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What happens when I sweat?
Introduces the sweat glands, discussing their function and secretions.
Book
Role of CFTR in epithelial physiology
Salt and fluid absorption and secretion are two processes that are fundamental to epithelial function and whole body fluid homeostasis, and as such are tightly regulated in epithelial tissues. The CFTR anion channel plays a major role in regulating both secretion and absorption in a diverse range of epithelial tissues, including the airways, the GI and reproductive tracts, sweat and salivary glands. It is not surprising then that defects in CFTR function are linked to disease, including life-threatening secretory diarrhoeas, such as cholera, as well as the inherited disease, cystic fibrosis (CF), one of the most common life-limiting genetic diseases in Caucasian populations. More recently, CFTR dysfunction has also been implicated in the pathogenesis of acute pancreatitis, chronic obstructive pulmonary disease (COPD), and the hyper-responsiveness in asthma, underscoring its fundamental role in whole body health and disease. CFTR regulates many mechanisms in epithelial physiology, such as maintaining epithelial surface hydration and regulating luminal pH. Indeed, recent studies have identified luminal pH as an important arbiter of epithelial barrier function and innate defence, particularly in the airways and GI tract. In this chapter, we will illustrate the different operational roles of CFTR in epithelial function by describing its characteristics in three different tissues: the airways, the pancreas, and the sweat gland.
Journal Article
Association of HPV42 with digital papillary adenocarcinoma and the use of in situ hybridization for its distinction from acral hidradenoma and diagnosis at non-acral sites
Digital papillary adenocarcinoma (DPAC) is a rare tumor of sweat gland origin that preferentially affects the digits and has the potential to metastasize. Its tumor diagnosis can be difficult. Well-differentiated variants of DPAC can be confused with a benign sweat gland tumor, in particular nodular hidradenoma. With the recent detection of HPV42 DNA in DPAC by next-generation sequence analysis, we reasoned that this association could be used for diagnostic purposes. To this end, we performed in situ hybridization for HPV42 on 10 tumors diagnosed as DPAC as well as 30 sweat gland tumors of various histology types, including 8 acral hidradenomas. All DPAC were positive for HPV42. Positive hybridization signals for HPV42 were seen in both primary and metastatic DPACs. All other tumors and normal tissues were negative. This study confirms the association of HPV42 with the tumor cells of DPAC through in situ hybridization. The positive test result in all lesions of DPAC and lack of detection of HPV42 in any of the acral hidradenomas or other sweat gland tumors examined in this series is encouraging for the potential diagnostic utility of the assay. As documented by two scrotal tumors of DPAC, the in situ hybridization test for HPV42 can also help support the rare occurrence of this tumor at a non-acral site.
Journal Article
Fingerprint ridges allow primates to regulate grip
Fingerprints are unique to primates and koalas but what advantages do these features of our hands and feet provide us compared with the smooth pads of carnivorans, e.g., feline or ursine species? It has been argued that the epidermal ridges on finger pads decrease friction when in contact with smooth surfaces, promote interlocking with rough surfaces, channel excess water, prevent blistering, and enhance tactile sensitivity. Here, we found that they were at the origin of a moisture-regulating mechanism, which ensures an optimal hydration of the keratin layer of the skin for maximizing the friction and reducing the probability of catastrophic slip due to the hydrodynamic formation of a fluid layer. When in contact with impermeable surfaces, the occlusion of the sweat from the pores in the ridges promotes plasticization of the skin, dramatically increasing friction. Occlusion and external moisture could cause an excess of water that would defeat the natural hydration balance. However, we have demonstrated using femtosecond laser-based polarization-tunable terahertz wave spectroscopic imaging and infrared optical coherence tomography that the moisture regulation may be explained by a combination of a microfluidic capillary evaporation mechanism and a sweat pore blocking mechanism. This results in maintaining an optimal amount of moisture in the furrows that maximizes the friction irrespective of whether a finger pad is initially wet or dry. Thus, abundant low-flow sweat glands and epidermal furrows have provided primates with the evolutionary advantage in dry and wet conditions of manipulative and locomotive abilities not available to other animals.
Journal Article
Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma
Poroma is a benign skin tumor exhibiting terminal sweat gland duct differentiation. The present study aimed to explore the potential role of gene fusions in the tumorigenesis of poromas. RNA sequencing and reverse transcription PCR identified highly recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poromas (92/104 lesions, 88.5%) and their rare malignant counterpart, porocarcinomas (7/11 lesions, 63.6%). A WWTR1-NUTM1 fusion was identified in a single lesion of poroma. Fluorescent in-situ hybridization confirmed genomic rearrangements involving these genetic loci. Immunohistochemical staining could readily identify the YAP1 fusion products as nuclear expression of the N-terminal portion of YAP1 with a lack of the C-terminal portion. YAP1 and WWTR1, also known as YAP and TAZ, respectively, encode paralogous transcriptional activators of TEAD, which are negatively regulated by the Hippo signaling pathway. The YAP1 and WWTR1 fusions strongly transactivated a TEAD reporter and promoted anchorage-independent growth, confirming their tumorigenic roles. Our results demonstrate the frequent presence of transforming YAP1 fusions in poromas and porocarcinomas and suggest YAP1/TEAD-dependent transcription as a candidate therapeutic target against porocarcinoma.
Journal Article
Physiological mechanisms determining eccrine sweat composition
Purpose
The purpose of this paper is to review the physiological mechanisms determining eccrine sweat composition to assess the utility of sweat as a proxy for blood or as a potential biomarker of human health or nutritional/physiological status.
Methods
This narrative review includes the major sweat electrolytes (sodium, chloride, and potassium), other micronutrients (e.g., calcium, magnesium, iron, copper, zinc, vitamins), metabolites (e.g., glucose, lactate, ammonia, urea, bicarbonate, amino acids, ethanol), and other compounds (e.g., cytokines and cortisol).
Results
Ion membrane transport mechanisms for sodium and chloride are well established, but the mechanisms of secretion and/or reabsorption for most other sweat solutes are still equivocal. Correlations between sweat and blood have not been established for most constituents, with perhaps the exception of ethanol. With respect to sweat diagnostics, it is well accepted that elevated sweat sodium and chloride is a useful screening tool for cystic fibrosis. However, sweat electrolyte concentrations are not predictive of hydration status or sweating rate. Sweat metabolite concentrations are not a reliable biomarker for exercise intensity or other physiological stressors. To date, glucose, cytokine, and cortisol research is too limited to suggest that sweat is a useful surrogate for blood.
Conclusion
Final sweat composition is not only influenced by extracellular solute concentrations, but also mechanisms of secretion and/or reabsorption, sweat flow rate, byproducts of sweat gland metabolism, skin surface contamination, and sebum secretions, among other factors related to methodology. Future research that accounts for these confounding factors is needed to address the existing gaps in the literature.
Journal Article
Human and rat ex vivo sweat glands for the observation of acetylcholine induced intracellular calcium signalling
Sweating is imperative for thermoregulatory function in humans. However, many individuals find it undesirable due to its associated malodorous nature. Despite these concerns, aluminium salts remain among the most efficacious sweat-inhibiting agents. Nevertheless, the discovery of novel antiperspirants is challenging due to restrictions on animal testing and the limitations of existing cellular models. Sweat glands, when isolated from human subjects, have been shown to possess only minor functional limitations. Consequently, they are regarded as a leading alternative, despite their limited availability. As the primary analytical metric for isolated sweat glands is sweat output, the objective of this study was to devise experiments that enhance both analysability and availability. We consequently present a method for the reliable observation of intracellular calcium responses in isolated human sweat glands ex vivo. Furthermore, we show that availability can be improved by demonstrating that isolated human sweat glands can be cryopreserved while preserving viability, structural integrity and functionality. In order to obtain these results with limited access to human sweat glands, we set up an experimental set-up using rat sweat glands and compared them to human sweat glands. The study demonstrates that isolated sweat glands from rats and humans exhibit a remarkably similar physiological calcium response to cholinergic stimulation. This validates the use of rat sweat glands as a suitable model for the development of novel experimental procedures, thus circumventing the scarcity of human sweat gland samples. This approach significantly enhanced the analysability and availability of human sweat gland samples. The calcium imaging method applied in this study facilitates the exploration of sweat gland physiology at the cellular level, thereby enabling a more detailed understanding of sweating disorders. This, in turn, enhances the suitability of the model for use in cosmetic testing and the discovery of new antiperspirant agents, thus circumventing the need for animal testing.
Journal Article
Syringocystadenocarcinoma papilliferum: a systematic review of clinical characteristics, reappraisal of associations, diagnostic pitfalls and management challenges
Syringocystadenocarcinoma papilliferum (SCACP) is a rare and aggressive malignant adnexal tumor originating from apocrine or pluripotent appendageal glands, often associated with a preceding syringocystadenoma papilliferum (SCAP) or nevus sebaceus (NS). This systematic review rigorously examines SCACP through an analysis of 78 cases documented between 1980 and 2024. The study aims to provide a comprehensive review of the clinical manifestations, diagnosis, treatment modalities, and outcomes associated with SCACP, while also reappraising its associations, particularly with NS. SCACP predominantly affects older adults, with an average age of 66.3 years and a slight male predominance, commonly presenting as ulcerated nodules or plaques on the scalp. This review highlights the aggressive nature of SCACP, evidenced by significant rates of metastasis and recurrence. Treatment is primarily surgical, with Mohs micrographic surgery offering potential benefits in terms of margin control and cosmetic outcomes. The association of SCACP with NS is critically evaluated, suggesting a complex etiopathogenesis and underscoring the importance of recognizing this association for timely diagnosis and management. Our review also briefly discusses potential pitfalls faced by clinicians in the diagnosis of SCACP. Our findings emphasize the need for standardized treatment protocols and further research into targeted therapies to improve patient outcomes in SCACP.
Journal Article
Wearable soft electrochemical microfluidic device integrated with iontophoresis for sweat biosensing
A soft and flexible wearable sweat epidermal microfluidic device capable of simultaneously stimulating, collecting, and electrochemically analyzing sweat is demonstrated. The device represents the first system integrating an iontophoretic pilocarpine delivery system around the inlet channels of epidermal polydimethylsiloxane (PDMS) microfluidic device for sweat collection and analysis. The freshly generated sweat is naturally pumped into the fluidic inlet without the need of exercising. Soft skin-mounted systems, incorporating non-invasive, on-demand sweat sampling/analysis interfaces for tracking target biomarkers, are in urgent need. Existing skin conformal microfluidic-based sensors for continuous monitoring of target sweat biomarkers rely on assays during intense physical exercising. This work demonstrates the first example of combining sweat stimulation, through transdermal pilocarpine delivery, with sample collection through a microfluidic channel for real-time electrochemical monitoring of sweat glucose, in a fully integrated soft and flexible multiplexed device which eliminates the need of exercising. The on-body operational performance and layout of the device were optimized considering the fluid dynamics and evaluated for detecting sweat glucose in several volunteers. Furthermore, the microfluidic monitoring device was integrated with a real-time wireless data transmission system using a flexible electronic board PCB conformal with the body. The new microfluidic platform paves the way to real-time non-invasive monitoring of biomarkers in stimulated sweat samples for diverse healthcare and wellness applications.
Journal Article
In-ear integrated sensor array for the continuous monitoring of brain activity and of lactate in sweat
Owing to the proximity of the ear canal to the central nervous system, in-ear electrophysiological systems can be used to unobtrusively monitor brain states. Here, by taking advantage of the ear’s exocrine sweat glands, we describe an in-ear integrated array of electrochemical and electrophysiological sensors placed on a flexible substrate surrounding a user-generic earphone for the simultaneous monitoring of lactate concentration and brain states via electroencephalography, electrooculography and electrodermal activity. In volunteers performing an acute bout of exercise, the device detected elevated lactate levels in sweat concurrently with the modulation of brain activity across all electroencephalography frequency bands. Simultaneous and continuous unobtrusive in-ear monitoring of metabolic biomarkers and brain electrophysiology may allow for the discovery of dynamic and synergetic interactions between brain and body biomarkers in real-world settings for long-term health monitoring or for the detection or monitoring of neurodegenerative diseases.
An in-ear integrated array of sensors for electroencephalography, electrooculography and electrodermal activity and for lactate can be used to concurrently monitor brain states and lactate levels in sweat.
Journal Article