Characterization of the Human Eccrine Sweat Proteome—A Focus on the Biological Variability of Individual Sweat Protein Profiles

The potential of eccrine sweat as a bio-fluid of interest for diagnosis and personalized therapy has not yet been fully evaluated, due to the lack of in-depth sweat characterization studies. Thanks to recent developments in omics, together with the availability of accredited sweat collection methods, the analysis of human sweat may now be envisioned as a standardized, non-invasive test for individualized monitoring and personalized medicine. Here, we characterized individual sweat samples, collected from 28 healthy adult volunteers under the most standardized sampling methodology, by applying optimized shotgun proteomics. The thorough characterization of the sweat proteome allowed the identification of 983 unique proteins from which 344 were identified across all samples. Annotation-wise, the study of the sweat proteome unveiled the over-representation of newly addressed actin dynamics, oxidative stress and proteasome-related functions, in addition to well-described proteolysis and anti-microbial immunity. The sweat proteome composition correlated with the inter-individual variability of sweat secretion parameters. In addition, both gender-exclusive proteins and gender-specific protein abundances were highlighted, despite the high similarity between human female and male sweat proteomes. In conclusion, standardized sample collection coupled with optimized shotgun proteomics significantly improved the depth of sweat proteome coverage, far beyond previous similar studies. The identified proteins were involved in many diverse biological processes and molecular functions, indicating the potential of this bio-fluid as a valuable biological matrix for further studies. Addressing sweat variability, our results prove the proteomic profiling of sweat to be a promising bio-fluid analysis for individualized, non-invasive monitoring and personalized medicine.

Evaluation of sweating responses in patients with collagen disease using the quantitative sudomotor axon reflex test (QSART): a study protocol for an investigator-initiated, prospective, observational clinical study

IntroductionSweat secretion is controlled by the sympathetic nervous system and is less active during winter than in the summer. Raynaud’s phenomenon is affected by an excessive strain of the sympathetic nerves after exposure to a cold environment, thus reducing the quality of life of patients with collagen disease. Herein, we focus on the eccrine sweat glands that receive both adrenergic and cholinergic innervation. Our hypothesis is that excessive activation of sympathetic nerve in Raynaud’s phenomenon can affect sweating, especially in winter. This study is designed to evaluate the neuroactive sweating responses in patients with collagen disease and to assess its association with skin findings in peripheral circulatory disorders.Methods and analysisThe study will be conducted at a single centre in Japan. Patients with systemic sclerosis, Sjogren’s syndrome, systemic lupus erythematosus, mixed connective tissue disease, and dermatomyositis will be assessed using the quantitative sudomotor axon reflex test. The primary outcomes will be sweat volume and reaction time due to axon reflex and the Raynaud’s condition score. The secondary outcomes will include patient background, skin symptoms (digital ulcers, pernio-like eruptions, subcutaneous calcifications, telangiectasia, nailfold capillary dilatation/bleeding and degree of skin sclerosis) and skin surface temperature. Evaluation will be done two times, during the summer and winter, allowing for the assessment of seasonal differences in sweating responses.Ethics and disseminationEthical approval of this study was certified by the clinical research review board of Nagasaki University Hospital (Reference number: CRB19-001). We will disseminate the findings of this study through peer-reviewed publications and conference presentations.Trial registration numberjRCTs072190009; pre-results.

Selection and Substantiation of Methods for Evaluating Cosmetic Products for Deodorant and Antiperspirant Action

The possibility of using simple and available methods for analyzing deodorants/antiperspirants has been studied. The gravimetric method was shown to have acceptable metrological characteristics under repeatability conditions when evaluating antiperspirant activity. A decrease in the number of microorganisms (CFU) on the axilla skin was observed in a rinse test experiment 4 h and 8 h after the application of deodorants/antiperspirants. The microbial population data were inversely proportional to the antiperspirant activity values of the tested compositions. The sweat secretion reducing decreases the amount of nutrients required for microbial development, which makes it possible to use the rinse test to indirectly evaluate deodorant activity in research and development of personal care products. However, due to its laboriousness and the need for volunteers, the method cannot be recommended for large-scale testing. It was shown that the disc diffusion method (DDM) used to detect Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis cannot be applied to the assessment of the intrinsic antimicrobial activity of the tested cosmetic compositions. This indicates the necessity of additional studies to select test microorganisms typical for the armpit area. In addition, DDM is useful if the deodorant effect of the composition is created by the addition of low-volatile antibacterial compounds. Therefore, microbiological methods have limited applications and are not suitable for widespread use. deodorant action; antiperspirant action, gravimetry, disc diffusion method, rinse test; deodorant; antiperspirant; cosmetic; efficiency; consumer properties, functional properties This work was supported by MUCTR (project no. K-2020-007).

Role of Bradykinin Type 2 Receptors in Human Sweat Secretion: Translational Evidence Does Not Support a Functional Relationship

Bradykinin increases skin blood flow via a cGMP mechanism but its role in sweating in vivo is unclear. There is a current need to translate cell culture and nonhuman paw pad studies into in vivo human preparations to test for therapeutic viability for disorders affecting sweat glands. Protocol 1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46–48°C) water through a tube-lined suit while bradykinin type 2 receptor (B2R) antagonist (HOE-140; 40 μM) and only the vehicle (lactated Ringer’s) were perfused intradermally via microdialysis. Heat stress increased sweat rate (HOE-140 = +0.79 ± 0.12 and vehicle = +0.64 ± 0.10 mg/cm²/min), but no differences were noted with B2R antagonism. Protocol 2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing pilocarpine (1.67 mg/mL) followed by the same B2R antagonist approach. Pilocarpine increased sweating (HOE-140 = +0.38 ± 0.16 and vehicle = +0.32 ± 0.12 mg/cm²/min); again no differences were observed with B2R antagonism. Last, 5 additional subjects were recruited for various control experiments which identified that a functional dose of HOE-140 was utilized and it was not sudorific during normothermic conditions. These data indicate B2R antagonists do not modulate physiologically or pharmacologically induced eccrine secretion volumes. Thus, B2R agonist/antagonist development as a potential therapeutic target for hypo- and hyperhidrosis appears unwarranted.

Role of bradykinin type 2 receptors in human sweat secretion: translational evidence does not support a functional relationship

Bradykinin increases skin blood flow via a cGMP mechanism but its role in sweating in vivo is unclear. There is a current need to translate cell culture and non-human paw pad studies into in vivo human preparations to test for therapeutic viability for disorders affecting sweat glands. Protocol 1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46-48°C) water through a tube-lined suit while bradykinin type 2 receptor (B2R) antagonist (HOE-140; 40 μM) and only the vehicle (lactated Ringer’s) were perfused intradermally via microdialysis. Heat stress increased sweat rate (HOE-140 = +0.79±0.12 and vehicle = +0.64±0.10 mg/cm2/min), but no differences were noted with B2R antagonism. Protocol 2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing pilocarpine (1.67 mg/ml) followed by the same B2R antagonist approach. Pilocarpine increased sweating (HOE-140 = +0.38±0.16 and vehicle = +0.32±0.12 mg/cm2/min); again no differences were observed with B2R antagonism. Lastly, 5 additional subjects were recruited for various control experiments which identified that a functional dose of HOE-140 was utilized and it was not sudorific during normothermic conditions. These data indicate B2R antagonists do not modulate physiologically-or pharmacologically-induced eccrine secretion volumes. Thus, B2R agonist/antagonist development as a potential therapeutic target for hypo- and hyperhidrosis appears unwarranted.

A new splice-site mutation of SPINK5 gene in the Netherton syndrome with different clinical features: A case report

Netherton syndrome (NS) is a rare genodermatosis characterized by the triad of ichthyosiform erythroderma, hair shaft abnormality and an atopic diathesis. We report a case of a 20-year-old male patient presented with pruritus, decreased sweat secretion and generalized erythema on his body. Netherton syndrome is caused by mutations in the SPINK5 gene that is a crucial role for epidermal barrier function in the skin. Different clinical and phenotypical features can occur based on various LEKTI-domains mutations. Diagnosis is made by the atopic story, hair shaft abnormality, cutaneous lesions and identification of the SPINK5 gene mutation. In our patient, we detected a new splice site mutation in the SPINK5 gene and pili annulati as hair abnormality. Affected patients are usually misdiagnosed because of cutaneous lesions such as atopic dermatitis. Therefore, each clinical finding should be evaluated together. We aimed to present a case with a new SPINK5 gene mutation and different clinical features in NS.