Thyroid and pituitary-adrenal activity in patients with asthma and endemic subclinical hypothyroidism in response of respiratory tract to a cold stimulus

Introduction. In patients with uncontrolled asthma, the stress-induced production of glucocorticosteroids in response to a cold bronchoprovocation test is increased, which is associated with an increase in the level of thyroidstimulating hormone (TSH), characteristic of the syndrome of subclinical hypothyroidism (SH). The peculiarities of thyroid hormone metabolism and changes in pituitary-adrenal homeostasis that develop in asthma in a goiter-endemic region under the influence of cold stress factors on the respiratory system are poorly studied.Aim. To assess the activity of the pituitary-thyroid and pituitary-adrenal systems in response to bronchoprovocation with cold air in asthma patients with cold airway hyperresponsiveness (CAHR) and SH living in conditions of goiter endemic in the Amur Region.Materials and methods. In 34 asthma patients with CAHR, without symptoms of thyroid diseases, the level of disease control was assessed using the Asthma Control Test (ACT) questionnaire. Lung function and airway reaction to a cold stimulus (ΔFEV1IHCA) during 3-minute isocapnic hyperventilation with cold (-20ºC) air (IHCA) were measured. Methods of immunological diagnostics in the blood of patients before and after the IHCA test were used to measure the concentrations of thyroid-stimulating (TSH) and adrenocorticotropic (ACTH) hormones, common and active forms of thyroxine (T4) and triiodothyronine (T3), thyroglobulin (TG), autoantibodies to thyroperoxidase (AB-TPO), cortisol. The content of cyclic adenosine monophosphate (cAMP) was determined in leukocytes.Results. The patients were divided into two groups: group 1 included 25 patients with an initially low (<4.0) TSH level (2.39±0.18 mU/L), group 2 included 9 patients with an initially high (>4, 0) TSH level (4.80±0.46 mU/L, p<0.0001). The ACT control level in groups 1 and 2 was 16.6±1.0 and 15.3±1.5 points (p>0.05), base FEV1 was 95.8±3.3 and 81.0±5.4% (p=0.026), ΔFEV1IHCA -11.9±0.96 and -13.5±2.7 (p>0.05), respectively. In group 1, in response to IHCA, the level of free T4 increased from 14.2±0.70 to 15.2±0.71 pmol/L (p<0.05), free T3 from 3.73±0.24 to 4.15±0.21 nmol/L (p<0.05). In group 2, a lower level of free T4 was recorded, both before (12.2±1.52 pmol/L) and after IHCA (11.6±1.60 pmol/L, p=0.041). In addition, in group 2 patients, the cortisol concentration at baseline and after IHCA (516.6±31.6 and 397.4±40.4 nmol/L, p<0.05) was significantly lower than in group 1 (628.3±27.5 and 608.3±34.1 nmol/L, p=0.042; p=0.002, respectively). A close correlation was found between ΔFEV1 and the T4 level before (r=0.54; p<0.01) and after the test (r=0.41; p<0.05), with the amount of cAMP up to (r=0.58; p=0.008) and after the test (r=0.47; p=0.009), as well as the correlation between ΔМEF50 and the initial level of cortisol in the blood serum (r=0.50; p=0.002).Conclusion. In asthma patients with CAHR living in the region of cold climate and goiter endemic, the presence of SH can be considered as a prognostic sign of the development of dysadaptation of the respiratory system to cold exposure.

BMP8 and activated brown adipose tissue in human newborns

The classical dogma states that brown adipose tissue (BAT) plays a major role in the regulation of temperature in neonates. However, although BAT has been studied in infants for more than a century, the knowledge about its physiological features at this stage of life is rather limited. This has been mainly due to the lack of appropriate investigation methods, ethically suitable for neonates. Here, we have applied non-invasive infrared thermography (IRT) to investigate neonatal BAT activity. Our data show that BAT temperature correlates with body temperature and that mild cold stimulus promotes BAT activation in newborns. Notably, a single short-term cold stimulus during the first day of life improves the body temperature adaption to a subsequent cold event. Finally, we identify that bone morphogenic protein 8B (BMP8B) is associated with the BAT thermogenic response in neonates. Overall, our data uncover key features of the setup of BAT thermogenesis in newborns.

Investigating sensory response to physical discomfort in children with autism spectrum disorder using near-infrared spectroscopy

Self-reporting of pain can be difficult in populations with communication challenges or atypical sensory processing, such as children with autism spectrum disorder (ASD). Consequently, pain can go untreated. An objective method to identify discomfort would be valuable to individuals unable to express or recognize their own bodily distress. Near-infrared spectroscopy (NIRS) is a brain-imaging modality that is suited for this application. We evaluated the potential of detecting a cortical response to discomfort in the ASD population using NIRS. Using a continuous-wave spectrometer, prefrontal and parietal measures were collected from 15 males with ASD and 7 typically developing (TD) males 10–15 years of age. Participants were exposed to a noxious cold stimulus by immersing their hands in cold water and tepid water as a baseline task. Across all participants, the magnitude and timing of the cold and tepid water-induced brain responses were significantly different (p < 0.001). The effect of the task on the brain response depended on the study group (group x task: p < 0.001), with the ASD group exhibiting a blunted response to the cold stimulus. Findings suggest that NIRS may serve as a tool for objective pain assessment and atypical sensory processing.

Free Thyroxine Levels are Associated with Cold Induced Thermogenesis in Healthy Euthyroid Individuals

Thyroid hormone (TH) is an important regulator of mammalian metabolism and facilitates cold induced thermogenesis (CIT) in brown adipose tissue (BAT). Profound hypothyroidism or hyperthyroidism lead to alterations in BAT function and CIT. In euthyroid humans the inter-individual variation of thyroid hormones is relatively large. Therefore, we investigated whether levels of free thyroxine (T4) or free triiodothyronine (T3) are positively associated with CIT in euthyroid individuals. We performed an observational study in 79 healthy, euthyroid volunteers (mean age 25.6 years, mean BMI 23.0 kg · m-2). Resting energy expenditure (REE) was measured by indirect calorimetry during warm conditions (EEwarm) and after a mild cold stimulus of two hours (EEcold). CIT was calculated as the difference between EEcold and EEwarm. BAT activity was assessed by 18F-FDG-PET after a mild cold stimulus in a subset of 26 participants. EEcold and CIT were significantly related to levels of free T4 (R2 = 0.11, p=0.0025 and R2 = 0.13, p=0.0011, respectively) but not to free T3 and TSH. Cold induced BAT activity was also associated with levels of free T4 (R2 = 0.21, p=0.018). CIT was approximately fourfold higher in participants in the highest tertile of free T4 as compared to the lowest tertile. Additionally, free T4 was weakly, albeit significantly associated with outdoor temperature seven days prior to the respective study visit (R2 = 0.06, p=0.037). These finding suggests that variations in thyroid hormone levels within the euthyroid range are related to the capability to adapt to cool temperatures and affect energy balance.

Hot–Cold Confusion: Inverse Thermal Sensation When Hot and Cold Stimuli Coexist in a Thermal Localization Task

We focused on the inverse thermal sensation caused by the presence of both hot and cold stimuli, which we named hot–cold confusion. Some researchers have shown that when participants touch a thermal stimulus simultaneously with two opposite thermal stimuli on both sides, the outer temperatures dominate the center temperature; for example, a hot stimulus between two cold stimuli is perceived as cold. However, there has not been sufficient research on the effect of the center stimulus on the outer stimuli. In the current study, we placed a participant’s forearm on an alignment where hot and cold stimuli were alternately placed in three locations and found that the participants sometimes selected the inverse thermal sensation of the presented surface not only at the center but also at the outer locations. Namely, opposite thermal stimuli applied at multiple locations affected each other, and the participants sometimes perceived the hot stimulus at the outer location as cold even when the two of three stimuli were hot, and vice versa. In addition, using various alignments of thermal stimuli, we revealed a directional bias of the effect from the cold stimulus and a difference in strength according to its location on the forearm.

Effect of Photobiomodulation Therapy Following Direct Pulp Capping on Postoperative Sensitivity by Thermal Stimulus: A Retrospective Study

Objective: The aim of this retrospective study was to investigate the effect of photobiomodulation therapy on postoperative pain provoked by thermal stimulation in direct pulp capping. Subject and methods: A retrospective study was performed using the records of patients who received direct pulp capping using mineral trioxide aggregate. Teeth irradiated with a laser were assigned as the photobiomodulation therapy group and non-irradiated teeth were considered as the control group. Before treatment and 6 hours, 1 day and 7 days after treatment, tooth sensitivity to a cold stimulus was recorded using a visual analog scale. Results: From a total of 123 documented direct pulp capping procedures, only 72 directly capped permanent teeth met the inclusion criteria. Age, gender, and tooth location were comparable between the groups. A statistically significant difference was found in sensitivity to cold stimulus between groups on day 7 (p=.007), but no difference was found at the preoperative, 6 hour, and day 1 time points (p=.055, p=.132, p=.100, respectively). In the intragroup evaluation, a significantly greater decrease was detected in the photobiomodulation therapy group compared to the control group, although both groups showed a reduction in discomfort throughout the follow-up period (p=.000). Conclusion: Photobiomodulation therapy is an effective method for enhancing patient comfort by reducing thermal sensitivity following direct pulp capping procedures.

Effects of Salt Intake on Sympathetic Neural and Pressor Responses to Cold Pressor Test in Premenopausal Women with A History of Normal Pregnancy

Excessive salt intake is considered a risk factor for the development of hypertension. Additionally, aberrant neuro-circulatory responses to a cold stimulus are associated with an increased risk of hypertension. This study aimed to determine whether salt loading versus salt reduction would impact hemodynamic and sympathetic neural responses during the cold pressor test (CPT) in premenopausal women with a history of normal pregnancy. Nine healthy premenopausal women [42±3 (SD) yr] were given a standardized isocaloric high salt (HS; 250 mEq sodium/day) or low salt (LS; 50 mEq sodium/day) diet for 1-week each (~2 months apart with the order randomized), while water intake was ad libitum. Laboratory testing was performed following each HS and LS period in the mid-luteal phase of the menstrual cycle. Subjects were in the supine position and beat-by-beat blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) were continuously measured during 1-minute baseline followed by 2-minute CPT and 3-minute recovery. BP and HR increased during the CPT (both P<0.001); the responses were similar between HS and LS. MSNA increased during the CPT, but the increment (D) was greater during HS than LS (29±6 vs. 15±4 bursts/min; P<0.001). The transduction of MSNA for vasoconstriction during the CPT was lower in HS (P<0.05). Thus, salt loading augments sympathetic neural reactivity to the cold stimulus with similar pressor responses compared to salt reduction, which may be attributed to the blunted neurovascular transduction ─ a compensatory mechanism for hemodynamic homeostasis in premenopausal women with a history of normal pregnancy.