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PubMed1983

Effects of skin cooling and warming on stretch responses of the muscle spindle primary and secondary afferent fibers from the cat's tibialis anterior.

Fusimotor activation induced by thermal stimuli to the skin was investigated by recording the stretch responses of primary as well as secondary spindle afferent fibers from the tibialis anterior of the barbiturate-anesthetized, spinal cats. A standard ramp-and-hold stretch was repeatedly given during warming or cooling (20 to 40 degrees C) the skin of the ipsilateral foot pads. In each response of the spindle afferent fiber to stretch, the peak (P) and static firing rates (S) were measured and the dynamic index was calculated to assess the type of fusimotor fiber influence as dynamic or static. Of 47 primary spindle afferent fibers, 22 (46%) were affected by changes in skin temperature. Cooling of the skin below a certain temperature produced a marked increase in the dynamic sensitivity of their response to stretch, and this also occurred on warming above it. Such a "critical temperature" at which a directional relationship between skin temperature and muscle spindle activity was completely altered was determined (mean +/- SD: 35.10 +/- 1.66 degrees C, N = 7). However, a marked increase in static firing accompanied by a significant decrease in the dynamic index was observed at the dynamic phase of heating the skin beyond the critical temperature. None of the seven secondary afferent fibers studied showed a detectable temperature response. We conclude that the activation of primary spindle afferent fibers by thermal stimulation of the skin is to be attributed predominantly to activation of dynamic fusimotor neurons and is significant for the initiation of cold shivering.

Animals↗
PubMed1983

Effect of hypothalamic cooling on the tonic vibration reflex of gastrocnemius muscle in cats.

The tonic vibration reflex (TVR) in a medial gastrocnemius muscle (MG) was analyzed in 28 cats anesthetized with pentobarbital sodium while the preoptic-anterior hypothalamic region (PO-AH) was locally cooled or warmed in a thermoneutral environment. Cooling of the PO-AH did not produce shivering or changes in rectal and skin temperatures, but it brought about facilitation (16/28 cats) or inhibition (9/28) of the TVR in the MG. A few cats (3/28) showed inconsistent alteration of the TVR. Warming of the PO-AH did not produce any changes in the TVR of the MG. Histological identification of thermode placements revealed that in cats having the facilitatory response of the TVR, the thermodes were localized at regions caudal to A 14.0 mm and most of the thermodes in those having the inhibitory response were rostral to A 14.0 mm, except for two cases. Bilateral microinjection of a small quantity of anesthetic agent into the medial forebrain bundle (MFB) at the level of the mamillary body abolished the facilitatory effect of PO-AH cooling on the TVR. The results suggest that the spinal motor system is influenced by the PO-AH's sensitivity to local temperature and that the MFB constitutes part of the efferent pathway of the hypothalamic influence.

Animals↗
PubMed1993

A threshold membrane potential accounts for controversial effects of fatty acids on mitochondrial oxidative phosphorylation.

The uncoupling effect of free fatty acids on oxidative phosphorylation in mitochondria has been known for more than 35 years. The mechanism of action, however, remains controversial. In this report the physicochemical basis of uncoupling was elucidated by studying the effect of free fatty acids on the proton permeability and membrane potential of proteoliposomes containing reconstituted cytochrome c oxidase (COX). A threshold membrane potential of about 125 mV was identified for fatty acid-induced proton permeability. Only above this potential do free fatty acids translocate protons across the biological membrane. The data explain the controversial effects of long-chain fatty acids on oxidative phosphorylation as well as their role on non-shivering thermogenesis in larger mammals.

Adipose Tissue↗
PubMed1983

Fatty acid activation in the brains of neurologically mutant mice.

1. Palmitoyl-CoA synthetase activity was assayed in subfractions of control and Quaking, Jimpy, Shiverer and Trembler mouse brain. 2. Mouse brain palmitoyl-CoA synthetase activity is not altered during myelination. 3. Mouse brain enzyme activity (homogenate 1.5 +/- 0.3 nmol palmitoyl carnitine/min/per mg protein crude mitochondria 0.6 +/- 0.1 nmol/min/per mg protein and microsomes 1.9 +/- 0.3 nmol/min/per mg protein) does not differ markedly from rat and rabbit brain activity. 4. The lesions of the above mutants which affect myelination and lipid synthesis do not include the enzyme palmitoyl-CoA synthetase.

Animals↗
PubMed1982

Characteristics of diet-induced brown adipose tissue growth and thermogenesis in rats.

The characteristics of regional brown (BAT) and white adipose tissue (WAT) growth and of thermogenesis following experimental overfeeding were studied in groups of male Sprague-Dawley rats fed lab chow or cafeteria diets for 8 weeks postweaning. Regional BAT and WAT growth was determined by dissection and weighing, and thermogenesis was characterized by measurements of resting and norepinephrine (NE)-stimulated oxygen consumption, of serum thyroid hormone concentrations, and of 24-hour urinary NE excretion levels. Cafeteria feeding resulted in a 113% increase in total BAT, with the most prominent increases in the interscapular, thoracic, and perirenal regions. Retroperitoneal, epididymal, and omental WAT were significantly greater in cafeteria than in chow-fed rats. Resting oxygen consumption of cafeteria-fed rads increased by 10% and NE excretion by 64% compared to chow-fed controls, while serum T3 concentrations were nearly doubled in the cafeteria-fed rats. The thermogenic response to NE injection in cafeteria-fed rats was 102% of their resting levels, compared to a 51% increase in the chow-fed controls. The results indicate that increased BAT growth occurs in all primary BAT depots following cafeteria-feeding in rats, and that the greater BAT mass is qualitatively proportional to their greater capacity for non-shivering thermogenesis. Also, the increased NE excretion and greater serum T3 concentration are consistent with increased sympathetic and thyroidal activity and may in part explain the thermogenic response to diet in the rat.

Adipose Tissue↗
PubMed1977

Metabolic and endocrine studies in a case of lipoatrophic diabetes.

A 20-yr-old female with congenital lipoatrophic diabetes was studied, with the following findings: (1) Serum insulin levels increased after both oral glucose and intravenous arginine administration; there was no growth hormone response to the latter. (2) The infusion of insulin (0.1 units and 0.5 units/kg) during the fed state and following at 110-hr fast produced only minimal changes of various fuels measured, with the exception of a decrease in the branched-chain amino acids. (3) There was a minimal production of ketones during the 110-hr fast. (4) Matabolic expenditure was markedly increased during the postabsorptive state (65-75 kcal/hr/sg m); it fell into the normal range during the 110-hr fast (31-35 kcal/hr/sq m). (5) Following meals, the patient experienced complaints ranging from cold and shivering to feeling hot with gross diaphoresis. These findings were associated with intermittent lability of her skin temperature, which varied 1 degree - 2 degrees F during a 3-hr period. (6) Progressive increases in doses of regular insulin before each meal resulted in up to a total of 9000 units/day being required before normal blood glucose levels were achieved. (7) A 2-wk therapeutic trial of pimozide provided no significant changes in a variety of hormones and fuels in the basal state or following insulin perturbations. (8) A variety of pituitary hormones and pituitary target organ hormones were studied in both the hypothyroid (Hashimoto's thyroiditis) and euthyroid state (following thyroid replacement). All the hormone responses were normal except that growth hormone did not rise during the slow wave sleep in either thyroid state.

Adult↗
PubMed1982

Histamine-induced rise in core temperature of chloral-anaesthetized rats: mediation by H2-receptors located in the preopticus area of hypothalamus.

Intracerebroventricular (i.c.v.) administration of histamine in chloral anaesthetized rats exposed to an ambient temperature of 22 C elicited a rise in their colonic temperature associated with a shivering. This effect was shared by the H2 receptor agonists dimaprit and impromidine. Impromidine is, in this respect, a partial agonist with an ED50 much lower than histamine. The histamine-induced rise in core temperature was antagonized by cimetidine administered either centrally (in doses of 25-40 micrograms, i.c.v.) or peripherally (large doses greater than or equal to 50 mg/kg i.p.) This constitutes an indication for the crossing of the blood-brain barrier by cimetidine. The H2 histamine receptors involved in this effect seem to be located mainly in the preopticus medialis nucleus (p.o.m.n.) of the hypothalamus since bilateral microinjections of histamine (5 ng) into this nucleus induced the effect, whereas cimetidine injected into the p.o.m.n., antagonised the relative hyperthermia elicited by an intracerebroventricular administration of histamine.

Animals↗
PubMed1985

Hypothalamic modulation of energy expenditure.

The acute effects of electrical stimulation of the hypothalamus on energy expenditure as measured by indirect calorimetry were investigated in 20 unanaesthetized rats. Thirty sec of stimulation increased both O2 consumption and respiratory quotient (R.Q.). The largest magnitude hypermetabolic response (39% mean peak increase in O2 consumption) was produced by stimulation of the ventromedial hypothalamic nucleus. Stimulation of the lateral hypothalamus produced hypermetabolic effects similar to but smaller than those produced by medial stimulation. A number of considerations suggest that the hypermetabolism is not secondary to changes in motor activity, carbohydrate utilization or blood glucose levels. Consequently, these data suggest that the hypothalamus modulates energy expenditure through changes in non-shivering thermogenesis. These metabolic changes may modulate the effects of various hypothalamic manipulations on body weight.

Animals↗
PubMed1987

Behavioral correlates of hippocampal type 2 theta in the rat.

Previous research has indicated that there are two types of theta activity which can be recorded from the hippocampus in most rodents. One type (type 1) of theta is correlated with voluntary movements while the second (type 2) occurs during immobility. A third waveform termed LIA (Large Amplitude Irregular Activity) occurs during more automatic behaviors, e.g., grooming, shivering or immobility. In the rabbit and guinea pig type 2 theta can readily be elicited in unrestrained animals. However, type 2 theta is rarely seen in the unrestrained rat. The purpose of the present study was to determine the stimulus conditions that are necessary for the elicitation of type 2 theta in the rat. In the present study 20 unrestrained rats were observed in the presence of a cat or a ferret. Movements by the cat or ferret produced theta in immobile rats. Sensory stimuli which did not ordinarily produce type 2 theta would reliably do so in the presence of the cat or ferret. It is hypothesized that type 2 theta in the unrestrained immobile rat occurs during sensory processing but only when the animal is in a high state of "arousal."

Acoustic Stimulation↗
PubMed1982

Effect of temperature on the ventilatory response curve to carbon dioxide in anaesthetized cats.

Effects of body temperature on the ventilatory control system were studied in 17 anaesthetized cats. At different body temperatures (stabilized within 0.1 degrees C) CO2 response curves were measured in each cat. In with chloralose-urethan anaesthetized cats it was found that in the body temperature range of 34-40 degrees C, in which neither shivering nor panting occurred, no statistically significant trend with temperature was found in the slope (S) and the extrapolated intercept on the PaCO2-axis (B) of the linear CO2 response curve during hyperoxia as well as hypoxia. In two with pentobarbital anaesthetized cats similar results were obtained. The resting ventilation (at FICO2 = 0) did not change significantly, while the resting PaCO2 during hyperoxia showed a trend to increase with temperature just reaching the level of significance (P less than 0.05). Breathing frequency increased significantly with temperature (P less than 0.0005). When body temperature was elevated above 41 degrees C both the slope (S) and the intercept of the CO2 response curve (B) decreased. In three cats ventriculo-cisternal perfusion was performed and no apparent influence of body temperature was found on the relation between the PCSFCO2 and PETCO2 and on the VE-PCSFCO2 response curves. These findings show that body temperature has no important modifying effect on the ventilatory response to CO2 in anaesthetized cats in the temperature range of 34-40 degrees C.

Anesthesia, General↗
PubMedDate not supplied

Accumulation of brown adipose tissue in patients with Chagas heart disease.

Brown adipose tissue (BAT) is an important source of non-shivering thermogenesis. Increased BAT amounts have been reported to occur in association with several diseases, including congestive heart failure. The objective of the present study was to determine whether BAT accumulation occurs in patients with Chagas disease. Histological sections of peri-adrenal tissue obtained at autopsy from 259 patients were examined. Of these patients, 58 had the digestive form of Chagas disease, 50 had the cardiac form without heart failure and 201 had the cardiac form with heart failure. All cases were investigated in terms of nutritional status and classified as malnourished, normotrophic or obese according to the Quetelet index. The results showed no correlation between BAT and the patients' nutritional status, and more BAT accumulation in patients with the cardiac form of Chagas disease compared to patients with the digestive form. Similarly, a history of heart failure was correlated with greater BAT accumulation. On the basis of the present data and of information reported in the literature, we propose that chronic hypoxia may be the cause of BAT accumulation in Chagas disease patients with heart failure.

Adipose Tissue, Brown↗
PubMed1994

Quantitative evaluations of gap junctions in old rat brown adipose tissue after cold acclimation: a freeze-fracture and ultra-structural study.

The morphological and functional modifications of brown adipose tissue (BAT), the tissue responsible for non-shivering thermogenesis, are well established during the phases of active stimulation (i.e. neonatal period and cold acclimation) in young animals. The 'active' brown adipocytes are filled with numerous small lipid vacuoles and large mitochondria packed with cristae rich in the protonophore uncoupling protein (UCP), whereas the 'quiescent' cell shows larger, confluent vacuoles and smaller mitochondria with rarefied cristae poor of the uncoupling protein. It is well known from literature that also gap junctions (gjs), responsible for the electrical coupling among adjacent adipocytes, modify their size following the physiological stimulus in young animals. This is in agreement with the morphology of the functionally active brown adipocyte, i.e. the multilocular, UCP-positive cell. Although the presence of the BAT in old animals is well documented, less is known about its reactivity to physiological stimuli. The present work demonstrates that after cold acclimation brown adipocytes of old rats (2 years) change their ultrastructure in a similar way as in young rats. A quantitative analysis of gap junction areas on replicas obtained by the freeze fracture technique, showed that gj increase in size (mean area 53.2 vs 110.4 x 10(-3) microns2, p = 0.003). All these morphological modifications are quite similar to those observed in BAT of young and young adult rats, supporting the hypothesis of a physiological role of brown adipose tissue at every age.

Acclimatization↗
PubMed1977

Cervical dilatation with 16,16 dimethyl PGE2 p-benzaldehyde semicarbazone ester prior to vacuum aspiration in first trimester nulliparae.

The efficacy of 16,16 dimethyl PGE2 p-benzaldehyde semicarbazone ester for cervical dilatation prior to evacuation of the uterus in 180 first trimester nulliparae has been studied. The drug was injected into the muscle of the cervix 3 hours before vacuum aspiration. In 143 patients (80%) the cervix had dilated adequately to enable evacuation of the uterus without mechanical dilatation. In the remaining 37 patients (20%) the cervix had dilated to 6 or 7 mm and additional mechanical dilatation could be performed easily in most of these patients. Side effects consisted of vomiting (11%), diarrhoea (7%), transient pyrexia and shivering (7%). There were no complications in any of the patients and no perforation of the uterus or damage to the cervix resulted during evacuation.

Abortion, Induced↗
PubMed1982

Termination of second trimester pregnancy with laminaria and intramuscular 16 phenoxy-omega-17, 18, 19, 20 tetranor PGE2 methylsulfonylamide (sulprostone)-A randomised study.

16 phenoxy-omega-17, 18, 19, 20 tetranor PGE2 methylsulfonylamide (Sulprostone) was used for termination of second trimester pregnancy in four groups of 30 patients. The drug was administered in intramuscular doses of either 0.5 mg four hourly or 1.0 mg 8 hourly. In two groups of 30 patients a medium size sterile laminaria was inserted into the cervical canal eight hours before the start of prostaglandin treatment. In the group treated with 1.0 mg sulprostone eight hourly, 96.7% of those with laminaria and 86.7% without laminaria aborted in respective mean times of 11.2 hrs and 17.5 hrs. All 30 patients (100%) in the laminaria group treated with 0.5 mg sulprostone four hourly aborted within 30 hours in a mean time of 10.4 hours compared with 26 patients (86.7%) in a mean time of 16.7 hours in the group without laminaria. One patient receiving 0.5 mg sulprostone four hourly (no laminaria) sustained a cervical tear requiring repair. The incidence of nausea, vomiting, diarrhoea, cold and shivering was low an similar in the four groups.

Abortifacient Agents↗
PubMed1991

Dissociation of hyperthermic and hyperglycemic effects of central prostaglandin F2 alpha.

We previously reported that intraventricular prostaglandins (PGs) produced hyperthermia and hyperglycemia in anesthetized rats. However, the relationship of them is little known. We examined the relationship between hyperthermia and hyperglycemia induced by intraventricular PGF2 alpha using curarized and adrenal demedullated rats. Iv curare completely prevented the PGF2 alpha-induced hyperthermia, but enhanced the hyperglycemic effect of PGF2 alpha. Adrenal demedullation completely prevented the hyperglycemia, but did not affect the hyperthermic effect of PGF2 alpha. To further assess the site of action concerned with PGF2 alpha-induced thermoregulation and glucoregulation in the central nervous system (CNS), we injected saline or PGF2 alpha into the preoptic area of the anterior hypothalamus (POA) in intact rats. After microinjection of PGF2 alpha into the POA, the rectal temperature rose, but the plasma glucose level did not increase significantly, as compared with saline-treated control rats. These results suggest that PGF2 alpha causes the central nervous system to produce hyperthermia via shivering, stimulated the somatic motor system, and to produce hyperglycemia by stimulating central sympathetic outflow to the adrenal medulla, but these operate independently under different neural regulation, and these sensitive sites are organically dissociated in the CNS.

Adrenal Medulla↗
PubMed1989

Colchicine lesions of ventromedial hypothalamus: effects on regulatory thermogenesis in the rat.

Experiments were carried out to test whether the ventromedial hypothalamus (VMH) is the site of a pathway that stimulates thermoregulatory heat production in brown adipose tissue (BAT). Adult Sprague-Dawley rats received bilateral 50 nl microinjections of colchicine solution into the VMH (0.1, 0.32, 1.0 or 3.2 micrograms per side). Beginning a day later, hyperphagia developed consistently with 0.32 microgram colchicine; and with higher doses there appeared the additional effect that for several days rats developed hypothermia when placed temporarily at 6 degrees C. The degree of hypothermia was limited by activation of nonshivering thermogenesis (NST) in BAT, as evidenced by increased shivering after propranolol injection to block NST, and by increased GDP binding measured in IBAT mitochondria after cold exposure. The findings suggest that chemical lesioning to induce the VMH hyperphagia syndrome does not produce an obligatory impairment of thermoregulation against cold unless the dose of neurotoxin and lesion area extends beyond that which underlies the overeating response. Furthermore, when tolerance to cold is thus compromised, the effect is not readily explained in terms of simply disconnecting a proposed stimulatory pathway from the VMH to BAT.

Animals↗
PubMed1992

Decrease in cold tolerance of aged rats caused by the enhanced endogenous adenosine activity.

During severe cold exposure, old rats (24-28 months) were less capable of maintaining their body temperature compared to young rats (3-6 months) due to lower rate of heat production. Single injection of adenosine deaminase (AD) (converts adenosine to inosine) significantly increased thermogenesis in both young and old rats. However, doubling the dose of AD was required for optimal thermogenic response in old rats. In contrast, the similar enhancements in both thermogenesis and cold tolerance were observed in both young and old rats receiving the same optimal doses of specific adenosine receptor antagonists. These results lead to the suggestion that the lower capability of aged rats to withstand cold exposure could be due to an increase in adenosine stimulation because of the decreased endogenous AD activity rather than an increase in adenosine receptor sensitivity. This notion is further supported by the finding that the AD activity in the neck muscle, a key site for shivering thermogenesis, was significantly lower in old rats as compared to their younger counterparts before and after cold exposure.

Adenosine↗
PubMed1983

Effects of ethanol on thermoregulation.

Clinical reports of accidental hypothermia in alcohol intoxicated individuals exposed to low ambient temperature ( Paton , 1983) have generally been borne out by experimental studies in healthy volunteers. Small doses of ethanol, given to human subjects at normal ambient temperature (Ta), have very little effect on body temperature but a combination of large dose, low Ta and vasodilatation provoked by strenuous exercise, causes a sharp fall in rectal temperature. In experimental animals, the use of relatively larger doses of alcohol and more extreme temperatures, both above and below the thermoneutral zone, has shown that the effect of ethanol is essentially poikilothermic, i.e. an impairment of adaptation to both heat and cold. This effect has been studied in greater detail, in relation to each of the basic thermoregulatory processes. Though small doses of alcohol may increase the metabolic rate under some circumstances, the most common effect at low Ta is inhibition of shivering and therefore reduction of thermogenesis. At the same time it tends to cause increased heat loss by cutaneous vasodilatation. This makes for a greater feeling of comfort in the cold exposed subjects but increases in rate of fall of core temperature. The combination of decreased thermogenesis and increased heat loss, despite falling body temperature, is suggestive of a lowering of the set-point of the thermoregulatory control mechanisms. Consistent with this is a slight increase in ventilatory heat loss after low doses of ethanol but larger doses cause respiratory depression, so that heat loss through the lungs is minor. However, at high Ta ethanol caused hyperthermia in experimental animals and shows enhanced lethality, so that impairment of thermoregulatory effector mechanisms seems to be at least as important as change in set-point. Studies of the effects of ethanol on electrophysiological activity of single neurons in the pre-optic area and anterior hypothalamus (POAH), biochemical activities of neuronal membranes, hypothalamic blood flow, conventional neurotransmitters, amino acid putative neurotransmitters, neuropeptides, prostaglandins and inorganic ions have all failed so far to yield a clear comprehensive picture of the mechanisms by which ethanol affects thermoregulation. In each case, contradictory evidence has been obtained concerning the consequences of ethanol administration, whether by oral, intraperitoneal, intravenous, intracerebroventricular, or direct local (POAH) route.(ABSTRACT TRUNCATED AT 400 WORDS)

Alcoholism↗