465 research outputs found

    Methods of temperature and metabolism reduction in rats and possible influence on human health

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    Thesis (M.S.) University of Alaska Fairbanks, 2017Spaceflight poses unique and significant hazards; the maintenance of human health remains a large part of the National Aeronautic and Space Administration (NASA) strategic goals and work remains to be done if we wish to maintain a long-term presence in space. The effects of ionizing radiation and bone density loss are some of the primary health related problems which need to be addressed. One of the main purposes of this research is to translate aspects of thermoregulation and metabolism reduction in hibernating species to a non-hibernating species in- order to devise alternative methods of preventing DNA damage and loss of bone density in astronauts. A second purpose for this research applies the same approach in emergency medicine, having potential as conjunctive therapy for cardiac arrest victims. Targeted temperature management (TTM; formerly known as therapeutic hypothermia) is the standard of care for these patients and is applied to increase survival rates and reduces neurological deficit. Stimulating Central Nervous System (CNS) A1 adenosine receptors inhibits shivering and non-shivering thermogenesis, inducing a hibernation-like response in hibernating species. A similar phenomenon occurs when using this technique in non-hibernating species such as rats. The adenosine A1 agonist, N6-cyclohexyladenosine (CHA) was utilized in all 3 of the experiments to determine how dose, diet, ambient temperature, and finally surface temperature affects the thermoregulatory response in Sprague-dawley rats. In addition to CHA, the partial agonist capadenoson was also tested for thermolytic efficacy (that is, the efficacy to abolish thermogenesis). Surface temperature control using a temperature controlled cage designed and built by myself in combination with IV CHA was found to be most effective in maintaining a target temperature of 32°C without risk of over-cooling. Results from these experiments suggests that the new standard technique in studying TTM using small animals should be similar to what is currently used in clinics; surface temperature modulation

    Over-the-counter drugs and non-febrile thermoregulation: is there cause for concern?

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    A thesis submitted to the University of Bedfordshire, in partial fulfilment of the requirement for the degree of Doctor of PhilosophyCore temperature (Tc) regulation is fundamental to mammalian survival, since hypothermia (Tc ≤ 35°C) and hyperthermia (Tc ≥ 40°C) are major risk factors for health and wellbeing. The purpose of this thesis was to determine if acetaminophen, an analgesic and antipyretic drug, increased the onset of hypothermia or hyperthermia during passive cold and heat stress, respectively. It was later investigated if acetaminophen induced inhibition of cyclooxygenase mediated these side-effects. In Study 1a, the plasma acetaminophen response to a dose of 20 mg·kg-1 of lean body mass was determined through enzyme linked immunosorbent assay. In Study 1b, the effect of acetaminophen administration on internal temperature (rectal; Tre) during a passive 2-hour mild cold (20°C, 40% relative humidity) exposure was examined. Study 1a showed that the plasma response was homogenous between subjects, reaching peak concentrations between 80-100 minutes (14 ± 4 μg·ml-1). In Study 1b, acetaminophen reduced Tre in all participants compared with baseline, and the average peak reduction was 0.19 ± 0.09°C. In contrast, Tre remained stable when participants ingested a sugar placebo. Study 1 is the first experiment which confirms a hypothermic side-effect of acetaminophen in healthy humans. Study 2 investigated whether acetaminophen augmented the rate of Tre rise during exposure to passive dry (45°C, 30% r.h.) and humid (45°C, 70% r.h.) heat stress for 2-hours and 45-minutes, respectively. This study showed that the rate of Tre rise in the dry (0.005 vs 0.006°C∙min-1) and humid (0.023 vs 0.021 °C∙min-1) conditions were similar between the acetaminophen and placebo trials (p > 0.05). Study 2 is the first experiment which confirms acetaminophen has no meaningful effect on thermoregulation during passive dry or humid heat exposure. Study 3 determined how the hypothermic effect of acetaminophen changes during exposure to a thermoneutral (25°C, 40% r.h.) and cold (10°C, 40% r.h.) environment for 2-hours. In summary, there was no hypothermic effect of acetaminophen in a thermoneutral environment (p > 0.05), whereas Tre fell by 0.40 ± 0.15°C compared with baseline during cold stress (p < 0.05). Compared with the placebo, Tre was ~0.35°C lower at 120 minutes, but was significantly lower from 70-minutes. Study 3 confirmed that there is a relationship between the level of cold stress and magnitude of the hypothermic effect of acetaminophen. Study 4 determined whether ibuprofen (400 mg), a cyclooxygenase inhibitor, reduced Tre during 2-hour passive cold stress (10°C, 40% r.h.) to a level comparable with acetaminophen. Ibuprofen administration did not influence Tre, vastus medialis shivering, or energy expenditure compared with a placebo throughout the cold exposure (p > 0.05). Taken together, this renders it unlikely that cyclooxygenase activity is required for thermogenesis induced by skin cooling. Study 4 provides evidence that acetaminophen induced hypothermia is not exclusively mediated by cyclooxygenase inhibition. In Summary, this series of experiments has shown that acetaminophen has a hypothermic side effect in healthy humans, which is amplified during acute cold stress. Ibuprofen had no such effect on thermoregulation during cold exposure, so it is unlikely that cyclooxygenase inhibition mediates the hypothermic side-effect of acetaminophen
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