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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.

PurposeTo determine the impact of altering dietary sodium intake for 3 days preceding exercise on sweat sodium concentration [Na+], and cardiovascular and thermoregulatory variables.MethodsFifteen male endurance athletes (runners n = 8, cyclists n = 7) consumed a low (LNa, 15 mg kg−1 day−1) or high (HNa, 100 mg kg−1 day−1) sodium diet, or their usual free-living diet [UDiet, 46 (37–56) mg kg−1 day−1] for 3 days in a double-blind, randomized cross-over design, collecting excreted urine (UNa) and refraining from exercise. On day 4, they completed 2 h running at 55% \\[V\\]O2max or cycling at 55% maximum aerobic power in Tamb 35 °C. Pre- and post-exercise blood samples were collected, and sweat from five sites using absorbent patches along the exercise protocol.ResultsUNa on days 2–3 pre-exercise [mean (95% CI) LNa 16 (12–19) mg kg−1 day−1, UDiet 46 (37–56) mg kg−1 day−1, HNa 79 (72–85) mg kg−1 day−1; p < 0.001] and pre-exercise aldosterone [LNa 240 (193–286) mg kg−1 day−1, UDiet 170 (116–224) mg kg−1 day−1, HNa 141 (111–171) mg kg−1 day−1; p = 0.001] reflected sodium intake as expected. Pre-exercise total body water was greater following HNa compared to LNa (p < 0.05), but not UDiet. Estimated whole-body sweat [Na+] following UDiet was 10–11% higher than LNa and 10–12% lower than HNa (p < 0.001), and correlated with pre-exercise aldosterone (1st h r =  − 0.568, 2nd h r =  − 0.675; p < 0.01). Rectal temperature rose more quickly in LNa vs HNa (40–70 min; p < 0.05), but was similar at the conclusion of exercise, and no significant differences in heart rate or perceived exertion were observed.ConclusionsThree day altered sodium intake influenced urinary sodium excretion and sweat [Na+], and the rise in rectal temperature, but had no effect on perceived exertion during moderate-intensity exercise in hot ambient conditions.

In vivo confocal Raman spectroscopy is a noninvasive optical method to obtain detailed information about the molecular composition of the skin with high spatial resolution. In vivo confocal scanning laser microscopy is an imaging modality that provides optical sections of the skin without physically dissecting the tissue. A combination of both techniques in a single instrument is described. This combination allows the skin morphology to be visualized and (subsurface) structures in the skin to be targeted for Raman measurements. Novel results are presented that show detailed in vivo concentration profiles of water and of natural moisturizing factor for the stratum corneum that are directly related to the skin architecture by in vivo cross-sectional images of the skin. Targeting of skin structures is demonstrated by recording in vivo Raman spectra of sweat ducts and sebaceous glands in situ. In vivo measurements on dermal capillaries yielded high-quality Raman spectra of blood in a completely noninvasive manner. From the results of this exploratory study we conclude that the technique presented has great potential for fundamental skin research, pharmacology (percutaneous transport), clinical dermatology, and cosmetic research, as well as for noninvasive analysis of blood analytes, including glucose.

BackgroundVX-809, a cystic fibrosis transmembrane conductance regulator (CFTR) modulator, has been shown to increase the cell surface density of functional F508del-CFTR in vitro.MethodsA randomised, double-blind, placebo-controlled study evaluated the safety, tolerability and pharmacodynamics of VX-809 in adult patients with cystic fibrosis (n=89) who were homozygous for the F508del-CFTR mutation. Subjects were randomised to one of four VX-809 28 day dose groups (25, 50, 100 and 200 mg) or matching placebo.ResultsThe type and incidence of adverse events were similar among VX-809- and placebo-treated subjects. Respiratory events were the most commonly reported and led to discontinuation by one subject in each active treatment arm. Pharmacokinetic data supported a once-daily oral dosing regimen. Pharmacodynamic data suggested that VX-809 improved CFTR function in at least one organ (sweat gland). VX-809 reduced elevated sweat chloride values in a dose-dependent manner (p=0.0013) that was statistically significant in the 100 and 200 mg dose groups. There was no statistically significant improvement in CFTR function in the nasal epithelium as measured by nasal potential difference, nor were there statistically significant changes in lung function or patient-reported outcomes. No maturation of immature F508del-CFTR was detected in the subgroup that provided rectal biopsy specimens.ConclusionsIn this study, VX-809 had a similar adverse event profile to placebo for 28 days in F508del-CFTR homozygous patients, and demonstrated biological activity with positive impact on CFTR function in the sweat gland. Additional data are needed to determine how improvements detected in CFTR function secondary to VX-809 in the sweat gland relate to those measurable in the respiratory tract and to long-term measures of clinical benefit.Clinical trial numberNCT00865904

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.

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.

The purpose of this study was to determine whether sweat sodium concentration ([Na + ] sweat ) during exercise in the heat differs between aerobically trained and untrained individuals. On three occasions, ten endurance-trained (Tr) and ten untrained (UTr) subjects (  = 4.0 ± 0.8 vs. 3.4 ± 0.7 L min −1 , respectively; P  < 0.05) cycled in a hot-ventilated environment (36 ± 1°C; 25 ± 2% humidity, airflow 2.5 m s −1 ) at three workloads (i.e., 40, 60, and 80% ). Whole-body (SR WB ) and back sweat rates (SR BACK ) were measured. At the conclusion of the study, Na + in sweat and blood samples was analyzed to calculate Na + secretion and reabsorption rates. SR WB and SR BACK were highly correlated in Tr and UTr ( r  = 0.74 and 0.79, respectively; P  < 0.0001). In both groups, SR BACK increased with the increases in exercise intensity ( P  < 0.05). Likewise, [Na + ] sweat increased with the exercise intensity in both groups ( P  < 0.05) and it tended to be higher in Tr than in UTr at 60 and 80% (~22 mmol L −1 higher; P  = 0.06). However, when normalized for SR BACK , [Na + ] sweat was not different between groups. In both groups, Na + secretion and reabsorption rates increased with the increases in SR BACK ( P  < 0.05). However, Na + reabsorption rate was lower in the Tr than in the UTr (mean slope = 48 vs. 82 ηmol cm −2  min −1 ; P  = 0.03). In conclusion, using a cross-sectional study design, our data suggest that aerobic fitness level does not reduce sweat Na + secretion or enhance Na + reabsorption during prolonged exercise in the heat that induced high sweat rates.

Purpose. To research the distribution and quantitative changes of UT-A1, UT-B1, and AQP5 in uremic skin tissue. Methods. 34 cases of uremic patients (UP) and 11 controls were recruited. Immunohistochemistry, immunofluorescence, RT-PCR, and Western Blot were used to identify the proteins in sweat glands. Results. AQP5, UT-A1, and UT-B1 were expressed and localized in human skin basal lines, skin sweat glands, and sweat ducts, both in UP and controls. Compared to controls, AQP5 mRNA abundance was significantly decreased in UP (P<0.01), and, with the decrease of eGFR, the AQP5 expression was significantly decreased (P<0.05). By contrast, UT-A1 and UT-B1 mRNA abundance was significantly increased in the skin of UP compared with the control (P<0.01), and, with the decrease of eGFR, the AQP5 expression was significantly increased (P<0.05). We found that the gene changes were coincident with the corresponding target proteins. The urea transporter subtypes, UT-A1 and UT-B1, were expressed in the skin basal cell layer and exocrine sweat glands. The abundance of UT-A1 and UT-B1 in uremic sweat glands was significantly increased in UP, while the expression of AQP5 was decreased. Conclusion. Elimination of urea through the skin by producing sweat is a potential therapeutic strategy for renal failure patients.

This study tested the hypothesis that the change in body mass (ΔBM) accurately reflects the change in total body water (ΔTBW) after prolonged exercise. Subjects (4 men, 4 women; 22–36 year; 66 ± 10 kg) completed 2 h of interval running (70% V O 2max ) in the heat (30°C), followed by a run to exhaustion (85% V O 2max ), and then sat for a 1 h recovery period. During exercise and recovery, subjects drank fluid or no fluid to maintain their BM, increase BM by 2%, or decrease BM by 2 or 4% in separate trials. Pre- and post-experiment TBW were determined using the deuterium oxide (D 2 O) dilution technique and corrected for D 2 O lost in urine, sweat, breath vapor, and nonaqueous hydrogen exchange. The average difference between ΔBM and ΔTBW was 0.07 ± 1.07 kg (paired t test, P  = 0.29). The slope and intercept of the relation between ΔBM and ΔTBW were not significantly different from 1 and 0, respectively. The intraclass correlation coefficient between ΔBM and ΔTBW was 0.76, which is indicative of excellent reliability between methods. Measuring pre- to post-exercise ΔBM is an accurate and reliable method to assess the ΔTBW.

We optically measured effects of orally available ivacaftor (Kalydeco®) on sweat rates of identified glands in 3 R117H subjects, each having a unique set of additional mutations, and compared them with 5 healthy control subjects tested contemporaneously. We injected β-adrenergic agonists intradermally to stimulate CFTR-dependent 'C-sweat' and methacholine to stimulate 'M-sweat', which persists in CF subjects. We focused on an R117H-7T/F508del subject who produced quantifiable C-sweat off ivacaftor and was available for 1 blinded, 3 off ivacaftor, and 3 on ivacaftor tests, allowing us to estimate in vivo fold-increase in sweat rates produced by ivacaftor's effect on the open probability (PO) of R117H-CFTR. Measured sweat rates must be corrected for sweat losses. With estimated sweat losses of 0.023 to 0.08 nl·gland-1·min-1, ivacaftor increased the average C-sweat rates 3-7 fold, and estimated function as % of WT were 4.1-12% off ivacaftor and 21.9-32% on ivacaftor (larger values reflect increased loss estimates). Based on single tests, an R117H-7T/ R117H-7T subject showed 6-9% WT function off ivacaftor and 28-43% on ivacaftor. Repeat testing of an R117H-5T/F508del subject detected only trace responding to ivacaftor. We conclude that in vivo, R117H PO is strongly increased by ivacaftor, but channel number, mainly determined by variable deletion of exon 10, has a marked influence on outcomes.