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PubMed1990

Liver and brown fat mitochondrial response to cold in the garden dormouse (Eliomys quercinus).

The involvement of two organs, i.e. the liver and the brown adipose tissue (BAT) in response to cold in a hibernating species such as the garden dormouse has been studied. 2. In animals living in the cold, mitochondrial respiratory rates significantly increased (with respect to those living at 28 degrees C) in both organs with a larger increase in the BAT (+152% in the BAT and 67% in the liver). 3. The increase in BAT activity was obtained by a concomitant increase in: (a) the BAT mass (+30%), (b) the total mitochondrial mass (+20%), and (c) the mitochondrial respiratory rate (+64%). In the liver the increase was due only to an augmentation in mitochondrial mass and activity. 4. These results indicate that: (a) the BAT exerts a pre-eminent role in the physiological response to cold of garden dormouse, (b) a certain non-shivering thermogenesis (NST) is present in the liver of such species. In addition we suggest that a local thermoregulatory response would take place in a metabolically important organ such as the liver.

Acclimatization↗
PubMed1993

Effect of cold acclimation on oxidative capacity and respiratory properties of liver and muscle mitochondria in ducklings, Cairina moschata.

1. The effect of cold acclimation on the oxidative capacity of the skeletal muscle (gastrocnemius and pectoralis) and the liver of ducklings was investigated. 2. In cold-acclimated (CA) ducklings, the oxidative capacity of the liver was higher (+40%) than in ducklings reared at thermoneutraility (TN). In these animals an increase in state 4 respiration and a decrease in the respiratory control index (RCI) was also found. 3. The oxidative capacity of both pectoralis and gastrocnemius muscles also increased in CA animals. 4. In these muscles the oxidatibe capacity of the subsarcolemmal mitochrondrial fraction of CA ducklings was higher (+96% in the gastrocnemius and +58% in the pectoralis) than the intermyofibrillar one (+51% in the gastrocnemius and +33% in the pectoralis). No variations were observed in either the RCI or the ADP/O ratios. 5. These findings indicate that the energy expenditure needed for non-shivering thermogenesis (NST) in cold-acclimated ducklings can be met by the increase in the oxidative capacity of the skeletal muscle and the liver, each by different mechanisms; the gastrocnemius muscle would seem to play a prominent role.

Acclimatization↗
PubMed1994

Alpha-adrenergic receptor-mediated thermogenesis in brown adipose tissue of rat.

1. The present studies were undertaken to characterize the thermogenic response to the alpha 1-adrenergic agonist phenylephrine, to compare this response with the beta-adrenergic response and to assess the role of brown adipose tissue (BAT). 2. Phenylephrine and the beta 3-adrenergic agonist CGP 12177A each caused similar increases in O2 consumption. No synergism was observed when combining the two drugs. Phenylephrine stimulated O2 consumption via an alpha-adrenergic mechanism, as indicated by effective blockade with phenoxybenzamine, but not propranolol. 3. Further evidence for the alpha-adrenergic mechanism of phenylephrine action was seen in studies with BAT membranes. Phenylephrine did not stimulate adenylyl cyclase and did not potentiate beta-adrenergic stimulation of adenylyl cyclase. 4. Skeletal muscle was not a major site of phenylephrine-stimulated O2 consumption, as the response was not inhibited by a concentration of dantrolene which inhibited cold-induced muscle shivering. 5. Phenylephrine caused an increase in the density of available 3H-GDP binding sites in BAT mitochondria, indicating an activation of BAT thermogenesis in vivo. This increase was equal in magnitude to what we have reported previously for CGP-12177A. No changes were observed in the affinity for 3H-GDP. 6. We concluded that phenylephrine stimulates O2 consumption by an alpha-adrenergic mechanism that involves activation of BAT thermogenesis. It remains to be determined whether the activation of BAT occurs by a direct or indirect mechanism.

Adenylyl Cyclases↗
PubMedDate not supplied

Alterations in body temperature elicited by intrahypothalamic administration of tetrodotoxin, ouabain and A23187 ionophore in the conscious cat.

Ouabain, tetrodotoxin, and calcium selective ionophore (A23187) were administered bilaterally into the hypothalamus of the unrestrained, fully conscious cat, while body temperature and other indicators of thermoregulatory responses were monitored continuously. Posterior hypothalamic microinjection of 2.0 to 10.0 ng or tissue perfusion with 1.1 X 10(-7) to 1.1 X 10(-8) M ouabain elicited dose dependent increases in body temperature accompanied by pinnae vasoconstriction, shivering and postural changes consistent with heat conservation. Tetrodotoxin, microinjected in doses of 0.5 and 5.0 ng or tissue perfusions with 7.8 X 10(-9) to 7.8 X 10(-7) M in the posterior hypothalamus elicited dose dependent falls in body temperature. However, tetrodotoxin microinjected into the anterior hypothalamic region elicited only increases in temperature. The calcium selective ionophore, A23187, at least at the concentrations used in this study, did not appear to produce any consistent effects on thermoregulation. These data support the hypothesis that the ionic milieu of the posterior hypothalamic region is essential in the maintenance of body temperature. Further, they suggest that increasing the [Ca++]/[Na+] acts in a manner similar to a depression in the firing frequency of a distinct population of cells, which may in turn determine in some way the "set-point" for body temperature. There is no evidence to support the concept that increasing the [Ca++]/[Na+] causes an increased release of the synaptic contents of the region.

Animals↗
PubMed1985

Impaired diet-induced thermogenesis in brown adipose tissue from rats made obese with parasagittal hypothalamic knife-cuts.

Two experiments were performed to determine if bilateral parasagittal hypothalamic knife-cuts (KCs), which produce long-term overeating and obesity, after biochemical indices of brown adipose tissue (BAT) reactivity to thermogenic stimuli. In the first study, responses to environmental cold were tested. Four weeks after surgery, KC rats had gained 4-5 times more weight than controls and were obese (increased Lee Obesity Index and weight of gonadal white fat). Before being sacrificed, groups of KC and control rats were exposed to 4 degrees C for 21 hr or remained at 28 degrees C. Interscapular BAT weighed 300% more in KC rats, due largely to increased white fat content. Functional indices of BAT thermogenic capacity (protein content, DNA content, cytochrome oxidase activity and mitochondrial guanosine diphosphate (GDP) binding) were normal at 28 degrees C. Exposure to 4 degrees C produced greatly enhanced responses but these were equivalent for both groups. This suggested an intact capacity for non-shivering thermogenesis in obese KC rats. In the second study, the same BAT responses were examined in other rats fed a palatable "cafeteria" diet (CAFE). One week after surgery, KC and control rats were subdivided into groups that received chow alone or chow plus four different palatable foods daily. Before sacrificing 4-5 weeks later, KC rats had gained 3-4 times more weight than controls and were obese. Interscapular BAT weighed 200-300% more in KC rats. CAFE feeding produced larger increments in all variables for KC vs. control rats. Most importantly, GDP binding was reduced in both KC groups, and significantly more so after CAFE feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗
PubMed1987

Brown adipose tissue thermogenesis induced by low level electrical stimulation of hypothalamus in rats.

Brown adipose tissue (BAT) is an energy dissipating form of adipose tissue implicated in non-shivering thermogenesis as well as diet-induced thermogenesis. In the present study, in vivo interscapular BAT (IBAT) temperature was recorded prior to and following low level electrical stimulation (a 30 sec train of 60 Hz, 100 microA 0.5 msec isolated pulses) of various hypothalamic regions in rats. Significant increases in IBAT temperature were observed after stimulation of the anterior, medial preoptic, paraventricular and dorsomedial hypothalamus but not after stimulation of either ventromedial or caudal hypothalamus. For positive sites, IBAT temperature typically increased at 3-4 minutes following stimulation, peaked at 7-8 minutes after stimulation and declined at 20 minutes after stimulation. Although alterations in diet-induced thermogenesis have been reported after ventromedial hypothalamic lesions, the increases in BAT temperature noted in the present study suggest that inhibitory fibers that course through the paraventricular hypothalamus may form part of the central nervous system control of brown adipose tissue thermogenesis induced by overfeeding.

Adipose Tissue, Brown↗
PubMed1988

Lateral and medial hypothalamic lesions do not acutely affect brown adipose tissue thermogenesis.

The acute effect of lateral (LH) and medial (MH) hypothalamic lesions on mitochondrial GDP binding in brown adipose tissue (BAT) (an index of thermogenic state) was studied one and two days postlesion. Groups of rats were lesioned, sham-lesioned, or unoperated and were all fasting. An additional group of unoperated rats had access to food throughout the study. The objective was to determine whether the hypermetabolic state and rapid weight loss known to be induced by LH lesions were attributable to the activation of BAT thermogenesis, and, if so, whether these effects were specific for LH lesions. No effect of either lesion on BAT thermogenic state could be detected at either time studied. Despite that fact, LH-lesioned rats, but not MH-lesioned rats, were hyperthermic at both times. We conclude that the prolonged hyperthermia which occurs shortly after LH lesions is not due to an activation of BAT thermogenesis. Instead, it can be likened to the febrile state in which an initial and brief activation of both nonshivering thermogenesis in BAT and shivering thermogenesis in muscles occurs only during the rising phase of the fever and is suppressed as soon as a stable hyperthermic state is reached. It thus appears unlikely that substantial and prolonged activation of BAT thermogenesis is a major mechanism that promotes exaggerated short-term weight loss in the LH-lesioned rat.

Adipose Tissue, Brown↗
PubMedDate not supplied

The placenta, PGE2 and parturition.

It is proposed that prostaglandin E2 (PGE2), secreted by the fetal placenta of the sheep, acts as a circulating regulator of the physiological function of many fetal organs (tissue) in a way analogous to catecholamines in the adult. The specificity of PGE2 action in different tissues is determined by three different receptor subtypes which regulate intracellular calcium concentrations via the IP3 pathway, or cyclic AMP concentrations via the adenylcyclase system. The placenta, by secreting PGE2 (and possibly other factors such as adenosine), modifies the function of key organ systems allowing the fetus to survive and develop in the aqueous environment of the uterus. During fetal development, fetal organs and metabolic pathways can mature while their function is suppressed by placental PGE2. At birth, by ligating the cord and removing the placenta as the source of these inhibitory substances, the newborn is able to adapt readily to its new environment with fully-functional, mature organ systems. This paper discusses how placental PGE2 may regulate fetal breathing movements, whether the removal of placental PGE2 is involved in the initiation of continuous breathing at birth, and whether it suppresses the activity of the peripheral chemoreceptors during fetal life. The ability of PGE2 to maintain a widely patent ductus arteriosus, to suppress non-shivering thermogenesis, to stimulate fetal insulin secretion and to suppress the hepatic gluconeogenic pathway in the fetus is also discussed. Finally, the ability of PGE2 to activate the fetal hypothalamo-pituitary-adrenal axis is discussed, raising the possibility that the placenta also plays a key role in the initiation of birth in this species.

Animals↗
PubMed1994

The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease.

There is a new, potentially fatal disorder that is infrequently reported. The apparent rareness may be because of a lack of recognition of the syndrome or its predisposing factors. Fluoxetine (Prozac, Dista Products Co, Division of Eli Lilly Co, Indianapolis, IN), sertraline (Zoloft, Roerig Division, Pfizer Inc, New York, NY), and paroxetine (Paxil, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) belong to a new class of antidepressant medication: the serotonin reuptake-inhibitors (SRIs). The relative safety profile of the SRIs has led to their widespread use. However, a syndrome of excessive serotonergic activity, the "serotonin syndrome" (SS), has recently been recognized. It is characterized by changes in mental status, hypertension, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. A high index of suspicion is required to make the diagnosis in these acutely ill patients. The most common agents implicated in SS are the monoamine oxidase inhibitors in combination with L-tryptophan or fluoxetine. A case of a patient with significant peripheral vascular disease who developed SS while taking paroxetine and an over-the-counter cold medicine is reported. There have been no prior reports of this interaction. Discontinuation of the offending agents, sedation, and supportive care are the mainstays of treatment. The interactions of serotonin with platelets and vascular endothelium are also discussed.

Acetaminophen↗
PubMedDate not supplied

The electrocardiographic features of hypothermia.

Hypothermia results in the development of several characteristic electrocardiographic changes. As the core body temperature decreases, several changes in cardiac rhythm occur. Prolongation of the PR, QRS, and QT intervals are also seen. Muscle tremor artifact may be present, even in the absence of clinical shivering. A characteristic secondary deflection on the terminal portion of the QRS complex (Osborn wave) is usually found. All of these features are reversible with rewarming.

Arrhythmias, Cardiac↗
PubMed1993

Migration pathways, differentiation and survival of macroglial cells from a xenograft implanted into the thalamus of newborn mice.

Embryonic rabbit corpus callosum transplants were grafted into thalamus of newborn shiverer mice in order to compare the fates of oligodendroglial and astroglial cells derived from the transplants. Our model allowed the identification of the two populations of macroglial cells. The thalamus was chosen as site of implantation because of its situation at a crossroad of numerous neuronal fascicles. Previous studies, where the dorsal striatum was used as site of implantation, had shown that corpus callosum was one of the favorite routes of migration for both populations of macroglial cells. In the present study special attention was given to the comparison of the migration pathways and areas of settlement of implanted astroglia and oligodendroglia. The internal capsule, the medial lemniscus, the crus cerebri and the thalamic radiations were used by both populations of transplant derived macroglial cells for their migrations through the host parenchyma. They integrated into the host tissue on these routes or further away in areas such as the putamen, the mesencephalon or the colliculi. Signs of degeneration of the implanted astroglia were often observed after 1 month post-implantation.

Animals↗
PubMed1993

Transplantation of oligodendrocyte precursors in the adult demyelinated spinal cord: migration and remyelination.

A demyelinating lesion induced by an injection of lysolecithin into the spinal cord can be partly repaired by oligodendrocyte precursors transplanted at a distance of 6-8 mm from the lesion. Using a non-toxic fluorescent dye (Hoechst 33342) as a cell marker, we demonstrate that transplanted oligodendrocyte precursors from different origins (periventricular zone fragments from newborn mouse and cultured rat oligodendrocyte progenitor cells) can migrate along specific pathways (i.e. white matter fasciculi, ependymal wall, meninges and blood vessels). These cells can be attracted when passing at the vicinity of the lesion as well as differentiate and remyelinate axons with the lesion. Myelin repair thus appears to be the result of distinct successive events: migration, specific attraction, differentiation and myelination. This can occur in both shiverer and normal adult hosts.

Animals↗
PubMed1987

Differential production of endogenous pyrogen by human peripheral blood leucocytes following interaction with H3N2 or H1N1 influenza viruses of differing virulence.

Fever and other constitutional effects of influenza (headache, myalgia, listlessness, nausea, shivering, anorexia and depression) result from liberation of endogenous pyrogen (EP) from phagocytes. These effects are milder for recent H1N1 influenza virus isolates than for H3N2 strains. Interaction with human peripheral blood leucocytes in vitro showed that H1N1 strains, A/USSR/90/77 and A/Fiji/15899/83, elicited significantly less EP (as assessed by the rabbit pyrogen assay) than two virulent clones, 7a and 64c, of the A/Puerto Rico/8/34-A/England/939/69 (H3N2) reassortant virus system. Similar observations were made with UV-inactivated A/Fiji/15899/69 and clone 64c. These results are in accord with the differential severity of fever produced by these strains in ferrets when intranasally infected or intracardially inoculated with live and inactivated viruses. They show that influenza virus strains differ in capacity to induce EP from phagocytes. Furthermore, the observations with inactivated virus show that certain virion components are pyrogenic and differ in quantity or nature between strains. These results are important in relation to the differential severity of influenza epidemics and the reactogenicity of vaccine strains.

Animals↗
PubMed1992

Sufentanil: clinical use as postoperative analgesic--epidural/intrathecal route.

Although morphine and fentanyl remain the predominant epidural opioids, sufentanil offers some unique advantages. Because of its greater lipophilicity and mu-receptor binding capacity, sufentanil has a faster onset of action and longer duration than epidural fentanyl. Compared with morphine, sufentanil has been associated with a lower incidence of side effects, particularly delayed respiratory depression. The effective doses and adverse effects profile of epidural sufentanil are relatively well understood. Ventilatory depression is minimal with both bolus and continuous administration. Rapid vascular uptake after large epidural bolus, however, has been associated with acute-onset respiratory depression and even respiratory arrest. Sufentanil is more ideally suited than morphine to continuous epidural administration. The faster onset in comparison with fentanyl may make sufentanil the ideal agent for patient-controlled epidural analgesia. The synergistic effect of combined sufentanil and low-concentration bupivacaine offers advantages over sufentanil alone. High doses of epidural sufentanil have been uniquely associated with cessation of shivering and hypothermia. As with fentanyl, the intrathecal administration of sufentanil for postoperative analgesia is limited by its short duration of action.

Analgesia, Epidural↗
PubMed1992

Effect of infusion of a diarrheogenic dose of PGE2 on gastrointestinal electrical activity in the conscious piglet.

In 5 conscious piglets with electrodes implanted on the antrum pylori and small intestine, phasic and integrated electrical activity was daily recorded. PGE2, 10 micrograms/kg/min, was infused intravenously during 1.5 h and the induced changes in electrical activity were analyzed. Clinical appearance was also studied. PGE2 induced an inhibition in both antral and intestinal activity. In the antrum this inhibition was characterized by a decrease in the frequency of electrical control activity and fast oscillations, and an increase in the duration of the inhibitory phase. Small intestinal recordings revealed an increase in the quiescence phase for the duodenum and a decrease in the integrated total activity for the duodenum, jejunum and ileum, induced by a decrease in phase II activity. PGE2 was without influence on phase III activity and the recycling of the migrating myoelectrical complexes. All piglets developed a severe diarrhea. Vomiting, sedation, fever and shivering were observed in most animals. These data suggest that the diarrheogenic effect of PGE2 is not provoked by an increase in small intestinal motility. Moreover, the direct effect of this PG is a partial inhibition of gastrointestinal electrical activity.

Animals↗
PubMed2005

A pilot study: the Noninvasive Surface Cooling Thermoregulatory System for Mild Hypothermia Induction in Acute Myocardial Infarction (the NICAMI Study).

BACKGROUND: Hypothermia reduces metabolic demands, limits reperfusion injury, and helps salvage the injured myocardium during ST-elevation myocardial infarction (STEMI). The aim of this study was to assess early induction of noninvasive mild hypothermia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (PCI). METHODS: This was a safety and feasibility study of the Medivance Arctic Sun noninvasive thermoregulatory system (Medivance Inc, Louisville, Colo), used as adjunctive therapy in patients with first-time STEMI. Cooling was initiated by circulating chilled water through the Arctic Sun Energy Transfer Pads placed on the patient before primary PCI. Target temperature was 34.5 degrees C, maintained during 3 hours. Shivering was controlled with intravenous meperidine, and meperidine-related nausea was prevented with intravenous ondansetron. RESULTS: Nine patients underwent successful noninvasive surface cooling. All patients were Killip class I with a mean age of 62 years (8/9 males). Successful primary stenting was performed in all patients with glycoprotein inhibitors administered in 6 of 9 cases. Mean cooling time from induction to target temperature was 79 minutes (49 minutes in the last 4 enrolled cases). Mean total cooling duration was 267 minutes. Mean peak troponin T was 5.81 microg/L. Final TIMI flow grade 3 and final TIMI perfusion grade 3 were achieved in 9 of 9 patients and in 3 of 9 patients, respectively. Mean infarct size (by Myoview single photon emission computed tomography scans) was 23%. No hemodynamic or arrhythmic instability were documented. CONCLUSION: Mild hypothermia can be safely induced with noninvasive surface cooling in patients with STEMI undergoing primary PCI, allowing earlier myocardial protection before mechanical reperfusion therapy.

Angioplasty, Balloon, Coronary↗
PubMed2005

Prospective randomized clinical trial of inpatient cervical ripening with stepwise oral misoprostol vs vaginal misoprostol.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of stepwise oral misoprostol vs vaginal misoprostol for cervical ripening before induction of labor. STUDY DESIGN: Two hundred and four women between 32 to 42 weeks of gestation with an unfavorable cervix (Bishop score < or = 6) and an indication for labor induction were randomized to receive oral or vaginal misoprostol every 4 hours up to 4 doses. The oral misoprostol group received 50 microg initially followed by 100 microg in each subsequent dose. The vaginal group received 25 microg in each dose. The primary outcome was the interval from first misoprostol dose to delivery. Patient satisfaction and side effects were assessed by surveys completed after delivery. RESULTS: Ninety-three (45.6%) women received oral misoprostol; 111 (54.4%) received vaginal misoprostol. There was no difference in the average interval from the first dose of misoprostol to delivery in the oral (21.1 + 7.9 hrs) and vaginal (21.5 + 11.0 hrs, P = NS) misoprostol groups. The incidence of hyperstimulation in the oral group was 2.2% vs 5.4% in the vaginal group, P = NS. Eighteen patients in the oral group (19.4%) and 36 (32.4%) in the vaginal group underwent cesarean section (P < .05). This difference was attributed to better tolerance of more doses of misoprostol by the women in the oral group. There was no difference in side effects (nausea, vomiting, diarrhea, shivering) between groups. Fourteen percent of women in the vaginal group versus 7.5% in the oral group were dissatisfied with the use of misoprostol (P = NS). CONCLUSION: Stepwise oral misoprostol (50 microg followed by 100 microg) appears to be as effective as vaginal misoprostol (25 microg) for cervical ripening with a low incidence of hyperstimulation, no increase in side effects, a high rate of patient satisfaction, and is associated with a lower cesarean section rate.

Abortifacient Agents, Nonsteroidal↗
PubMed2005

A prospective, randomized comparison of vaginal misoprostol versus intra-amniotic prostaglandins for midtrimester termination of pregnancy.

OBJECTIVE: The purpose of this study was to compare the efficacy and adverse effects of vaginal misoprostol and intra-amniotic PGF2alpha for midtrimester abortion. STUDY DESIGN: One hundred thirty-two women between 12 and 24 weeks' gestation, seeking abortion in a tertiary hospital, were randomized to receive vaginal misoprostol (400 microg every 3 hours) or intra-amniotic PGF2alpha (carboprost 1.5 mg). Main outcome measures were induction-to-abortion interval, success rates at 24 and 48 hours, and adverse effects. RESULTS: Successful abortion rates at 24 and 48 hours between intra-amniotic PGF2alpha and vaginal misoprostol were not statistically different. However, vaginal misoprostol results in a significantly shorter mean induction-to-abortion interval, compared with intra-amniotic PGF2alpha (misoprostol: 16.2 hours; intra-amniotic PGF2alpha: 20.8 hours; P = .006), particularly among multiparous women (misoprostol: 13.1 hours; intra-amniotic PGF2alpha 18.3 hours; P = .011) and for gestation below 130 days (misoprostol: 14.6 hours; intra-amniotic PGF2alpha: 20.2 hours; P = .015). Fever and shivering were commoner with vaginal misoprostol. CONCLUSION: Vaginal misoprostol should be the regimen of choice for midtrimester abortion, particularly for multiparous women and women in the early second trimester.

Abortifacient Agents, Nonsteroidal↗