Alterations In Body Temperature Research Articles

Topically applied novel TRPV1 receptor antagonist, ACD440 Gel, reduces evoked pain in healthy volunteers, a randomized, double-blind, placebo-controlled, crossover study.

The TRPV1 receptor is a key molecule in pain generation. Previous development of oral TRPV1-antagonists was halted due to systemic heat insensitivity and body temperature alterations. The present Phase 1b study investigated the efficacy, safety and plasma exposure of a topically administered TRPV1-antagonist (ACD440 Gel) in healthy subjects. The study comprised two parts. In part 1, 24 healthy subjects were included in this randomized double-blind, placebo-controlled, crossover trial. ACD440 Gel or Placebo was applied once daily and wiped off after 1 h, for 5 consecutive days. Assessments were done in normal skin, skin optimized for penetration (by stripping and occlusive gel application) and UVB-irradiated skin. Pain induced by thermo-nociceptive CO2 laser impulses generated laser-evoked potentials (LEPs), with readouts of peak-to-peak (PtP) amplitude in vertex-EEG and pain assessments by VAS (0-100). Endpoints include effects at 1 hour post-dose, AUC(Days 1-5) and AUC(0-24, Day 4). In UVB-irradiated skin, also pain on pinprick and skin redness were assessed. Part 2 explored the plasma pharmacokinetics of ACD440. ACD440 Gel reduced LEP PtP amplitude and VAS pain, p < 0.001, in all skin conditions, versus placebo. In UVB-irradiated skin, pinprick pain was also reduced, p = 0.047. Effects were significant after 1 h, maintaining for at least 9 h. There were no adverse events or drug-induced erythema. Plasma exposures of ACD440 were too low to establish an elimination half-life of ACD400. Topical ACD440 Gel demonstrated a significant analgesic effect on LEP, VAS score and pinprick pain, with low systemic exposures, supporting further clinical development. This study demonstrates that the topical administration of a TRPV1-antagonist, ACD440 Gel, has potential as a new treatment for painful conditions affecting the skin, such as chronic peripheral neuropathic pain, without any local or systemic side effects.

Elevated body temperature is associated with depressive symptoms: results from the TemPredict Study

Correlations between altered body temperature and depression have been reported in small samples; greater confidence in these associations would provide a rationale for further examining potential mechanisms of depression related to body temperature regulation. We sought to test the hypotheses that greater depression symptom severity is associated with (1) higher body temperature, (2) smaller differences between body temperature when awake versus asleep, and (3) lower diurnal body temperature amplitude. Data collected included both self-reported body temperature (using standard thermometers), wearable sensor-assessed distal body temperature (using an off-the-shelf wearable sensor that collected minute-level physiological data), and self-reported depressive symptoms from > 20,000 participants over the course of ~ 7 months as part of the TemPredict Study. Higher self-reported and wearable sensor-assessed body temperatures when awake were associated with greater depression symptom severity. Lower diurnal body temperature amplitude, computed using wearable sensor-assessed distal body temperature data, tended to be associated with greater depression symptom severity, though this association did not achieve statistical significance. These findings, drawn from a large sample, replicate and expand upon prior data pointing to body temperature alterations as potentially relevant factors in depression etiology and may hold implications for development of novel approaches to the treatment of major depressive disorder.

Hypothalamic Thyroid Hormone Receptor α1 Signaling Controls Body Temperature.

Background: The importance of thyroid hormones (THs) for peripheral body temperature regulation has been long recognized, as medical conditions such as hyper- and hypothyroidism lead to alterations in body temperature and energy metabolism. In the past decade, the brain actions of THs and their respective nuclear receptors, thyroid hormone receptor α1 (TRα1) and thyroid hormone receptor beta (TRβ), coordinating body temperature regulation have moved into focus. However, the exact roles of the individual TR isoforms and their precise neuroanatomical substrates remain poorly understood. Methods: Here we used mice expressing a mutant TRα1 (TRα1+m) as well as TRβ knockouts to study body temperature regulation using radiotelemetry in conscious and freely moving animals at different ambient temperatures, including their response to oral 3,3',5-triiodothyronine (T3) treatment. Subsequently, we tested the effects of a dominant-negative TRα1 on body temperature after adeno-associated virus (AAV)-mediated expression in the hypothalamus, a region known to be involved in thermoregulation. Results: While TRβ seems to play a negligible role in body temperature regulation, TRα1+m mice had lower body temperature, which was surprisingly not entirely normalized at 30°C, where defects in facultative thermogenesis or tail heat loss are eliminated as confounding factors. Only oral T3 treatment fully normalized the body temperature profile of TRα1+m mice, suggesting that the mutant TRα1 confers an altered central temperature set point in these mice. When we tested this hypothesis more directly by expressing the dominant-negative TRα1 selectively in the hypothalamus via AAV transfection, we observed a similarly reduced body temperature at room temperature and 30°C. Conclusion: Our data suggest that TRα1 signaling in the hypothalamus is important for maintaining body temperature. However, further studies are needed to dissect the precise neuroanatomical substrates and the downstream pathways mediating this effect.

Analgesic effect of neohesperidin is mediated by TRPV1 antagonism

Context: Transient receptor potential vanilloid type 1 (TRPV1) is a non-specific cation channel. It is one of the most important targets in pain research. Aims: To evaluate new TRPV1 antagonists without altering body temperature. Methods: Docking simulation was performed, and one of the candidate compounds, neohesperidin, was tested using thermal and chemical pain models in BALB/c mice. Rectal body temperature was measured using a temperature meter with a thermocouple probe detector, and the capsaicin-evoked calcium response was determined in dorsal root ganglia (DRG) neurons. Results: Docking resulted in the identification of 30 compounds able to interact with the essential amino acids required for the antagonistic activity of TRPV1. Neohesperidin was chosen for further investigations because of its good binding energy (-6.63 kcal/mol) and because its TRPV1 antagonistic activity was not tested before. This study reported for the first time that neohesperidin exerted analgesic activity through TRPV1 antagonism without altering body temperature. Its activity was comparable to the known TRPV1 antagonist N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC). In the writhing test, acetic acid-induced abdominal cramps decreased by 66% using 30 mg/kg of neohesperidin. All tested doses of neohesperidin significantly decreased paw-licking time in the capsaicin-induced paw-licking test. A significant increase in the latency time in hot plate and tail flick tests was observed using 30 and 60 mg/kg of neohesperidin. In DRG neurons, neohesperidin reduced capsaicin-evoked calcium responses. Conclusions: Neohesperidin exerts a significant analgesic activity without altering body temperature, which could be due, at least partially, to its antagonistic activity against TRPV1.

Sleep and Core Body Temperature Alterations Induced by Space Radiation in Rats.

Sleep problems in astronauts can arise from mission demands and stress and can impact both their health and ability to accomplish mission objectives. In addition to mission-related physical and psychological stressors, the long durations of the proposed Mars missions will expose astronauts to space radiation (SR), which has a significant impact on the brain and may also alter sleep and physiological functions. Therefore, in this study, we assessed sleep, EEG spectra, activity, and core body temperature (CBT) in rats exposed to SR and compared them to age-matched nonirradiated rats. Male outbred Wistar rats (8-9 months old at the time of the study) received SR (15 cGy GCRsim, n = 15) or served as age- and time-matched controls (CTRL, n = 15) without irradiation. At least 90 days after SR and 3 weeks prior to recording, all rats were implanted with telemetry transmitters for recording EEG, activity, and CBT. Sleep, EEG spectra (delta, 0.5-4 Hz; theta, 4-8 Hz; alpha, 8-12 Hz; sigma, 12-16 Hz; beta, 16-24 Hz), activity, and CBT were examined during light and dark periods and during waking and sleeping states. When compared to the CTRLs, SR produced significant reductions in the amounts of dark period total sleep time, total nonrapid eye movement sleep (NREM), and total rapid eye movement sleep (REM), with significant decreases in light and dark period NREM deltas and dark period REM thetas as well as increases in alpha and sigma in NREM and REM during either light or dark periods. The SR animals showed modest increases in some measures of activity. CBT was significantly reduced during waking and sleeping in the light period. These data demonstrate that SR alone can produce alterations to sleep and temperature control that could have consequences for astronauts and their ability to meet mission demands.

The Acute Effect of Chlorpromazine on Body Temperature in Intensive Care Unit Patients

Aim: Hypothermia is a rare complication of antipsychotic drugs but serious outcomes including death may result. In this study, we aimed to investigate body temperature alterations in acute phase of chlorpromazine treatment, the relationship of inflammatory indicators and risk factors for hypothermic effect in intensive care unit (ICU) patients.&#x0D; Materials and methods: 63 intensive care patients who needed sedative treatment due to agitation were divided into two groups as Group 1 (n = 30) with temperatures ≤ 38°C, and Group 2 (n = 33) with temperatures &gt; 38°C according to baseline body temperatures. Also, recurrent measurements for 12 hours were made at specific intervals following 25 mg intravenous chlorpromazine. &#x0D; Results: In Group 1, decrease in body temperatures was significant from 4th to 12th hours (p &lt; 0.01), while in Group 2, significant decreases in body temperatures at all measurement hours were observed (p &lt; 0.01). Temperature changes (delta temperature) observed at specific measurement intervals were significantly higher in Group 2 compared to Group 1. That difference was statistically significant at all intervals except for ΔTemperature B-6 (p &lt; 0.05). The odds of hypothermic effects by chlorpromazine were 16%, 46%, 3%, and 18% for Acute Physiology and Chronic Health Evaluation II, procalcitonin, C-reactive protein, and white blood cells, respectively. &#x0D; Conclusion: Chlorpromazine treatment applied for agitation in ICU patients was associated with acute hypothermic effect. Severity of disease and comorbidities might increase risk of hypothermia, and inflammatory biomarkers might be predictors of adverse drug reaction.

AARC Clinical Practice Guidelines: Capillary Blood Gas Sampling for Neonatal and Pediatric Patients.

In the absence of an indwelling arterial catheter, capillary blood gas sampling may be used to evaluate the acid/base and ventilation status of neonatal and pediatric patients with cardiorespiratory conditions. These guidelines were developed from a comprehensive review of the literature to provide guidance for the collection, handling, and interpretation of blood obtained from an arterialized capillary sample. Capillary and venous blood gas measurements are a useful alternative to arterial blood gas measurements for neonatal and pediatric patients who do not require close monitoring of [Formula: see text] In the presence of alterations in body temperature, blood pressure, or peripheral perfusion, agreement between a capillary blood gas with an arterial sample is recommended to determine whether changes in these physiologic conditions reduce reliability. Perfusion to the sample site should be assessed and preference given to blood sampling from a well perfused site, and blood should be analyzed within 15 min of sampling to minimize the propensity for pre-analytical errors. Clinicians should consider re-collecting a blood sample, obtained from an artery, vein, or capillary, when the blood gas or analyte result interpretation does not align with the patient's clinical presentation. A pneumatic tube system can be reliably used to transport blood gas samples collected in a syringe and capillary tube to a clinical laboratory for analysis. To reduce the cumulative pain effect and risk of complications, the capillary puncture procedure should be minimized when possible. Non-pharmacologic interventions should be used to reduce pain associated with capillary blood gas sampling. Automatic lancets are preferred to puncture the skin for capillary blood gas collection.

Self-assembly drug-albumin nanocomposites for nonalcoholic fatty liver disease treatment

Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease closely related to obesity, which has become a global health problem. However, current pharmacological therapies for NAFLD are limited by potential side effects, low effectiveness and poor aqueous solubility. Herein, we designed functionalized drug-albumin nanocomposites (BAM15@BSA NPs), which were prepared by self-assembly of the anti-obesity small-molecule drug (BAM15) and bovine serum albumin (BSA), for treatment of NAFLD. The proposed BAM15@BSA NPs not only improve aqueous solubility and half-life of BAM15 but also exhibit hepatic-targeted capacity and an increased therapeutic efficacy. In vitro experiments revealed that BAM15@BSA NPs possessed excellent biocompatibility, and improved resistance to adipogenesis and reduced lipid accumulation in human hepatocellular carcinoma cells. In vivo, BAM15@BSA NPs showed liver targeting ability and powerful anti-obesity effects without altering body temperature or affecting food intake, and could effectively alleviate hepatic steatosis and improve therapeutic efficacy for NAFLD treatment. The above findings demonstrated that BAM15@BSA NPs potentially served as a safe and effective drug for NAFLD treatment.

A preoptic neuronal population controls fever and appetite during sickness.

During infection, animals exhibit adaptive changes in physiology and behaviour aimed at increasing survival. Although many causes of infection exist, they trigger similar stereotyped symptoms such as fever, warmth-seeking, loss of appetite and fatigue1,2. Yet exactly how the nervous system alters body temperature and triggers sickness behaviours to coordinate responses to infection remains unknown. Here we identify a previously uncharacterized population of neurons in the ventral medial preoptic area (VMPO) of the hypothalamus that are activated after sickness induced by lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid. These neurons are crucial for generating a fever response and other sickness symptoms such as warmth-seeking and loss of appetite. Single-nucleus RNA-sequencing and multiplexed error-robust fluorescence in situ hybridization uncovered the identity and distribution of LPS-activated VMPO (VMPOLPS) neurons and non-neuronal cells. Gene expression and electrophysiological measurements implicate a paracrine mechanism in which the release of immune signals by non-neuronal cells during infection activates nearby VMPOLPS neurons. Finally, we show that VMPOLPS neurons exert a broad influence on the activity of brain areas associated with behavioural and homeostatic functions and are synaptically and functionally connected to circuit nodes controlling body temperature and appetite. Together, these results uncover VMPOLPS neurons as a control hub that integrates immune signals to orchestrate multiple sickness symptoms in response to infection.

Behavior and body temperature alterations in piglets anesthetized for castration during a four-hour recovery phase

One way to eliminate pain during surgical castration is to provide general anesthesia by intramuscular injection. However, its disadvantage is the long recovery phase, during which anesthetized piglets have to be separated from the sow and managed appropriately. In this study, rectal temperatures, respiration rate, soiling and behavior changes were monitored in 119 piglets for 4 h after the intramuscularly administration of a ketamine-azaperone-mixture for general anesthesia and castration. The study aimed to identify the least distressing form of separation. For this, different types of separation containers, farm equipment and heat sources were used in 3 individual trials during separation of piglets. Over the course of the recovery period, body temperatures and behaviors of piglets underwent significant alterations. The temperature span was largest after 2 h in all trials (35.0–42.6 °C). Rectal temperatures were influenced by the kind of separation, heat provision, and age: Piglets separated in boxes were warmer than piglets separated in crate corners (P = 0.0016). Non-warmed piglets had lower temperatures than fully (P < 0.0001) warmed piglets. Additionally, rectal temperatures of 4-days old piglets were lower than those of 5-days old ones after 2 h (P < 0.0001). Piglets were more soiled after 4 h when they were not warmed compared to piglets in containers fully warmed (P < 0.0001). The kind of container also had an effect on soiling, as scores were higher after 2 h for piglets kept in buckets than those in perforated boxes (P = 0.0522). Warmed piglets breathed more frequently than non-warmed piglets (P = 0.0039). The behaviors pedaling and lying were more prominent in the first 2 h of the recovery period, while moving forward and head bumping occurred more often in the later half. The behavior slipping was only observed in buckets. It was concluded that the recovery phase is a stressful experience, especially for very young piglets. This means that piglets need to be taken care of appropriately to ensure that animal welfare is not reduced past a general anesthesia, which was originally applied to increase welfare during a painful intervention. Anesthetized piglets need to be warmed and possibly dried during the recovery phase to avoid life-threatening cooling.

Single-surface Intensive Phototherapy or Double-Surface Intensive Phototherapy in Neonatal Non-Hemolytic Hyperbilirubinemia: A Comparison of Effectiveness and Complications.

Background: Severe indirect hyperbilirubinemia causes neurotoxicity, leading to potential permanent injuries to the neonatal nervous system. The present study intended to compare the effectiveness and complications of Single-Surface Intensive Phototherapy (SSIP) and Double-Surface Intensive Phototherapy (DSIP) in treating non-hemolytic hyperbilirubinemia in the neonatal ward of the Besat Hospital, Hamadan, Iran. Methods: In this prospective randomized clinical trial, 150 healthy full-term neonates born between 37-42 weeks gestation with ages <14 days old and birth weights ≥2500 gr who were affected by non-hemolytic hyperbilirubinemia with total serum bilirubin of 15-20 mg/dL were randomly allocated to two groups. Each group (n=75) underwent either SSIP or DSIP. Demographics, bilirubin level alterations, weight, platelet count, number of defecation per day, and body temperature of the patients were monitored and recorded in a specific questionnaire. Data analysis was performed using SPSS version 26.0 software, with the Chi-square and independent t-test. Results: The pre-intervention levels of indirect bilirubin were 17.07±1.46 mg/dL in the SSIP group and 17.10±1.54 mg/dL in the DSIP group (P-value = 0.853). After 24 and 48 hours of treatment, the mean indirect bilirubin level of the SSIP group reduced to 13.12±1.71 mg/dL and 9.69±1.68 mg/dL, respectively. In the DSIP group, the levels were 11.85±2.17 mg/dL and 8.43±1.56 mg/dL after 24 and 48 hours of treatment, respectively. The absolute reductions of indirect bilirubin were 7.76±3.28 mg/dL for the SSIP group and 8.96±4.49 mg/dL for the DSIP group (P-value = 0.458). Therefore, the indirect bilirubin levels were significantly different between the groups after 24 and 48 hours of treatment and at the time of discharge (P<0.05). There were no significant inter-group differences in weight, platelet count, and incidence of skin rash, while the number of defecation and body temperature were higher in the DSIP group (P <0.05). However, body temperature alterations had no clinical relevance. Conclusion: Compared to the SSIP, the DSIP showed faster effectiveness and led to a shorter hospital stay, while it did not entail higher levels of complications.

Rational Design of a Modality-Specific Inhibitor of TRPM8 Channel against Oxaliplatin-Induced Cold Allodynia.

Platinum‐based compounds in chemotherapy such as oxaliplatin often induce peripheral neuropathy and neuropathic pain such as cold allodynia in patients. Transient Receptor Potential Melastatin 8 (TRPM8) ion channel is a nociceptor critically involved in such pathological processes. Direct blockade of TRPM8 exhibits significant analgesic effects but also incurs severe side effects such as hypothermia. To selectively target TRPM8 channels against cold allodynia, a cyclic peptide DeC‐1.2 is de novo designed with the optimized hot‐spot centric approach. DeC‐1.2 modality specifically inhibited the ligand activation of TRPM8 but not the cold activation as measured in single‐channel patch clamp recordings. It is further demonstrated that DeC‐1.2 abolishes cold allodynia in oxaliplatin treated mice without altering body temperature, indicating DeC‐1.2 has the potential for further development as a novel analgesic against oxaliplatin‐induced neuropathic pain.

TRPM8 modulates temperature regulation in a sex-dependent manner without affecting cold-induced bone loss.

Trpm8 (transient receptor potential cation channel, subfamily M, member 8) is expressed by sensory neurons and is involved in the detection of environmental cold temperatures. TRPM8 activity triggers an increase in uncoupling protein 1 (Ucp1)-dependent brown adipose tissue (BAT) thermogenesis. Bone density and marrow adipose tissue are both influenced by rodent housing temperature and brown adipose tissue, but it is unknown if TRPM8 is involved in the co-regulation of thermogenesis and bone homeostasis. To address this, we examined the bone phenotypes of one-year-old Trpm8 knockout mice (Trpm8-KO) after a 4-week cold temperature challenge. Male Trpm8-KO mice had lower bone mineral density than WT, with smaller bone size (femur length and cross-sectional area) being the most striking finding, and exhibited a delayed cold acclimation with increased BAT expression of Dio2 and Cidea compared to WT. In contrast to males, female Trpm8-KO mice had low vertebral bone microarchitectural parameters, but no genotype-specific alterations in body temperature. Interestingly, Trpm8 was not required for cold-induced trabecular bone loss in either sex, but bone marrow adipose tissue in females was significantly suppressed by Trpm8 deletion. In summary, we identified sex differences in the role of TRPM8 in maintaining body temperature, bone microarchitecture and marrow adipose tissue. Identifying mechanisms through which cold temperature and BAT influence bone could help to ameliorate potential bone side effects of obesity treatments designed to stimulate thermogenesis.

The role of body temperature on respiratory rate in children with acute respiratory infections.

The World Health Organization (WHO) recommends the use of tachypnea as a proxy to the diagnosis of pneumonia. The purpose of this study was to examine the relationship between body temperature alterations and respiratory rate (RR) difference (RRD) in children with acute respiratory infections(ARI). This cross-sectional study included 297 children with age 2-60 months who presented with cough and fever at the pediatric emergency and outpatient clinics in the Department of Pediatrics, Baskent University Hospital, from January 2016 through June 2018. Each parent completed a structured questionnaire to collect background data. Weight and height were taken. Body temperature, respiratory rate, presence of the chest indrawing, rales, wheezing and laryngeal stridor were also recorded. RRD was defined as the differences in RR at admission and after 3 days of treatment. Both respiratory rate and RRD were moderately correlated with body temperature (r=0.71, p<0.001 and r=0.65, p<0.001; respectively). For every 1°C increase in temperature, RRD increased by 5.7/minutes in overall, 7.2/minute in the patients under 12 months of age, 6.4/minute in the female. The relationship between body temperature and RRD wasn't statistically significant in patients with rhonchi, chest indrawing, and low oxygen saturation. Respiratory rate should be evaluated according to the degree of body temperature in children with ARI. However, the interaction between body temperature and respiratory rate could not be observed in cases with rhonchi and severe pneumonia.

Conditional knockout of kisspeptin signaling in brown adipose tissue increases metabolic rate and body temperature and lowers body weight.

The peptide kisspeptin and its receptor, Kiss1r, act centrally to stimulate reproduction. Evidence indicates that kisspeptin signaling is also important for body weight (BW) and metabolism. We recently reported that Kiss1r KO mice develop obesity, along with reduced metabolism and energy expenditure, independent of estradiol levels. Outside the brain, Kiss1r is expressed in several metabolic tissues, including brown adipose tissue (BAT), but it is unknown which specific tissue is responsible for the metabolic phenotype in Kiss1r KOs. We first determined that global Kiss1r KO mice have significant alterations in body temperature and BAT thermogenic gene expression, perhaps contributing to their obesity. Next, to test whether kisspeptin signaling specifically in BAT influences BW, metabolism, or body temperature, we used Cre/lox technology to generate conditional Kiss1r knockout exclusively in BAT (BAT-Kiss1r KO). Unlike global Kiss1r KOs, BAT-Kiss1r KOs (lacking Kiss1r in just BAT) were not hypogonadal, as expected. Surprisingly, however, BAT-Kiss1r KOs of both sexes displayed significantly lower BW and adiposity than controls. This novel BAT-Kiss1r KO phenotype was of greater magnitude in females and was associated with improved glucose tolerance, increased metabolism, energy expenditure, and locomotor activity, along with increased body temperature and BAT gene expression, specifically Cox8b. Our findings suggest that the previously observed obesity and decreased metabolism in global Kiss1r KOs reflect impaired kisspeptin signaling in non-BAT tissues. However, the novel finding of increased metabolism and body temperature and lower BW in BAT-Kiss1r KOs reveal a previously unidentified role for endogenous kisspeptin signaling in BAT in modulating metabolic and thermogenic physiology.

Kinetic studies on clinical and immunological modulations by intramuscular injection of Escherichia coli LPS in laying hens.

The present study investigated clinical and immunological modulations due to intramuscular injection of Escherichia coli LPS in 49-wk-old laying hens over 48 h post injection (p.i.). LPS induced characteristic sickness behavior but no significant body temperature alterations (P > 0.05). During experimental period decreases in blood albumin, calcium, phosphorus and tryptophan concentrations, hyperglycemia, increased plasma nitrite concentrations, leucopenia, decreased thrombocyte counts, lymphopenia, heterophilia and an increased heterophilic granulocyte/lymphocyte (H/L) ratio were observed after LPS administration. Time-dependent effects were shown on T and B cell subsets in caecal tonsils (CT) and on splenic CD3+/CD4+/CD8+ proportions, on IL-1β and -10 and inducible NO synthase mRNA expression in peripheral blood lymphocytes (PBL), liver, spleen and CT, and on the mRNA expression of the TLR4 in PBL, liver and spleen p.i. (P < 0.05). The main responding period of mentioned alterations due to LPS appears to include the period from 2 until 8 h p.i. According to the H/L ratio, the most stressful phase was 5 h p.i. T and B cell subsets in CT, the IL-1β and TLR4 mRNA expression in liver and plasma nitrite concentrations seemed to be affected for a longer period.

Hypercapnic and Hypoxic Respiratory Response During Wakefulness and Sleep in a Streptozotocin Model of Alzheimer’s Disease in Rats

Besides the typical cognitive decline, patients with Alzheimer's disease (AD) develop disorders of the respiratory system, such as sleep apnea, shortness of breath, and arrhythmias. These symptoms are aggravated with the progression of the disease. However, the cause and nature of these disturbances are not well understood. Here, we treated animals with intracerebroventricular streptozotocin (STZ, 2 mg/kg), a drug that has been described to cause Alzheimer-like behavioral and histopathological impairments. We measured ventilation (V̇E), electroencephalography, and electromyography during normocapnia, hypercapnia, and hypoxia in Wistar rats. In addition, we performed western blot analyses for phosphorylated tau, total tau, and amyloid-β (Aβ) peptide in the locus coeruleus (LC), retrotrapezoid nucleus, medullary raphe, pre-Bötzinger/Bötzinger complex, and hippocampus, and evaluated memory and learning acquisition using the Barnes maze. STZ treatment promoted memory and learning deficits and increased the percentage of total wakefulness during normocapnia and hypercapnia due to a reduction in the length of episodes of wakefulness. CO2-drive to breathe during wakefulness was increased by 26% in STZ-treated rats due to an enhanced tidal volume, but no changes in V̇E were observed in room air or hypoxic conditions. The STZ group also showed a 70% increase of Aβ in the LC and no change in tau protein phosphorylation. In addition, no alteration in body temperature was observed. Our findings suggest that AD animals present an increased sensitivity to CO2 during wakefulness, enhanced Aβ in the LC, and sleep disruption.

The Transient Receptor Potential Vanilloid Type 1 Ion Channel in Hypometabolic Response to Hypoxia

When challenged with low levels of available oxygen (hypoxia), larger mammals, including humans, attempt to maintain a consistent oxygen supply by increasing their rate of respiration. Smaller rodents and newborn mammals, on the other hand, respond to hypoxia by curtailing oxygen consumption. This latter process (hypoxic hypometabolism) involves actively regulated reductions in both metabolic rate and body temperature (3; 4; 9). Despite more than 50 years of investigation, the molecular mechanisms of this intriguing process are still unclear. Recently, the transient receptor potential vanilloid type 1 (TRPV1) receptor (best known for its response to capsaicin) has been implicated in the regulation of body temperature (5). Evidence includes the ability of TRPV1 receptor agonists and antagonists to lower and raise body temperature respectively (6; 7), as well as a demonstrated site of action within thehypothalamus (the area of the brain responsible for the regulation of body temperature) (1; 2). Based on the parallel but separately identified roles of hypoxia and TRPV1 in controlling body temperature, we reasoned that the TRPV1 ion channel may be implicated in hypoxia-induced alterations in body temperature. This present study investigates the potential involvement of the TRPV1 ion channel in hypoxia mediated hypothermia by comparing the hypoxic responses of wild-type mice and transgenetic knockout animals lacking a functional TRPV1 gene. We hypothesize that the TRPV1 knockout animals will show a blunted hypothermic response to hypoxic challenge.

Rectal and Bladder Temperatures vs Forehead Core Temperatures Measured With SpotOn Monitoring System.

Methods and frequency of temperature monitoring in intensive care unit patients vary widely. The recently available SpotOn system uses zero-heat-flux technology and offers a noninvasive method for continuous monitoring of core temperature of critical care patients at risk for alterations in body temperature. To evaluate agreement between and precision of a zero-heat-flux thermometry system (SpotOn) and continuous rectal and urinary bladder thermometry during fever and defervescence in adult patients in intensive care units. Prospective comparison of SpotOn vs rectal and urinary bladder thermometry in eligible patients enrolled in a randomized clinical trial on the effect of acetaminophen on core body temperature and hemodynamic status. A total of 748 paired temperature measurements from 38 patients who had both SpotOn monitoring and either continuous rectal or continuous bladder thermometry were analyzed. Temperatures during the study were from 36.6°C to 39.9°C. The mean difference for SpotOn compared with bladder thermometry was -0.07°C (SD, 0.24°C; 95% limits of agreement, ± 0.47°C [-0.54°C, 0.40°C]). The mean difference for SpotOn compared with rectal thermometry was -0.24°C (SD, 0.29°C; 95% limits of agreement, ± 0.57°C [-0.81°C, 0.33°C]). Most differences in temperature between methods were within ± 0.5°C in both groups (96% bladder and 85% rectal). The SpotOn thermometry system has excellent agreement and good precision and is a potential alternative for noninvasive continuous monitoring of core temperature in critical care patients, especially when alternative methods are contraindicated or not available.

Estradiol alters body temperature regulation in the female mouse

ABSTRACTHot flushes are due to estrogen withdrawal and characterized by the episodic activation of heat dissipation effectors. Recent studies (in humans and rats) have implicated neurokinin 3 (NK3) receptor signaling in the genesis of hot flushes. Although transgenic mice are increasingly used for biomedical research, there is limited information on how 17β-estradiol and NK3 receptor signaling alters thermoregulation in the mouse. In this study, a method was developed to measure tail skin temperature (TSKIN) using a small data-logger attached to the surface of the tail, which, when combined with a telemetry probe for core temperature (TCORE), allowed us to monitor thermoregulation in freely-moving mice over long durations. We report that estradiol treatment of ovariectomized mice reduced TCORE during the light phase (but not the dark phase) while having no effect on TSKIN or activity. Estradiol also lowered TCORE in mice exposed to ambient temperatures ranging from 20 to 36°C. Unlike previous studies in the rat, estradiol treatment of ovariectomized mice did not reduce TSKIN during the dark phase. Subcutaneous injections of an NK3 receptor agonist (senktide) in ovariectomized mice caused an acute increase in TSKIN and a reduction in TCORE, consistent with the activation of heat dissipation effectors. These changes were reduced by estradiol, suggesting that estradiol lowers the sensitivity of central thermoregulatory pathways to NK3 receptor activation. Overall, we show that estradiol treatment of ovariectomized mice decreases TCORE during the light phase, reduces the thermoregulatory effects of senktide and modulates thermoregulation differently than previously described in the rat.