Changes in body temperature after administration of antipyretics, LSD, Δ9-THC, CNS depressants and stimulants, hormones, inorganic ions, gases, 2,4-DNP and miscellaneous agents

Clark, William G.; Clark, Yvonne L.

doi:10.1016/0149-7634(81)90039-7

Cited by 44 publications

(17 citation statements)

References 853 publications

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confidence: 99%

“…DNP has been used in humans and many animals and has been shown to stimulate brain metabolism in goats when injected intravenously (28). However, there are no previous studies outlining the drug's effects on swine (29,30).The goal of this manuscript is twofold: (i) to characterize the whole-body metabolic effects of large animal injection of DNP to assess its suitability for studies of metabolism, and (ii) to demon- …”

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Mapping of cerebral oxidative metabolism with MRI

Mellon

Beesam

Elliott

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Using a T 1ρ MRI based indirect detection method, we demonstrate the detection of cerebral oxidative metabolism and its modulation by administration of the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) in a large animal model with minimum utilization of 17 O 2 gas. The study was performed by 17 O 2 inhalation in swine during imaging on clinical MRI scanners. Metabolic changes in swine were determined by two methods. First, in a series of animals, increased metabolism caused by DNP injection was measured by exhaled gas analysis. The average whole-body metabolic increase in seven swine was 11.9% þ ∕ − 2.5% per mg∕kg, stable over three hours. Secondly, hemispheric brain measurements of oxygen consumption stimulated by DNP injection were made in five swine using T 1ρ MRI following administration of 17 O 2 gas. Metabolism was calculated from the change in the T 1ρ weighted MRI signal due to H 2 17 O generated from 17 O 2 inhalation before and after doubling of metabolism by DNP. These results were confirmed by direct oxygen-17 MR spectroscopy, a gold standard for in vivo H 2 17 O measurement. Overall, this work underscores the ability of indirect oxygen-17 imaging to detect oxygen metabolism in an animal model with a lung capacity comparable to the human with minimal utilization of expensive 17 O 2 gas. Given the demonstrated high efficiency in use of 17 O 2 and the proven feasibility of performing such measurements on standard clinical MRI scanners, this work enables the adaption of this technique for human studies dealing with a broad array of metabolic derangements.2,4-dinitrophenol | cerebral metabolic rate of oxygen consumption | CMRO2 | oxygen-17 D erangement of oxidative metabolism is noted in numerous conditions including Alzheimer's disease, cerebral ischemia, cancer, and aging. Despite the known derangements in oxidative metabolism that occur in many diseases, there are still no routine clinical, nonradioactive technologies that directly assess oxidative metabolism. To address this need, a number of studies have investigated techniques based on 17 O, the only stable, naturally occurring, NMR-visible isotope of oxygen. These techniques utilize either proton detection of 17 O through the strong 1 H-17 O J-coupling in water (1), termed "indirect" imaging (2-5), or "direct" spectroscopy based upon imaging of the 17 O nucleus in H 2 17 O (6-10).While the direct detection methods are highly specific to 17 O, their inherent low SNR requires either long acquisition times or ultrahigh magnetic fields, which precludes their implementation in the routine clinical setting. In contrast, indirect detection methods exploit the higher sensitivity of proton MR and can be implemented on routine clinical scanners. Using both direct and indirect 17 O MR detection methods, oxidative metabolism has been demonstrated in small animals such as cats, rats, and mice (4, 11-13). To date there have been only two published abstracts of direct 17 O NMR studies of healthy humans (14, 15). There have been no reports of indirect de...

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confidence: 99%

Mapping of cerebral oxidative metabolism with MRI

Mellon

Beesam

Elliott

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Clark in Neuroscience and Biobehavioral Reviews [29][30][31][32][33][34][35][36]. According to the author, "this survey … intended to provide an immediate source of information on drug-induced changes in thermoregulation" [31].…”

Section: Visualizing Drug-induced Changes In Body Temperaturementioning

confidence: 99%

“…Change in Tb upon exposure to pharmacological agents. All presented data are derived from reviews published by Clark et al [29][30][31][32][33][34][35][36]. These reviews total 18,808 reports on changes in Tb (ΔTb) following exposure to a biochemical agent.…”

Section: Visualizing Drug-induced Changes In Body Temperaturementioning

confidence: 99%

“…This finding is in direct contradiction to anapyrexia, in which the lowered Tb would manifest itself by heat avoidance rather than reinforcement. In addition, the experiments performed in rats were performed in a temperature range of 0-26 °C [32]. The observation that DMSO caused such a large change in Tb in a small species such as a rat ( Figure 3A, C) may in part be explained by the heavy cold thermal load.…”

Section: Dimethyl Sulfoxidementioning

confidence: 99%

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Survey and critical appraisal of pharmacological agents with potential thermo-modulatory properties in the context of artificially induced hypometabolism

Dirkes

Gulik

Heger

2015

JCTRes

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A reduction in body temperature can be achieved by a downward adjustment of the termoneutral zone, a process also described as anapyrexia. Pharmacological induction of anapyrexia could enable numerous applications in medicine. However, little is known about the potential of pharmacological agents to induce anapyrexic signaling. Therefore, a review of literature was performed and over a thousand pharmacologically active compounds were analyzed for their ability to induce anapyrexia in animals. Based on this analysis, eight agents (helium, dimethyl sulfoxide, reserpine, (oxo)tremorine, pentobarbital, (chlor) promazine, insulin, and acetaminophen) were identified as potential anapyrexia-inducing compounds and discussed in detail. The translational pitfalls were also addressed for each candidate compound. Of the agents that were discussed, reserpine, (oxo)tremorine, and (chlor) promazine may possess true anapyrexic properties based on their ability to either affect the thermoneutral zone or its effectors and facilitate hypothermic signaling. However, these properties are currently not unequivocal and warrant further examination in the context of artificially-induced hypometabolism. Keywords:thermoneutral zone hypothermia induction pharmacological agents animals body temperature

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