Sweat Production Research Articles

Upper extremity sympathectomy

Hyperhidrosis is a condition in which there is excessive production of sweat that is disproportional to thermoregulation needs and that profoundly hampers the quality of life (QOL) of the population that is affected by it. The disorder is typically limited to the palms, the plantar and craniofacial regions, armpits, and manifests itself in a symmetrical fashion in addition to being associated to family history. At present, sympathectomy is considered the golden standard treatment and there are a number of approaches a surgeon may elect to adopt in its care. The clinical treatment with oxybutynin also improves screening of the group of patients that will benefit the most with this indication. However, the efficacy of the surgical method, what most counts for a successful outcome is the occurrence or not of compensatory hyperhidrosis whose intensity may impact the results. All patients are and must be thoroughly informed of this possibility prior to surgery. For the others indications, is also one of the final approaches necessary for a fruitful treatment.

Spatial and temporal migration of sweat: from skin to clothing

PurposeMoisture accumulation in clothing affects human performance and productivity through its impact on thermal balance and various aspects of discomfort. Building on our laboratory’s work on mapping sweat production across the body, this study aimed to obtain detailed spatial and temporal maps showing how this sweat migrates into a single clothing layer (T-shirt) during physical exercise.MethodEight male participants performed running exercise in a warm environment. Garment sweat absorption was mapped over a total running time of 50 min, in 10 separated running trials of different durations (5 min increments). After running, the garment was dissected into 22 different parts and local sweat absorption (ABSlocal) was quantified by weighing each garment part before and after drying. From ABSlocal, garment total sweat absorption (ABStotal) was estimated.ResultsAfter 50 min, Tcore rose from 37 ± 0.2 to 38.6 ± 0.3 °C, HR increased from 69 ± 15 to 163 ± 12 bpm (p < 0.001), GSL was 586 ± 86 g m−2. Clear patterns of sweat absorption reduction from superior-to-inferior and from medial-to-lateral T-shirt zones were observed, with the mid back medial and the low front hem showing the highest, respectively.ConclusionsQuantitative data on garment total and regional sweat absorption were obtained and considerable variation between different garment zones was identified. These data can support the development of sport and personal protective clothing with the end goal to prevent workers’ heat-related injuries as well as maximise human performance and productivity.

Topical glycopyrronium tosylate for the treatment of primary axillary hyperhidrosis: Results from the ATMOS-1 and ATMOS-2 phase 3 randomized controlled trials

Glycopyrronium tosylate (GT) is a topical anticholinergic developed for once-daily treatment of primary axillary hyperhidrosis. Assess the efficacy and safety of GT for primary axillary hyperhidrosis. ATMOS-1 and ATMOS-2 were replicate randomized, double-blind, vehicle-controlled, 4-week phase 3 trials. Patients were randomized 2:1 to GT 3.75% or vehicle applied once daily to each axilla for 4weeks. Coprimary endpoints were responder rate (≥4-point improvement from baseline) on item 2 (severity of sweating) of the Axillary Sweating Daily Diary (ASDD), which is a newly developed patient-reported outcome measure, and absolute change from baseline in axillary gravimetric sweat production at week 4. Safety evaluation included treatment-emergent adverse events. Pooled data, which are consistent with the individual trial results, show that significantly more GT-treated patients achieved an ASDD-Item 2 response than did those treated with vehicle (59.5% vs 27.6%), and they had reduced sweat production from baseline (-107.6mg/5min vs -92.1mg/5min) at week 4 (P<.001 for both coprimary end points). Most treatment-emergent adverse events were mild or moderate and infrequently led to discontinuation. Short trial duration and inherent challenges in gravimetrically assessing sweat production. GT applied topically on a daily basis over 4weeks reduced the severity of sweating as measured by ASDD-Item 2, reduced sweat production as measured gravimetrically, and was generally well tolerated in patients with primary axillary hyperhidrosis.

Publisher's Note

Abstract When environmental temperatures exceed 25°C, horses are potentially subjected to thermal stress. It has therefore been recommended that horses should be provided with shade during hot days. However, this is not possible for horses grazing on many Australian rural properties. Although the positive effect that solar radiation blocking can have on reducing heat absorption is understood by some, conflicting views, mostly anecdotal, exist on the use of a light cotton rug on horses for this purpose. The aim of this pilot study was to examine the effects of wearing a light-colored cotton rug on horse heart rate (HR), respiratory rate (RR), rectal temperature (RT), sweat production, and selected stress-related behaviors. Data were collected for 2 groups of university-owned horses (n = 8 and 10, respectively). The horses were tied in an outdoor arena in direct sunlight for 2 hours on 2 different days (D1 and D2). Baseline behavioral and physiological data (T0) were noted, recording frequency (n/10 min) of tail swishing, licking-chewing, pawing, repeated head movements, and self-care and recording HR, RR, RT, and sweat production using a sweat score (0 = none to 5 = excessive). Half of the horses were then fitted with a light cotton rug, and all horses were observed and monitored at regular 15-minute intervals for a further 2 hours (T1-T8). The effect of repetition (D1 and D2) and time (T0-T8) was not significant; therefore, the data were combined and analyzed using the Mann-Whitney U -test with rug (rugged/unrugged) as the independent variable. RT and sweat score were significantly lower in unrugged horses compared to rugged horses (37.4 ± 0.3 vs. 37.7 ± 0.3°C; 0.5 ± 0.8 vs. 1.9 ± 1.3, respectively; P P P = 0.018). Although wearing a rug did not have an effect on the other parameters, it is worth noting that HR, RR, and the occurrence of stress-related behaviors were higher than normal values for equids, suggesting that horses were potentially prone to discomfort. Overall, it appears that the use of light-colored cotton rugs may help reduce the irritation caused to horses by flying insects as evidenced by less tail swishing but may also lead to an increase in internal temperature and subsequently sweat production, increasing the risk of thermal stress and loss of electrolytes. Wearing a rug is not an adequate substitute for the provision of shade when ambient temperatures exceed 25°C.

Cutaneous adrenergic nerve blockade attenuates sweating response during incremental exercise in habitually trained and untrained men

Human eccrine sweat glands are governed by adrenergic nerves and noradrenergic agonists can elicit sweating. However, it remained unknown whether this neural adrenergic mechanism functionally contributes to sweat production during exercise. To clarify the mechanisms of adrenergic sweat production during exercise associated with habitual exercise training, this study examined 1) whether a blockade of cutaneous noradrenaline release from adrenergic nerve terminals attenuates sweating response during incremental exercise, and 2) whether the neural adrenergic sweating, if any, would be greater in habitually trained individuals relative to untrained counterparts. Nine habitually trained and 10 untrained males (VO2max: 57.6±5.1 and 38.9±6.7 ml kg−1 min−1, respectively, P &lt; 0.05) performed incremental semi‐recumbent cycling (20W min−1) until exhaustion. Sweat rates (ventilated capsule) were measured at two bilateral forearm skin sites that were transdermally administered via iontophoresis with either 10 mM bretylium tosylate (BT, an inhibitor of noradrenaline release from sympathetic adrenergic nerve terminals) or saline (Control). Ninety min after the iontophoresis, foot cold water immersion was performed for 2 min to verify bretylium tosylate abolishes adrenergic cutaneous vasoconstriction associated with cold stress. Sweat rate was evaluated as a function of relative (percentage of maximum workload) exercise intensities. Trained individuals exhibited higher sweat production compared with untrained counterparts at exercise intensity of ≥70% relative workload (all P &lt; 0.05). In trained individuals, sweat rate at the BT site was attenuated compared to the Control at relative exercise intensities of 70% (0.12±0.16 vs. 0.24±0.22 ml cm−2 min−1), 80% (0.32±0.25 vs. 0.48±0.28ml cm−2 min−1), 90% (0.48±0.29 vs. 0.66±0.29 ml cm−2 min−1), and 100% (0.60±0.29 vs. 0.77±0.29ml cm−2 min−1), respectively (all P &lt; 0.05). Similarly, sweat rate measured in untrained group was reduced at BT vs. Control site at relative exercise intensities of 80% (0.04±0.08 vs. 0.10±0.09 ml cm−2 min−1), 90% (0.12±0.14 vs. 0.20±0.14 ml cm−2 min−1), and 100% (0.22±0.17 vs. 0.30±0.19 ml cm−2 min−1), respectively (all P &lt; 0.05). BT‐induced reduction in sweat rate was greater in trained than in untrained individuals during exercise at the intensities of 70% (−0.12±0.11 vs. 0.00±0.03 ml cm−2 min−1), 80% (−0.16±0.12 vs. −0.06±0.10 ml cm−2 min−1), and 90% (−0.18±0.14 vs. −0.08±0.14 ml cm−2 min−1), respectively (all P &lt; 0.05). To the best of our knowledge, this is the first study demonstrating noradrenaline release from sympathetic adrenergic nerve terminal does modulate sweating during high intensity exercise (i.e., &gt;70% maximum) with habitually trained males exhibiting greater adrenergic sweating in comparison to untrained counterparts.Support or Funding InformationThis study was supported by a Grant‐in‐Aid for Scientific Research (no. 16K16521) from the Japan Society for the Promotion of Science from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Critical Environmental Limits for Prolonged Work in the Heat Using a Simulated Burn Injury Model

Following a deep burn injury, excision of devitalized skin and subsequent grafting impair sweat production within grafted sites. Since the capacity for whole‐body evaporative heat dissipation is dependent on sweat production and the total non‐injured skin area available for heat dissipation, burn injuries likely reduce the capacity for whole‐body heat dissipation in proportion to the size of the burn injury during heat stress. To test this possibility, four healthy subjects (1 female; 28 ± 7 years, 71.1 ± 9.0 kg, 1.87 ± 0.12 m2) visited the laboratory on separate days to complete an incremental humidity protocol while cycling at a fixed metabolic heat production (5 W/kg, equivalent to ~35% maximum oxygen uptake) in 40°C with and without simulated burn injuries of 20%, 40%, or 60% of total body surface area. During each trial, exercise was performed at an initial relative humidity (RH) of 25% for 30 min to achieve thermal equilibrium, after which exercise continued as RH was increased by 3% every 5 min up to 90 min. A ‘critical’ RH was identified as the RH value above which a steady‐state esophageal temperature could no longer be maintained, thus providing an indication of maximum evaporative heat dissipation. Burn injuries were simulated by covering skin on the torso, arms, and legs with highly absorbent, vapor‐impermeable material that prevents sweat evaporation. The results show that the average critical RH declined with the size of the simulated burn injury up to 40% (0%: 44.1 ± 2.4%; 20%: 41.8 ± 2.3%; 40%: 31.4 ± 5.1%), with significant reductions in the critical RH at 40% vs. 0% and 20% simulated burn injuries (P=0.009). However, a critical RH value could not be discerned in one subject with a 40% simulated burn injury or in any subject with a 60% simulated burn injury, indicating physiologically uncompensable conditions throughout the experimental protocol. These preliminary data suggest that under the current environmental conditions, burn survivors with injuries of ≥40% have a substantially attenuated capacity for heat dissipation, placing them at greater risk of heat‐related illness during prolonged work and heat stress. Such information may be incorporated into exposure guidelines for burn survivors working under severe occupational heat stress such as military personnel.Support or Funding InformationFunding: Department of Defense – US Army, W81XWH‐15‐1‐0647This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Environmental heat stress enhances crystallization in urine

Over the past several decades, agriculture and plantations have been used as the main livelihood of most of the Karanganyar residents. However, these two sources of living are now replaced by industrial areas that employ thousands of people in that district. The development of this industry triggers multiple environmental impacts, including ecosystem and temperature changes. In consequence, there is an increase in air temperature that can cause a variety of diseases, especially in the workplace. According to the International Labour Organization (ILO) data in 2013, one worker dies every 15 second due to a work accident and 160 workers are suffering from the occupational disease. In Indonesia, the incidence of crystallization in urine is actually still unknown, but it is estimated that there are 170,000 cases annually. A high temperature or called heat stress is one among many factors causing this disease to appear. The workers in the textile industry, especially in the Finishing Department Kusumahadi Co. Ltd that exposed heat stress from the finishing machines and inadequate ventilation. This hot working climate causes the human body to adapt in the form of body cooling mechanism or called sweating This adaptation can cause an increase in sweat production and decrease the production of urine. If it is not followed by consuming the recommended amount of water intake, it can result in the precipitation of body salts that, in a long time, will cause crystallization in urine. The research used the analytic observational designs for a cross-sectional study. There were 34 samples collected from 57 finishing workers. The data were analyzed using Spearman correlation test. The results showed that heat stress (p=0,015) and water intake (p=0,034) has a significant correlation with crystallization in urine.

Prenatal diagnosis of cystic fibrosis in combination with herpetic infection in parents with uncompensated family history

Cystic fibrosis (CF) is a chronic genetic disorder that affects the exosecretory glands responsible for the production of mucus and sweat; as well as respiratory, digestive and reproductive systems. The article describes a brief description of this disease, the features of intrauterine manifestations and differential diagnosis with other conditions.In most cases, prenatal diagnosis of CF is offered to a family that already has children with CF. Regarding the prospective prenatal diagnosis of CF in families without CF history, as well as in couples with established status of heterozygous carrier of mutations in the CFTR gene, it is presented mainly in sporadic cases. In all other cases, prenatal diagnosis of CF is based on ultrasound detection of increased intestinal echogenicity. The hyperechogenic intestine is observed in 50–75% fetuses with CF. The incidence of intrauterine infection in fetuses with the hyperechogenic intestine is varies from 0 to 10%. The spectrum of perinatal infections is more often represented by cytomegalovirus, herpes, syphilis, toxoplasmosis, rubella and parvovirus B19.The second trimester amniotic fluid contains two main enzymes (alkaline phosphatase and gamma-glutamyltranspeptidase), whose decline of level is a reliable marker for CF. The article presents a clinical case of prenatal diagnosis of CF in combination with intrauterine infection with herpes simplex virus in 20 weeks pregnancy in a fetus with a hyperechoic intestine. Whenthe amniotic fluid was investigated in a fetus with a normal karyotype are revealed decline of alkaline phosphatase and gamma-glutamyltranspeptidase levels, the mutation delF508 CFTR in the homozygous state and the DNA regions homologous HSV I, II types. Taking into account the unfavorable morbid prognosis, the fetus with CF was eliminated for 22 weeks pregnancy at the family’s request. At autopsy were found the typical manifestations of CF in the female abortus. The molecular gene study of both parents confirmed the heterozygous carrier state. The family received recommendations on the mandatory prenatal diagnosis in subsequent pregnancies.

The evolution of eccrine sweat glands in human and nonhuman primates

Sweating is an unusual thermoregulatory strategy for most mammals, yet is critical for humans. This trait is commonly hypothesized to result from human ancestors moving from a forest to a warmer and drier open environment. As soft tissue traits do not typically fossilize, this idea has been difficult to test. Therefore, we used a comparative approach to examine 15 eccrine gland traits from 35 primate species. For each trait we measured phylogenetic signal, tested three evolutionary models to explain trait variation, and used phylogenetic models to examine how traits varied in response to climate variables. Phylogenetic signal in traits varied substantially, with the two traits exhibiting the highest values being gland distribution on the body and percent eccrine vs. apocrine glands on the body. Variation in most traits was best explained by an Ornstein-Uhlenbeck model suggesting the importance of natural selection. Two traits were strongly predicted by climate. First, species with high eccrine gland glycogen content were associated with habitats exhibiting warm temperatures and low rainfall. Second, species with increased capillarization were associated with high temperature. Glycogen is a primary energy substrate powering sweat production and sodium reabsorption in the eccrine gland, and increased capillarization permits greater oxygen, glucose and electrolyte delivery. Thus, our results are evidence of natural selection for increased sweating capacity in primate species with body surface eccrine glands living in hot and dry climates. We suggest that selection for increased glycogen content and capillarization may have been part of initial increases in hominin thermoregulatory sweating capacity.

Electrodermal Activity Is Sensitive to Cognitive Stress under Water.

When divers are at depth in water, the high pressure and low temperature alone can cause severe stress, challenging the human physiological control systems. The addition of cognitive stress, for example during a military mission, exacerbates the challenge. In these conditions, humans are more susceptible to autonomic imbalance. Reliable tools for the assessment of the autonomic nervous system (ANS) could be used as indicators of the relative degree of stress a diver is experiencing, which could reveal heightened risk during a mission. Electrodermal activity (EDA), a measure of the changes in conductance at the skin surface due to sweat production, is considered a promising alternative for the non-invasive assessment of sympathetic control of the ANS. EDA is sensitive to stress of many kinds. Therefore, as a first step, we tested the sensitivity of EDA, in the time and frequency domains, specifically to cognitive stress during water immersion of the subject (albeit with their measurement finger dry for safety). The data from 14 volunteer subjects were used from the experiment. After a 4-min adjustment and baseline period after being immersed in water, subjects underwent the Stroop task, which is known to induce cognitive stress. The time-domain indices of EDA, skin conductance level (SCL) and non-specific skin conductance responses (NS.SCRs), did not change during cognitive stress, compared to baseline measurements. Frequency-domain indices of EDA, EDASymp (based on power spectral analysis) and TVSymp (based on time-frequency analysis), did significantly change during cognitive stress. This leads to the conclusion that EDA, assessed by spectral analysis, is sensitive to cognitive stress in water-immersed subjects, and can potentially be used to detect cognitive stress in divers.

IVIg for apparently autoimmune small-fiber polyneuropathy: first analysis of efficacy and safety.

Objectives:Small-fiber polyneuropathy (SFPN) has various underlying causes, including associations with systemic autoimmune conditions. We have proposed a new cause; small-fiber-targeting autoimmune diseases akin to Guillain-Barré and chronic inflammatory demyelinating polyneuropathy (CIDP). There are no treatment studies yet for this ‘apparently autoimmune SFPN’ (aaSFPN), but intravenous immunoglobulin (IVIg), first-line for Guillain-Barré and CIDP, is prescribed off-label for aaSFPN despite very high cost. This project aimed to conduct the first systematic evaluation of IVIg’s effectiveness for aaSFPN.Methods:With IRB approval, we extracted all available paper and electronic medical records of qualifying patients. Inclusion required having objectively confirmed SFPN, autoimmune attribution and other potential causes excluded. IVIg needed to have been dosed at ⩾1 g/kg/4 weeks for ⩾3 months. We chose two primary outcomes – changes in composite autonomic function testing (AFT) reports of SFPN and in ratings of pain severity – to capture objective as well as patient-prioritized outcomes.Results:Among all 55 eligible patients, SFPN had been confirmed by 3/3 nerve biopsies, 62% of skin biopsies, and 89% of composite AFT. Evidence of autoimmunity included 27% of patients having systemic autoimmune disorders, 20% having prior organ-specific autoimmune illnesses and 80% having ⩾1/5 abnormal blood-test markers associated with autoimmunity. A total of 73% had apparent small-fiber-restricted autoimmunity. IVIg treatment duration averaged 28 ± 25 months. The proportion of AFTs interpreted as indicating SFPN dropped from 89% at baseline to 55% (p ⩽ 0.001). Sweat production normalized (p = 0.039) and the other four domains all trended toward improvement. Among patients with pre-treatment pain ⩾3/10, severity averaging 6.3 ± 1.7 dropped to 5.2 ± 2.1 (p = 0.007). Overall, 74% of patients rated themselves ‘improved’ and their neurologists labeled 77% as ‘IVIg responders’; 16% entered remissions that were sustained after IVIg withdrawal. All adverse events were expected; most were typical infusion reactions. The two moderate complications (3.6%) were vein thromboses not requiring discontinuation. The one severe event (1.8%), hemolytic anemia, remitted after IVIg discontinuation.Conclusion:These results provide Class IV, real-world, proof-of-concept evidence suggesting that IVIg is safe and effective for rigorously selected SFPN patients with apparent autoimmune causality. They provide rationale for prospective trials, inform trial design and indirectly support the discovery of small-fiber-targeting autoimmune/inflammatory illnesses.

Reducing the sensation of electrical stimulation with dry electrodes by using an array of constant current sources

Hydrogel electrodes are commonly used for functional and other electrical stimulation applications since the hydrogel layer has been shown to considerably reduce the perception of stimulation compared to dry electrodes. However, these hydrogel electrodes must be changed regularly as they dry out or become contaminated with skin cells and sweat products, thus losing their adhesiveness and resistive properties. Dry electrodes are longer lasting but are more uncomfortable due to unequal current distribution (current hogging). We hypothesise that if current through a dry electrode is equally shared amongst an array of small sub-electrodes, current hogging and thus the sensitivity perceived due to stimulation will be reduced. We constructed an 8 × 8 array of millimetre sized dry electrodes that could either be activated as individual current sources, or together as one large source. A study was performed with 13 participants to investigate the differences in sensation between the two modes of operation. The results showed that 12 out of 13 participants found the new (distributed-constant-current) approach allowed higher stimulation for the same sensation. The differences in sensation between single and multiple sources became larger with higher intensity levels.

Experimental study on using PCMs of different melting temperatures in one cooling vest to reduce its weight and improve comfort

This study aims at evaluating experimentally phase change material (PCM) cooling vest performance when incorporating two types of PCM with different melting temperatures with varied PCM placement on the lower, upper, front and back of the torso. Experiments on a thermal manikin were conducted to assess cooling rate observed with the various PCM arrangements while experiments on six male subjects were conducted to assess associated physiological and comfort votes after exercising for 45min.The main findings of manikin testing were that an improved cooling effect can be achieved by covering the upper torso with PCM packets at 28°C melting temperature while covering the lower torso with the 18°C packets. Human subject testing established that similar improvements in thermal comfort and sensation levels could be attained when covering the back or lower torso segments with 18°C instead of covering all the torso. In addition, a maximum reduction in local skin temperatures of 5.45±1°C was achieved accompanied with a reduction of 64W in body heat storage. Covering the chest and upper back segments with the 18°C packets suppressed sweat production and improved wetness sensation. Finally, 16% lower vest weight might be possible with prolonged working periods of two hours at 35°C.

Do nitric oxide synthase and cyclooxygenase contribute to sweating response during passive heating in endurance-trained athletes?

The aim of our study was to determine if habitual endurance training can influence the relative contribution of nitric oxide synthase (NOS) and cyclooxygenase (COX) in the regulation of sweating during a passive heat stress in young adults. Ten trained athletes and nine untrained counterparts were passively heated until oral temperature (as estimated by sublingual temperature, Tor) increased by 1.5°C above baseline resting. Forearm sweat rate (ventilated capsule) was measured at three skin sites continuously perfused with either lactated Ringer's solution (Control), 10 mmol/L NG‐nitro‐L‐arginine methyl ester (L‐NAME, non‐selective NOS inhibitor), or 10 mmol/L ketorolac (Ketorolac, non‐selective COX inhibitor) via intradermal microdialysis. Sweat rate was averaged for each 0.3°C increase in Tor. Sweat rate at the L‐NAME site was lower than Control following a 0.9 and 1.2°C increase in Tor in both groups (all P ≤ 0.05). Relative to the Control site, NOS‐inhibition reduced sweating similarly between the groups (P = 0.51). Sweat rate at the Ketorolac site was not different from the Control at any levels of Tor in both groups (P > 0.05). Nevertheless, a greater sweat rate was measured at the end of heating in the trained as compared to the untrained individuals (P ≤ 0.05). We show that NOS contributes similarly to sweating in both trained and untrained individuals during a passive heat stress. Further, no effect of COX on sweating was measured for either group. The greater sweat production observed in endurance‐trained athletes is likely mediated by factors other than NOS‐ and COX‐dependent mechanisms.

Oral manifestations, dental management, and a rare homozygous mutation of the PRDM12 gene in a boy with hereditary sensory and autonomic neuropathy type VIII: a case report and review of the literature

BackgroundHereditary sensory and autonomic neuropathy type VIII is a rare autosomal recessive inherited disorder. Chen et al. recently identified the causative gene and characterized biallelic mutations in the PR domain-containing protein 12 gene, which plays a role in the development of pain-sensing nerve cells. Our patient’s family was included in Chen and colleagues’ study. We performed a literature review of the PubMed library (January 1985 to December 2016) on hereditary sensory and autonomic neuropathy type I to VIII genetic disorders and their orofacial manifestations. This case report is the first to describe the oral manifestations, and their treatment, of the recently discovered hereditary sensory and autonomic neuropathy type VIII in the medical and dental literature.Case presentationWe report on the oral manifestations and dental management of an 8-month-old white boy with hereditary sensory and autonomic neuropathy-VIII over a period of 16 years. Our patient was homozygous for a mutation of PR domain-containing protein 12 gene and was characterized by insensitivity to pain and thermal stimuli, self-mutilation behavior, reduced sweat and tear production, absence of corneal reflexes, and multiple skin and bone infections. Oral manifestations included premature loss of teeth, associated with dental traumata and self-mutilation, severe soft tissue injuries, dental caries and submucosal abscesses, hypomineralization of primary teeth, and mandibular osteomyelitis.ConclusionsThe lack of scientific knowledge on hereditary sensory and autonomic neuropathy due to the rarity of the disease often results in a delay in diagnosis, which is of substantial importance for the prevention of many complications and symptoms. Interdisciplinary work of specialized medical and dental teams and development of a standardized treatment protocols are essential for the management of the disease. There are many knowledge gaps concerning the management of patients with hereditary sensory and autonomic neuropathy-VIII, therefore more research on an international basis is needed.

Altered paracellular cation permeability due to a rare CLDN10B variant causes anhidrosis and kidney damage.

Claudins constitute the major component of tight junctions and regulate paracellular permeability of epithelia. Claudin-10 occurs in two major isoforms that form paracellular channels with ion selectivity. We report on two families segregating an autosomal recessive disorder characterized by generalized anhidrosis, severe heat intolerance and mild kidney failure. All affected individuals carry a rare homozygous missense mutation c.144C>G, p.(N48K) specific for the claudin-10b isoform. Immunostaining of sweat glands from patients suggested that the disease is associated with reduced levels of claudin-10b in the plasma membranes and in canaliculi of the secretory portion. Expression of claudin-10b N48K in a 3D cell model of sweat secretion indicated perturbed paracellular Na+ transport. Analysis of paracellular permeability revealed that claudin-10b N48K maintained cation over anion selectivity but with a reduced general ion conductance. Furthermore, freeze fracture electron microscopy showed that claudin-10b N48K was associated with impaired tight junction strand formation and altered cis-oligomer formation. These data suggest that claudin-10b N48K causes anhidrosis and our findings are consistent with a combined effect from perturbed TJ function and increased degradation of claudin-10b N48K in the sweat glands. Furthermore, affected individuals present with Mg2+ retention, secondary hyperparathyroidism and mild kidney failure that suggest a disturbed reabsorption of cations in the kidneys. These renal-derived features recapitulate several phenotypic aspects detected in mice with kidney specific loss of both claudin-10 isoforms. Our study adds to the spectrum of phenotypes caused by tight junction proteins and demonstrates a pivotal role for claudin-10b in maintaining paracellular Na+ permeability for sweat production and kidney function.

Sustained increases in skin blood flow are not a prerequisite to initiate sweating during passive heat exposure.

Some studies have observed a functional relationship between sweating and skin blood flow. However, the implications of this relationship during physiologically relevant conditions remain unclear. We manipulated sudomotor activity through changes in sweating efficiency to determine if parallel changes in vasomotor activity are observed. Eight young men completed two trials at 36°C and two trials at 42°C. During these trials, air temperature remained constant while ambient vapor pressure increased from 1.6 to 5.6 kPa over 2 h. Forced airflow across the skin was used to create conditions of high (HiSeff) or low (LoSeff) sweating efficiency. Local sweat rate (LSR), local skin blood flow (SkBF), as well as mean skin and esophageal temperatures were measured continuously. It took longer for LSR to increase during HiSeff at 36°C (HiSeff: 99 ± 11 vs. LoSeff: 77 ± 11 min, P < 0.01) and 42°C (HiSeff: 72 ± 16 vs. LoSeff: 51 ± 15 min, P < 0.01). In general, an increase in LSR preceded the increase in SkBF when expressed as ambient vapor pressure and time for all conditions (P < 0.05). However, both responses were activated at a similar change in mean body temperature (average across all trials, LSR: 0.26 ± 0.15 vs. SkBF: 0.30 ± 0.18°C, P = 0.26). These results demonstrate that altering the point at which LSR is initiated during heat exposure is paralleled by similar shifts for the increase in SkBF. However, local sweat production occurs before an increase in SkBF, suggesting that SkBF is not necessarily a prerequisite for sweating.

Evidence for β-adrenergic modulation of sweating during incremental exercise in habitually trained males.

The aim of the present study was to determine the β-adrenergic contribution to sweating during incremental exercise in habitually trained males. Nine habitually trained and 11 untrained males performed incremental cycling until exhaustion (20 W/min). Bilateral forearm sweat rates (ventilated capsule) were measured at two skin sites that were transdermally administered via iontophoresis with either 1% propranolol (Propranolol, a nonselective β-adrenergic receptor antagonist) or saline (Control). The sweat rate was evaluated as a function of both relative (percentage of maximum workload) and absolute exercise intensities. The sweat rate at the Propranolol site was lower than the control during exercise at 80 (0.57 ± 0.21 and 0.45 ± 0.19 mg·cm-2·min-1 for Control and Propranolol, respectively) and 90% (0.74 ± 0.22 and 0.65 ± 0.17 mg·cm-2·min-1, respectively) of maximum workload in trained males (all P < 0.05). By contrast, no between-site differences in sweat rates were observed in untrained counterparts (all P > 0.05). At the same absolute intensity, higher sweat rates on the control site were observed in trained males relative to the untrained during exercise at 160 (0.23 ± 0.20 and 0.04 ± 0.05 mg·cm-2·min-1 for trained and untrained, respectively) and 180 W (0.40 ± 0.20 and 0.13 ± 0.13 mg·cm-2·min-1, respectively) (all P < 0.05), whereas this between-group difference was not observed at the Propranolol site (all P > 0.05). We show that the β-adrenergic mechanism does modulate sweating during exercise at a submaximal high relative intensity in habitually trained males. The β-adrenergic mechanism may in part contribute to the greater sweat production in habitually trained males than in untrained counterparts during exercise.NEW & NOTEWORTHY We demonstrated for the first time that the β-adrenergic mechanism does modulate sweating (i.e., β-adrenergic sweating) during exercise using a localized β-adrenoceptor blockade in humans in vivo. β-Adrenergic sweating was evident in habitually trained individuals during exercise at a submaximal high relative intensity (80-90% maximal work). This observation advances our understanding of human thermoregulation during exercise and of the mechanism that underlies sweat gland adaptation to habitual exercise training.

The Effect Of Drink Temperature On Sweating Response And Performance During Exercise In The Heat

Drink temperature disproportionately influences sweating rate and volume during low intensity exercise in temperate conditions that permit full sweat evaporation. Specifically, cold drinks may reduce sweat production and hot drinks are thought to increase it by stimulation of a gut thermoreceptor. Consequently, cold drinks may have a negative influence on thermoregulatory responses during exercise in the heat. PURPOSE: The effect of drink temperature has yet to be examined on the sweat response, thermoregulation and performance in hot, dry conditions using an ecologically valid protocol with measurement of regional sweating responses. METHODS: Ten trained cyclists completed three trials prior to and during which they ingested 3.2 mL.kg-1 of a COLD (5.3 ± 1.7 °C) or HOT drink (49.0 ± 1.9 °C), which was contrasted to a no drink CONTROL. They cycled in hot, dry conditions (34.5 ± 0.6 °C & 22 ± 1% RH) for 60-minutes at 55% of pre-determined maximal power output (Pmax) and then completed a test to exhaustion at 80% Pmax. Thermal (rectal temperature Trec, 8-site skin temperature Tmsk) and local sweat rate responses (absorbent sweat pad & galvanic skin conductance GSC) were recorded. TTE duration indicated the performance effect. Comparisons were made using ANOVA. Data are displayed as mean [SD]. RESULTS: Participant’s TTE performance was significantly worse in the CONTROL (170 [132] s) condition (p<0.05) than the COLD (371 [272] s) and HOT drink (367 [301] s) conditions which did not differ. Throughout the fixed intensity exercise period, local sweat responses at the bicep and upper back were not different (p>0.05) between any of the test conditions (e.g. grand mean [SD] Bicep GSC CONTROL 15.2 [8.0] μS, HOT 17.3 [8.0] μS & COLD 14.0 [6.0] μS). Temperature responses were higher (p<0.05) in the CONTROL than both drink conditions at the core (Trec, CONTROL 38.3 [0.5] °C, COLD 38.0 [0.5] °C, HOT 38.1 [0.5] °C) but not the skin (CONTROL 34.5 [0.2] °C, COLD 34.5 [0.3] °C, HOT 34.6 [0.3] °C). CONCLUSION: Drink temperature did not influence performance, temperature responses or regional sweat responses during high-intensity exercise in hot, dry conditions. Consumption of fluid, irrespective of its temperature, provided a benefit to exercise performance in the heat in contrast to not drinking. Supported by European Hydration Institute Grant.

Core Temperature Responses To Exercise Using A Simulated Burn Injury Model

BACKGROUND: The US Army’s Standards of Medical Fitness indicate that a burn injury spanning ≥40% of total body surface area (BSA) “does not meet the standard.” While whole-body sweat production and thus evaporation are diminished in burn survivors with extensive skin grafts, the impact of a 40% BSA burn injury on core temperature regulation during exercise is likely dependent on body size, as larger individuals will have a greater absolute skin area that can still participate in heat loss despite the same percentage BSA burn injury. PURPOSE: Using a simulated burn injury model, we tested the hypothesis that the detrimental effect of a 40% BSA “burn injury” would be exacerbated in individuals of smaller versus larger body size during exercise due to a lower absolute (i.e., in m2) skin area available for heat loss. METHODS: On separate occasions, healthy non-burned individuals of small (SM: n=8, 62.4 ± 5.8 kg, 1.69 ± 0.11 m2) or large (LG: n=8, 99.1 ± 8.4 kg, 2.25 ± 0.09 m2) body size cycled to elicit ~500 W of metabolic heat production for 1 h in a 39°C and 20% relative humidity environment with and without (0%) a simulated burn injury of 40% BSA. Burn injuries were simulated by affixing a highly absorbent, vapor-impermeable material to the torso (20% BSA), arms (10% BSA), and legs (10% BSA) to prevent sweat evaporation. Core temperature was measured in the gastrointestinal tract (Tgi). RESULTS: Greater increases in Tgi were observed in SM at 0% (SM: 1.09 ± 0.33°C; LG: 0.64 ± 0.22°C; P=0.03) and 40% (SM: 1.65 ± 0.32°C; LG: 1.14 ± 0.23°C; P=0.01). However, the exacerbated rise in Tgi from 0% to 40% was not different between groups (SM: 0.57 ± 0.28°C; LG: 0.49 ± 0.24°C; P=0.60). CONCLUSIONS: Preliminary data suggest that the exacerbated rise in core temperature with a simulated burn is not dependent on body size. Nevertheless, SM subjects with a simulated burn exercising at the same rate of metabolic heat production experienced the highest absolute Tgi and would therefore be at the greatest risk for a heat-related injury. Funding support: Department of Defense - US Army, W81XWH-15-1-0647.