Subclinical effects of botulinum toxin A and microwave thermolysis for axillary hyperhidrosis: A descriptive study with line-field confocal optical coherence tomography and histology.

Botulinum toxin A (BTX) and microwave thermolysis (MWT) are standard axillary hyperhidrosis treatments, but comparison of their subclinical effects is lacking. Line-field confocal optical coherence tomography (LC-OCT) is a promising non-invasive imaging tool for visualizing tissue-interactions. This study aimed to describe subclinical effects of BTX and MWT for axillary hyperhidrosis with LC-OCT-imaging compared to histology. This study derived from an intra-individual, randomized, controlled trial, treating axillary hyperhidrosis with BTX versus MWT. Subclinical effects based on LC-OCT images from baseline and 6-month follow-up (n = 8 patients) were evaluated and compared to corresponding histological samples. At baseline, LC-OCT visualized eccrine pores at the skin surface and ducts in the upper dermis (500 µm), but not deeper-lying sweat glands. Histology identified entire sweat glands. Six months post-treatment, LC-OCT revealed no detectable morphology changes in any BTX-treated axillae (100%), while recognizing obstructed eccrine pores and atrophy of eccrine ducts in most MWT-treated axillae (75%). Histology corroborated LC-OCT findings, while also showing substantial changes to entire sweat glands. LC-OCT enabled visualization of subclinical alterations of superficial eccrine ducts after MWT and unchanged morphology after BTX. LC-OCT is a promising tool for non-invasive assessment of treatment-specific tissue-interactions that can be complementary to histology.

Quantitative ion determination in eccrine sweat gland cells correlates to sweat reduction of antiperspirant actives.

OBJECTIVE: Axillary wetness represents an unwanted effect of the physiologically vital sweating mechanism, especially when it becomes excessive. Cosmetic products reducing sweat secretion rely on aluminium salts as the active ingredient acting by physically blocking the sweat gland. Driven by the interest to better understand the sweat mechanism and to develop alternative technologies against excessive sweating a search for an effective testing approach started as up to now, cost- and time-consuming in vivo studies represent the standard procedure for testing and identifying these alternatives. MATERIAL AND METHODS: The herein described in vitro test system is based on the measurement of intracellular changes of the ion equilibrium in cultured eccrine sweat gland cells. Subsequently, in vivo studies on the back of volunteers were conducted to verify the sweat-reducing effect of in vitro newly discovered substance. RESULTS: In this study, we describe an effective cell-based in vitro method as a potent tool for a more targeted screening of alternatives to aluminium salts. Testing the commonly used aluminium chlorohydrate as one example of an aluminium-based active in this screening procedure, we discovered a distinct influence on the ion equilibrium: Intracellular levels of sodium ions were decreased while those of chloride increased. Screening of various substances revealed a polyethyleneimine, adjusted to pH 3.5 with hydrochloric acid, to evoke the same alterations in the ion equilibrium as aluminium chlorohydrate. Subsequent in vivo studies showed its substantial antiperspirant action and confirmed the high efficiency of the polyethyleneimine solution in vivo. Further, specific investigations connecting the chloride content of the tested substances with the resulting sweat reduction pointed towards a substantial impact of the chloride ions on sweating. CONCLUSION: The newly described in vitro cell-based screening method represents an effective means for identifying new antiperspirant actives and suggests an additional biological mechanism of action of sweat-reducing ingredients which is directed towards unbalancing of the ion equilibrium inside eccrine sweat gland cells.

OBJECTIF: l'humidité axillaire représente un effet indésirable du mécanisme physiologiquement vital de la sudation, en particulier lorsqu'elle devient excessive. Les produits cosmétiques réduisant la sécrétion de sueur reposent sur les sels d'aluminium comme principe actif agissant en bloquant physiquement la glande sudoripare. Motivée par l'intérêt de mieux comprendre le mécanisme de la sudation et de développer des technologies alternatives contre l'hypersudation, une recherche pour une approche de test efficace a commencé car, jusqu'à présent, les études in vivo coûteuses et chronophages représentent la procédure standard pour tester et identifier ces alternatives. MATÉRIELS ET MÉTHODES: le système de test in vitro décrit ici est basé sur la mesure des changements intracellulaires de l'équilibre ionique dans les cellules des glandes sudoripares exocrines cultivées. Par la suite, des études in vivo sur le dos de volontaires ont été menées pour vérifier l'effet réducteur de la sudation d'une substance nouvellement découverte in vitro. RÉSULTATS: dans cette étude, nous décrivons une méthode cellulaire efficace in vitro en tant qu'outil puissant pour un dépistage plus ciblé des alternatives aux sels d'aluminium. En testant le chlorohydrate d'aluminium couramment utilisé comme exemple d'un principe actif à base d'aluminium dans cette procédure de dépistage, nous avons découvert une influence distincte sur l'équilibre ionique : les taux intracellulaires d'ions sodium ont diminué tandis que ceux du chlorure ont augmenté. La recherche de diverses substances a révélé une polyéthylèneimine, ajustée au pH 3,5 avec de l'acide chlorhydrique, pour évoquer les mêmes altérations de l'équilibre ionique que le chlorohydrate d'aluminium. Des études in vivo ultérieures ont montré son action anti-transpirante substantielle et ont confirmé la haute efficacité de la solution de polyéthylèneimine in vivo. De plus, des études spécifiques établissant un lien entre la teneur en chlorure des substances testées et la réduction de la sudation qui en résulte ont indiqué que les ions chlorure ont un impact substantiel sur l'hypersudation. CONCLUSION: la nouvelle méthode de dépistage cellulaire in vitro décrite représente un moyen efficace d'identifier de nouveaux agents anti-transpirants actifs et suggère un mécanisme d'action biologique supplémentaire des ingrédients réducteurs de la sudation, dirigé vers le déséquilibre de l'équilibre ionique à l'intérieur des cellules des glandes sudoripares exocrines.

Cholinergic- rather than adrenergic-induced sweating play a role in developing and developed rat eccrine sweat glands.

Both cholinergic and adrenergic stimulation can induce sweat secretion in human eccrine sweat glands, but whether cholinergic and adrenergic stimulation play same roles in rat eccrine sweat glands is still controversial. To explore the innervations, and adrenergic- and cholinergic-induced secretory response in developing and developed rat eccrine sweat glands, rat hind footpads from embryonic day (E) 15.5-20.5, postanal day (P) 1-14, P21 and adult were fixed, embedded, sectioned and subjected to immunofluorescence staining for general fiber marker protein gene product 9.5 (PGP 9.5), adrenergic fiber marker tyrosine hydroxylase (TH) and cholinergic fiber marker vasoactive intestinal peptide (VIP), and cholinergic- and adrenergic-induced sweat secretion was detected at P1-P21 and adult rats by starch-iodine test. The results showed that eccrine sweat gland placodes of SD rats were first appeared at E19.5, and the expression of PGP 9.5 was detected surrounding the sweat gland placodes at E19.5, TH at P7, and VIP at P11. Pilocarpine-induced sweat secretion was first detected at P16 in hind footpads by starch-iodine test. There was no measurable sweating when stimulated by alpha- or beta-adrenergic agonists at all the examined time points. We conclude that rat eccrine sweat glands, just as human eccrine sweat glands, co-express adrenergic and cholinergic fibers, but different from human eccrine sweat glands, cholinergic- rather than adrenergic-induced sweating plays a role in the developing and developed rat eccrine sweat glands.

Does the iontophoretic application of bretylium tosylate modulate sweating during exercise in the heat in habitually trained and untrained men?

NEW FINDINGS: What is the central question of this study? Does the administration of the adrenergic presynaptic release inhibitor bretylium tosylate modulate sweating during exercise in the heat, and does this response differ between habitually trained and untrained men? What is the main finding and its importance? Iontophoretic administration of bretylium tosylate attenuates sweating during exercise in the heat in habitually trained and untrained men. However, a greater reduction occurred in trained men. The findings demonstrate a role for cutaneous adrenergic nerves in the regulation of eccrine sweating during exercise in the heat and highlight a need to advance our understanding of neural control of human eccrine sweat gland activity. ABSTRACT: We recently reported an influence of cutaneous adrenergic nerves on eccrine sweat production in habitually trained men performing an incremental exercise bout in non-heat stress conditions. Based on an assumption that increasing heat stress induces cholinergic modulation of sweating, we evaluated the hypothesis that the contribution of cutaneous adrenergic nerves on sweating would be attenuated during exercise in the heat. Twenty young habitually trained and untrained men (n = 10/group) underwent three successive bouts of 15 min of light-, moderate- and vigorous-intensity cycling (equivalent to 30, 50, and 70% of peak oxygen uptake ( V̇O2peak ) respectively), each separated by a 15 min recovery while wearing a perfusion suit perfused with warm water (43°C). Sweat rate (ventilated capsule) was measured continuously at two bilateral forearm skin sites treated with 10 mm bretylium tosylate (an inhibitor of neurotransmitter release from adrenergic nerve terminals) and saline (control) via transdermal iontophoresis. A greater sweat rate was measured during vigorous exercise only in trained as compared to untrained men (P = 0.014). In both groups, sweating was reduced at the bretylium tosylate versus control sites, albeit the magnitude of reduction was greater in the trained men (P ≤ 0.024). These results suggest that cutaneous adrenergic nerves modulate sweating during exercise performed under a whole-body heat stress, albeit a more robust response occurs in trained men. While it is accepted that a cholinergic mechanism plays a primary role in the regulation of sweating during an exercise-heat stress, our findings highlight the need for additional studies aimed at understanding the neural control of human eccrine sweating.

Does α1-adrenergic receptor blockade modulate sweating during incremental exercise in young endurance-trained men?

PURPOSE: Human eccrine sweat glands respond to α1-adrenergic receptor agonists. We recently reported that adrenergic mechanisms contribute to sweating in endurance-trained men during an incremental exercise to volitional fatigue. However, it remains unclear if this response is mediated by α1-adrenergic receptor activation. METHODS: Twelve endurance-trained men performed an incremental cycling bout until exhaustion while wearing a water-perfused suit to clamp skin temperature at ~ 34 °C. Bilateral forearm sweat rates were measured wherein the distal area was treated with either 1% terazosin (α1-adrenergic receptor antagonist) or saline solution on the opposite limb (Control) via transdermal iontophoresis. We also measured proximal bilateral forearm sweat rate in untreated sites to confirm that no between-limb differences in forearm sweat rate occurred. Once sweat rate returned to pre-exercise resting levels at ~ 20 min postexercise, 0.25% phenylephrine (α1-adrenergic receptor agonist) was iontophoretically administered to skin to verify α1-adrenergic receptor blockade. RESULTS: Sweat rates at the proximal untreated right and left forearm sites were similar during exercise (interaction, P = 0.581). Similarly, no effect of terazosin on sweat rate was measured relative to control site (interaction, P = 0.848). Postexercise administration of phenylephrine increased sweat rate at the control site (0.08 ± 0.09 mg cm-2 min-1), which was suppressed by ~ 90% at the terazosin-treated site (0.01 ± 0.02 mg cm-2 min-1) (P = 0.026), confirming that α1-adrenergic receptor blockade was intact. CONCLUSION: Our findings demonstrate that α1-adrenergic receptors located at eccrine sweat glands do not contribute to eccrine sweating during incremental exercise in young endurance-trained men.

Pressure-and dose-controlled, needle-free, transcutaneous pneumatic injection of botulinum neurotoxin-A for the treatment of primary axillary and palmoplantar hyperhidrosis.

BACKGROUND: Botulinum neurotoxin (BoNT) effectively downregulates the secretion of eccrine sweat glands in patients with axillary and palmoplantar primary hyperhidrosis (PH). OBJECTIVE: To demonstrate the efficacy and safety of pressure- and dose-controlled, needle-free, transcutaneous pneumatic injection (TPI) of BoNT-A for treating axillary and palmoplantar PH. METHODS: Needleless TPI-BoNT-A treatments were delivered on the axillary or palmoplantar skin at a pneumatic pressure of 2.05 bars and an injection volume of 0.08 mL/shot. The efficacy thereof was assessed by evaluating starch-iodine test results and Hyperhidrosis Disease Severity Scale (HDSS) scores. RESULTS: At baseline, median HDSS scores were 3 (IQR, 3-4) for axillary lesions and 4 (IQR, 3.5-4) for palmoplantar lesions. Median HDSS scores at 1 month after TPI-BoNT-A treatment significantly decreased to 1 (IQR, 1-1.75) for axillary lesions (P < .001) and 1 (IQR, 1-2) for palmoplantar lesions (P < .001). Median global improvement scale scores were 4 (IQR, 3.25-4) for axillary PH and 3 (IQR, 2.5-4) for palmoplantar PH (P > .05). In all patients, pain was tolerable during treatments for both axillary and palmoplantar PH after the application of topical anesthetic cream. CONCLUSION: Pressure- and dose-controlled, needle-free, BoNT delivery effectively and safely decreased sweating in axillary and palmoplantar skin.

TEA-sensitive K+ channels and human eccrine sweat gland output.

Cholinergic-activated sweating depends on an influx of Ca2+ from extracellular fluid. It is thought that the opening of K+ channels on secretory epithelial cells facilitates Ca2+ entry. We examined the hypothesis that tetraethylammonium (TEA)-sensitive K+ channels participate in sweat production. We used a pre-post experimental design and initiated cholinergic-mediated sweating with intradermal electrical stimulation, monitored local sweat rate (SR) with a small sweat capsule mounted on the skin, and delivered 50 mM TEA via intradermal microdialysis. Local SR was activated by intradermal stimulation frequencies of 0.2-64 Hz, and we generated a sigmoid-shaped stimulus-response curve by plotting the area under the SR-time curve versus log10 stimulus frequency. Peak local SR was reduced from 0.372 ± 0.331 to 0.226 ± 0.190 mg·min-1·cm-2 (P = 0.0001) during application of 50 mM TEA, whereas the EC50 and Hill slopes were not altered. The global sigmoid-shaped stimulus-response curves for control and 50 mM TEA were significantly different (P < 0.0001), and the plateau region was significantly reduced (P = 0.0023) with the TEA treatment. The effect of TEA on peak local SR was similar in male and female subjects. However, we did note a small effect of sex on the shape of the stimulus-response curves during intradermal electrical stimulation. Overall, these data support the hypothesis that cholinergic control of sweat gland activity is modulated by the presence of TEA-sensitive K+ channels in human sweat gland epithelial cells.NEW & NOTEWORTHY The contribution of various potassium channels to the process of cholinergic-mediated human eccrine sweat production is unclear. Using a novel model for cholinergic-mediated sweating in humans, we provide evidence that tetraethylammonium-sensitive K+ channels (KCa1.1 and Kv channels) contribute to eccrine sweat production.

Detection of fluid secretion of three-dimensional reconstructed eccrine sweat glands by magnetic resonance imaging.

We previously showed three-dimensional (3D) reconstructed eccrine sweat glands have similar structures as native eccrine sweat glands, but whether the 3D reconstructed sweat glands appropriately secrete fluid is still unknown. In this study, Matrigel-embedded human eccrine sweat gland cells or Matrigel alone were implanted into the groin subcutis of the nude mice. Ten weeks post-implantation, images of the subcutaneously formed plugs, as well as footpads of rats, pre- and post-pilocarpine/normal saline (NS) injection were acquired using a fat-suppressed proton density-weighted magnetic resonance imaging (MRI) sequence at 7.0 T, and the regions of interest (ROIs) in plugs and rat footpads were analysed and graphed. A significant increase in the ROI mean proton intensity occurred in both 3D reconstructed and native eccrine sweat glands after pilocarpine injection. The mean proton intensity had no noticeable changes in ROIs of Matrigel plugs between pre- and post-pilocarpine injection, and in ROIs of rat footpads between pre- and post-NS injection. In conclusion, the 3D reconstructed sweat glands possess fluid secretion, which is detectable by fat-suppressed proton density-weighted MRI.

Local inhibition of carbonic anhydrase does not decrease sweat rate.

BACKGROUND: The purpose of this study was to measure sweat rate during exercise in the heat after directly inhibiting carbonic anhydrase (CA) in eccrine sweat glands via transdermal iontophoresis of acetazolamide. It was hypothesized that if CA was important for sweat production, local administration of acetazolamide, without the confounding systemic effects of dehydration typically associated with past studies, would have a significant effect on sweat rate during exercise. METHODS: Ten healthy subjects volunteered to exercise in the heat following acetazolamide or distilled water iontophoresis on the forearm. RESULTS: The distilled water iontophoresis site had a mean sweat rate during exercise in the heat of 0.59±0.31 µL/cm2/min, while the acetazolamide iontophoresis site had a mean sweat rate of 0.63±0.36 µL/cm2/min (p>0.05). CONCLUSIONS: The most important finding of the current study was that iontophoresis of acetazolamide did not significantly decrease sweat rate during exercise in the heat. Such results suggest that in past studies it was systemic dehydration, and not CA inhibition at the level of the sweat gland, that caused the reported decreased sweat rate.

Nicotinic receptor activation augments muscarinic receptor-mediated eccrine sweating but not cutaneous vasodilatation in young males.

NEW FINDINGS: What is the central question of this study? Acetylcholine released from cholinergic nerves can activate both muscarinic and nicotinic receptors. Although each receptor can independently induce cutaneous vasodilatation and eccrine sweating, it remains to be elucidated whether the two receptors interact in order to mediate these responses. What is the main finding and its importance? We show that although nicotinic receptor activation does not modulate muscarinic cutaneous vasodilatation, it lowers the muscarinic receptor agonist threshold at which onset for eccrine sweating (augmentation of muscarinic eccrine sweating) occurs in young men in normothermic resting conditions. These results provide new insights into the physiological significance of nicotinic receptors in the regulation of cutaneous perfusion and eccrine sweating. Acetylcholine released from cholinergic nerves can activate both muscarinic and nicotinic receptors; each is known independently to induce cutaneous vasodilatation and eccrine sweating in humans. However, it is not known whether the two receptors interact in order to mediate cutaneous vasodilatation and eccrine sweating. In 10 young men (27 ± 6 years old), cutaneous vascular conductance and sweat rate were evaluated at intradermal microdialysis sites that were continuously perfused with either lactated Ringer's solution (control) or three different concentrations of nicotine (0.1, 1 and 10 mm), a nicotinic receptor agonist. Co-administration of methacholine, a muscarinic receptor agonist, was performed at all skin sites in a dose-proportional fashion (0.0125, 0.25, 5, 100 and 2000 mm, each for 25 min). Administration of nicotine alone caused dose-dependent transient increases in cutaneous vascular conductance and sweat rate (all P ≤ 0.05), which thereafter returned to pre-nicotine levels, except that a portion of transient responses remained with continuous administration of 10 mm nicotine (both P ≤ 0.05). Cutaneous vascular conductance was increased by administration of ≥0.25 mm methacholine at the control site, and this response was likewise observed in the presence of co-administration of all doses of nicotine used (all P ≤ 0.05). Sweat rate at the control site was increased by administration of ≥0.25 mm methacholine, but the lowest dose of methacholine (0.0125 mm) was able to increase sweat rate in the presence of 10 mm nicotine (P ≤ 0.05). We conclude that nicotinic receptor activation lowers the muscarinic receptor agonist threshold for eccrine sweating (augmentation of muscarinic sweating) but does not affect muscarinic cutaneous vasodilatation in young men in normothermic resting conditions.

Targeting the adnexal epithelium: an unusual case of syringometaplasia in a patient on vemurafenib.

Cutaneous adverse events (cAEs) are reported in 90% of all patients on selective BRAF inhibitors and contribute significantly to patient morbidity. Two weeks after initiating vemurafenib for metastatic melanoma, our patient developed a pruritic eruption with numerous, 1-2 mm pink hyperkeratotic follicular papules over his trunk and upper extremities. A biopsy demonstrated squamous metaplasia of the eccrine ducts with irregular hyperplasia of hair follicles sparing the interfollicular epidermis. Diffuse adnexal metaplasia is a novel and unusual cutaneous response to vemurafenib. The patient was started on acitretin 10 mg daily with improvement of the eruption after 4 weeks. We report an unusual cAE of vemurafenib selectively targeting the adnexal epithelium with relative sparing of the interfollicular epidermis. Interval improvement was noted after 4 weeks of acitretin, which is an effective therapeutic option for patients with cAEs involving squamous hyperplasia secondary to vemurafenib. Our case illustrates the particular sensitivity of the adnexal epithelium for vemurafenib-induced dysfunction in proliferation and differentiation, providing the basis for common cAEs observed on this medication.

Olanzapine-induced eccrine squamous syringometaplasia.

Eccrine squamous syringometaplasia is a histopathologic pattern that has mainly been described in patients receiving chemotherapy. Its association to nonchemotherapeutic agents is rare, with very few cases reported in the literature. We present the case of a 55-year-old patient with schizophrenia, who developed a skin eruption 5 weeks after initiating treatment with olanzapine. The histopathologic study revealed squamous syringometaplasia of the dermal eccrine ducts.

Eccrine hidradenitis sine neutrophils: a toxic response to chemotherapy.

We present a case of hidradenitis occurring in a patient after chemotherapy for acute myeloid leukemia (AML) in the setting of profound neutropenia. Neutrophilic eccrine hidradenitis (NEH) presents as tender erythematous papules and plaques and is often associated with chemotherapy for AML. NEH is postulated to be due to toxic injury to the sweat glands followed by neutrophilic inflammation. Alternatively, some hypothesize that NEH represents a primary neutrophilic process. Our patient's clinical presentation was similar to previously reported cases of NEH; however, degenerative changes of the sweat ducts were noted on microscopy without neutrophilic inflammation. She had fewer than 0.01 thousand neutrophils per microliter for 4 days preceding the biopsy. At the same time, a separate area of superficial skin infection developed because of Staphylococcus epidermidis and also lacked neutrophilic inflammation. The similar clinical course and shared histopathologic features between our case and NEH argue that neutrophils are a secondary response to a toxic effect rather than the primary effector in NEH. Neutrophil-poor variants of hidradenitis, both infectious and due to drug toxicity, should be considered diagnostically in neutropenic patients.

Localized ß-adrenergic receptor blockade does not affect sweating during exercise.

The purpose of the current study was to determine the effect of a locally administered nonselective ß-adrenergic antagonist on sweat gland function during exercise. Systemically administered propranolol has been reported to increase, decrease, or not alter sweat production during exercise. To eliminate the confounding systemic effects associated with orally administered propranolol, we used iontophoresis to deliver it to the eccrine sweat glands within a localized area on one forearm prior to exercise. This allowed for determination of the direct effect of ß-adrenergic receptor blockade on sweating during exercise. Subjects (n = 14) reported to the laboratory (23 ± 1°C, 35 ± 3% relative humidity) after having refrained from exercise for ≥12 h. Propranolol (1% solution) was administered to a 5-cm(2) area of the flexor surface of one forearm via iontophoresis (1.5 mA) for 5 min. A saline solution was administered to the opposing arm via iontophoresis. Each subject then exercised on a motor-driven treadmill at 75% of their age-predicted maximal heart rate for 20 min, while sweat rate was measured simultaneously in both forearms. Immediately after cessation of exercise, the number of active sweat glands was measured by application of iodine-impregnated paper to each forearm. The sweat rate for the control and propranolol-treated forearm was 0.62 ± 41 and 0.60 ± 0.44 (SD) mg·cm(-2)·min(-1), respectively (P = 0.86). The density of active sweat glands for the control and propranolol-treated forearm was 130 ± 6 and 134 ± 5 (SD) glands/cm(2), respectively, (P = 0.33). End-exercise skin temperature was 32.9 ± 0.2 and 33.1 ± 0.3°C for the control and propranolol-treated forearm, respectively (P = 0.51). Results of the current study show that when propranolol is administered locally, thus eliminating the potential confounding systemic effects of the drug, it does not directly affect sweating during the initial stages of high-intensity exercise in young, healthy subjects.

Eccrine sweat response in children with asthma.

BACKGROUND: Even though there is a general conviction among parents of asthmatic children and pediatricians that asthmatic children sweat more than healthy ones, this has not been formally tested. AIM: To determine sweating response and factors affecting this response in children with asthma and compare these findings with healthy children. METHOD: Eighty-two children with asthma and 51 healthy controls aged 6-18 years were enrolled in the study. Transepidermal water loss (TEWL) was measured on palmar, volar, forehead, and back surfaces before and after exercise and was expressed as the difference between the measurements recorded before and after exercise. RESULTS: Transepidermal water loss measurements (after exercise - resting) on the palmar surface were higher in children with asthma [22.8 g/m(2 )h (15-34.3)] compared with healthy children [15.2 g/m(2) h (6-22.2)] (P < 0.001). However, a gender stratified analysis showed that the TEWL measurements were higher on all surfaces only in boys but not in girls. Within the group of asthmatic children, TEWL measurements on the volar surface and back were lower in patients using anti-inflammatory therapy compared with those who were on as needed bronchodilator therapy only. CONCLUSION: Our results show that asthma is associated with a higher rate of sweating response to exercise in boys, and anti-inflammatory treatment decreases the amount of sweating. The relationship of eccrine sweating with muscarinic receptor response and methacholine hyperresponsiveness remains to be determined.

Is active sweating during heat acclimation required for improvements in peripheral sweat gland function?

We investigated whether the eccrine sweat glands must actively produce sweat during heat acclimation if they are to adapt and increase their capacity to sweat. Eight volunteers received intradermal injections of BOTOX, to prevent neural stimulation and sweat production of the sweat glands during heat acclimation, and saline injections as a control in the contralateral forearm. Subjects performed 90 min of moderate-intensity exercise in the heat (35 degrees C, 40% relative humidity) on 10 consecutive days. Heat acclimation decreased end-exercise heart rate (156 +/- 22 vs. 138 +/- 17 beats/min; P = 0.0001) and rectal temperature (38.2 +/- 0.3 vs. 37.9 +/- 0.3 degrees C; P = 0.0003) and increased whole body sweat rate (0.70 +/- 0.29 vs. 1.06 +/- 0.50 l/h; P = 0.030). During heat acclimation, there was no measurable sweating in the BOTOX-treated forearm, but the control forearm sweat rate during exercise increased 40% over the 10 days (P = 0.040). Peripheral sweat gland function was assessed using pilocarpine iontophoresis before and after heat acclimation. Before heat acclimation, the pilocarpine-induced sweat rate of the control and BOTOX-injected forearms did not differ (0.65 +/- 0.20 vs. 0.66 +/- 0.22 mg x cm(-2) x min(-1)). However, following heat acclimation, the pilocarpine-induced sweat rate in the control arm increased 18% to 0.77 +/- 0.21 mg x cm(-2) x min(-1) (P = 0.021) but decreased 52% to 0.32 +/- 0.18 mg x cm(-2) x min(-1) (P < 0.001) in the BOTOX-treated arm. Using complete chemodenervation of the sweat glands, coupled with direct cholinergic stimulation via pilocarpine iontophoresis, we demonstrated that sweat glands must be active during heat acclimation if they are to adapt and increase their capacity to sweat.

Estradiol rapidly induces the translocation and activation of the intermediate conductance calcium activated potassium channel in human eccrine sweat gland cells.

BACKGROUND AND AIMS: Steroid hormones target K+ channels as a means of regulating electrolyte and fluid transport. In this study, ion transporter targets of Estradiol (E2) were investigated in the human eccrine sweat gland cell line NCL-SG3. RESULTS: Whole cell patch-clamp studies revealed E2 (10 nM) rapidly activates a whole cell K+ conductance, which is abolished by clotrimazole (30 microM), an inhibitor of the intermediate conductance calcium activated K+ channel (IKCa). The estrogen receptor (ER) antagonist ICI 182, 780 had no effect on this E2 activated K+ conductance, suggesting an estrogen receptor independent mechanism of activation. Confocal microscopy studies revealed under basal conditions that the IKCa channel is located within the cell cytoplasm and in the presence of E2, rapidly translocates to both the apical and basolateral membrane. In the presence of E2, tyrosine phosphorylation of calmodulin, which is known to regulate trafficking of the IKCa channel, is increased, and treatment of cells with the calmodulin inhibitor trifluoperazine (TFP) prevents the E2-induced translocation. CONCLUSIONS: Estradiol rapidly regulates a K+ conductance through the IKCa channel in an estrogen receptor independent manner. E2 stimulates the translocation of IKCa to the cell membrane in a calmodulin dependent manner, representing a novel paradigm of estrogen action in sweat gland epithelial cells.