Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some stroke patients suffering acute middle cerebral artery (MCA) infarction develop massive brain edema and herniation, a condition known as malignant MCA infarction. Severe swelling increases intracranial pressure (ICP) and leads to progressive brainstem dysfunction. Once ICP reaches critical values (>30 mm Hg) herniation occurs, usually within 2 to 5 days. Patients rarely survive (80% mortality) with standard treatment, and those who do are often severely disabled. Malignant MCA infarction is often missed by neurologists, despite well-defined clinical and neuroimaging (CT scan) diagnostic criteria. After diagnosis, conventional treatments such as osmotherapy, barbiturates, buffers, and hyperventilation center on reducing ICP. The goal of hyperosmolar therapy is to increase the serum osmolarity to approximately 315-320 mOsm/L. Enteric glycerol is used routinely to reduce ICP. In more severe cases and when glycerol fails, mannitol may be administered. Other therapies are also available, including hypertonic saline solution, THAM (Tris-hydroxy-methyl-aminomethane) buffer, and high-dose barbiturates. Hyperventilation also helps reduce ICP. All measures work effectively for a short time only. Other approaches to control elevated ICP, including decompression surgery and hypothermia, have shown promising results. In the Heidelberg decompression surgery trial, mortality in surgically treated patients was significantly lower (32%) than in non-treated patients (76%) despite conventional treatment. Importantly, of the surviving treated patients, 66% were rated independent with only mild to moderate disability. Moderate hypothermia (33-36 degrees C) has recently been shown to be effective in severe MCA infarction. Hypothermia induction within 14 hours of ischemic injury and maintained for 72 hours significantly reduced ICP and mortality (44%).
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PMID:Treatment options for large hemispheric stroke. 1155 58

According to the statistics compiled by the Institute for Traffic Accident Research and Data Analysis, the total number of head trauma patients has stayed virtually the same for the last 10 years in Japan, although a fraction of people suffering minor head trauma has shown a trend to increase. The Japan Society of Neurotraumatology is in the process of establishing a guideline for head trauma management. No major difference is noted in surgical procedures selected by neurosurgeons in Japan as compared to those in other countries. It appears, however, that the ventriculostomy may be less frequently employed to control elevated intracranial pressure, and the jugular bulb venous oximetry is far more frequently employed to detect cerebral deoxygenation in Japan. There appear to be two obvious differences in selection of pharmacological therapies among neurosurgeons in Japan and those in other countries; neurosurgeons in Japan prefer glycerol to mannitol for osmotic control of intracranial pressure, and barbiturate to morphine as sedatives. Two drugs are currently available in Japan for promoting the recovery from disturbance of consciousness after head trauma: cytidine diphosphate choline (CDP)-choline (Nicholin, Takeda Chemical Industries, Ltd., Osaka) and protirelin tartrate (Hirtonin; thyrotropinreleasing hormone (TRH) analogue, Takeda). Another TRH analogue, NS-3 (montirelin hydrate), is currently submitted to the Ministry of Health and Welfare for approval. A multi-institutional controlled study to examine the efficacy of therapeutic hypothermia for head trauma management is now in progress in Japan. The Japan Neurotrauma Data Bank System was inaugurated 2 years ago, enabling joint statistical processing at 10 major neurotrauma centers. Utilizing such a system, more detailed analysis of head trauma management will be possible, and clinical trials will be conducted systematically and more promptly in future.
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PMID:Neurosurgical trauma in Japan. 1157 59

The first endocannabinoid, anandamide, was discovered in 1992. Since then, two other endocannabinoid agonists have been identified, 2-arachidonyl glycerol and, more recently, noladin ether. Here, we report the identification and pharmacological characterization of a novel endocannabinoid, virodhamine, with antagonist properties at the CB1 cannabinoid receptor. Virodhamine is arachidonic acid and ethanolamine joined by an ester linkage. Concentrations of virodhamine measured by liquid chromatography atmospheric pressure chemical ionization-tandem mass spectrometry in rat brain and human hippocampus were similar to anandamide. In peripheral tissues that express the CB2 cannabinoid receptor, virodhamine concentrations were 2- to 9-fold higher than anandamide. In contrast to previously described endocannabinoids, virodhamine was a partial agonist with in vivo antagonist activity at the CB1 receptor. However, at the CB2 receptor, virodhamine acted as a full agonist. Transport of [(14)C]anandamide by RBL-2H3 cells was inhibited by virodhamine. Virodhamine produced hypothermia in the mouse and acted as an antagonist in the presence of anandamide both in vivo and in vitro. As a potential endogenous antagonist at the CB1 receptor, virodhamine adds a new form of regulation to the endocannabinoid system.
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PMID:Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. 1202 33

The aim of this study was to monitor the metabolism and blood flow in the interstitium of the skeletal muscle during cardiac surgery with cardiopulmonary bypass (CPB) and in the early postoperative period by means of microdialysis and to compare metabolic changes during CPB at normothermia (NT) and hypothermia (HT). Surgical revascularization using CPB was performed in 50 patients, 25 patients (group HT) were operated using hypothermic CPB, 25 (group NT) using normothermic CPB. Interstitial microdialysis was performed by two CMA 60 probes (CMA Microdialysis AB, Solna, Sweden) inserted into the patient's deltoid muscle. Constituents analysed in the obtained dialysates, collected at intervals, were glucose, urea, glycerol and lactate. Tissue blood flow was monitored by dynamic microdialysis with gentamicin as a marker. In both groups, NT versus HT, similar dynamics of concentrations were found. Low initial concentrations were followed by gradual increases during CPB and in the following phase of the operation. Concentrations were higher in the NT group. Immediately after the operation, the decrease in values continued, with a gradual increase in the succeeding postoperative period in both groups. Similar dynamic changes in the lactate concentration were found in both groups. The gentamicin concentrations were lower in the NT group (versus the HT group). The results showed dynamic changes in the interstitial concentrations of glucose, urea, glycerol and lactate, which depend on the phase of the surgery in the CPB and early postoperative phase in the both groups of patients. Higher tissue perfusion of the skeletal muscle was noted in those patients operated on in normothermia. The dynamics of the concentration changes of these substances in the interstitium of the skeletal muscle has been proven to be caused by both the metabolic activity of the tissue and by the blood flow through the interstitium of the muscle.
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PMID:Changes in metabolism and blood flow in peripheral tissue (skeletal muscle) during cardiac surgery with cardiopulmonary bypass: the biochemical microdialysis study. 1507 56

1. The present study was carried out to explain the resistance of rats injected subcutaneously with risperidone, the atypical antipsychotic drug, for 21 consecutive days at 0.1 mg/kg per day (a dose equivalent to the one used for patients) to result in an excessive bodyweight despite the increase in diet-uptake in rats against risperidone-induced decrease in body temperature. 2. Rectal temperature measurements were made in 8-week-old male Sprague-Dawley rats maintained under standard laboratory conditions using a 12 h daylight cycle. A s.c. injection of risperidone (0.05 mg/kg) produced hypothermia in rats, which was observed during the daily injection for 21 consecutive days. 3. Sera, white and brown adipose tissues, skeletal muscle and liver were extracted from 8-week-old male Sprague-Dawley rats injected subcutaneously with risperidone (0.01 or 0.1 mg/kg per day) or a vehicle for 21 consecutive days. Serum levels of lipids, ketones and thyroid hormone were measured. The mRNA expression levels in these tissues and organs of the genes encoding the substances involved in heat production and/or lipid metabolism were investigated by using quantitative real-time polymerase chain reaction amplification. 4. Serum nonesterified fatty acid levels in risperidone 0.1 mg/kg per day s.c. injected rats were significantly lower than those in vehicle-injected ones. Serum beta-hydroxybutyrate levels in risperidone-injected rats tended to decrease compared with those in vehicle-injected ones. The serum level of neither triiodothyronine nor thyroxine was affected by risperidone s.c. injection at the doses examined, although their values were within normal limits. 5. Risperidone injection (0.1 mg/kg per day) for 21 consecutive days upregulated mRNA expressions in white adipose tissue of uncoupling protein 3 which dissipates energy as heat; peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha which activates mitochondrial biogenesis to expand the oxidative machinery; and PPARalpha which is necessary for the fat-depletion of adipocytes for thermogenesis. The mRNA of lipogenic enzymes (acetyl-CoA carboxylase alpha, fatty-acid synthase and glycerol-3-phosphate acyltransferase), hormone sensitive lipase and beta1-adrenoceptor were also enhanced in white adipose tissue by the injection of 0.1 mg/kg per day risperidone. 6. These findings suggest that the materials for heat generation in white adipose tissue would be readily supplied, which in turn would reduce a storage of lipids in white adipose tissue resulting in the lower rate of bodyweight gain of rats.
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PMID:Resistance to excessive bodyweight gain in risperidone-injected rats. 1581 Sep 92

The present study was conducted to assess whether Premarin, a water-soluble estrogen sulfate, can act via estrogen receptors (ERs) to rescue mice from heat-induced lethality. Unanesthetized, unrestrained mice were exposed to ambient temperature of 42.4 degrees C to induce heatstroke (HS). Another group of mice was exposed to room temperature (24 degrees C) and used as normothermic controls. They were given isotonic sodium chloride solution, Premarin (0.1 - 1.0 mg/kg of body weight, i.p.), or Premarin (1 mg/kg of body weight, i.p.) plus the nonselective ER antagonist ICI 182, 780 (0.25 mg/kg of body weight, i.p.) 1 h after the termination of heat stress. Their physiologic and biochemical parameters were continuously monitored. Mice that survived on day 4 of heat treatment were considered survivors. When the vehicle-treated mice underwent heat, the fraction survival and core temperature at +4 h of body heating were found to be 0 of 12 and 34.4 degrees C +/- 3 degrees C, respectively. Administration of Premarin (1 mg/kg) 1 h after the cessation of heat stress rescued the mice from heat-induced death (fraction survival, 12/12) and reduced the hypothermia (core temperature, 37.3 degrees C). The beneficial effects of Premarin in ameliorating lethality and hypothermia can be abolished by simultaneous administration of ICI 182, 780. Both IL-10 (an anti-inflammatory cytokine) and estradiol in the serum were increased significantly in heat-stressed mice administered Premarin compared with vehicle-treated HS group. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl-transferase-mediated alpha UDP-biotin nick end-labeling staining, in the spleen, liver, and kidney were significantly reduced by Premarin. The increased levels of cellular ischemia (e.g., glutamate, lactate-to-pyruvate ratio, and nitrite) and damage (e.g., glycerol) markers and iNOS expression in the hypothalamus during HS were decreased significantly by Premarin therapy. The levels of proinflammatory cytokines (e.g., IL-1 beta and TNF-alpha) and renal and hepatic dysfunction markers in plasma that are up-regulated in heat stressed mice were significantly lower in Premarin-administered mice. The data indicate that Premarin may act via ERs to rescue mice form HS-induced lethality.
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PMID:Premarin can act via estrogen receptors to rescue mice from heatstroke-induced lethality. 1849 35

Alan Parkes was one of the most influential figures in the field of reproductive biology in the twentieth century. He had a huge impact on its growth and development during that time, and the legacy of his work still remains.His research was highly innovative and original because of his imaginative and inquiring mind, which, coupled with an entrepreneurial bent, led him into several very different fields and into unchartered waters. He played a leading role in the spectacular rise of reproductive endocrinology in Britain in the 1920s and 1930s when the nature and activity of many of the reproductive processes in animals and humans and was an essential factor in the development of methods for their control. Even more pioneering was his research in low-temperature biology in the years after World War II. This was sparked off by the discovery that glycerol had a remarkable property of protecting spermatozoa against damage during freezing and storage at very low temperatures. Far-reaching applications arose from this discovery, especially in the preservation of bull semen, which led to a worldwide revolution in artificial insemination in cattle. Later, many other cells and tissues were also successfully frozen, including red blood cells, ovarian tissue and bone marrow, and a new branch of biological science, which became known as 'cryobiology', was born, Effects of deep hypothermia, including freezing, on whole animals were also investigated at that time. Having successfully launched a new area of science, it was characteristic of Alan Parkes to switch to new fields. First he became interested in the influence of pheromones on mammalian reproduction. Then, resuming a long-standing interest in comparative aspects of reproductive physiology in British wild mammals, he became involved in the work of the Nuffield Unit of Tropical Animal Ecology in Uganda, where similar studies were carried out on African animals. Even after retirement from the academic field, he was for some years a consultant to an enterprise in the conservation and captive breeding of green sea turtles in the Cayman Islands. In addition to his research, Alan Parkes was just as influential through the huge amount of work that he did for committees and other activities. Over the years he was on 35 different committees, study groups or advisory groups, and these were concerned with a wide variety of interests. He often served as chairman or secretary and had a great ability to take on a large amount of work and responsibility. He threw himself wholeheartedly into promoting the interests of reproductive biology and was a founding member of both the Society of Endocrinology and the Society for the Study of Fertility. He also played a leading role in the establishment and running of the Journal of Endocrinology and the Journal of Reproduction and Fertility. Getting these journals established often required a considerable amount of financial acumen. One of his special concerns was a long-standing interest in demographic and population issues, which led to his working closely with the International Planned Parenthood Federation and the Family Planning Association. He saw the 'population explosion' as a growing threat to the environment and to human welfare, and he was an outstanding proponent of measures to effect population control. Sometimes this led him into controversial areas. He spoke strongly in support of women's right to abortion and questioned the morality of expensive measures to overcome infertility. Throughout his life he was a prolific and lucid writer and his many publications remain a lasting monument to his contribution to science. He entitled the first volume of his autobiography Off-beat biologist, which is perhaps a very apt description of this remarkable man.
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PMID:Sir Alan Sterling Parkes: 10 September 1900 - 17 July 1990. 1854 75

Inhibition of the metabolism of the endocannabinoids, anandamide (AEA) and 2-arachidonyl glycerol (2-AG), by their primary metabolic enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively, has the potential to increase understanding of the physiological functions of the endocannabinoid system. To date, selective inhibitors of FAAH, but not MAGL, have been developed. The purpose of this study was to determine the selectivity and efficacy of N-arachidonyl maleimide (NAM), a putative MAGL inhibitor, for modulation of the effects of 2-AG. Our results showed that NAM unmasked 2-AG activity in a tetrad of in vivo tests sensitive to the effects of cannabinoids in mice. The efficacy of 2-AG (and AEA) to produce hypothermia was reduced compared with Delta(9)-tetrahydrocannabinol; however, 2-AG differed from AEA by its lower efficacy for catalepsy. All tetrad effects were partially CB(1) receptor-mediated because they were attenuated (but not eliminated) by SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-H-pyrazole-3-carboxamide HCl] and in CB(1)(-/-) mice. In vitro, NAM increased endogenous levels of 2-AG in the brain. Furthermore, NAM raised the potency of 2-AG, but not AEA, in agonist-stimulated guanosine 5'-O-(3-[(35)S]thio)triphosphate binding assay, a measure of G-protein activation. These results suggest that NAM is an MAGL inhibitor with in vivo and in vitro efficacy. NAM and other MAGL inhibitors are valuable tools to elucidate the biological functions of 2-AG and to examine the consequences of dysregulation of this endocannabinoid. In addition, NAM's unmasking of 2-AG effects that are only partially reversed by SR141716A offers support for the existence of non-CB(1), non-CB(2) cannabinoid receptors.
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PMID:N-arachidonyl maleimide potentiates the pharmacological and biochemical effects of the endocannabinoid 2-arachidonylglycerol through inhibition of monoacylglycerol lipase. 1868 68

The first part of this review devotes (A) to mechanisms of cold arrest of isolated heart (rapid cooling), (B) to mechanisms of loss of heart work capacity during long hypothermia and B) to methods of recovery of the work of isolated heart (perfusion by warm oxygenated perfusat, and as well as on low temperatures by means of low [K+] in perfusate, by norepinephrine's stimulation, by electric impulses etc.). Protection of the heart damaging by long hypothermia achived usually by chemical cardioplegia (e.g. by increased [K+] in perfusate). Second part of review devotes to mechanisms of heart damage when cooling below 0 degrees C. Necessary condition of the protection of heart from freezing (ice crystals formation in the heart tissue) is saturating of the heart tissue by crioprotectors (glycerol, dimethilsulfoxide etc.), what prevent to ice crystallization. Cooling to -25 degrees C conducted successfully. Cooling to temperature of liquid nitrogen boiling (-196 degrees) for the present not lead to well reproducible recovery of the heart contractions. Closing part of the review devotes to recovery of the heart, arrested in situ (when hypothermia of the whole organism). Successfully recovered heart contractions and life of the whole organism with local heating of the heart and artificial breathing.
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PMID:[Recovery of the mammalian heart contractions after their arrest from cooling]. 1924 5

Hypothermic arrest and selective antegrade cerebral perfusion (SACP) is widely used during aortic arch surgery. The microdialysis technique monitors biomarkers of cellular metabolism and cellular integrity over time. In this study, the cerebral changes during hypothermic circulatory arrest (HCA) at 20 degrees C and HCA with SACP at two different temperatures, 20 and 28 degrees C, were monitored. Twenty-three pigs were divided into three groups. A microdialysis probe was fixated into the forebrain. Circulatory arrest started at a brain and body temperature of 20 degrees C or 28 degrees C. Arrest with/without cerebral perfusion (flow 10 ml/kg, max carotid artery pressure 70 mmHg) lasted for 80 min followed by reperfusion and rewarming during 40 min and an observation period of 120 min. The microdialysis markers were registered at six time-points. The lactate/pyruvate ratio (L/P ratio) and the lactate/glucose ratio (L/G ratio) increased significantly (P<0.05), during arrest, in the HCA group. The largest increase of glycerol was found in the group with tepid cerebral perfusion (28 degrees C) and the HCA group (P<0.05). This study supports the use of SACP over arrest. It also suggests that cerebral metabolism and cellular membrane integrity may be better preserved with SACP at 20 degrees C compared to 28 degrees C.
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PMID:Selective antegrade cerebral perfusion at two different temperatures compared to hypothermic circulatory arrest--an experimental study in the pig with microdialysis. 1944 95


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