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In humans, perspiration regulates core body temperature. Therefore, objectively evaluating it is essential for studying sweat gland function and mechanisms, particularly in antiperspirant efficacy studies. Various approaches have been developed for measuring human perspiration and evaluating antiperspirant efficacy, but are unsuitable for robust and routine clinical testing applications. This paper shows how infrared thermography, utilizing both high- and low-resolution modes, functions as a multiscale imaging modality. The high-resolution mode extracts physiological parameters (respiratory ~ 0.3 Hz and heart rate ~ 1.0 Hz) and visualizes the reduction of the sweat pore radii (from 359 ± 155 μm to 161 ± 47 μm) after antiperspirant application, consistent with known mechanisms of pore plugging and constriction induced by aluminum salts. The low-resolution mode quantitatively maps sweat retention in underarm clothing. All study participants in a clinical trial showed reduced sweat retention on their T-shirts due to antiperspirants, with reductions ranging from approximately 37-97% and an average reduction of 77.7 ± 22.1% using the developed methodology and tested antiperspirant. Overall, this non-invasive technique presents significant potential for clinical and personal care product evaluations, particularly in the early stages of product development., (© 2024. The Author(s).)

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., (© 2024 The Author(s). Experimental Dermatology published by John Wiley & Sons Ltd.)

The process of sweating plays an important role in the human body, including thermoregulation and maintenance of the environment and health of the skin. It is known that the conditions of hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion and can result in severe skin conditions such as pruritus and erythema, which significantly reduce the patient's quality of life. However, there are many aspects of the signaling mechanisms in the process of sweating that have not been clarified, and no effective therapies or therapeutic agents have yet been discovered. Previously, it was reported that pituitary adenylate cyclase-activating polypeptide (PACAP) promotes sweating, but details of the underlying mechanism has not been clarified. We used immortalized human eccrine gland cells (NCL-SG3 cell) to investigate how sweat secretion is induced by PACAP. Intracellular Ca 2+ levels were increased in these cells following their exposure to physiological concentrations of PACAP. Intracellular Ca 2+ was not elevated when cells were concomitantly treated with PA-8, a specific PAC1-R antagonist, suggesting that PAC1-R is involved in the elevation of intracellular Ca 2+ levels in response to PACAP treatment. Furthermore, immunocytochemistry experiments showed that aquaporin-5 was translocated from the cytoplasm to the cell membrane by PACAP. These results suggest that PACAP acts on eccrine sweat glands to promote sweat secretion by translocation of aquaporin-5 to the cell membrane in response to increased levels of intracellular Ca 2+ . These findings also provide a solid basis for future research initiatives to develop new therapies to treat sweating disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Optical measurement of CFTR-dependent sweat secretion stimulated by a beta-adrenergic cocktail (C-phase) vs. CFTR-independent sweat secretion induced by methacholine (M-phase) can discriminate cystic fibrosis (CF) patientts from controls and healthy carriers by the ratio of sweat rate in the C-phase vs. the M-phase (C/M ratio). However, image analysis is experimentally demanding and time-consuming. Here, sweat droplet number (SDN) in the C-phase, corresponding to the number of sweat-secreting glands, was a statistically significant predictor for detecting the effects of CFTR-targeted therapy. We show that in 44 non-CF subjects and 110 CF patients, SDN in the C-phase provides a linear readout of CFTR function that is more sensitive than that using the C/M ratio. In CF patients, increased SDN in the C-phase during treatment with (LUMA/IVA) was associated with a trend toward improved lung function (FEV1). Our method is suitable for multicenter monitoring of the effects of CFTR modulators., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Hyperhidrosis (HH) is defined as perspiration beyond the level required to maintain temperature regulation. HH affects nearly 4.8% of the population in the United States. It can have a great impact on patient’s quality of life by disturbing daily activity, performance, confidence, social interactions, and mental health. In the majority of patients with HH (93%), the etiology of excess sweating is idiopathic, which classifies it as primary focal HH. Mild HH may be controlled with topical antiperspirants and lifestyle modifications. Based on the location of involvement, iontophoresis and botulinum toxin may be considered if the patient does not respond to topical therapies. Despite minimizing sweating, chronic use of systemic anticholinergics, in particular oxybutynin, may result in detrimental adverse effects such as dementia. Local surgery, radiofrequency, microwave, and lasers are other potential modalities for HH. Sympathectomy can be a last resort for the treatment of focal HH of the palmar, plantar, axillary, and craniofacial areas after failure of less invasive therapeutic options. In this review, we conducted a comprehensive search in the PubMed electronic database to summarize an algorithmic approach for the treatment of HH. This can help broaden options for managing this difficult disease. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5774.

Fifteen adult Soay rams were employed in this study to investigate the effect of melatonin on the scrotal skin using histological, histochemical, and morphometrical analysis. The results revealed that the melatonin treated group showed a significant increase in the thickness of the epidermis, the cross-sectional area of blood capillaries and nerve fibers compared with the control one. In addition, obvious hypertrophy and hyperplasia were detected in the sebaceous glands in association with a significant increase in the number and diameter of apocrine sweat glands with well-developed secretory activity. S100 protein and cytokeratin-19 strongly stained the basal cells of sebaceous glands in the melatonin treated group incomparable to the control group. Moreover, the nerve fibers were intensively immunoreacted for S100 and cytokeratin proteins in the melatonin treated group in contrast to the control one. A high number of telocytes (TCs) could be identified in the treated group around the nerve fibers and blood vessels in the dermis. The number of Langerhans cells showed a significant increase in the melatonin groups that were identified by MHC II and PGP 9.5 within the epidermal layer. Furthermore, a significant increase in the number of dendritic cells was identified in the melatonin group, which were distributed within the dermis, around hair follicles, sebaceous glands, and sweat glands and were strongly expressed PGP-9.5, MHC-II, VAMP, SNAP, keratin-5, and cytokeratin-19 immunoreactivity. Notably, Merkel cells showed a significant increase in the number in the melatonin group that could be stained against nestin, SNAP, and VAMP. On the other hand, the secretory granules in sweat glands were exhibited a strong positive reactivity for synaptophysin in melatonin group. The current study showed that the administration of melatonin induced a stimulatory effect on keratinocytes, non-keratinocytes, sebaceous and sweat glands, hair follicles, as well as the vascular, neuronal, and cellular constituents of the dermis.

Hyperhidrosis is a dermatological condition defined by excessive sweating beyond thermoregulatory needs with significant effects on patients' quality of life. Hyperhidrosis is categorized as primary or secondary: primary hyperhidrosis is mostly focal and idiopathic, whereas secondary hyperhidrosis is commonly generalized and caused by an underlying medical condition or use of medications. Various surgical and nonsurgical therapies exist for primary hyperhidrosis. Although botulinum toxin is one of the deadliest toxins known, when used in small doses, it is one of the most effective therapies for primary hyperhidrosis. Botulinum toxin injections are widely used as a second-line primary hyperhidrosis treatment option once topical treatment strategies have failed. This article provides an overview of the commercially available botulinum toxin formulations and their applications in the treatment of primary hyperhidrosis., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Mesenchymal stem cells (MSCs) encapsulation by three-dimensionally (3D) printed matrices were believed to provide a biomimetic microenvironment to drive differentiation into tissue-specific progeny, which made them a great therapeutic potential for regenerative medicine. Despite this potential, the underlying mechanisms of controlling cell fate in 3D microenvironments remained relatively unexplored. Here, we bioprinted a sweat gland (SG)-like matrix to direct the conversion of MSC into functional SGs and facilitated SGs recovery in mice. By extracellular matrix differential protein expression analysis, we identified that CTHRC1 was a critical biochemical regulator for SG specification. Our findings showed that Hmox1 could respond to the 3D structure activation and also be involved in MSC differentiation. Using inhibition and activation assay, CTHRC1 and Hmox1 synergistically boosted SG gene expression profile. Together, these findings indicated that biochemical and structural cues served as two critical impacts of 3D-printed matrix on MSC fate decision into the glandular lineage and functional SG recovery., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: The efficacy of botulinum toxin A (BTX-A) therapy in axillary hyperhidrosis has been documented; however, there are a few studies reporting the efficacy of BTX-A in treating axillary bromhidrosis. The histological changes occurring in sweat glands after BTX-A treatment are also unknown., Objective: The authors report on the efficacy and safety of BTX-A in the treatment of axillary bromhidrosis and on the histological changes in sweat glands after BTX-A treatment., Materials and Methods: Nineteen patients were included in this study. The patients were administered BTX-A injection in one axilla and sterile normal saline as placebo in the other axilla. The degree of malodor was evaluated subjectively by the patients before and 3 months after treatment. Sweat secretion was quantified by the gravimetric method. All patients underwent standard apocrinectomy in both axillary regions., Results: The mean degree of malodor and mean sweat production in the BTX-A-treated axilla were significantly lower than those in the control axilla (2.42 vs 8.00; p < .0001 and 13.33 vs 33.75 mg/min; p = .0028, respectively) at 3 months after therapy. The histological studies showed apocrine sweat glands with atrophic changes and hypoplasia in treated axilla., Conclusion: BTX-A injection is an easy, fast, noninvasive method of treating axillary bromhidrosis.

Little attention has been given to the involvement of sweat glands/ducts in the pathogenesis of prurigo nodularis (PN). According to recent studies, PN is likely to develop under conditions characterized by dry skin, such as atopic dermatitis (AD), suggesting a strong impact of skin dryness on PN development. No therapeutic modalities produced complete resolution of PN without exacerbations. We previously reported that increases in skin dryness by sweating disturbance could initiate the development of AD. We investigated whether sweating responses were impaired in refractory PN lesions; and, if so, we asked whether the PN lesions could resolve by restoring sweating disturbance. Using the impression mold technique, which allows an accurate quantification of individual sweat gland/duct activity, we examined basal sweating under quiescent conditions and inducible sweating responses to thermal stimulus in PN lesions and normal-appearing skin in the same patients before and after treatment with a moisturizer or topical corticosteroids. Sweating disturbance, either basal or inducible, was most profoundly detected in the "hub" structure corresponding to the center of PN papule before the treatment. This sweating disturbance was immunohistochemically associated with the leakage of sweat into the dermis. This disturbance was restored by treatment with a moisturizer. Our limitations include a relatively small patient cohort and lack of blinding. Sweating disturbance could be one of the aggravating factors of PN development. Refractory PN with low skin hydration may resolve by restoring sweating disturbance.

Background: Excessive sweating is a clinical condition that can be improved with type-A botulinum toxin (BTX-A)., Objectives: To evaluate and compare the largest diameter of sweating inhibition halo (SIH) of 5 different commercially available BTX-A, in five different doses, in a 6-month-long clinical evaluation., Methods: Twenty-five adult female volunteers were injected in the dorsal trunk area with both 100 units (100UI) and 500 units (500UI) BTX-A products, reconstituted in a ratio of 1:2.5 IU, respectively. Products were applied in five different concentrations (1:2.5U, 2:5U, 3:7.5U, 4:10U, and 5:12.5U). After 30, 60, 90, 120, 150, and 180 days, a starch-iodine test was performed to obtain the largest diameter of each SIH., Results: The higher the number of units used, the larger the SIH p < 0.05 for all BTX-A. However, Botox®, Botulift®, Dysport®, and Prosigne® have pretty likewise SIH along the study, with some few differences for some doses and months between one and another. However, Xeomin® is the BTX-A with the smallest SIH, in comparison with all others, in any dose and period., Conclusions: Differences were observed among all brands of BTX-As, based on dose and time after injection. Xeomin® provides the smallest SIH in comparison with others BTX-A., (© 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

To determine if ivacaftor (Kalydeco) influences non-CF human CFTR function in vivo, we measured CFTR-dependent (C-sweat) and CFTR-independent (M-sweat) rates from multiple identified sweat glands in 8 non-CF adults. The two types of sweating were stimulated sequentially with intradermal injections of appropriate reagents; each gland served as its own control via alternating off-on drug tests on both arms, given at weekly intervals with 3 off and 3 on tests per subject. We compared drug effects on C-sweating stimulated by either high or low concentrations of β-adrenergic cocktail, and on methacholine-stimulated M-sweating. For each subject we measured ~700 sweat volumes from ~75 glands per arm (maximum 12 readings per gland), and sweat volumes were log-transformed for statistical analysis. T-tests derived from linear mixed models (LMMs) were more conservative than the familiar paired sample t-tests, and show that ivacaftor significantly increased C-sweating stimulated by both levels of agonist, with a larger effect in the low cocktail condition; ivacaftor did not increase M-sweat. Concurrent sweat chloride tests detected no effect of ivacaftor. We conclude that ivacaftor in vivo increases the open channel probability (P O ) of WT CFTR, provided it is not already maximally stimulated.

Non-invasive wearable biosensors provide real-time, continuous, and actionable health information. However, difficulties detecting diluted biomarkers in excreted biofluids limit practical applications. Most biomarkers of interest are transported paracellularly into excreted biofluids from biomarker-rich blood and interstitial fluid during normal modulation of cellular tight junctions. Calcium chelators are reversible tight junction modulators that have been shown to increase absorption across the intestinal epithelium. However, calcium chelators have not yet been shown to improve the extraction of biomarkers. Here we show that for glucose, a paracellularly transported biomarker, the flux into sweat can be increased by >10x using citrate, a calcium chelator, in combination with electroosmosis. Our results demonstrate a method of increasing glucose flux through the sweat gland epithelium, thereby increasing the concentration in sweat. Future work should examine if this method enhances flux for other paracellularly transported biomarkers to make it possible to detect more biomarkers with currently available biosensors., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Co-author Jason Heikenfeld has an equity interest in Eccrine Systems, Inc., a company that may potentially benefit from the research results, and also serves on the company’s Board. The terms of this arrangement have been reviewed and approved by the University of Cincinnati in accordance with its conflict of interest policies. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The transfer of sweat to the skin surface without leakage is important for the homeostatic regulation of skin and is impaired in atopic dermatitis. Although the precise composition of the leakage barrier remains obscure, there is a large contribution from claudins, the major components of tight junctions. In humans, claudin-1, -3, and -15 are expressed on sweat ducts, and claudin-3 and -10 are expressed on secretory coils. Although only two claudins are expressed in murine sweat glands, we found that the expression of claudin-3 is conserved. Atopic dermatitis lesional skin had decreased claudin-3 expression in sweat glands, which was accompanied by sweat leakage. This critical role in water barrier function was confirmed in Cldn3 -/- and Cldn3 +/- mice and those with experimentally decreased claudin-3. Our results show the crucial role of claudin-3 in preventing sweat gland leakage and suggest that the pathogenesis of dermatoses accompanied by hypohidrosis involves abnormally decreased claudin-3., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To determine in vivo effects of CFTR modulators on mutation S945L., Methods: We measured effects of CFTR modulators on CFTR-dependent sweating ('C-sweat') in two pancreatic sufficient cystic fibrosis (CF) subjects. S1 (S945L/G542X) took ivacaftor and S2 (S945L/F508del) took ivacaftor+tezacaftor. Sweating was stimulated pharmacologically to produce sequentially both CFTR-independent (methacholine stimulated) M-sweat and C-sweat; and the ratio of these was compared. Sweat secretion was measured with two methods: real time secretory rate quantitative recording and by optically measuring the growth of sweat bubbles under oil from multiple identified glands., Results: Using the quantitative recorder, we saw zero C-sweat secretion off-drug, but when on-drug the C-sweat responses for both subjects were comparable to those seen in carriers. The on-drug response was further quantified using the sweat bubble method. Each subject again showed robust C-sweat responses, with C-sweat/M-sweat ratios~half of the ratio determined for a cohort of 40 controls tested under identical conditions., Conclusion: These in vivo results, consistent with prior in vitro findings, indicate that the drug treatments restore near-normal function to S945L-CFTR, and support the use of ivacaftor as a treatment for CF patients who carry this allele., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Continuous non-invasive sampling and sensing of multiple classes of analytes could revolutionize medical diagnostics and wearable technologies, but also remains highly elusive because of the many confounding factors for candidate biofluids such as interstitial fluid, tears, saliva, and sweat. Eccrine sweat biosensing has seen a recent surge in demonstrations of wearable sampling and sensing devices. However, for subjects at rest, access to eccrine sweat is highly limited and unpredictable compared to saliva and tears., Objective: Reported here is a prolonged and localized sweat stimulation by iontophoretic delivery of the slowly-metabolized nicotinic cholinergic agonist carbachol., Methods: Presented here are detailed measurements of natural baseline sweat rates across multiple days, confirming a clear need for localized sweat stimulation. Iontophoresis was performed with either carbachol or pilocarpine in order to stimulate sweat in subjects at rest. Furthermore, improved methods of quantifying sweat generation rates (nL/min/gland) are demonstrated., Results: In-vivo testing reveals that carbachol stimulation can surpass a major goal of 24-h sweat access, in some cases providing more than an order of magnitude longer duration than stimulation with commonly-used pilocarpine. Also demonstrated is reduction of the traditional iontophoretic dosage for sweat stimulation (<5.25-42mC/cm 2 ). This increases the viability of repeated dosing as demonstrated herein, and for carbachol is as much as 100-1000X less than used for other applications., Conclusion: This work is not only significant for wearable sweat biosensing technology, but could also have broader impact for those studying topical skin products, antiperspirants, textiles and medical adhesives, nerve disorders, the effects of perspiration on skin-health, skin related diseases such as idiopathic pure sudomotor failure and hyperhidrosis, and other skin- and perspiration-related applications., (Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

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, T or ) 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 N G -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 T or Sweat rate at the L -NAME site was lower than Control following a 0.9 and 1.2°C increase in T or 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 T or 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., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

There is a need for quantitative, precise assessment of small fiber peripheral nerve function. We tested a customized camera device and protocol designed to quantify secretions of individual sweat glands (SGs). Testing was performed on 178 healthy controls and 20 neuropathy subjects. Sweating was stimulated on a 2.25 cm 2 skin area by iontophoresis of pilocarpine. The camera imaged sweat from 50 to 400 sweat ducts. We calculated secretion rate of individual SGs, total sweat volume, and number of secreting SGs at four body sites. Neuropathy subjects were tested at the two distal sites to demonstrate the device's capability to detect abnormal sudomotor function. Normal ranges were calculated for each body site. Neuropathy subjects had lower sweat rates per SG, lower total sweat, and lower SG density. The normal values decreased with advancing age, were lower in females, and differed between body sites. There was good agreement with repeat testing. The device provides reliable, precise quantitative measures of sweat secretion from single SGs for characterization of sudomotor nerve function in healthy control subjects and in subjects with known peripheral neuropathy. The test combines the capabilities of existing tests of sudomotor function while providing additional capabilities., (© 2017 Peripheral Nerve Society.)

Hyperhidrosis is the excessive production of sweating, which can be primary and focal or secondary to various pathologies. The exact cause of primary focal hyperhidrosis is still unknown, although a genetic basis is recognized, and its prevalence varies from 1% to 2.8%. The most affected sites are the armpits, palms, soles and face. It causes much discomfort, affects the quality of life, and is estimated to be undervalued by health professionals. Many treatment options are proposed, both clinical and surgical. The aim of this review is to focus on the treatment of hyperhidrosis with oxybutynin, an anticholinergic drug originally used to control overactive bladder.

Na + /K + -ATPase has been shown to regulate the sweating and cutaneous vascular responses during exercise; however, similar studies have not been conducted to assess the roles of the Na-K-2Cl co-transporter (NKCC) and K + channels. Additionally, it remains to be determined if these mechanisms underpinning the heat loss responses differ with exercise intensity. Eleven young (24 ± 4 years) males performed three 30-min semirecumbent cycling bouts at low (30% VO 2peak ), moderate (50% VO 2peak ), and high (70% VO 2peak ) intensity, respectively, each separated by 20-min recovery periods. Using intradermal microdialysis, four forearm skin sites were continuously perfused with either: (1) lactated Ringer solution (Control); (2) 6 mmol·L -1 ouabain (Na + /K + -ATPase inhibitor); (3) 10 mmol·L -1 bumetanide (NKCC inhibitor); or (4) 50 mmol·L -1 BaCl 2 (nonspecific K + channel inhibitor); sites at which we assessed local sweat rate (LSR) and cutaneous vascular conductance (CVC). Inhibition of Na + /K + -ATPase attenuated LSR compared to Control during the moderate and high-intensity exercise bouts (both P ˂ 0.01), whereas attenuations with NKCC and K + channel inhibition were only apparent during the high-intensity exercise bout (both P ≤ 0.05). Na + /K + -ATPase inhibition augmented CVC during all exercise intensities (all P ˂ 0.01), whereas CVC was greater with NKCC inhibition during the low-intensity exercise only (P ˂ 0.01) and attenuated with K + channel inhibition during the moderate and high-intensity exercise conditions (both P ˂ 0.01). We show that Na + /K + -ATPase, NKCC and K +  channels all contribute to the regulation of sweating and cutaneous blood flow but their influence is dependent on the intensity of dynamic exercise., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Many studies have aimed to identify the controllers of sweating using ventilated capsules with intradermal microdialysis. It is unclear, however, if the surface area covered by the capsule influences the observed response as a result of differences in the number of sweat glands affected by the infused pharmacological agent relative to the total glands captured by the capsule. We evaluated the area of skin perfused with agents delivered via microdialysis. Thereafter, we developed a specialized sweat capsule (1.1 cm(2)) and compared the sweating response with a classic capsule (2.8 cm(2)). InProtocol 1(n = 6), methacholine was delivered to forearm skin in a dose-dependent manner (1-2000 mmol L(-1)). The area of activated sweat glands was assessed via the modified iodine-paper technique. InProtocol 2(n = 6), the area of inhibited sweat glands induced by ouabain and atropine was assessed during moderate-intensity cycling. Marked variability in the affected skin area was observed (0.9 ± 0.4 to 5.2 ± 1.1 cm(2)). InProtocol 3(n = 6), we compared the attenuation in local sweat rate (LSR) induced by atropine between the new and classic capsule during moderate-intensity cycling. Atropine attenuated sweating as assessed using the new (control: 0.87 ± 0.23 mg min(-1) cm(-2)vs. atropine: 0.54 ± 0.22 mg min(-1) cm(-2);P < 0.01) and classic (control: 0.85 ± 0.33 mg min(-1) cm(-2)vs. atropine: 0.60 ± 0.26 mg min(-1) cm(-2);P = 0.05) capsule designs. Importantly, responses did not differ between capsule designs (P = 0.23). These findings provide critical information regarding the skin surface area perfused by microdialysis and suggest that use of a larger capsule does not alter the mechanistic insight into the sweating response gained when using microdialysis., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Objective: The autonomic nervous system (ANS) modulates exocrine gland function. Available data show poor correlation between the degree of function and destruction of the exocrine glands in primary Sjögren's syndrome (SS), suggesting that other mechanisms, such as autonomic dysfunction, may be important in these patients. The aim of this study was to perform a comprehensive analysis of sympathoneural and sympathetic cholinergic function in well-characterized patients with primary SS., Methods: Twenty-one patients with primary SS (mean ± SEM age 44.2 ± 2.8 years) and 13 healthy control subjects (mean ± SEM age 50.8 ± 1.9 years) were assessed during orthostasis and intravenous injection of edrophonium (10 mg). The postganglionic sympathetic cholinergic system was evaluated by assessing sweat production by means of the Quantitative Sudomotor Axon Reflex Test (QSART). Tests of gastric emptying were used to assess the gastrointestinal ANS in primary SS patients., Results: The velocity index and the acceleration index were significantly higher (P < 0.05) in patients with primary SS as compared to controls, both before and during the orthostatic and edrophonium tests. Findings of other hemodynamic and neurochemical parameters did not differ between primary SS patients and controls during the orthostasis and edrophonium test; however, the edrophonium-induced saliva increment was lower in primary SS patients (P = 0.002). Abnormally low sweat production was found in 4 primary SS patients but in none of the controls, as determined by the QSART. Gastric empting was delayed in 53% of primary SS patients., Conclusion: We observed subtle differences in several ANS domains, including the gastrointestinal and sympathocholinergic systems, suggesting the presence of a complex ANS dysfunction in primary SS. The impact was greatest on the exocrine glands, with subtle differences in the cardiac parasympathetic function that were independent of glandular inflammation and atrophy, suggesting an alternative mechanism of disease pathogenesis in primary SS., (© 2015, American College of Rheumatology.)

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is eleven times more common among people with diabetes than the general population and is treatable with appropriate immunotherapy. Treatment response is usually measured clinically (symptomatic and functional improvement). We present a case of a patient with type 2 diabetes (T2D) and CIDP whose treatment response was measurable with the Sudoscan sudomotor function test. This test may represent a new objective evaluation of the treatment of CIDP., Case Description: The patient is a 60year old male initially referred to our center in August 2012, at which time he was diagnosed with CIDP based on AAN electrodiagnostic criteria (NCS). Autonomic functions were significant for low heart rate variability response to expiration/inspiration (E/I), Valsalva maneuver and the ratio of the RR interval for the 30th to the 15th beat upon standing (1.08, 1.12, 1.05 respectively), and frequency analysis of the total spectral power, the standard deviation of the normal RR intervals (sdNN) and their root mean squared (rmsSD). Sudoscan electrochemical skin conductances (ESC), measuring small nerve fiber function on the palms and soles, were very low: 23 μS in the feet and 32 μS in the hands. After one cycle of intravenous immunoglobulin (IVIG: 6 doses total, 75g each) the patient had no change in symptoms of burning, numbness, shooting pains, and gait impairment. However, E/I, Valsalva, and 30:15 ratios (1.19, 1.36, 1.39 respectively) were improved, as were NCS. Sudoscan scores for feet and hands were unchanged (23 μS and 32 μS). In March 2013, the patient's autonomic functions worsened (E/I, Valsalva, and 30:15 ratios 1.1, 1.07, 1.12 respectively), but feet and hand ESC started to show improvement (35 μS and 52 μS respectively). Azathioprine was started. Eight days after a second cycle of IVIG in January 2014, the patient reported for the first time less burning, shooting pains and tingling. E/I, Valsalva, and 30:15 ratios remained low (1.03, 1.07, and not analyzable, respectively), while foot and hand ESC scores continued to improve (43 μS and 55 μS respectively)., Discussion: CIDP diagnosis and treatment response are difficult in the diabetic patient. We found that NCS and autonomic function tests did not correlate well with clinical status while numerical Sudoscan scores matched closely symptomatic changes. ESC have been found to correlate well with peripheral small fiber function and neuropathic symptoms in DPN. The findings in this patient warrant further investigation of the use of Sudoscan to monitor CIDP response to therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Cystic fibrosis (CF) is the most common genetic life-shortening condition in Caucasians. Despite being a multi-organ disease, CF is classically diagnosed by symptoms of acute/chronic respiratory disease, with persistent pulmonary infections and mucus plugging of the airways and failure to thrive. These multiple symptoms originate from dysfunction of the CF transmembrane conductance regulator (CFTR) protein, a channel that mediates anion transport across epithelia. Indeed, establishment of a definite CF diagnosis requires proof of CFTR dysfunction, commonly through the so-called sweat Cl(-) test. Many drug therapies, including mucolytics and antibiotics, aim to alleviate the symptoms of CF lung disease. However, new therapies to modulate defective CFTR, the basic defect underlying CF, have started to reach the clinic, and several others are in development or in clinical trials. The novelty of these therapies is that, besides targeting the basic defect underlying CF, they are mutation specific. Indeed, even this monogenic disease is influenced by a large number of different genes and biological pathways as well as by environmental factors that are difficult to assess. Accordingly, every person with CF is unique and so functional assessment of patients' tissues ex vivo is key for diagnosing and predicting the severity of this disease. Of note, such assessment will also be crucial to assess drug responses, in order to effectively treat all CF patients. It is not because it is a monogenic disorder that personalized treatment for CF is much easier than for complex disorders., (© 2014 The Association for the Publication of the Journal of Internal Medicine.)

Background: The classic sweat test (CST) is the golden standard for cystic fibrosis (CF) diagnosis. Then, our aim was compare the production and volume of sweat, and side effects caused by pulsed direct current (PDC) and constant direct current (CDC). To determine the optimal stimulation time (ST) for the sweat collection. To verify the PDC as CF diagnosis option., Methods: Prospective study with cross-sectional experimental intervention. Experiment 1 (right arm): PDC and CDC. ST at 10 min and sweat collected at 30 min. Currents of 0.5; 0.75; 1.0 and 1.5 mA and frequencies of 0, 200, 1,000 and 5,000 Hz applied. Experiment 2 (left arm): current of 1.0 mA, ST at 5 and 10 min and sweat collected at 15 and 30 min with frequencies of 0; 200; 1,000 and 5,000 Hz applied Experiments 1 and 2 were performed with current density (CD) from 0.07 to 0.21 mA/cm2. Experiment 3: PDC was used in typical CF patients with two CFTR mutations screened and or with CF diagnosis by rectal biopsy and patients with atypical CF., Results: 48 subjects (79.16% female) with average of 29.54 ± 8.87 years old were enrolled. There was no statistical difference between the interaction of frequency and current in the sweat weight (p = 0.7488). Individually, positive association was achieved between weight sweat and stimulation frequency (p = 0.0088); and current (p = 0.0025). The sweat production was higher for 10 min of stimulation (p = 0.0023). The sweat collection was better for 30 min (p = 0.0019). The skin impedance was not influenced by ST and sweat collection (p > 0.05). The current frequency was inversely associated with the skin impedance (p < 0.0001). The skin temperature measured before stimulation was higher than after (p < 0.0001). In Experiment 3 (29 subjects) the PDC showed better kappa index compared to CDC (0.9218 versus 0.5205, respectively)., Conclusions: The performance of the CST with CDC and PDC with CD of 0.14 to 0.21 mA/cm2 showed efficacy in steps of stimulation and collection of sweat, without side effects. The optimal stimulation time and sweat collection were, respectively, 10 and 30 min.

Objective: In the current study, we investigated the efficiency of botulinum toxin-A (BTX-A) on wound and skin graft contractions., Methods: Thirty adult female Wistar rats weighing 150 to 200 g were used. The rats were divided into 2 groups. As each rat in these groups underwent 2 different procedures, those groups also were divided into 2 subgroups. Group 1 (n = 15) was assigned as the control group. Pair of full-thickness skin grafts of 40 × 20 mm was harvested from the 2 sides of the dorsal regions of the rats. The full-thickness skin graft harvested from the left side was readapted (Group 1A), and the right side was left as an open wound (Group 1B). The rats in the second group (n = 15) underwent the same procedures and botulinum toxin-A (BTX-A) 0.5-international unit injection to the graft area (Group 2A) and open wound area (Group 2B)., Results: A decrease in the amount of the contraction was observed in the groups, which underwent BTX-A injection. In the histologic examination, it was observed that inflammation and collagen amount was higher, and the arrangement of the collagen was different in the groups, which underwent BTX-A injection., Conclusions: It has been determined that BTX-A injection reduces wound and graft contraction, and also, it is effective on reducing the amount of sebaceous cells and hair follicles.

A regulatory effect of arginine vasopressin (AVP) on sweat water conservation has been hypothesized but not definitively evaluated. AVP-mediated insertion of sweat and salivary gland aquaporin-5 (AQP5) water channels through activation of the vasopressin type 2 receptor (V2R) remains an attractive, yet unexplored, mechanism that could result in a more concentrated sweat with resultant decreased water loss. Ten runners participated in a double-blind randomized control treadmill trial under three separate pharmacological conditions: a placebo, V2R agonist (0.2 mg desmopressin), or V2R antagonist (30 mg tolvaptan). After a familiarization trial, runners ran for 60 min at 60% of peak speed followed by a performance trial to volitional exhaustion. Outcome variables were collected at three exercise time points: baseline, after the steady-state run, and after the performance run. Body weight losses were <2% across all three trials. Significant pharmacological condition effects were noted for urine osmolality [F = 84.98; P < 0.0001] and urine sodium concentration ([Na(+)]) [F = 38.9; P < 0.0001], which verified both pharmacological activation and inhibition of the V2R at the kidney collecting duct. Plasma osmolality and [Na(+)] demonstrated significant exercise (F = 26.0 and F = 11.1; P < 0.0001) and condition (F = 5.1 and F = 3.8; P < 0.05) effects (osmolality and [Na(+)], respectively). No significant exercise or condition effects were noted for either sweat or salivary [Na(+)]. Significant exercise effects were noted for plasma [AVP] (F = 22.3; P < 0.0001), peak core temperature (F = 103.3; P < 0.0001), percent body weight change (F = 6.3; P = 0.02), plasma volume change (F = 21.8; P < 0.0001), and thirst rating (F = 78.2; P < 0.0001). Performance time was not altered between conditions (P = 0.80). In summary, AVP acting at V2R does not appear to regulate water losses from body fluids other than renal excretion during exercise., (Copyright © 2014 the American Physiological Society.)

To determine if oral dosing with the CFTR-potentiator ivacaftor (VX-770, Kalydeco) improves CFTR-dependent sweating in CF subjects carrying G551D or R117H-5T mutations, we optically measured sweat secretion from 32-143 individually identified glands in each of 8 CF subjects; 6 F508del/G551D, one G551D/R117H-5T, and one I507del/R117H-5T. Two subjects were tested only (-) ivacaftor, 3 only (+) ivacaftor and 3 (+/-) ivacaftor (1-5 tests per condition). The total number of gland measurements was 852 (-) ivacaftor and 906 (+) ivacaftor. A healthy control was tested 4 times (51 glands). For each gland we measured both CFTR-independent (M-sweat) and CFTR-dependent (C-sweat); C-sweat was stimulated with a β-adrenergic cocktail that elevated [cAMP]i while blocking muscarinic receptors. Absent ivacaftor, almost all CF glands produced M-sweat on all tests, but only 1/593 glands produced C-sweat (10 tests, 5 subjects). By contrast, 6/6 subjects (113/342 glands) produced C-sweat in the (+) ivacaftor condition, but with large inter-subject differences; 3-74% of glands responded with C/M sweat ratios 0.04%-2.57% of the average WT ratio of 0.265. Sweat volume losses cause proportionally larger underestimates of CFTR function at lower sweat rates. The losses were reduced by measuring C/M ratios in 12 glands from each subject that had the highest M-sweat rates. Remaining losses were estimated from single channel data and used to correct the C/M ratios, giving estimates of CFTR function (+) ivacaftor  = 1.6%-7.7% of the WT average. These estimates are in accord with single channel data and transcript analysis, and suggest that significant clinical benefit can be produced by low levels of CFTR function.

Sweating has been associated with the exacerbation of atopic dermatitis (AD) in diverse ways. Acetylcholine (ACh)-mediated sweating is known to be attenuated in AD, but its cause remains obscure. To address this issue, the impact of histamine on ACh-induced sweating was evaluated. Sweating was measured by counting the number of active sweat pores by the starch-iodine reaction and dynamic optical coherence tomography; sweat was visualized using two-photon excitation fluorescence microscopy in mice and the quantitative sudomotor axon reflex test in humans. Both histamine receptor antagonists and H1 receptor (H1R)-knockout (KO) mice were used to determine methodological specificity. Histamine demonstrably inhibited ACh-induced sweating in both mice and humans via H1R-mediated signaling. In sweat glands, ACh inactivated glycogen synthase kinase 3β (GSK3β), a kinase involved in endocytosis and secretion, whereas simultaneous stimulation with histamine activated GSK3β. Results of two-photon excitation fluorescence microscopy confirmed the dynamic motion of sweat and sweat glands after ACh treatment, showing that simultaneous stimulation with histamine altered their dynamic properties. These results indicate that histamine inhibits sweat gland secretions by blocking ACh-induced inactivation of GSK3β. Histamine-mediated hypohidrosis might be involved in the mechanism of abnormal skin dryness in patients with AD.

Objectives: Mesenchymal stem cells (MSCs) have the potential for multi-directional differentiation and can be induced to differentiate into sweat gland cells under certain conditions. Epimorphin (EPM) plays an important role in the promotion of epithelial cell morphogenesis; however, its effect on sweat gland-cell differentiation of MSCs remains unknown. The purpose of this study was to investigate how EPM regulates sweat gland cell differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs)., Materials and Methods: hUCMSCs were labeled with 5-bromo-2-deoxyuridine (BrdU) before differentiation induction; were cultured in common culture medium, conditioned medium, or EPM-conditioned medium; and then induced to differentiate into sweat gland cells. Five days after induction, the expression rates of the sweat gland-cell antigens cytokeratin 14 (CK14), cytokeratin 19 (CK19), and carcinoembryonic antigen (CEA) in hUCMSCs were detected by flow cytometry, and the messenger ribonucleic acid (mRNA) and protein levels of CK14, CK19, and CEA were determined by reverse transcription polymerase chain reaction (RT-PCR) and western blot, respectively., Results: hUCMSCs can be induced to differentiate into sweat gland cells in conditioned medium, and expression of CEA was detected by immunofluorescence assay. Flow cytometry results showed that the expression rate of the sweat gland-cell antigens CK14, CK19, and CEA in the conditioned medium were significantly lower than that in the EPM conditioned medium (p < 0.05). RT-PCR and western blot results showed that the mRNA and protein levels of CK14, CK19, and CEA in the conditioned medium were all significantly lower than that in the EPM-conditioned medium (p < 0.01)., Conclusions: These results suggest that EPM can effectively induce the differentiation of hUCMSCs into sweat gland cells.

Importance: This article provides new data on a controversial issue, the influence of doses on the diffusion characteristics of 2 botulinum toxins type A. OBJECTIVE To assess the fields of effect of abobotulinumtoxinA and onabotulinumtoxinA at the same labeled unit dose (1:1 U) comparing sweat gland and muscle activity., Design, Setting, and Participants: A prospective, single-center, randomized, double-blind study was conducted at the Brazilian Center for Studies in Dermatology in Porto Alegre, Brazil. The participants included 19 women., Interventions: Each patient received 2 U of abobotulinumtoxinA on one side of the forehead and 2 U of onabotulinumtoxinA on the other side., Main Outcomes and Measures: Horizontal and vertical diameter and area of the fields of anhidrotic effect, the amplitude of evoked compound muscle action potentials, and the 4-point validated Wrinkle Severity Scale were assessed at 28 days., Results: The horizontal and vertical diameters of the fields of effect and the areas were significantly larger for onabotulinumtoxinA than those obtained for abobotulinumtoxinA. There were no significant differences between the products in the Wrinkle Severity Scale scores and Evoked Compound Muscle Action Potentials. OnabotulinumtoxinA had significantly more diffusion than abobotulinumtoxinA when isovolumetric injections of the same labeled unit dose of the products were injected. CONCLUSIONS AND RELEVANCE Although many studies state that diffusion is product dependent and abobotulinumtoxinA diffuses more than onabotulinumtoxinA, findings from the present study confirm that diffusion is dose dependent and the more potent dose tested diffuses more. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01732809.

To assess CFTR function in vivo, we developed a bioassay that monitors and compares CFTR-dependent and CFTR-independent sweat secretion in parallel for multiple (~50) individual, identified glands in each subject. Sweating was stimulated by intradermally injected agonists and quantified by optically measuring spherical sweat bubbles in an oil-layer that contained dispersed, water soluble dye particles that partitioned into the sweat bubbles, making them highly visible. CFTR-independent secretion (M-sweat) was stimulated with methacholine, which binds to muscarinic receptors and elevates cytosolic calcium. CFTR-dependent secretion (C-sweat) was stimulated with a β-adrenergic cocktail that elevates cytosolic cAMP while blocking muscarinic receptors. A C-sweat/M-sweat ratio was determined on a gland-by-gland basis to compensate for differences unrelated to CFTR function, such as gland size. The average ratio provides an approximately linear readout of CFTR function: the heterozygote ratio is ~0.5 the control ratio and for CF subjects the ratio is zero. During assay development, we measured C/M ratios in 6 healthy controls, 4 CF heterozygotes, 18 CF subjects and 4 subjects with 'CFTR-related' conditions. The assay discriminated all groups clearly. It also revealed consistent differences in the C/M ratio among subjects within groups. We hypothesize that these differences reflect, at least in part, levels of CFTR expression, which are known to vary widely. When C-sweat rates become very low the C/M ratio also tended to decrease; we hypothesize that this nonlinearity reflects ductal fluid absorption. We also discovered that M-sweating potentiates the subsequent C-sweat response. We then used potentiation as a surrogate for drugs that can increase CFTR-dependent secretion. This bioassay provides an additional method for assessing CFTR function in vivo, and is well suited for within-subject tests of systemic, CFTR-directed therapeutics.

(1) The effects of local sensory blockade (topical anaesthesia) on eccrine sweat glands and cutaneous circulation are not well understood. This study aimed to determine whether topical lidocaine/prilocaine alters eccrine sweat gland and cutaneous blood vessel responses. (2) Sweating (capacitance hygrometry) was induced via forearm intradermal microdialysis of five acetylcholine (ACh) doses (1 × 10(-4) to 1 × 10(0) m, 10-fold increments) in control and treated forearm sites in six healthy subjects. Nitric oxide-mediated vasodilatory (sodium nitroprusside) and adrenergic vasoconstrictor (noradrenaline) agonists were iontophoresed in lidocaine/prilocaine-treated and control forearm skin in nine healthy subjects during blood flow assessment (laser Doppler flowmetry, expressed as% from baseline cutaneous vascular conductance; CVC; flux/mean arterial pressure). (3) Non-linear regression curve fitting identified no change in the ED50 of ACh-induced sweating after sensory blockade (-1.42 ± 0.23 logM) compared to control (-1.27 ± 0.23 logM; P > .05) or in Emax (0.43 ± 0.08 with, 0.53 ± 0.16 mg cm(-2) min(-1) without lidocaine/prilocaine; P > .05). Sensory blockade did not alter the vasodilator response to sodium nitroprusside (1280 ± 548% change from baseline CVC with, 1204 ± 247% without lidocaine/prilocaine) or vasoconstrictor response to noradrenaline (-14 ± 4% change from baseline CVC with, -22 ± 14% without lidocaine/prilocaine; P > 0.05). (4) Cutaneous sensory blockade does not appear to alter nitric oxide-mediated vasodilation, adrenergic vasoconstriction, or cholinergic eccrine sweating dose-response sensitivity or responsiveness to maximal dose. Thus, lidocaine/prilocaine treatment should not affect sweat gland function or have blood flow implications for subsequent research protocols or clinical procedures., (© 2013 John Wiley & Sons Ltd.)

The choice of environmental conditions when conducting antiperspirant studies greatly affects the quantity of sweat output. Our initial goal in this work was to develop an in-house procedure to test the efficacy of antiperspirant products using replica techniques in combination with image analysis. To ameliorate the skin replica method, we conducted rheological studies using dynamic mechanical analysis of the replica formulation. In terms of sweat output quantification, our preliminary results revealed a considerable amount of variation using the replica technique, leading us to conduct more fundamental studies of the factors that influence sweating behavior and how to best design the experimental strategy. In accordance with the FDA's protocol for antiperspirant testing, we carried out gravimetric analyses of axillae sweating under a variety of environmental conditions including temperature and humidity control. Subjects were first acclimatized in an environmentally controlled room for 30 min, and then placed in a sauna for an additional 30 or 45 min, depending on which test we administered. In Test 1 (30 min total in the sauna), the first 10 min in the sauna was another equilibration period, followed by a 20 min sweat production stage. We monitored axillae sweating during the last 20 min in the sauna by gravimetric analysis. At time (t) = 30 min in the sauna, skin replicas were taken and later analyzed using imaging and image analysis techniques. Test 1 was carried out on over 25 subjects, both male and female, from various racial backgrounds. In Test 2, subjects spent 45 min in the sauna after the initial 30-min period in the environmental room. During the 45 min, we obtained gravimetric readings of absorbent pads placed in the axillae. We conducted studies at various temperature and relative humidity settings. We also studied the influence of several external parameters on sudoriferous activity. Test 2 was a range-finding experiment on two subjects to determine the optimized environmental conditions for the hot room procedure. In addition to the replica and gravimetric techniques, we also measured flux density to determine the onset of firing of sweat glands to ensure that our environmental preconditioning step (30 min in the environmental room) brought subjects to the point that their sweat glands were activated. Although flux density measurements are usually carried out to determine transepidermal water loss (TEWL), we found that they can be equally useful for monitoring the onset of sweat production. Thermal infrared imaging experiments were also carried out allowing us to generate full-body images of subjects containing anatomical thermal distribution data with high accuracy. Overall, we conclude that our in-house hot room procedure offers much potential as an effective and cost-efficient screening tool for narrowing copious antiperspirant formulations to a select few for expensive clinical evaluation.

Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B (probably effective). Oral agents (oxybutynin and methantheline bromide) are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona), while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo) in axillary hyperhidrosis (AH), collectively depicting Level A evidence (established) for botulinumtoxinA (BoNT-A). In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco) no placebo controlled studies exist; thus, efficacy is Level C (possibly effective) based solely on the aforementioned class II comparator study. For RimabotulinumtoxinB (B/Rima), one class III study has suggested Level U efficacy (insufficient data). In palmar hyperhidrosis (PH), there are 3 class II studies for A/Ona and 2 for A/Abo (individually and collectively level B for BoNT-A) and no blinded study for A/Inco (level U). For B/Rima the level of evidence is C (possibly effective) based on 1 class II study. Botulinum toxins (BoNT) provide a long lasting effect of 3-9 months after one injection session. Studies on BoNT-A iontophoresis are emerging (2 class II studies; level B); however, data on duration and frequency of application is inconsistent.

Introduction: Sudomotor dysfunction is one of the earliest neurophysiologic abnormalities to manifest in distal small fiber neuropathy. SUDOSCAN® was developed to provide a non invasive, quick, simple and quantitative measurement of sweat function. The aim of this observational study was to assess sweat function in a diabetes outpatient consult clinic in Germany., Methods: The study was conducted from February 2009 to March 2011 on patients of a diabetes outpatient clinic in Germany with type 1 and type 2 diabetes, and was conducted parallel to standard care. Sweat function was evaluated by measuring the electrochemical conductance (ESC) of the hands and feet. The method's reproducibility between 2 devices and a follow-up according to insulin administration were also assessed., Results: 52 patients with type 1 diabetes and 115 patients with type 2 diabetes (69 receiving insulin) were involved in this observational study. Hand and foot conductances were lower in patients with type 2 diabetes when compared to patients with type 1 diabetes. A slight decrease in hand and foot conductances was observed in patients with type 2 diabetes without insulin, while an increase was observed in patients receiving insulin (-3.8±9.7 vs. 1.0±9.7 µS, p=0.02 for the hands and -2.2±7.5 vs. 4.1±8.8 µS, p<0.001 for the feet). Coefficient of correlation between measurements performed with the 2 different devices was 0.85 for hands and 0.93 for feet, p<0.001. No safety concern was reported and none of the subjects experienced discomfort during the tests., Conclusion: This preliminary study shows that the assessment of small C fiber neuropathy can be performed non invasively, quickly and effectively in standard diabetes outpatient practice with very good reproducibility. The observation that electrochemical skin conductance improves with intensified insulin treatment must be confirmed in a clinical study performed on a larger population., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

The purpose of the current study was to test the hypothesis that the beta-adrenergic innervation of the human eccrine sweat gland facilitates greater sweat production following heat acclimation. Eight healthy subjects (mean ± SD age: 25.1 ± 4.1 years, weight: 79.0 ± 16.1 kg, and VO(2)max: 48.5 ± 8.0 ml/kg/min) underwent active heat acclimation by walking at 40% of their VO(2)max for 8 days (90 min a day) in an environmental chamber (35.3 ± 0.8°C and 40.2 ± 2.1% rH). To test the hypothesis, the adrenergic component of sweat gland innervation was inhibited by continuously administering a 0.5% solution of the beta-adrenergic antagonist propranolol via iontophoresis to a 5 cm(2) area of one forearm during each 90-min exercise bout. The opposing control forearm underwent iontophoresis with a saline solution. Following heat acclimation, mean sweat rate in the inhibited and control forearm was 0.47 ± 0.30 mg/cm(2)/min and 0.44 ± 0.25mg/cm(2)/min, respectively. Findings of the current study fail to support the hypothesis that adrenergic innervation facilitates human eccrine sweat gland function during heat acclimation, as no significant differences in sweating were observed. In light of the above, the physiological significance of the dual cholinergic and adrenergic innervation of the eccrine sweat gland has yet to be determined., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The dose equivalence of commonly used commercial preparations of botulinum toxin type A, Dysport (abotulinumtoxinA [ABO] 500 U, Ipsen Biopharm Limited, Wrexham, United Kingdom) and Botox (onabotulinumtoxinA [ONA] 100 U, Allergan, Irvine, CA), remains unclear., Objective: We sought to evaluate the field effect for ABO and ONA at dose equivalences of 2.5:1.0 U and 2.0:1.0 U, in both muscular and sweat gland activity., Methods: In all, 59 female patients with forehead wrinkles were enrolled. Patients were randomized for dose equivalence between ABO and ONA, group A (2.0:1.0 U, ABO:ONA) or group B (2.5:1.0 U, ABO:ONA) administered in the frontalis muscles. Clinical assessment, Minor test, and electromyography evaluations were performed at baseline, 28 days, and 112 days., Results: In group B, the field of anhidrotic effect of ABO showed a greater area and larger horizontal diameter than ONA at 28 and 112 days. At maximum frontalis muscle activity (day 112) patients receiving ABO demonstrated greater improvement based on the Wrinkle Severity Scale. No differences were found in frontalis muscle activity at rest between groups A and B based on results of Wrinkle Severity Scale, electromyography, and interindividual variability data at 28 and 112 days., Limitations: Currently, there are no objective measurements other than electromyography to evaluate the field effect of botulinum toxin type A in muscles., Conclusion: At a dose equivalence of 2.0:1.0 U (ABO:ONA), similar field effects were found for both muscle and sweat gland activity. At a higher dose equivalence of 2.5:1.0 U (ABO:ONA), injections of ABO showed greater area and larger horizontal diameter in field of anhidrotic effect at 28 and 112 days than ONA., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Blister formation and eccrine sweat gland necrosis is a cutaneous manifestation associated with states of impaired consciousness, most frequently reported after overdoses of central nervous system depressants, particularly phenobarbital. The case of a 45-year-old woman who developed "coma blisters" at six distinct anatomic sites after confirmed (laboratory) phenobarbital poisoning, associated with other central nervous system depressants (clonazepam, promethazine, oxcarbazepine and quetiapine), is presented. A biopsy from the left thumb blister taken on day 4 revealed focal necrosis of the epidermis and necrosis of sweat gland epithelial cells; direct immunofluorescence was strongly positive for IgG in superficial blood vessel walls but negative for IgM, IgA, C3 and C1q. The patient was discharged on day 21 with no sequelae.

Background: Sweating is variably altered by physical exercise, diabetic neuropathy and antiperspirants., Methods: Skin temperature, skin surface water loss (SSWL), the Corneometer(®) average capacitance (CMAC) and skin capacitance mapping (SCM) were measured before and after moderate physical exercise in 20 healthy subjects. The effect of 5% aluminium chloride hexahydrate (ACH) in a water solution was similarly tested. The same assessments were performed in 20 diabetic patients at rest., Results: Diabetic neuropathy appeared at rest as an increased (compensatory) SCM on the forearms without obvious modification on the hypohidrotic legs. On ACH sites after exercise, SCM revealed both a lowered number of active sweat glands and a lighter stratum corneum (SC) (dryness). In addition, CMAC and SSWL were decreased on ACH sites at rest and at completion of exercise., Conclusion: In diabetic neuropathy, the compensatory hyperhidrosis is more easily disclosed than the hypohidrosis. ACH affects both sweat excretion and the SC hydration., (© 2011 John Wiley & Sons A/S.)

Mechanisms accounting for sex-related differences in the sweat response remain to be elucidated. In the present study, we focused on differences in sweat gland cholinergic sensitivity between males and females. Since, males usually possess higher aerobic capacity than females, we investigated sweating in males and females grouped according to aerobic capacity (.VO(2peak)). Forty-four subjects were assigned to four groups: males with higher (MH) and lower (ML), and females with higher (FH) and lower (FL) .VO(2peak). Forearm sweating was induced by iontophoretic administration (1.5 mA, 60 muA cm(-2), 5 min) of pure water or varying concentrations of pilocarpine hydrochloride (0.125, 0.250, 0.5, 1.0 and 2.0%). Local sweat rate (absorbent paper) and the number of activated sweat glands (iodine impregnated paper) were computed. Maximal pilocarpine-induced sweat rate (SR(max)) and the pilocarpine concentration which elicited 50% of maximal sweating response (K (m)) were calculated. Sweat rate and active gland density increased in response to greater doses of pilocarpine (p < 0.05). Inter-group differences were evident: SR(max) was greatest for MH and lowest for FL (p < 0.05), but no significant differences were observed between ML and FH (p = 0.24). Higher SR(max) were observed, within-sex, for those with greater aerobic capacity (p < 0.05). Furthermore, males' K (m) values were higher than females', indicating greater sweat gland affinity for pilocarpine even for groups having similar aerobic capacity (p < 0.05). In summary, we confirmed that the human sudomotor response is affected by aerobic capacity but, also, that sex-related differences in sweat gland cholinergic sensitivity exist and are not necessarily associated with the typical differences in .VO(2peak) observed between sexes.

Topiramate is an anticonvulsant medication that is widely used for migraine prophylaxis. Hypohidrosis and hyperthermia are 2 rare adverse effects of topiramate treatment, which have mainly occurred in pediatric epilepsy patients. Herein, we describe the first case of reversible hypohidrosis in an adult patient treated with topiramate for chronic migraine.

Background: For nearly 50 years the diagnosis of cystic fibrosis (CF) has depended on measurements of sweat chloride concentration. While the validity of this test is universally accepted, increasing diagnostic challenges and the search for adequate biomarker assays to support curative-orientated clinical drug trials have created a new demand for accurate, reliable and more practical CF tests. A novel concept is proposed that may provide a more efficient real-time method for assessing CFTR function in vivo., Methods: Cholinergic and beta-adrenergic agonists were iontophoresed to stimulate sweating. The bioelectric potential from stimulated sweat glands (SPD) was measured in vivo using a standard ECG electrode applied to the skin surface. SPD and sweat chloride concentrations were compared in cohorts predicted to express a range of CFTR function as presented by healthy controls (HC), heterozygotes (Hz), pancreatic sufficient (CFPS) and pancreatic insufficient patients with CF (CFPI)., Results: The median SPD was hyperpolarized in patients with CF compared with control subjects (-47.4 mV vs -14.5 mV, p<0.001). In distinguishing between control and CF subjects, SPD (area under receiver operator curve (AUC) = 0.997) was similar to sweat chloride concentration (AUC = 0.986). Sequential cholinergic/beta-adrenergic sweat stimulation dramatically depolarised the SPD in patients with CF (p<0.001) but had no effect in control subjects (p = 0.6) or on the sweat chloride concentration in either group (p>0.5). Furthermore, the positive SPD response was larger in CFPI than in CFPS subjects (p = 0.04)., Conclusion: These results support the concept that skin surface voltages arising from stimulated sweat glands can be exploited to assess expressed CFTR function in vivo and may prove to be a useful diagnostic tool.

Background: Botulinum toxin A (BTX) disrupts neurotransmitter release from cholinergic nerves. The effective duration of impaired sweat secretion with BTX is longer relative to that of impaired muscle contraction, suggesting different mechanisms in these tissues., Objectives: The aim of this study was to test the hypothesis that BTX is capable of altering sweating by reducing the responsiveness of the sweat gland to acetylcholine., Methods: BTX was injected into the dorsal forearm skin of healthy subjects at least 3 days before subsequent assessment. On the day of the experiment, intradermal microdialysis probes were placed within the BTX-treated area and in an adjacent untreated area. Incremental doses of acetylcholine were administered through the microdialysis membranes while the sweat rate (protocol 1; n = 8) or a combination of sweat rate and skin blood flow (protocol 2; n = 8) were assessed., Results: A relative absence of sweating was observed at the BTX site for both protocols (protocol 1: 0.05 +/- 0.09 mg cm(-2) min(-1); protocol 2: 0.03 +/- 0.04 mg cm(-2) min(-1), both at the highest dose of acetylcholine), while the sweat rate increased appropriately at the control sites (protocol 1: 0.90 +/- 0.46 mg cm(-2) min(-1); protocol 2: 1.07 +/- 0.67 mg cm(-2) min(-1)). Cutaneous vascular conductance increased to a similar level at both the BTX and control sites., Conclusions: These results demonstrate that BTX is capable of inhibiting sweat secretion by reducing the responsiveness of the sweat gland to acetylcholine, while not altering acetylcholine-mediated cutaneous vasodilatation.