Thermoregulatory Effects Research Articles

Mitigating Effect of the Sea on Temperatures Along Mediterranean Coastal Areas: The Case of the Vine Territory of the Matera DOP in Basilicata (Italy)

This study aims to assess temperature variations caused by ongoing climate change in the Basilicata region, southern Italy—Ionian side of the Gulf of Taranto—on the territory of the Matera DOP vineyard. In particular, it aims to assess the influence of the sea on temperature trends, and particularly to its “mitigating effect” in the context of ongoing climate change. Temperature trends were analyzed using ERA5-Land data from 1981 to 2022 and data from weather stations of the Lucanian Agency for Development and Innovation in Agriculture from 2000 to 2023. Temperature trends were studied considering both the period of the vegetative-productive season of the vineyards and the whole year. The results of this study show that, for the historical period analyzed, the Matera DOP area showed a significant upward trend in temperatures, particularly in the inland areas. This increase, especially for minimum temperatures, is more evident at higher elevations than at lower elevations near the sea. Indeed, coastal areas benefit from the thermoregulatory effect of the Ionian Sea, which moderates temperature increases at lower elevations. It follows that the Matera DOP wine-growing areas, and particularly those furthest from the coastal strip, will have to adapt to harsh climatic conditions that will certainly affect the quality and typicality of the wines.

Fisher activity patterns show potential for behavioral adaptations to human modified landscapes

Animals alter their diel activity in response to physiological constraints and ecological conditions. Fisher (Pekania pennanti) activity is known to vary through the diel cycle and change in response to cold stress and generally through both the climatic and biological seasons. However, less is known whether thermoregulatory effects impact fisher activity in milder climates and in areas of high human disturbance. We focused on two distinct research objectives to understand the 1) physiological constraints, and 2) ecological components of fisher activity in a highly disturbed landscape with a relatively mild climate. We used accelerometer data from 34 individual live-captured fisher in Rhode Island, USA from 2021 to 2023. We found that fisher activity patterns were primarily driven by diel cycle with higher activity levels at night than during the day. We did not observe any physiological influence of ambient temperature on fisher activity; daily minimum temperatures did not constrain fisher activity in the colder months, nor did daily maximum temperatures in warmer months. We did find that female activity levels differed by breeding status with non-pregnant females having higher activity levels than pregnant females. Considering ecological components, we found fisher decreased activity levels in higher road density areas during warmer months that coincide with higher traffic volumes. For fisher living in areas with lower road densities, we saw higher activity in the breeding season and summer than in winter. In contrast, fisher living in areas with high road densities had lower activity in the breeding season and summer than in winter. We conclude that fisher largely do not shift their activity to mitigate thermoregulatory costs in areas where temperatures do not reach extremes for extended periods of time. However, our findings suggest that behavioral shifts in activity are impacted by human disturbance and fisher minimize activity in risky areas.

Central Hemodynamic and Thermoregulatory Responses to Food Intake as Potential Biomarkers for Eating Detection: Systematic Review.

Diet-related diseases, such as type 2 diabetes, require strict dietary management to slow down disease progression and call for innovative management strategies. Conventional diet monitoring places a significant memory burden on patients, who may not accurately remember details of their meals and thus frequently falls short in preventing disease progression. Recent advances in sensor and computational technologies have sparked interest in developing eating detection platforms. This review investigates central hemodynamic and thermoregulatory responses as potential biomarkers for eating detection. We searched peer-reviewed literature indexed in PubMed, Web of Science, and Scopus on June 20, 2022, with no date limits. We also conducted manual searches in the same databases until April 21, 2024. We included English-language papers demonstrating the impact of eating on central hemodynamics and thermoregulation in healthy individuals. To evaluate the overall study quality and assess the risk of bias, we designed a customized tool inspired by the Cochrane assessment framework. This tool has 4 categories: high, medium, low, and very low. A total of 2 independent reviewers conducted title and abstract screening, full-text review, and study quality and risk of bias analysis. In instances of disagreement between the 2 reviewers, a third reviewer served as an adjudicator. Our search retrieved 11,450 studies, and 25 met our inclusion criteria. Among the 25 included studies, 32% (8/25) were classified as high quality, 52% (13/25) as medium quality, and 16% (4/25) as low quality. Furthermore, we found no evidence of publication bias in any of the included studies. A consistent postprandial increase in heart rate, cardiac output, and stroke volume was observed in at least 95% (heart rate: 19/19, cardiac output: 18/19, stroke volume: 11/11) of the studies that investigated these variables' responses to eating. Specifically, cardiac output increased by 9%-100%, stroke volume by 18%-41%, and heart rate by 6%-21% across these studies. These changes were statistically significant (P<.05). In contrast, the 8 studies that investigated postprandial thermoregulatory effects displayed grossly inconsistent results, showing wide variations in response with no clear patterns of change, indicating a high degree of variability among these studies. Our findings demonstrate that central hemodynamic responses, particularly heart rate, hold promise for wearable-based eating detection, as cardiac output and stroke volume cannot be measured by any currently available noninvasive medical or consumer-grade wearables. PROSPERO CRD42022360600; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=360600.

Air speed and direction affect metabolic and thermoregulatory responses during walking and running in a temperate environment.

Revisiting classical experiments on the impact of air resistance on metabolic rate, we aimed to overcome limitations of previous research, notably: low participant numbers (n = 1-3), highly turbulent wind, and confounding effects of rising body temperature. In a custom-built wind tunnel with reduced turbulence, 14 participants (8 males, 6 females) walked (5 km·h-1) and ran on a treadmill (70%V̇o2max) at 0, 2, 4, and 6 m·s-1 headwind or tailwind in a counterbalanced design, with rest breaks between each exposure to avoid rises in body core temperature. Oxygen consumption (V̇o2) exhibited strong linear relationships versus wind direction, dynamic pressure, and air speed squared (Vwr2), lower in magnitude for headwind than tailwind. A moderate linear relationship was observed between heart rate, wind direction, dynamic pressure, and Vwr2. Below 4 m·s-1, the effect of wind was well within inter- and intraindividual variation and equipment uncertainty, and only at wind speeds ≥4 m·s-1 did the differences in physiological responses reach statistical significance. Our data indicate that at running speeds below 4 m·s-1 (14.4 km/h), indoor treadmills and outdoor running are comparable in terms of the metabolic impact of air movement relative to the person. However, this does not extend to the thermoregulatory effect of wind, with outdoor running providing a higher cooling rate due to the self-generated wind created during running. By removing the confounding impact of core temperature rises, the observed effects of headwind were lower and those of tailwind larger than observed previously. In the context of middle-distance running, the headwind created by running at 21.5 km·h-1 would result in a 2.2% increase of V̇o2. A relative tailwind of the same speed would lead to a 3.1% reduction.NEW & NOTEWORTHY Revisiting classical work by Pugh and Davies on the metabolic effects of air speed and direction, shortcomings in the original studies were addressed. Using more participants, less turbulent wind, and avoiding confounding effects of work-induced core temperature increases, new equations describing the impact of air speed/direction were developed. This study observed a lower impact of headwind and a larger impact of tailwind in the absence of an exercise-induced core temperature increase.

Mitigation of urban heat island in China (2000–2020) through vegetation-induced cooling

City afforestation serves as a robust strategy for thermal mitigation. Employing multisource satellite data, we explored the impact of vegetation cover on temperature dynamics across urban and rural sectors in Chinese cities. Our analysis reveals that a 1 % increase in vegetation coverage corresponds to a reduction in surface temperature by 0.099 °C to 0.102 °C in urban environments. However, the cooling effect diminishes from urban to rural areas, where increased vegetation occasionally results in warming. Further, the temperature reduction tends to stabilize at higher vegetation levels, as demonstrated in grid-based evaluations. Significantly, variations in urban population density substantially modulate these cooling effects. Over the period 2000–2020, afforestation increased vegetation coverage by 4.35 % in urban areas, which led to cooling in 67.43 % of the analyzed cities, with an average surface temperature decline of 0.58 °C. Additionally, our findings document a notable attenuation of the urban heat island (UHI) effect over time, with an average decrease of 0.56 ± 0.35 °C. This reduction primarily results from the thermoregulatory effects of changes in vegetation coverage, which cool urban areas and may warm rural ones. Our study underscores the critical role of afforestation in urban climate management and its efficacy in attenuating urban heat waves and UHI effects.

Prolonged FGF21 treatment increases energy expenditure and induces weight loss in obese mice independently of UCP1 and adrenergic signaling

Fibroblast growth factor 21 (FGF21) reduces body weight, which was attributed to induced energy expenditure (EE). Conflicting data have been published on the role of uncoupling protein 1 (UCP1) in this effect. Therefore, we aimed to revisit the thermoregulatory effects of FGF21 and their implications for body weight regulation.We found that an 8-day treatment with FGF21 lowers body weight to similar extent in both wildtype (WT) and UCP1-deficient (KO) mice fed high-fat diet. In WT mice, this effect is solely due to increased EE, associated with a strong activation of UCP1 and with excess heat dissipated through the tail. This thermogenesis takes place in the interscapular region and can be attenuated by a β-adrenergic inhibitor propranolol. In KO mice, FGF21-induced weight loss correlates with a modest increase in EE, which is independent of adrenergic signaling, and with a reduced energy intake. Interestingly, the gene expression profile of interscapular brown adipose tissue (but not subcutaneous white adipose tissue) of KO mice is massively affected by FGF21, as shown by increased expression of genes encoding triacylglycerol/free fatty acid cycle enzymes.Thus, FGF21 elicits central thermogenic and pyretic effects followed by a concomitant increase in EE and body temperature, respectively. The associated weight loss is strongly dependent on UCP1-based thermogenesis. However, in the absence of UCP1, alternative mechanisms of energy dissipation may contribute, possibly based on futile triacylglycerol/free fatty acid cycling in brown adipose tissue and reduced food intake.

Keystone seabird may face thermoregulatory challenges in a warming Arctic

Climate change affects the Arctic more than any other region, resulting in evolving weather, vanishing sea ice and altered biochemical cycling, which may increase biotic exposure to chemical pollution. We tested thermoregulatory impacts of these changes on the most abundant Arctic seabird, the little auk (Alle alle). This small diving species uses sea ice-habitats for foraging on zooplankton and resting. We equipped eight little auks with 3D accelerometers to monitor behavior, and ingested temperature recorders to measure body temperature (Tb). We also recorded weather conditions, and collected blood to assess mercury (Hg) contamination. There were nonlinear relationships between time engaged in different behaviors and Tb. Tb increased on sea ice, following declines while foraging in polar waters, but changed little when birds were resting on water. Tb also increased when birds were flying, and decreased at the colony after being elevated during flight. Weather conditions, but not Hg contamination, also affected Tb. However, given our small sample size, further research regarding thermoregulatory effects of Hg is warranted. Results suggest that little auk Tb varies with behavior and weather conditions, and that loss of sea ice due to global warming may cause thermoregulatory and energic challenges during foraging trips at sea.

Thermoregulation in Two Models of Trail Run Socks with Different Fabric Separation.

Trail running socks with the same fibers and design but with different separations of their three-dimensional waves could have different thermoregulatory effects. Therefore, the objective of this study was to evaluate the temperatures reflected on the sole of the foot after a mountain race with the use of two models of socks with different wave separations. In a sample of 34 subjects (twenty-seven men and seven women), the plantar temperature was analyzed with the thermal imaging camera Flir E60bx® (Flir systems, Wilsonville, OR, USA) before and after running 14 km in mountainous terrain at a hot temperature of 27 °C. Each group of 17 runners ran with a different model of separation between the waves of the tissue (2 mm versus 1 mm). After conducting the post-exercise thermographic analysis, a Likert-type survey was conducted to evaluate the physiological characteristics of both types of socks. There was a significant increase in temperature in all areas of interest (p < 0.001) after a 14 km running distance with the two models of socks. The hallux zone increased in temperature the most after the race, with temperatures of 8.19 ± 3.1 °C and 7.46 ± 2.1 °C for the AWC 2.2 and AWC 3, respectively. However, no significant differences in temperature increases were found in any of the areas analyzed between the two groups. Runners perceived significant differences in thermal sensation between AWC 2.2 socks with 4.41 ± 0.62 points and AWC 3 with 3.76 ± 1.03 points (p = 0.034). Both models had a similar thermoregulatory effect on the soles of the feet, so they can be used interchangeably in short-distance mountain races. The perceived sensation of increased thermal comfort does not correspond to the temperature data.

Constitutive and conditional deletion reveals distinct phenotypes driven by developmental versus neurotransmitter actions of the neuropeptide PACAP.

Neuropeptides may exert trophic effects during development, and then neurotransmitter roles in the developed nervous system. One way to associate peptide-deficiency phenotypes with either role is first to assess potential phenotypes in so-called constitutive knockout mice, and then proceed to specify, regionally and temporally, where and when neuropeptide expression is required to prevent these phenotypes. We have previously demonstrated that the well-known constellation of behavioral and metabolic phenotypes associated with constitutive pituitary adenylate cyclase-activating peptide (PACAP) knockout mice are accompanied by transcriptomic alterations of two types: those that distinguish the PACAP-null phenotype from wild-type (WT) in otherwise quiescent mice (cPRGs), and gene induction that occurs in response to acute environmental perturbation in WT mice that do not occur in knockout mice (aPRGs). Comparing constitutive PACAP knockout mice to a variety of temporally and regionally specific PACAP knockouts, we show that the prominent hyperlocomotor phenotype is a consequence of early loss of PACAP expression, is associated with Fos overexpression in hippocampus and basal ganglia, and that a thermoregulatory effect previously shown to be mediated by PACAP-expressing neurons of medial preoptic hypothalamus is independent of PACAP expression in those neurons in adult mice. In contrast, PACAP dependence of weight loss/hypophagia triggered by restraint stress, seen in constitutive PACAP knockout mice, is phenocopied in mice in which PACAP is deleted after neuronal differentiation. Our results imply that PACAP has a prominent role as a trophic factor early in development determining global central nervous system characteristics, and in addition a second, discrete set of functions as a neurotransmitter in the fully developed nervous system that support physiological and psychological responses to stress.

Topical application of isolated menthol and combined menthol-capsaicin creams: Exercise tolerance, thermal perception, pain, attentional focus and thermoregulation in the heat

ABSTRACT We determined the effects of topically applied (i) isolated menthol cream, (ii) menthol and capsaicin co-application or (iii) placebo cream on exercise tolerance, thermal perception, pain, attentional focus and thermoregulation during exercise in the heat. Ten participants cycled at 70% maximal power output until exhaustion in 35°C and 20% relative humidity after application of (i) 5% isolated menthol, (ii) 5% menthol and 0.025% capsaicin co-application or (iii) placebo cream. Thermo-physiological responses were measured during exercise, with attentional focus and pain determined post-exercise on a 0-to-10 scale. Across the three conditions, time to exhaustion was 13.4 ± 4.8 min, mean ± SD infrared tympanic and skin temperature was 37.2 ± 0.6°C and 35.1 ± 1.2°C, respectively, and heart rate was 152 ± 47 bpm, with no changes between conditions (p > 0.05). Perceived exertion was lower in the isolated menthol vs. all other conditions (p < 0.05, ηp2 = 0.44). Thermal sensation was higher in menthol-capsaicin co-application vs. isolated menthol (p < 0.05, d = 1.1), while sweat rate was higher for capsaicin and menthol co-application compared to menthol (p < 0.05, d = 0.85). The median and interquartile range scores for pain were lower (p < 0.05) in the menthol condition (8, 7-8) compared to both menthol and capsaicin (10, 9-10) and placebo (9, 9-10), which was coupled with a greater distraction (p < 0.05) in the menthol condition (9, 7-10) compared to placebo (6, 5-7). Despite no performance effects for any topical cream application condition, these data reiterate the advantageous perceptual and analgesic role of menthol application and demonstrate no advantage of co-application with capsaicin. Highlights Topical application of isolated menthol cream to cold-sensitive areas of the body during exhaustive exercise in the heat, elicited reduced perception of pain and enhanced sensation of cooling. While this reduction in generally unpleasant feelings (i.e. pain and heat) were coupled with lower RPE scores in the menthol condition and could be considered beneficial, there was no apparent ergogenic effect in an exercise tolerance test. Co-application of capsaicin and menthol appeared to inhibit the positive sensory effects elicited by menthol. Isolated menthol can induce changes in cognitive processes related to pain and exertion, while also reducing thermal sensation; however, the decision to use menthol creams must be balanced with the limited performance or thermoregulatory effects reported herein during exercise in hot environments.

Robust aversive effects of trace amine-associated receptor 1 activation in mice.

Drugs that stimulate the trace amine-associated receptor 1 (TAAR1) are under clinical investigation as treatments for several neuropsychiatric disorders. Previous studies in a genetic mouse model of voluntary methamphetamine intake identified TAAR1, expressed by the Taar1 gene, as a critical mediator of aversive methamphetamine effects. Methamphetamine is a TAAR1 agonist, but also has actions at monoamine transporters. Whether exclusive activation of TAAR1 has aversive effects was not known at the time we conducted our studies. Mice were tested for aversive effects of the selective TAAR1 agonist, RO5256390, using taste and place conditioning procedures. Hypothermic and locomotor effects were also examined, based on prior evidence of TAAR1 mediation. Male and female mice of several genetic models were used, including lines selectively bred for high and low methamphetamine drinking, a knock-in line in which a mutant form of Taar1 that codes for a non-functional TAAR1 was replaced by the reference Taar1 allele that codes for functional TAAR1, and their matched control line. RO5256390 had robust aversive, hypothermic and locomotor suppressing effects that were found only in mice with functional TAAR1. Knock-in of the reference Taar1 allele rescued these phenotypes in a genetic model that normally lacks TAAR1 function. Our study provides important data on TAAR1 function in aversive, locomotor, and thermoregulatory effects that are important to consider when developing TAAR1 agonists as therapeutic drugs. Because other drugs can have similar consequences, potential additive effects should be carefully considered as these treatment agents are being developed.

Euendolithic Infestation of Mussel Shells Indirectly Improves the Thermal Buffering Offered by Mussel Beds to Associated Molluscs, but One Size Does Not Fit All

Mussel beds form important intertidal matrices that provide thermal buffering to associated invertebrate communities, especially under stressful environmental conditions. Mussel shells are often colonized by photoautotrophic euendoliths, which have indirect conditional beneficial thermoregulatory effects on both solitary and aggregated mussels by increasing the albedo of the shell. We investigated whether euendolithic infestation of artificial mussel beds (Perna perna) influences the body temperatures of four associated mollusc species during simulated periods of emersion, using shell temperature obtained via non-invasive infrared thermography as a proxy. Shell temperatures of the limpet Scutellastra granularis and the chiton Acanthochitona garnoti were higher in non-infested than infested mussel beds during simulated low tides under high solar irradiance and low wind speeds. However, this was not the case for the limpet Helcion pectunculus or the top shell Oxystele antoni. Morphological differences in mollusc shape and colour could, in part, explain this contrast between species. Our results indicated that endolith-induced improvements in humidity and temperature in mussel beds could benefit associated molluscs. The beneficial thermal buffering offered by euendolithic infestation of the mussel beds was effective only if the organism was under heat stress. With global climate change, the indirect beneficial effect of euendolithic infestation for invertebrate communities associated with mussel beds may mitigate intertidal local extinction events triggered by marine heatwaves.

Thermal Response in Two Models of Socks with Different 3-D Weave Separations

Socks with the same three-dimensional plantar design but with different compositions in the separation of their weaves could have different thermoregulatory effects. The objective of this study was therefore to evaluate the temperatures on the sole of the foot after a 10-km run using two models of socks with different weave separations. In a sample of 20 individuals (14 men and 6 women), plantar temperatures were analyzed using a Flir E60bx® (Flir Systems) thermographic camera before and after a run of 10 km wearing two models of socks that had different separations between the fabric weaves (5 mm versus 3 mm). After the post-exercise thermographic analysis, the participants responded to a Likert-type survey to evaluate the physiological characteristics of the two models of socks. There was a significant increase of temperature (+4 °C, p &lt; 0.001) after the 10-km run with both models of sock. However, the temperature under the 1st metatarsal head was higher with the AWC 2.1 model than with the AWC 1 (33.6 ± 2.0 °C vs. 33.2 ± 2.1 °C, p = 0.014). No significant differences were found in the scores on the physiological characteristics comfort survey (p &gt; 0.05 in all cases). The two models presented similar thermoregulatory effects on the soles of the feet, although the model with the narrowest weave separation generated greater temperatures (+0.4 °C) under the first metatarsal head.

Investigation of obesogenic effects of hexachlorobenzene, DDT and DDE in male rats

Obesity has become a very important public health problem and is increasing globally. Genetics, individual and environmental factors play roles in the etiology of this complex disorder. Recently, several environmental pollutants have been suggested to have obesogenic activities. Peroxisome proliferator activating receptor gamma (PPARγ), uncoupling protein-1 (UCP1) and their expression in white adipose tissue (WAT) and brown adipose tissue (BAT) play key roles in adipogenesis. UCP3 and irisin were reported to play roles in non-shivering thermogenesis. Our primary aim was to investigate obesogenic effects of hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) in rats. In addition, thermoregulatory effects of HCB, DDT and DDE were also investigated by analyzing the levels of Ucp3 and irisin. Thirty-two adult male Sprague-Dawley rats were randomly divided into four groups as control, HCB, DDT and DDE. Animals were administered with organochlorine pesticides (OCPs; 5 mg/kg bw) by oral gavage every other day for five weeks. At the end of the experimental period, the animals were sacrificed, BAT and WAT samples were collected to analyze Pparγ, Ucp1 and Ucp3 levels. Moreover, skeletal muscle samples were collected to examine Ucp3 and irisin levels. Serum glucose, cholesterol and triglyceride levels were also determined. Body weight and core temperature of the animals were not significantly affected by any of the OCP administration. Serum glucose, cholesterol and triglyceride levels were similar among the experimental groups. Pparγ expression was significantly elevated by HCB administration only in WAT (p < 0.05). On the other hand, both Pparγ and Ucp1 expressions were diminished in WAT and BAT (p < 0.01) by DDT treatment, while in WAT, DDE significantly decreased Pparγ expression without altering its expression in BAT (p < 0.001). Ucp3 and irisin levels in skeletal muscle were not altered. Our findings show that both DDT and DDE reduce the browning of WAT by suppressing white adipocytes and thus may have obesogenic activity in male rats without altering thermoregulation. In addition, HCB, DDT and DDE-induced alterations in expression of Pparγ and Ucp1 in WAT implicates differential regulation of adipogenic processes.

Bright Light Decreases Peripheral Skin Temperature in Healthy Men: A Forced Desynchrony Study Under Dim and Bright Light (II).

Human thermoregulation is strictly regulated by the preoptic area of the hypothalamus, which is directly influenced by the suprachiasmatic nucleus (SCN). The main input pathway of the SCN is light. Here, thermoregulatory effects of light were assessed in humans in a forced desynchrony (FD) design. The FD experiment was performed in dim light (DL, 6 lux) and bright white light (BL, 1300 lux) in 8 men in a semi-randomized within-subject design. A 4 × 18 h FD protocol (5 h sleep, 13 h wake) was applied, with continuous core body temperature (CBT) and skin temperature measurements at the forehead, clavicles, navel, palms, foot soles and toes. Skin temperature parameters indicated sleep-wake modulations as well as internal clock variations. All distal skin temperature parameters increased during sleep, when CBT decreased. Light significantly affected temperature levels during the wake phase, with decreased temperature measured at the forehead and toes and increased navel and clavicular skin temperatures. These effects persisted when the lights were turned off for sleep. Circadian amplitude of CBT and all skin temperature parameters decreased significantly during BL exposure. Circadian proximal skin temperatures cycled in phase with CBT, while distal skin temperatures cycled in anti-phase, confirming the idea that distal skin regions reflect heat dissipation and proximal regions approximate CBT. In general, we find that increased light intensity exposure may have decreased heat loss in humans, especially at times when the circadian system promotes sleep.

Structure-Based Virtual Screening Identifies Novobiocin, Montelukast, and Cinnarizine as TRPV1 Modulators with Anticonvulsant Activity In Vivo.

The transient receptor potential vanilloid 1 (TRPV1) receptor is a nonselective cation channel, known to be involved in the regulation of many important physiological and pathological processes. In the last few years, it has been proposed as a promising target to develop novel anticonvulsant compounds. However, thermoregulatory effects associated with the channel inhibition have hampered the path for TRPV1 antagonists to become marketed drugs. In this regard, we conducted a structure-based virtual screening campaign to find potential TRPV1 modulators among approved drugs, which are known to be safe and thermally neutral. To this end, different docking models were developed and validated by assessing their pose and score prediction powers. Novobiocin, montelukast, and cinnarizine were selected from the screening as promising candidates for experimental testing and all of them exhibited nanomolar inhibitory activity. Moreover, the in vivo profiles showed promising results in at least one of the three models of seizures tested.

Physiological Effects of Binary Mixtures of Common Bath Salt Constituents: Studies with MDPV, Methylone, and Caffeine in Rats

It is becoming increasingly clear among treatment providers, policy makers, and basic scientists alike, that polysubstance abuse is the norm rather than the exception. This is supported by the increased incidence of drug mixtures in drug overdoses, both fatal and nonfatal. In particular, toxicity produced via use of multiple substances has been highlighted by “bath salts” mixtures, often comprising at least one synthetic cathinone (e.g. 3,4‐methylenedioxypyrovalerone [MDPV] or 3,4‐methylenedioxy‐N‐methylcathinone [methylone]), in addition to other stimulants such as caffeine. Use of these drug mixtures has garnered much attention in the popular press due to frequent reports of bizarre behaviors, and adverse psychiatric (paranoia, hallucinations, aggression) and physiological (tachycardia, hypertension, hyperthermia) events leading to large numbers of emergency room visits and/or death. Although synergistic interactions between the reinforcing effects of common “bath salts” constituents have been observed (e.g., greater than predicted breakpoints under a progressive ratio schedule of reinforcement and greater economic demand), much less is known regarding interactions between the physiological effects of these drugs. The goal of the current study was to characterize the behavioral, cardiovascular, and thermoregulatory effects of MDPV, methylone, and caffeine, and subsequently, to determine the nature of the interactions between binary mixtures of these drugs. Male Sprague Dawley rats were implanted with an intravenous catheter and a radio‐telemetric probe capable of recording core body temperature, heart rate, blood pressure, and locomotor activity. Rats were habituated to the test chamber for one hour before receiving an intravenous infusion of either MDPV (0.032‐3.2 mg/kg), methylone (0.1‐10 mg/kg), caffeine (0.32‐32 mg/kg), or a binary mixture (3:1, 1:1, or 1:3) of methylone+MDPV, methylone+caffeine, or MDPV+caffeine. Recordings continued for six hours following drug administration. MDPV, methylone, and caffeine produced dose‐dependent increases in core body temperature (caffeine &gt; MDPV &gt; methylone), blood pressure (MDPV &gt; caffeine &gt; methylone), heart rate (methylone &gt; MDPV &gt; caffeine), and locomotor activity (MDPV &gt; caffeine = methylone) relative to baseline measurements. MDPV was more potent than methylone, which was more potent than caffeine. Binary mixtures of methylone+MDPV, methylone+caffeine, and MDPV+caffeine resulted in largely additive interactions across all endpoints, with possible departures from additivity observed at the largest dose‐pairs evaluated. These data demonstrate that intravenous administration of either MDPV, methylone, or caffeine alters temperature, heart rate, blood pressure, and locomotor activity in a dose‐dependent manner, consistent with what has been reported in “bath salts” users in emergency room settings. To more deeply characterize the interactions between these constituents, future studies will determine the degree to which the reinforcing and physiological effects of these drug mixtures could be mediated by pharmacokinetic interactions between individual constituents.

Thermoregulatory and cardiovascular responses to up-step change transient thermal environments: A risk factor in individuals with prosthetic heart valves

Exposure to step-change thermal environments can trigger the human body's thermoregulatory processes. The reactivation of thermoregulatory mechanisms is usually accompanied by the excitation of cardiovascular responses. This paper presents a combined thermoregulatory-cardiovascular model for predicting the effect of transient thermal environments on heart rate and cardiovascular responses. The proposed model was validated against multiple sets of experimental data reported in the literature. The validation results showed that the proposed model, which considers the thermoregulatory effects, could predict heart rate more accurately compared to the Givoni and Goldman practical model. The impacts of different up-step temperature changes on cardiovascular responses were investigated using the proposed model. The results showed that exposure to a relatively small (10°C), medium (20°C), and large (30°C) up-step temperature changes increased the heart rate by about 7%, 20%, and 35%, respectively. It was also found that ambient relative humidity did not have remarkable effects on cardiovascular responses. The results of our analysis performed in the temperature range of 20°C to 50°C showed that the heart rate could reflect the reactivation of the body's thermoregulatory mechanisms. The findings indicated that in people with artificial heart valves, sudden exposure to temperature step-changes of 10°C to 30°C could increase the heart valve pressure drop by about 14%–85%, greatly increasing the risk of blood damage. Furthermore, it is concluded that the proposed model can pave the path for utilizing integrated wearable devices for predicting individualized thermal comfort and managing cardiovascular health risks associated with ambient heat stresses.

Терморегуляторные эффекты производных трийодтиронина: in vivo исследование и обзор потенциальных нейропротекторных свойств

Актуальность. Согласно результатам многочисленных клинико-экспериментальных исследований, транзиторная гипотермия представляет собой перспективный способ нейропротекции при ишемическом инсульте. Однако существующие способы индукции гипотермии (как физические, так и фармакологические) обладают значительным количеством нежелательных васкулярных, метаболических и эндокринных побочных эффектов. В течение последних лет все больше внимания уделяется новым индукторам гипотермии, одними из которых являются производные тиреоидных гормонов. Цель исследования: изучить воздействие синтетического аналога тиронамина Т(0)AM на изменение ректальной температуры у белых лабораторных крыс с применением ингаляционного наркоза. Материалы и методы. Исследование было выполнено на 12 белых беспородных лабораторных крысах, разделенных на экспериментальную и контрольную группы. Крысам контрольной группы вводили интраперитонеально 2 мл воды для инъекций, крысам экспериментальной группы — синтетический аналог Т(0)АМ в концентрации 50 мг/кг, растворенный в 2 мл воды для инъекций. У животных всех групп под галотановым ингаляционным наркозом измеряли ректальную температуру в течение 30 минут с интервалом в 3 минуты. Также однократно измеряли температуры через 60 минут после введения препарата у проснувшихся крыс. Статистическую обработку полученных данных проводили с помощью программ Microsoft Office Excel 2007 и MedCalc 14.1. Для сравнения различий между группами использовали t-тест для независимых выборок и тест ANOVA. Для сравнения температурных данных до и после введения синтетического аналога тиронамина использовали W-критерий Уилкоксона. Результаты. В ходе экспериментального исследования нами описано криогенное действие синтетического аналога дейодированной формы тиронамина T(0)AM. Показано, что внутрибрюшинное введение 50 мг/кг препарата лабораторным крысам приводит к быстрому обратимому снижению температуры тела в среднем на 2,5 °С (95% доверительный интервал 2,2–2,8 °С). Продемонстрировано независимое от другого индуктора гипотермии (галотана) действие синтетического аналога тиронамина. В обзоре литературы с акцентом на нейропротекцию предпринята попытка идентифицировать механизмы гипотермического действия тиронамина и обосновать выбор направлений для дальнейших клинико-экспериментальных исследований. Выводы. Полученные в ходе исследования данные подтверждают влияние синтетического аналога тиронамина Т(0)AM на процессы термогенеза, при этом гипотермические эффекты тиронамина не связаны с действием ингаляционного наркоза. Паттерн снижения температуры тела на фоне введения синтетического аналога тиронамина свидетельствует об отличном от галотана механизме действия.

Ethanol pre-exposure differentially impacts the rewarding and aversive effects of α-pyrrolidinopentiophenone (α-PVP): Implications for drug use and abuse

RationaleExposure to a drug can subsequently impact its own reactivity as well as that of other drugs. Given that users of synthetic cathinones, i.e., “bath salts”, typically have extensive and varied drug histories, an understanding of the effects of drug history on the behavioral and physiological consequences of synthetic cathiones may be important to their abuse liability. ObjectivesThe goal of the current work was to assess the effects of an ethanol pre-exposure on the rewarding and aversive effects of α-PVP. MethodsAdult male Sprague Dawley rats were exposed to ethanol prior to combined conditioned taste avoidance/conditioned place preference training in which rats were injected with 1.5, 3 or 5 mg/kg of racemic α-PVP or vehicle. Following a 7-day washout period, rats were then tested for thermoregulatory effects of α-PVP using subcutaneous probes to measure body temperature changes over the course of 8 h. This was followed 10 days later by assessments for α-PVP-induced locomotor activity and stereotypies over a 1-h session. Resultsα-PVP induced significant dose- and trial-dependent taste avoidance that was significantly attenuated by ethanol history and dose- and time-dependent increases in locomotor activity that were significantly increased by ethanol. α-PVP also induced place preferences and dose- and time-dependent increases in body temperature, but these measures were unaffected by ethanol history. Conclusionsα-PVP's aversive effects (as measured by taste avoidance) were attenuated, while its rewarding effects (as indexed by place preference conditioning) were unaffected, by ethanol pre-exposure. Such a pattern may indicate increased α-PVP abuse liability, as changes in the balance of aversion and reward may impact overall drug effects and likelihood of drug intake. Future self-administration studies will be necessary to explore this possibility.