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PubMed2004

Thermogenesis of interscapular brown adipose tissue selectively influences pontine and preoptic-hypothalamic temperatures during sleep in the rat.

The thermal influence of dorsal cervical and interscapular brown adipose tissue (ISBAT) on pontine and preoptic-hypothalamic temperatures was studied in unrestrained adult male rats across the non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM) sleep states. The animals had chronically implanted electrodes and thermistors for electroencephalographic and temperature recordings. After acclimation to either low (4 degrees C) or neutral (30 degrees C) ambient temperatures, the rats were studied before and after ISBAT excision. The warming influence of ISBAT thermogenesis activated by low ambient temperature reached the pontine and the preoptic-hypothalamic areas. ISBAT thermogenesis is necessary to maintain the homeothermy of the preoptic-hypothalamic area in NREM sleep at low ambient temperature. Such an ISBAT thermal effect may contribute to the integrated control of non-shivering and shivering thermogenesis.

Adipose Tissue, Brown↗
PubMed2026

Integrated transcriptomic analysis of mRNA and miRNA in Brown adipose tissue of the greater horseshoe bats during hibernation.

Hibernation enables animals survive harsh environments by conserving energy through reduced metabolism and body temperature. Brown adipose tissue (BAT) plays a critical role in non-shivering thermogenesis, crucial for warming up during arousal phase. The greater horseshoe bats (Rhinolophus nippon) are typical hibernators and non-shivering thermogenesis in BAT tissue may persist throughout the arousal process in bats. This study examines gene expression and regulatory changes in BAT of these bats across active, hibernation, and arousal phases using transcriptome and miRNA sequencing. A total of 2721 differentially expressed mRNAs and 268 differentially expressed miRNAs were identified. The results reveal that the BAT transcriptome undergoes state-dependent remodeling throughout the hibernation process. The most pronounced divergence occurs between the active phase and torpor, involving cell cycle arrest, immunosuppression, thermogenic signal desensitization, and upregulation of lipid metabolism and autophagy pathways, reflecting the coordinated adaptation of energy conservation and thermogenic reserve. In contrast, transcriptional alterations between torpor and arousal are extremely limited, indicating that torpid BAT is already pre-primed for thermogenesis and requires only modest transcriptional adjustments to activate heat production. Notably, although body temperature recovers to active-phase levels during arousal, the molecular signature of BAT remains highly similar to that of the torpid state. Furthermore, the core thermogenic gene UCP1 showed no significant expression differences across the three groups. In conclusion, this study systematically delineates the miRNA-mRNA regulatory landscape of bat BAT across the hibernation process, and deepens our understanding of the thermoregulatory mechanisms underlying mammalian hibernation.

BAT↗
PubMed2006

The relationship of plasma indicators of lipid metabolism and muscle damage to overnight temperature in winter-acclimatized small birds.

Plasma glycerol and triglyceride levels and creatine kinase (CK) activity may increase during long-distance flights in migratory birds, but plasma profiles of these metabolites have not previously been reported for small birds during thermoregulation in cold climates. We measured early morning levels of plasma glycerol, triglycerides and CK activity in four species of small birds overwintering in South Dakota, Junco hyemalis, Spizella arborea, Passer domesticus, and Carduelis tristis. We hypothesized that metabolite levels and CK activity might vary with overnight temperature (measured as the temperature just prior to dawn), with higher levels during colder temperatures which require elevated thermogenesis. Triglyceride and glycerol levels were not significantly related to temperature for any of the four species. Triglyceride levels were significantly positively associated with time since sunrise in J. hyemalis and C. tristis, and the time-temperature interaction was significant for S. arborea, suggesting rapid replacement of fat stores. Plasma glycerol levels were also significantly positively related to time since sunrise in J. hyemalis and C. tristis, but not in other species. Plasma CK activity showed a significant negative relationship to overnight temperature only for S. arborea. These results suggest that triglycerides do not comprise a major contribution to lipid supply during intense shivering in small birds. Similarly, intense shivering does not generally appear to result in muscle damage in small birds.

Acclimatization↗
PubMed2005

Sublingual misoprostol versus oxytocin infusion to reduce blood loss at cesarean section.

OBJECTIVE: To compare the effectiveness of sublingual misoprostol administered immediately after delivery of the neonate at cesarean section, with intravenous oxytocin infusion in prevention of uterine atony and thereby reducing blood loss at cesarean section. METHODS: One hundred women with singleton term pregnancy undergoing elective or emergency lower segment cesarean section under spinal anesthesia were included in this study. They were randomly allocated to receive either misoprostol 400 mug sublingually or intravenous infusion of 20 units of oxytocin soon after delivery of the neonate. The main outcome measures were blood loss at cesarean section, change in hemoglobin levels, need for additional oxytocics and drug related side effects. RESULTS: The mean blood loss estimated was significantly lower in misoprostol group compared to oxytocin group (819 ml versus 974 ml; p = 0.004). The number of women who had blood loss exceeding 500 ml and the change in hemoglobin, however, was comparable between the two groups. There was a need for additional oxytocic therapy in 16% and 18% after use of misoprostol and oxytocin respectively (p = 0.673). The incidence of side effects such as pyrexia, shivering and metallic taste was significantly higher in misoprostol group compared to oxytocin group. CONCLUSION: Sublingual misoprostol appears to be as effective as intravenous infusion of oxytocin in reducing blood loss at cesarean section. However, occurrence of transient side effects such as shivering and pyrexia were noted more frequently with the use of misoprostol.

Administration, Sublingual↗
PubMed2005

Fos activation in hypothalamic neurons during cold or warm exposure: projections to periaqueductal gray matter.

The hypothalamus, especially the preoptic area, plays a crucial role in thermoregulation, and our previous studies showed that the periaqueductal gray matter is important for transmitting efferent signals to thermoregulatory effectors in rats. Neurons responsible for skin vasodilation are located in the lateral portion of the rostral periaqueductal gray matter, and neurons that mediate non-shivering thermogenesis are located in the ventrolateral part of the caudal periaqueductal gray matter. We investigated the distribution of neurons in the rat hypothalamus that are activated by exposure to neutral (26 degrees C), warm (33 degrees C), or cold (10 degrees C) ambient temperature and project to the rostral periaqueductal gray matter or caudal periaqueductal gray matter, by using the immunohistochemical analysis of Fos and a retrograde tracer, cholera toxin-b. When cholera toxin-b was injected into the rostral periaqueductal gray matter, many double-labeled cells were observed in the median preoptic nucleus in warm-exposed rats, but few were seen in cold-exposed rats. On the other hand, when cholera toxin-b was injected into the caudal periaqueductal gray matter, many double-labeled cells were seen in a cell group extending from the dorsomedial nucleus through the dorsal hypothalamic area in cold-exposed rats but few were seen in warm-exposed rats. These results suggest that the rostral periaqueductal gray matter receives input from the median preoptic nucleus neurons activated by warm exposure, and the caudal periaqueductal gray matter receives input from neurons in the dorsomedial nucleus/dorsal hypothalamic area region activated by cold exposure. These efferent pathways provide a substrate for thermoregulatory skin vasomotor response and non-shivering thermogenesis, respectively.

Animals↗
PubMed2001

Misoprostol versus oxytocin in the third stage of labor.

OBJECTIVES: A double blind randomized controlled trial was performed at the tertiary hospital in Harare, Zimbabwe to compare oral misoprostol with intramuscular oxytocin in the management of third stage of labor. METHODS: A total of 499 women were randomized to receive either 400 microg misoprostol orally or 10 IU oxytocin intramuscularly. The incidences of postpartum hemorrhage and side effects were examined. RESULTS: The demographic and labor characteristics were comparable. Postpartum hemorrhage occurred in 15.2% of women given misoprostol and in 13.3% of those given oxytocin (P=0.534). Measured blood loss of more than 1000 ml occurred in 3.7% of the misoprostol group compared with 2% in the oxytocin group (P=0.237). There was no significant difference in the need for additional oxytocic drugs or blood transfusion in women given misoprostol (P values 0.137 and 0.600, respectively). Significant side effects of misoprostol were shivering [RR=1.32 (95% CI 1.11-1.58); P=0.002) and a rise in temperature [RR=2.02 (95% CI 1.75-2.33); P<0.001]. CONCLUSIONS: Oral misoprostol is as effective as intramuscular oxytocin in the prevention of PPH. Shivering and transient pyrexia were specific side effects of misoprostol. Misoprostol has potential in reducing the high incidence of PPH in developing countries.

Administration, Oral↗
PubMed2002

Systematic review of randomized controlled trials of misoprostol to prevent postpartum hemorrhage.

OBJECTIVE: To assess the effects of prophylactic misoprostol use in the third stage of labor compared with injectable uterotonics or placebo or no treatment. DATA SOURCES: The Cochrane Pregnancy and Childbirth Group trials register; the Cochrane Library, including databases such as the database of systematic reviews and the Cochrane Controlled Trials Register; and MEDLINE were searched. Researchers in the field were also contacted. The date of the latest search was March 1, 2002. METHODS OF STUDY SELECTION: Randomized trials comparing misoprostol with injectable oxytocin or oxytocin-ergot preparations to prevent postpartum hemorrhage or placebo/no treatment as active management of the third stage of labor were eligible for inclusion. Eligibility and trial quality were assessed following selected criteria. Data were extracted and analyzed using RevMan software. TABULATION, INTEGRATION, AND RESULTS: Sixteen randomized trials with a total of 28,138 women were considered. Data were available for 27,498 women. Oral misoprostol (600 microg) is less effective than injectable uterotonics in reducing blood loss at least 1000 mL (relative risk [RR] 1.36, 95% confidence interval [CI] 1.17, 1.58) and increases the use of additional uterotonics. Shivering and pyrexia (temperature greater than 38C) are the main side effects of misoprostol and are dose related. Compared with injectable uterotonics, the RR of "any shivering" with misoprostol (600 microg) is 3.27 (95% CI 3.01, 3.56) and pyrexia is 6.96 (95% CI 5.65, 8.57). The RR of blood loss of 500 mL or more is 1.11 (95% CI 0.87, 1.43) and the RR of use of additional uterotonics is 1.80 (1.13, 2.85) in the three trials (1441 women) comparing rectal misoprostol (400 microg) with injectable uterotonics. CONCLUSION: Injectable oxytocin or oxytocin-ergot preparations are more effective than misoprostol as part of the active management of the third stage of labor.

Administration, Oral↗
PubMed1998

Hypoxia inhibits cold-induced huddling in rat pups.

We asked to what extent hypoxia would modify the huddling behaviour of young rats during cold exposure. Sets of five animals (postnatal age 9+/-1 days) were placed at predetermined positions in a chamber maintained at approximately 33 degrees C (warm) or approximately 15 degrees C (cold), in normoxia or hypoxia (10% inspired O2), and their movements monitored for 30 min by a video camera. The surface areas (SA) of each individual pup (SAi) and of the whole set of pups (SAset) was measured every 5 min. In warm, the rats spread out, and both SAi and SAset were the greatest, whether in normoxia or hypoxia. In hypoxia, the total travelled distance (TTD) was much greater than in normoxia. In cold, during normoxia, SAi and SAset were decreased because of postural changes and huddling, and body temperature, measured at the end of the exposure, was also decreased. In hypoxic-cold, compared to normoxic-cold, fewer pups were in contact with one another, SAi and SAset did not decrease and the drop in body temperature was larger. Differently from hypoxia, hypercapnia (5% CO2) did not modify the responses observed during breathing air, whether in warm or cold conditions. We conclude that hypoxia, in addition to inhibiting shivering and non-shivering thermogenesis, can also limit behavioural thermogenesis, with the effect of further lowering body temperature.

Animals↗
PubMed1999

How newborn mammals cope with hypoxia.

The most immediate response to acute hypoxia in newborn mammals is hyperventilation, like in the adult. However. hyperventilation is often achieved by a reduction in metabolic rate (hypometabolism), rather than by an increase in ventilation (hyperpnea). This response is a regulated phenomenon largely based on inhibition of thermogenesis in all its forms, shivering, non-shivering and behavioural, with a resetting of the thermocontrol at a lower value of body temperature (Tb). Forcing Tb to the normoxic value in an hypoxic newborn can therefore provoke responses that are disadvantageous to the general strategy against hypoxia. The small or absent hyperpnea in the hypoxic newborn is the expected response to the decrease in metabolic rate; therefore, it should not be necessarily regarded as an expression of inadequate ventilatory control. However, during hypoxia the low metabolic rate can enhance the relative efficacy of inputs inhibitory on breathing, and this could be a mechanism contributing to ventilatory irregularities and apneas. The advantages of the hypometabolic strategy are numerous, and are at the basis of the extraordinary ability of newborn mammals to survive periods of severe hypoxia. The disadvantages become apparent with chronic hypoxia, because the reduced growth of tissues and organs may be incompatible with survival, or could lead to long-lasting structural and functional alterations.

Animals↗
PubMed1998

Differential recognition of MBP epitopes in BALB/c mice determines the site of inflammatory disease induction.

Although myelin basic protein (MBP)-recognizing T cells are not readily obtained after immunization of BALB/c mice with MBP (reflecting the BALB/c resistance to actively induced experimental autoimmune encephalomyelitis (EAE)), they can be expanded and cloned after several rounds of in vitro culture. The majority of BALB/c-derived clones recognize an epitope defined by MBP peptide 59-76. When transferred to naive BALB/c recipients, these clones cause classical EAE, with characteristic inflammation and demyelination of the central nervous system (CNS). We previously showed that two related clones recognizing a minor epitope, defined by MBP peptide 151-168, cause inflammation and demyelination preferentially of the peripheral nervous system (PNS). Because MBP has alternatively spliced isoforms, residues 151-168 are not present contiguously in all MBP isoforms. In order to determine whether induction of PNS disease is idiosyncratic to these sister clones, or related to their properties of epitope recognition, an independent T-cell line with similar recognition properties was studied. Clone 116F, derived from a BALB/c shiverer mouse, expresses a different T-cell receptor (TCR), with distinct TCR contact residues, but like the previously described T cells, this clone requires residues from both exons 6 and 7 for optimal stimulation. When adoptively transferred to BALB/c recipients, this clone preferentially induces disease of the PNS. A control BALB/c shiverer-derived MBP 59-76-recognizing clone, in contrast, induces CNS disease. These data strongly suggest that the site of disease initiation may correlate with epitope recognition, particularly when alternative isoforms are involved.

Alternative Splicing↗
PubMedDate not supplied

[Malignant hyperthermia during alcohol withdrawal].

Heat shock is the consequence of malignant hyperthermia triggered by general anaesthesia, the use of neuroleptic drugs, or strenuous muscular exercise. Chronic alcoholism could be a contributing factor by facilitating the triggering of malignant hyperthermia. We describe two cases of malignant hyperthermia which occurred during the summer in undernourished chronic alcoholics showing withdrawal syndrome during their stay in hospital. General anaesthesia and neuroleptics were excluded as the origin of their malignant hyperthermia, and we looked for new mechanisms to explain the heat shock, other than shivering associated with the withdrawal syndrome or the high temperature of the season. These two patients were considered deficient in thiamine on admission, their plasma pyruvic acid level being sharply increased (185 mumol/l and 304 mumol/l respectively; normal range: 45.6-91.2 mumol/l). This deficiency can lead to disregulation of thermal centres. Other metabolic disorders, frequently observed in alcoholics, could facilitate heat release during withdrawal syndrome shivering. The risk of heat shock during abrupt alcohol withdrawal should not be underestimated.

Adult↗
PubMed2000

Morphometric analysis of the myelin-associated oligodendrocytic basic protein-deficient mouse reveals a possible role for myelin-associated oligodendrocytic basic protein in regulating axonal diameter.

Myelin-associated oligodendrocytic basic protein is a member of the proteins constituting the central nervous system myelin. By morphometric analysis, we demonstrated that axons of myelin-associated oligodendrocytic basic protein-deficient mice had larger diameters and more myelin lamellae as compared to those of wild-type mice at the same age. It is known that the number of myelin lamellae increases linearly with axonal diameter, and that the rate of radial axonal growth is the factor controlling the rate of myelin formation. In line with these observations, we found that the regression line for axonal diameter and the number of myelin lamellae in myelin-associated oligodendrocytic basic protein-deficient mice appeared to be identical to that in wild-type mice, indicating that the increase in the number of myelin lamellae was the result of the increase in axonal diameter. Furthermore, we generated myelin basic protein/myelin-associated oligodendrocytic basic protein-double-deficient mice through mating myelin-associated oligodendrocytic basic protein-deficient mice with shiverer mice, an autosomal recessive mutant characterized by a lack of all isoforms of myelin basic protein. With these knock-out mice, we showed that axons of the double-deficient mice had larger diameters and smaller form factor, an index of the deformation of the fiber contour, in ensheathed fibers than those of shiverer mice, although there was no difference in axonal diameter of unmyelinated fibers between them. Taken together, myelin-associated oligodendrocytic basic protein seemed to play a role in controlling axonal diameter and in keeping axons round.

Animals↗
PubMed2000

Body temperature regulation in the rat.

In loosely-restrained adult conscious rats exposed to stepwise changes in ambient temperature (T(a)) from 25 to 5 degrees C or from 20 to 35 degrees C, we have recorded body and tail temperatures, metabolic rate (VO(2)), shivering and ventilation (V). It was found that VO(2) and V vary with T(a) and show a nadir for a T(a) of 30 degrees C whereas shivering starts at 20 degrees C and increases progressively with cold exposure. T(tail) follows changes in T(a) whereas T(body) decreases slightly in cold and increases markedly in warm exposure. These results suggest that the control of T(body) interacts with the control of breathing in order to increase VO(2) during cold exposure and to facilitate evaporative respiratory heat dissipation during warm exposure.

Journal Article↗
PubMed2002

Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the safety and feasibility of endovascular cooling during primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: In experimental models of AMI, mild systemic hypothermia has been shown to reduce metabolic demand and limit infarct size. METHODS: In a multi-center study, 42 patients with AMI (<6 h from symptom onset) were randomized to primary PCI with or without endovascular cooling (target core temperature 33 degrees C). Cooling was maintained for 3 h after reperfusion. Skin warming, oral buspirone, and intravenous meperidine were used to reduce the shivering threshold. The primary end point was major adverse cardiac events at 30 days. Infarct size at 30 days was measured using (99m)Tc-sestamibi SPECT imaging. RESULTS: Endovascular cooling was performed successfully in 20 patients (95%). All achieved a core temperature below 34 degrees C (mean target temperature 33.2 +/- 0.9 degrees C). The mean temperature at reperfusion was 34.7 +/- 0.9 degrees C. Cooling was well tolerated, with no hemodynamic instability or increase in arrhythmia. Nine patients experienced mild episodic shivering. Major adverse cardiac events occurred in 0% vs. 10% (p = NS) of treated versus control patients. The median infarct size was non-significantly smaller in patients who received cooling compared with the control group (2% vs. 8% of the left ventricle, p = 0.80). CONCLUSIONS: Endovascular cooling can be performed safely as an adjunct to primary PCI for AMI. Further clinical trials are required to determine whether induction of mild systemic hypothermia with endovascular cooling will limit infarct size in patients undergoing reperfusion therapy.

Adult↗
PubMed1998

Epidural analgesia in labour using intermittent doses determined by midwives.

Since 1985 midwives have been responsible for choice of drug and timing of epidural top-up doses for women in labour at Flinders Medical Centre. The midwife may choose from one of three different prescribed preparations, namely: bupivacaine 12.5 mg plus pethidine 25 mg, bupivacaine 25 mg, and bupivacaine 50 mg - each made up in a volume of 10 ml. This prospective study examined the incidence of adverse effects and level of patient satisfaction with midwife-managed epidural analgesia. Between 1987 and 1992, 6935 women received midwife-managed epidural analgesia. The pethidine/bupivacaine mixture was generally used for the first dose (75% of women) with a shift towards bupivacaine 25 mg or 50 mg for subsequent top-ups. Sixty-one per cent of women had normal vaginal deliveries, 25% instrumental and 14% caesarean deliveries. The most common side-effects were shivering, hypotension and itch. Shivering occurred following 11% of bupivacaine, and 2% of bupivacaine/pethidine top-ups. Itching was more common after bupivacaine/pethidine (3%) than after bupivacaine (1%). Women reported a high level of satisfaction with the overall experience of childbirth, though this was lower for instrumental and caesarean deliveries than for vaginal deliveries. On the other hand, satisfaction with pain relief provided by the epidural was greater in women who had caesarean or instrumental deliveries. The most commonly cited benefits of epidurals were good pain relief (83%), ability to cope (74%), feeling relaxed (67%), and being aware (60%), while feeling numb (23%) and experiencing severe pain at delivery (17%) were the most common causes of dissatisfaction.

Journal Article↗
PubMed1998

Elevation of plasma interleukin-6 level is involved in postoperative fever following major oral and maxillofacial surgery.

OBJECTIVE: The purpose of this study was to evaluate whether the changes in plasma cytokine levels including interleukin-6 (IL-6) interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) are involved in postoperative fever following oral and maxillofacial surgery. STUDY DESIGN: Ten patients undergoing elective oral and maxillofacial surgery were studied. We investigated the plasma cytokine levels by using an enzyme-linked immunosorbent assay and measured the core temperature and degree of postoperative shivering and peripheral vasoconstriction after surgery. The relationships between the changes in plasma cytokine levels and postoperative fever were statistically evaluated using Spearman's rank correlation coefficients. RESULTS: The elevation of plasma IL-6 level was significantly correlated with the increase in core temperature after surgery and with the degree of postoperative shivering and vasoconstriction, whereas the changes in plasma II-1 beta or TNF-alpha levels were not. CONCLUSIONS: Elevation of plasma IL-6 level is probably involved in postoperative fever following oral and maxillofacial surgery.

Aged↗
PubMed1997

Interaction between dextromethorphan and norpethidine in rats.

With increasing interest in the application of dextromethorphan in pain control, it is probable that patients will receive this drug in combination with analgesics such as opioids, giving rise to the potential for previously unobserved drug interactions. The interaction between dextromethorphan, and its pharmacologically active metabolite dextrorphan, and norpethidine, a toxic metabolite of pethidine, was examined in rats. Rats were assigned to receive dextromethorphan (0, 20 or 40 mg/kg) or dextrorphan (0, 15 or 30 mg/kg) combined with norpethidine (0, 28 or 42 mg/kg). The occurrence of seizures, myoclonic jerks and shivering was recorded for 60 min after drug administration. Norpethidine produced dose-related increases in the incidence of seizures, myoclonic jerks and shivering. Dextromethorphan, but not dextrorphan, increased the incidence of these behaviours. It is recommended that extreme caution be exercised if dextromethorphan and pethidine are to be used together.

Journal Article↗
PubMedDate not supplied

Patient-controlled epidural analgesia in labor: the addition of clonidine to bupivacaine-fentanyl.

BACKGROUND AND OBJECTIVES: Epidural clonidine has not been evaluated as a component of patient-controlled epidural analgesia (PCEA) solutions during labor. A randomized, double-blind trial was conducted to investigate the efficacy and side effects of PCEA using bupivacaine and fentanyl, with or without clonidine. METHODS: Seventy-five healthy parturients in active labor were assigned to a PCEA solution of 0.0625% bupivacaine and fentanyl 2 microg/mL (4 mL demand bolus, 15 min lockout), with or without clonidine 4.5 microg/mL. The primary outcome measure was parturient rating of analgesia; others assessments included pain scores, drug utilization, supplementation and side effects. RESULTS: Thirty-one parturients received clonidine (group BFC) and 38 received control solution (group BF). Eight (6 group BF, 2 group BFC, P = .28) failed to achieve satisfactory epidural analgesia. There was a trend for parturient ratings of pain relief to be higher in group BFC, with significantly more reporting excellent first-stage analgesia (81% v. 57%, P<.05). Pain scores were similar. Clonidine (median dose, 28 microg/h) reduced total bupivacaine and fentanyl use (P<.01), and reduced supplementation (P<.01). Maternal blood pressure (BP) and recordings of systolic BP below 100 mm Hg did not differ. Group BFC had higher sedation scores (P<.01), but no one appeared oversedated. Shivering was reduced in group BFC (P<.01). CONCLUSIONS: The addition of clonidine to epidural bupivacaine and fentanyl for PCEA in labor improved analgesia, reduced the supplementation rate, and reduced shivering. Increased sedation and lower BP were not clinically important.

Adjuvants, Anesthesia↗