Dorothea Schweiger

Glutathione‐conjugated sulfanylalkanols are substrates for ABCC11 and γ‐glutamyl transferase 1: a potential new pathway for the formation of odorant precursors in the apocrine sweat gland

We have previously shown that precursors of odorous components characteristic of axillary sweat are hardly detectable or undetectable in individuals carrying the 538G > A SNP in the ABCC11 transporter gene. However, it is unclear, whether ABCC11 is directly involved in the transport of these compounds. To approach this question, transport of peptide‐conjugated potential precursors of 3‐methyl‐3‐sulfanylhexanol (3M3SH), a key determinant of axillary malodour, was measured using membrane vesicles of Sf9 insect cells overexpressing human ABCC11. Whilst no ABCC11‐mediated transport was detected for the dipeptide precursor Cys‐Gly‐3M3SH, the glutathione conjugate of 3M3SH (SG‐3M3SH) was robustly taken up by ABCC11 at a transport rate of 0.47 pmol/mg/min. Collectively, these results illuminate SG‐3M3SH as a putative precursor of 3M3SH, which then may undergo intra‐vesicular maturation to generate Cys‐Gly‐3M3SH. Critically, the apocrine sweat gland was demonstrated to express γ‐glutamyl transferase 1 (GGT1) protein, which is known to catalyse the deglutamylation of glutathionyl conjugates. Additionally, we provide evidence that recombinant and isolated hepatic human GGT1 is capable of transforming SG‐3M3SH to Cys‐Gly‐3M3SH in vitro. To sum up, we demonstrate that the functionality of ABCC11 is likely to play an important role in the generation of axillary malodour. Furthermore, we identify GGT1 as a key enzyme involved in the biosynthesis of Cys‐Gly‐3M3SH.

Hair and stress: A pilot study of hair and cytokine balance alteration in healthy young women under major exam stress

Mouse models show that experimental stress mimicking prolonged life-stress exposure enhances neurogenic inflammation, induces adaptive immunity cytokine-imbalance characterized by a shift to Type 1 T-helper cell cytokines and increases apoptosis of epithelial cells. This affects hair growth in otherwise healthy animals. In this study, we investigate whether a prolonged naturalistic life-stress exposure affects cytokine balance and hair parameters in healthy humans. 33 (18 exam, 15 comparison) female medical students with comparable sociobiological status were analyzed during a stressful final examination period, at three points in time (T) 12 weeks apart. T1 was before start of the learning period, T2 between the three-day written exam and an oral examination, and T3 after a 12 week rest and recovery from the stress of the examination period. Assessments included: self-reported distress and coping strategies (Perceived Stress Questionnaire [PSQ], Trier Inventory for the Assessment of Chronic Stress [TICS]), COPE), cytokines in supernatants of stimulated peripheral blood mononucleocytes (PBMCs), and trichogram (hair cycle and pigmentation analysis). Comparison between students participating in the final medical exam at T2 and non-exam students, revealed significantly higher stress perception in exam students. Time-wise comparison revealed that stress level, TH1/TH2 cytokine balance and hair parameters changed significantly from T1 to T2 in the exam group, but not the control. However, no group differences were found for cytokine balance or hair parameters at T2. The study concludes that in humans, naturalistic stress, as perceived during participation in a major medical exam, has the potential to shift the immune response to TH1 and transiently hamper hair growth, but these changes stay within a physiological range. Findings are instructive for patients suffering from hair loss in times of high stress. Replication in larger and more diverse sample populations is required, to assess suitability of trichogram analysis as biological outcome for stress studies.

Efficacy of a New Tonic Containing Urea, Lactate, Polidocanol, and Glycyrrhiza inflata Root Extract in the Treatment of a Dry, Itchy, and Subclinically Inflamed Scalp

Background/Aims: Dry, itchy and inflamed scalp conditions are common and often associated with diseases such as atopic dermatitis or psoriasis. To improve these symptoms, we investigated the efficacy of a new tonic containing the active ingredients urea, lactate, polidocanol, and Glycyrrhiza inflata root extract, containing licochalcone A. Study Design/Methods: 30 subjects with dry and itchy scalp conditions underwent a randomized half-head study for 4 weeks, applying the leave-on tonic three times a week on one side of the scalp. Tonic effects on skin hydration, itching, lipids, microinflammation, and substantivity of tonic compounds were determined using corneometry, middle-infrared spectroscopy, direct analysis in real-time mass spectrometry, and enzyme-linked immunosorbent assay. Volunteers performed a self-assessment; changes in scalp condition were documented by in vivo microscopy. Results: After tonic treatment, scalp moisture was significantly increased, whereas scalp itching and tautness were significantly reduced. Results also demonstrated a high substantivity of urea and lactate on the scalp, an increase in triglyceride, and a decrease in free fatty acid levels. The amount of total lipids was unchanged. Analyses of scalp wash-ups verified a significant reduction in important pro-inflammatory markers. Conclusion: Due to the actives urea, lactate, polidocanol, and the anti-inflammatory licochalcone A, the new scalp tonic exhibited excellent performance in alleviating scalp dryness, itching, microinflammation, and in normalizing disturbances of scalp lipids.

Highly efficient and compatible shampoo for use after hair transplant

Background Sensitive or hyperreactive skin is a common condition defined by prickling, burning, pain, and pruritus. Although this skin problem was initially described on the face, the scalp is often affected. A sensitive scalp can react with irritation to harsh surfactants or other additives which are often present in shampoos. For this reason, we developed a new rinse-off hypertolerant shampoo specifically designed for the hypersensitive and problematic scalp. Methods The shampoo formulation is based on an extremely mild surfactant system and contains bisabolol, an anti-irritant and anti-inflammatory ingredient of chamomile. The shampoo is free of additives such as perfumes, silicones, colorants, parabens, paraffins, and betaine. Since skin can remain in a hyperreactive state after wounding, the status after hair transplantation was chosen as a model system to test the shampoo. Scalp condition and compatibility of each volunteer were analyzed by a plastic surgeon directly after hair transplant and after stitch removal. The plastic surgeons also rated whether they would recommend the further use of the test shampoo. Additionally, volunteers completed a self-assessment questionnaire. Results Following hair transplantation, regular use of the shampoo resulted in a significant reduction in the extent of scabbing and erythema. This was confirmed by dermatological scalp examinations performed by the plastic surgeon as well as in volunteers’ self-assessments. The plastic surgeon highly recommended the further use of the test shampoo after hair transplant to all study participants. Conclusion Application of the test shampoo demonstrated excellent skin compatibility and product efficacy after hair transplant. The test shampoo significantly reduced the extent of scabs and erythema. Therefore, the shampoo is ideally suited for use after hair transplantation and for the treatment of sensitive scalp. The excellent skin compatibility is because of the mild surfactant system, the calming ingredient bisabolol, and the absence of potentially irritating ingredients.

ABCC11 – as key anti-odor target

Background In a previous publication, we showed that the ABCC11 transporter is crucial for the formation of the characteristic axillary odor and that a 538G>A single nucleotide polymorphism (SNP) in the gene, prominent in Asians, leads to a nearly complete loss of the typical sweat odor components in these carriers. As it is unclear, whether ABCC11 is directly involved in the transport of these components, we performed ABCC11-mediated transporter experiments with various potential odor precursors and also studied possible pathways for the formation of these precursors.

Towards a Body Hair Atlas of Women of Caucasian Ethnicity

A preliminary study was conducted in 17 female volunteers (mean age 29.8 years) to gain deeper insights into the characteristics of terminal Caucasian female body hair of different body parts. The focus on Caucasian women was driven by the high number of different scalp hair phenotypes in this ethnicity and intended to identify relevant differences between body areas to improve body hair removal approaches.

Is TH17 immunity altered by chronically perceived stress

Inflammatory injury requires tissue regeneration, a process hampered by chronic stress exposure in many experimental settings. The reported shift of the immune balance towards adaptive humoral immunity reported in chronically stressed mice and man may be the functional link. We here report results obtained in females exposed to exam stress. In these individuals subjective perception of anxiety (state and trait anxiety index – STAI) as well as a nervous mood (multidimensional mood questionnaire – MDMQ) prominently characterized chronic stress perception throughout a twelve week examination preparation and execution period. During the same time period exam participants displayed reduced morning serum cortisol levels prior to exam (exam preparation) and during exam execution when compared to expression levels in participants not exposed to exam stress. They also showed significantly increased serum level of the neurotrophin brain derived neurotrophic factor (BDNF). Correspondingly, the summary score for cytokines conducting the TH17 response differed significantly between exam participants and controls during exam preparation. These results link decreased hypothalamus pituitary adrenal axis function during chronic stress exposure with increased neurotrophin expression and TH17 dominated immunity. Future research will determine relevance for chronic inflammatory diseases driven by respective immune-dysfunction.