temperature (Tre) decreased similarly at all altitudes. Vo2 of the highlanders in the cold was significantly greater at sea level than at their resident altitudes, although shivering activity was less intense; Tsk stabilized at significantly lower levels at 150 m than at either altitude. These results indicate that altitude exposure reduces the calorigenic response of man to cold, and that this effect is not moderated by acclimatization to altitude, yet is reversible immediately on descent to sea level. The component of cold thermogenesis which appeared to be reduced by altitude exposure was nonshivering thermogenesis rather than visible shivering.

Acclimatization↗

Human temperature regulation during narcosis induced by inhalation of 30% nitrous oxide.

The study investigated the effect of inhalation of 30% nitrous oxide (N2O) on temperature regulation in humans. Seven male subjects were immersed to the neck in 28 degrees C water on two separate occasions. They exercised at a rate equivalent to 50% of their maximum work rate on an underwater cycle ergometer for 20 min and remained immersed for an additional 100 min after the exercise. In one trial (AIR) the subjects inspired compressed air, and in the other trial (N2O) they inspired a gas mixture containing N2O (20.93% O2-30% N2O-49.07% N2). Sweating, measured at the forehead, and shivering thermogenesis, as reflected by O2 uptake, were monitored throughout the 100-min recovery period. The threshold core temperatures at which sweating was extinguished and shivering was initiated were established relative to resting preexercise levels. Neither the magnitude of the sweating response nor the core threshold at which it was extinguished was significantly affected by the inhalation of N2O. In contrast, shivering thermogenesis was both significantly reduced during the N2O condition and initiated at significantly lower core temperatures [change in esophageal temperature (delta T(es)) = -0.98 +/- 0.33 degrees C and change in rectal temperature (delta T(re)) = -1.26 degrees C] during the N2O than during the AIR condition (delta T(es) = -0.36 +/- 0.31 degrees C and delta T(re) = -0.44 +/- 0.22 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of ambient temperature during 1st day of life on thermoregulation in lambs delivered by cesarean section.

We examined the effect of delivering near-term twin lambs by cesarean section into a warm (30 degrees C) or cool (15 degrees C) ambient temperature on the control of thermoregulation. Heat production was measured 20-30 h after birth during non-rapid-eye-movement sleep at 29 and 14 degrees C. At 29 degrees C there was no difference in heat production between groups, but at 14 degrees C cool-delivered (CD) lambs exhibited a 62% greater metabolic response. Irrespective of delivery temperature, 15 of the 18 lambs used shivering thermogenesis during cold exposure, indicating a reduction in the ability to use nonshivering thermogenesis in brown adipose tissue (BAT). Mean plasma concentrations of thyroxine and triiodothyronine were 35 and 45% greater, respectively, in CD lambs than in warm-delivered lambs. The level of guanosine 5'-diphosphate binding in BAT was lower than in normally delivered lambs and was not different between CD and warm-delivered lambs. Cesarean section delivery prevents the rise in BAT thermogenic activity, which results in an increased reliance on shivering thermogenesis to maintain colonic temperature. Under these conditions, delivery into a cool environment increases the plasma concentration of thyroid hormones, which benefits the neonate by enabling a greater thermogenic response via shivering.

Adipose Tissue, Brown↗

Heat balance precedes stabilization of body temperatures during cold water immersion.

Certain previous studies suggest, as hypothesized herein, that heat balance (i.e., when heat loss is matched by heat production) is attained before stabilization of body temperatures during cold exposure. This phenomenon is explained through a theoretical analysis of heat distribution in the body applied to an experiment involving cold water immersion. Six healthy and fit men (mean +/- SD of age = 37.5 +/- 6.5 yr, height = 1.79 +/- 0.07 m, mass = 81.8 +/- 9.5 kg, body fat = 17.3 +/- 4.2%, maximal O2 uptake = 46.9 +/- 5.5 l/min) were immersed in water ranging from 16.4 to 24.1 degrees C for up to 10 h. Core temperature (Tco) underwent an insignificant transient rise during the first hour of immersion, then declined steadily for several hours, although no subject's Tco reached 35 degrees C. Despite the continued decrease in Tco, shivering had reached a steady state of approximately 2 x resting metabolism. Heat debt peaked at 932 +/- 334 kJ after 2 h of immersion, indicating the attainment of heat balance, but unexpectedly proceeded to decline at approximately 48 kJ/h, indicating a recovery of mean body temperature. These observations were rationalized by introducing a third compartment of the body, comprising fat, connective tissue, muscle, and bone, between the core (viscera and vessels) and skin. Temperature change in this "mid region" can account for the incongruity between the body's heat debt and the changes in only the core and skin temperatures. The mid region temperature decreased by 3.7 +/- 1.1 degrees C at maximal heat debt and increased slowly thereafter. The reversal in heat debt might help explain why shivering drive failed to respond to a continued decrease in Tco, as shivering drive might be modulated by changes in body heat content.

Adipose Tissue↗

Development changes in the febrile response to endotoxin in rabbit.

The pyrogenicity of E. coli endotoxin (lipopolysaccharide, LPS) was measured at both 25 degrees C and neutral temperatures (Tn) in day -1 to adult rabbits. Intravenous injection of endotoxin (0.5 micrograms/kg) produced febrile response at Tn in day -1 rabbits, but not at 25 degrees C. A similar response was observed when endotoxin was injected s.c. (1.0 micrograms/kg) or intracisternally (0.0001 micrograms/kg). The mean magnitude of the rise of rectal temperature increased with the advance of age. Propranolol abolished the endotoxin-fever in day 3 rabbits. The inhibitory effect of propranolol was incomplete in day 14 rabbits and was not seen in day 28 rabbits. The inhibitory effect of phentolamine was not observed in day 3 and day 28 rabbits, but the blocker reduced the febrile response in day 14 rabbits. No shivering activity was evident in day 3 rabbits after injection of endotoxin. In the day 7 and 14 rabbits, shivering was less significant and of shorter duration than in the case of day 28 rabbits. The endotoxin caused no significant decrease in ear skin temperature in day 3 rabbits. A decrease in ear skin temperature was observed in rabbits older than 14 days. Thus, pyrogenic sensitivity is apparent even in day -1 rabbits. The mechanism of the heat production underlying endotoxin-fever gradually shifted from the nonshivering thermogenesis mediated by catecholamines to shivering thermogenesis during the first month of life.

Animals↗

Effects of feeding supplemental fat to beef cows on cold tolerance in newborn calves.

Our objectives were to examine the effects of added fat in late-gestation cow diets on neonatal response to cold. In Exp. 1, pregnant fall-calving heifers received control (n = 5), safflower seed (n = 5), or whole cottonseed (n = 5) diets. The hay-based, isonitrogenous, and isocaloric diets, fed for 47 d prepartum, contained 1.5, 4.0, and 5.0% fat for control, safflower, and whole cottonseed diets, respectively. At calving, calf BW and vigor score, as well as fat, lactose, and IgG in colostrum were not affected (P > 0.30) by diet. Heifers fed the safflower diet tended to have greater colostral solids (P < 0.10) than heifers fed the control or whole cottonseed diets. At 6.5 h of age, calves were placed in a 5 degrees C cold room for 90 min. Calf vigor, shivering, body temperature, and blood samples were taken every 15 min. During cold stress, calf body temperature decreased 0.7 degrees C (P < 0.03). Across all diets, shivering and serum glucose concentrations increased (P < 0.05), whereas calf vigor and cortisol concentrations decreased (P < 0.02) during cold exposure. In Exp. 2, pregnant spring-calving cows (n = 98) received a control (n = 47) or whole cottonseed (n = 51) supplement. Hay-based diets fed for 68 d prepartum contained 2.0 and 5.0% fat for control and whole cottonseed diets, respectively. Calf BW, vigor, shivering, dystocia score, time to stand, time to nurse, serum glucose concentrations, and serum IgG were not affected (P > 0.50) by diet. Between 30 and 180 min, body temperature of calves from dams fed the whole cottonseed supplement decreased (P < 0.05) more than calves from dams fed the control supplement. Serum glucose concentrations in calves were not affected by diet (P > 0.30). Serum cortisol concentrations tended (P < 0.09) to be greater for calves from dams fed whole cottonseed than control calves. When ambient temperature was < 6 degrees C, calves born to dams fed whole cottonseed had greater (P < 0.05) BW, tended (P < 0.1) to stand earlier, and had greater serum IgG concentrations. We conclude that calves from dams fed high-fat diets containing safflower or whole cottonseed respond similarly to cold stress, but these responses may not be consistent with greater cold resistance. In addition, high-fat dietary supplementation of late-gestation cows may only be beneficial during calving seasons with prolonged cold weather.

Adaptation, Physiological↗

Cooling effects and comfort of four cooling blanket temperatures in humans with fever.

Adult patients with fever (N = 89) were randomized into four blanket temperature groups: 7.2, 12.8, 18.3, and 23.9 degrees C. With their extremities protected, subjects were given acetaminophen and placed between two cooling blankets. There were no differences in the mean time (in minutes) to cool to a body temperature of 38.9 degrees C among groups. Although there were no differences in mean time for shivering, a trend of less shivering was apparent with warmer blanket temperatures. Few patients shivered (n = 17). There were no differences in the mean time (in minutes) for afterfall among the groups. The mean amount of afterfall for the 7.2 degrees C group (1.04 degrees C, SD = 0.50) was significantly greater than the 23.9 degrees C group (0.68 degrees C, SD = 0.47). Comfort scores significantly improved with warmer blanket temperatures. Thus, warmer blanket temperatures provided similar rates of cooling as the colder temperatures, yet were perceived to be more comfortable by the patient.

Acetaminophen↗

Forced-air warming and fluid warming minimize core hypothermia during abdominal surgery.

OBJECTIVE: To evaluate the effect of intraoperative combined forced-air warming and fluid warming system on patient's core temperature, blood loss, transfusion demand, extubation time, and incidence of postoperative shivering. METHODS: Forty patients with American Society of Anesthesiologists physical status I and II, aged 18-70 years, scheduled for elective abdominal surgery were randomly assigned to receive intraoperative warming from a forced-air blanket and fluid warming system or conventional cotton blanket, 20 in each group. The core temperature was recorded every 20 minutes during the operation, as well as the blood loss, blood transfusion, extubation time, and incidence of postoperative shivering. RESULTS: The core temperature at the end of the surgery in the warming group was significantly different from that in the control group (36.4 +/- 0.4 degrees C vs. 35.3 +/- 0.5 degrees C, P < 0.001). Application of intraoperative warming significantly shortened the time between the end of the surgery and extubation (P < 0.01). Postoperative shivering occurred in 30% of the patients in the control group compared to no patient in the warming group (P < 0.01). CONCLUSION: Active warming with air-forced blanket and fluid warming system provides sufficient heat to prevent hypothermia during abdominal surgery.

Abdomen↗

Skin and central temperatures during continuous epidural analgesia and general anaesthesia in patients subjected to open prostatectomy.

The effects of continuous lumbar epidural analgesia and general anaesthesia with artificial ventilation upon body temperatures were studied by measuring aural, nasopharyngeal, deltoid skin, calf and big toe temperatures in 33 patients subjected to open prostatectomy. The patients were randomly allocated to two groups. 17 were allocated to epidural analgesia, during which the rate of temperature decrease was slight and lasted about two hours. 21 were allocated to general anaesthesia, during which the core temperature fell relatively steeply for four hours. The resulting difference in core temperatures between the groups was statistically significant (P less than 0.05). Consequently the number of patients with core temperatures below 35 degrees C was significantly higher after general anaesthesia than after epidural analgesia (11 vs. 1; P less than 0.01). Seven of the 17 epidural patients (41%) shivered during the latency period of the blockade or operation. Two of the 21 general anaesthetic patients (10%) shivered later in the recovery room. There existed no relationship between shivering and the core temperature. The general anaesthetic patients showed a significant negative correlation between the body mass index (body weight (kg)/height (m2)) and the decrease in core temperature indicating a protective function of the fat layer against heat loss. After epidural analgesia no such correlation was found.

Aged↗

Thermoregulation and afterdrop during hypothermia in patients with poikilothermia.

The pathophysiology of afterdrop of core temperature during rewarming in patients with induced or accidental hypothermia remains controversial. We studied the effect of cooling and rewarming in four female patients with acquired poikilothermia and in four normal females. Exposure to cold air (16.5 degrees C) induced shivering and adequate vasoconstriction in normal individuals, without a fall in rectal temperature (Tr; 36.3 +/- 0.2 degrees C [mean +/- SD]); subsequent heating (40 degrees C) induced a rise in Tr to 37.0 +/- 0.3 degrees C and generalized sweating. The four patients all had spontaneous hypothermia (Tr 34.1 +/- 0.9 degrees C) before cooling. Tr decreased by 0.3-0.9 degrees C during cold exposure, and a marked afterdrop of Tr (0.3-0.5 degrees C) occurred during rewarming: this did not occur in normal individuals. Cooling failed to induce shivering and vasoconstriction in three patients. No patient showed visible sweating during heating despite a Tr of up to 38.0-38.5 degrees C and skin temperature of up to 37.7-38.5 degrees C. The basal metabolic rate was decreased by 71-82% in all patients during steady-state hypothermia and remained lowered during normothermia in two patients. We conclude that during hypothermia three of the four patients showed severe disorders of peripheral vasomotor function and shivering response. These data provide evidence for thermal conduction as the major mechanism of afterdrop during hypothermia.

Adult↗

Thermoregulation and hyperthermia.

Despite minor daily and monthly cyclical variations, body temperature remains relatively constant. Core temperature is maintained by thermoregulatory responses such as sweating, vasoconstriction and shivering, which are largely controlled by the hypothalamus. Within the hierarchy of neural structures regulating autonomic thermoregulatory responses, the preoptic area of the anterior hypothalamus plays a dominant role. In contrast, the posterior hypothalamus mediates behavioral defenses. Neurons in both regions sense core temperature and integrate central and peripheral thermal information. The setpoint temperature is then determined by relative synaptic inputs to warm-sensitive, cold-sensitive, and temperature-insensitive neurons. Fever is a regulated elevation in the preoptic setpoint temperature. Endogenous pyrogens and other fever mediators inhibit preoptic warm-sensitive neurons that normally facilitate heat loss and suppress heat production. This elevates the setpoint temperature for all thermoregulatory responses and activates cold-defenses such as vasoconstriction (which decreases heat loss) and shivering (which increases metabolic heat production). When pyrogen concentrations decrease, the setpoint temperature returns towards normal, triggering active vasodilation and sweating, which increases heat loss from the skin surface. The increasing phase of fever is often associated with shivering, which can markedly increase heart rate and cardiac output. Defervescence (and passive hyperthermia) is also often accompanied by tachycardia resulting from active precapillary vasodilation. Thus, cardiovascular complications are common throughout the febrile course and constitute the major clinical consequence of fever.

Body Temperature↗

GFAP-positive and myelin marker-positive glia in normal and pathologic environments.

The data herein demonstrate that in addition to the well-characterized myelin marker-positive, glial fibrillary acidic protein (GFAP)-negative, membrane sheet-bearing oligodendrocytes, another type of myelin marker-positive, process-bearing glia exists in normal and pathologic conditions. This second type of myelin marker-positive glia expresses GFAP, and therefore these cells have been referred to as mixed phenotype glia. Although mixed phenotype glia have been documented previously, their identity and function have remained a mystery. The goal of this immunocytochemical study was to further characterize these cells. Using the MBPlacZ transgenic mouse in which beta-galactosidase is under the control of the myelin basic protein (MBP) gene promoter, GFAP-positive/beta-galactosidase-positive and myelin/oligodendrocyte-specific protein (MOSP)-positive/beta-galactosidase-positive cells were detected in subcortical white matter and in perivascular locations within cerebral white and gray matter. In cultures prepared from highly enriched myelin marker-positive immature glia, mixed phenotype glia were detected that were GFAP-positive and either MOSP-, MBP-, O1-, and O4-positive. The expression of multiple myelin markers by mixed phenotype glia may suggest that these cells are of oligodendrocyte origin. Increased numbers of MOSP-positive/GFAP-positive mixed phenotype glia were detected in sections from adult hypomyelinated brain from shiverer, quaking, and PKU mice compared to myelinated control adult mouse brain. Similarly, cultures from control brain exposed to elevated pH for 2-3 weeks showed dramatically increased numbers of mixed phenotype glia (80%) compared to control (<10%). Increased numbers of mixed phenotype glia also were detected in shiverer cultures (40%). Since increases in the number of mixed phenotype glia occur in shiverer, quaking, and PKU mouse brain, these data suggest that mixed phenotype glia contribute to gliosis in pathologic white matter.

Animals↗

Cell-cell interactions during the migration of myelin-forming cells transplanted in the demyelinated spinal cord.

In the present paper, Dil-labeled myelin-forming cells were traced after their transplantation at a distance from a lysolecithin induced lesion in the adult wild-type and shiverer mouse spinal cord. Optical and ultrastructural observations indicate that after their transplantation, Dil-labeled Schwann cells and oligodendrocyte progenitors were found at the level of the graft as well as at the level of the lesion thus confirming that myelin-forming cells were able to migrate in the adult lesioned CNS (Gout et al., Neurosci Lett 87:195-199, 1988). Between the graft and the lesion, labeled Schwann cells and oligodendrocyte progenitors were absent in the gray matter, but were found as previously described, in specific locations (Baron-Van Evercooren et al., J Neurosci Res 35:428-438, 1993; Vignais et al., J Dev Neurosci 11:603-612, 1993). Both cell types were found along blood vessel walls and more precisely in the Virchow-Robin perivascular spaces. They were identified in the meninges among meningeal cells, collagen fibers, or occasionally in direct contact with the basement membrane forming the glia limitans. In addition to these findings, three major observations were made. In the ependymal region, myelin-forming cells were localized between or at the basal pole of ependymocytes. While Dil-labeled oligodendrocyte progenitors were noted to migrate along the outer surface of myelin sheats in CNS wild-type and shiverer white matter, Schwann cells were excluded from this structure in the wild-type mouse spinal cord. Moreover, in the shiverer mouse, migrating Schwann cells did not seem to interact directly with myelin sheats nor with mature oligodendrocytes. Finally, both cell types were seen to invade extensively the spinal peripheral roots. Our ultrastructural observations clearly suggest that multiple cell-cell and cell-substrate interactions rule the migration of myelin-forming cells in the adult CNS infering that multiple mechanisms are involved in this process.

Animals↗

Prostaglandins for prevention of postpartum haemorrhage.

BACKGROUND: Prostaglandins have mainly been used for postpartum haemorrhage when other measures fail. Misoprostol, a new and inexpensive prostaglandin E1 analogue, has been suggested as an alternative for routine management of the third stage of labour. OBJECTIVES: To assess the effects of prophylactic prostaglandin use in the third stage of labour. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register (March 2003). SELECTION CRITERIA: Randomized or quasi-randomized trials comparing a prostaglandin agent with another uterotonic or no prophylactic uterotonic (nothing or placebo) as part of management of the third stage of labour. There were no language preferences. DATA COLLECTION AND ANALYSIS: Eligibility, trial quality and data extraction were done by two reviewers independently. MAIN RESULTS: Twenty-four misoprostol and eight intramuscular prostaglandin trials (34,203 participants) were included. The data comparing oral misoprostol to no uterotonics/placebo are from five trials and difficult to interpret because of the heterogeneity between trials. However, the data do not suggest a substantive reduction in the rate of postpartum haemorrhage or other measures of blood loss. Oral misoprostol 600 mcg shows clinically and statistically significantly more blood loss = 1000 ml compared with conventional injectable uterotonics (seven trials, 22,749 women, 3.6% versus 2.7%; relative risk (RR) 1.34, 95% confidence interval (CI) 1.16 to 1.55). Shivering and elevated body temperature (> 38 masculine C) are the main side-effects of misoprostol and are dose related (600 mcg versus 400 mcg: shivering - two trials, RR: 1.33; 95% CI: 1.07 to 1.64). Compared to oxytocin the RR of any shivering with 600 mcg oral misoprostol is 3.29 (seven trials, 22746 women; 19.7% versus 6.0%, 95% CI 3.03 to 3.56) and temperature greater than 38 masculine C is RR 6.78 (seven trials, 22,09 women; 6.3% versus, 95% CI 5.55 to 8.30). Injectable prostaglandins are associated with reduced mean blood loss in the third stage of labour (weighted mean difference -70 ml, 95% CI -73 to -67 ml) when compared to conventional injectable uterotonics but have more side-effects. There are scarce data from this comparison on severe postpartum haemorrhage and the use of additional uterotonics, the primary outcomes of this review. REVIEWER'S CONCLUSIONS: Neither intramuscular prostaglandins nor misoprostol are preferable to conventional injectable uterotonics as part of the active management of the third stage of labour especially for low-risk women. Future research on prostaglandin use after birth should focus on the treatment of postpartum haemorrhage rather than prevention where they seem to be more promising.

Female↗

Differential expression of selected mitochondrial genes in hibernating little brown bats, Myotis lucifugus.

High rates of non-shivering thermogenesis by brown adipose tissue accompanied by additional shivering thermogenesis in skeletal muscle provide the powerful reheating of body organs that allows hibernating mammals to return from their state of cold torpor back to euthermic function. Previous studies have suggested that changes to brown adipose mitochondria occur during hibernation and are partially responsible for its capacity for non-shivering thermogenesis. The current study shows that selected mitochondrial enzyme activities are elevated and selected genes and proteins are induced during torpor in brown adipose tissue of the little brown bat, Myotis lucifugus. Cytochrome oxidase activity in brown adipose tissue was more than 3-fold higher during torpor than in euthermic animals. Transcript levels of mitochondria-encoded genes, coxII and nad4, were also 3-4-fold higher during torpor, as evidenced by northern blotting. By contrast, transcripts of these genes were unchanged in skeletal muscle during torpor. Protein levels of carnitine palmitoyl transferase-1beta, an enzyme embedded in the outer membrane of the mitochondria that is the rate-limiting step enzyme in beta-oxidation, were also elevated by 2-fold during torpor in brown adipose but were unchanged in skeletal muscle. Cloning and sequencing of a 624 bp segment of cpt-1beta revealed a number of amino acid substitutions in the bat protein as compared to CPT-1beta from other mammals; these may be beneficial for enzyme function at low body temperatures during torpor. This study provides further evidence for a key role of mitochondria in hibernation.

Adipose Tissue, Brown↗