The Hypothermic Effect of Hydrogen Sulfide Is Mediated by the Transient Receptor Potential Ankyrin-1 Channel in Mice

Hydrogen sulfide (H2S) has been shown in previous studies to cause hypothermia and hypometabolism in mice, and its thermoregulatory effects were subsequently investigated. However, the molecular target through which H2S triggers its effects on deep body temperature has remained unknown. We investigated the thermoregulatory response to fast-(Na2S) and slow-releasing (GYY4137) H2S donors in C57BL/6 mice, and then tested whether their effects depend on the transient receptor potential ankyrin-1 (TRPA1) channel in Trpa1 knockout (Trpa1−/−) and wild-type (Trpa1+/+) mice. Intracerebroventricular administration of Na2S (0.5–1 mg/kg) caused hypothermia in C57BL/6 mice, which was mediated by cutaneous vasodilation and decreased thermogenesis. In contrast, intraperitoneal administration of Na2S (5 mg/kg) did not cause any thermoregulatory effect. Central administration of GYY4137 (3 mg/kg) also caused hypothermia and hypometabolism. The hypothermic response to both H2S donors was significantly (p < 0.001) attenuated in Trpa1−/− mice compared to their Trpa1+/+ littermates. Trpa1 mRNA transcripts could be detected with RNAscope in hypothalamic and other brain neurons within the autonomic thermoeffector pathways. In conclusion, slow- and fast-releasing H2S donors induce hypothermia through hypometabolism and cutaneous vasodilation in mice that is mediated by TRPA1 channels located in the brain, presumably in hypothalamic neurons within the autonomic thermoeffector pathways.

Proof-of-Concept for the Analgesic Effect and Thermoregulatory Safety of Orally Administered Multi-Target Compound SZV 1287 in Mice: A Novel Drug Candidate for Neuropathic Pain

SZV 1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime) is a novel multi-target candidate under preclinical development for neuropathic pain. It inhibits amine oxidase copper containing 3, transient receptor potential ankyrin 1 and vanilloid 1 (TRPV1) receptors. Mainly under acidic conditions, it is transformed to the cyclooxygenase inhibitor oxaprozin, which is ineffective for neuropathy. Therefore, an enterosolvent capsule is suggested for oral formulation, which we investigated for nociception, basic kinetics, and thermoregulatory safety in mice. The antihyperalgesic effect of SZV 1287 (10, 20, 50, and 200 mg/kg, p.o.) was determined in partial sciatic nerve ligation-induced traumatic neuropathy by aesthesiometry, brain and plasma concentrations by HPLC, and deep body temperature by thermometry. Its effect on proton-induced TRPV1 activation involved in thermoregulation was assessed by microfluorimetry in cultured trigeminal neurons. The three higher SZV 1287 doses significantly, but not dose-dependently, reduced neuropathic hyperalgesia by 50% of its maximal effect. It was quickly absorbed; plasma concentration was stable for 2 h, and it entered into the brain. Although SZV 1287 significantly decreased the proton-induced TRPV1-mediated calcium-influx potentially leading to hyperthermia, it did not alter deep body temperature. Oral SZV 1287 inhibited neuropathic hyperalgesia and, despite TRPV1 antagonistic action and brain penetration, it did not influence thermoregulation, which makes it a promising analgesic candidate.

Perceived Thermal Response of Stone Quarry Workers in Hot Environment

Introduction: Impact of heat on health of workers goes unrecognized by the virtue of the indispensable fact that every individual has varied perception and tolerance capacity. The present study determine the physiological signs with perceived subjective responses under the thermal stress.Materials and Methods: The study was spread on open field stone quarry workers (N = 934) during the summer (May to June), post monsoon (September to October), and winter (December to January).Results: In the summer months, dry bulb temperature range from 36.1 to 43.2°C and the distribution of Wet Bulb Globe temperature (WBGT) outdoor values were outlier-prone than normal distribution indicated heat vulnerability. The environmental effect on weighted average skin temperature (Tsk) local segmental Tsk and deep body temperature (Tcr) were greater than the effects that might be attributed to work severity. The tolerance time level in summer months (65 ± 13 min at WBGT 35 ± 2.3°C) was less than in other two season. About 85% of workers in summer, 68% in post monsoon and 79% in winter recorded working heart rate greater than 90 beats/min. Physiological and subjective responses to heat stress indicated that during summer month the workers complained of excessive sweating (93.5%), feeling of thirst/dry mouth (88.7%), elevated Core temperature (Tcr) (58.7%) and decreased working capacity (75.6%). The observation found that around 14% workers were vulnerable to heat stress and the workers had no knowledge to mitigate the heat related illnesses.Discussion and Conclusions: The stone quarry work as compared to other outdoor workers have environmental adversaries which becomes confounding variables in the study of such occupations. There was significant difference (p &lt; 0.001) as far as the physiological and thermoregulatory responses were concerned in three different months of investigation.

Going through the motions

In Going through the motions Mike Gibson briefly explores an experiment he was involved in using radio-pills to measure deep body temperature in pilots, at the RAF Institute of Aviation Medicine.

THE USE OF ANALGESICS TO MANAGE BACK PAIN IN PREHOSPITAL, IN-HOSPITAL AND OUTPATIENT CARE. CONTINUITY AND CONTROL

Ketoprofen («Ketonal») proved to be significantly efficient in pre-hospital care when administered intramuscularly at a dose of 100 mg to treat pain in the neck (n=31), thoracic spine (n=53), and lower back (n=50), according to a visual analogue scale (VAS). During the in-hospital and outpatient care (n=33), a continued use of Ketoprofen in multiple therapy (muscle relaxants and chondroprotective agents) for lower back pain significantly improved the quality of life (Roland–Morris questionnaire) and reduced the pain twice according to VAS. At the end of the 3-week treatment, the maximum deep body temperature (measured by microwave radiothermometry) decreased in the lower back but did not return to normal. High correlation coefficients between the deep and skin temperature did not return to normal after treatment. Stabilometric parameters remained ‘rigid’, except for patient’s overall equilibrium (R) that became reliably normal in all directions. The control methods used indicate the need for a longer therapy.

The Effects of Hyperbaric Exposure on Immediate and Delayed Changes in Core Temperature and Its Circadian Fluctuations

Changes observed in the core body temperature of divers are the result of a multifaceted response from the body to the change of the external environment. In response to repeated activities, there may be a chronic, physiological adaptation of the body’s response system. This is observed in the physiology of experienced divers while diving. The purpose of this study is to determine the immediate and delayed effects of hyperbaric exposure on core temperature, as well as its circadian changes in a group of three experienced divers. During compression at 30 and 60 meters, deep body temperature values tended to increase. Subsequently, deep body temperature values showed a tendency to decrease during decompression. All differences in core temperature values obtained by the group of divers at individual time points in this study were not statistically significant.