Intrinsic and extrinsic factors affecting axillary odor variation. A comprehensive review.

Humans produce odorous secretions from multiple body sites according to the microbiomic profile of each area and the types of secretory glands present. Because the axilla is an active, odor-producing region that mediates social communication via the sense of smell, this article focuses on the biological mechanisms underlying the creation of axillary odor, as well as the intrinsic and extrinsic factors likely to impact the odor and determine individual differences. The list of intrinsic factors discussed includes sex, age, ethnicity, emotions, and personality, and extrinsic factors include dietary choices, diseases, climate, and hygienic habits. In addition, we also draw attention to gaps in our understanding of each factor, including, for example, topical areas such as the effect of climate on body odor variation. Fundamental challenges and emerging research opportunities are further outlined in the discussion. Finally, we suggest guidelines and best practices based on the factors reviewed herein for preparatory protocols of sweat collection, data analysis, and interpretation.

TRPC1 channel clustering during store-operated Ca2+ entry in keratinocytes.

Skin is the largest organ in the human body with ∼95% of its surface made up of keratinocytes. These cells maintain a healthy skin barrier through regulated differentiation driven by Ca2+-transcriptional coupling. Many important skin conditions arise from disruption of this process although not all stages are fully understood. We know that elevated extracellular Ca2+ at the skin surface is detected by keratinocyte Gαq-coupled receptors that signal to empty endoplasmic reticulum Ca2+ stores. Orai channel store-operated Ca2+ entry (SOCE) and Ca2+ influx via "canonical" transient receptor potential (TRPC)-composed channels then activates transcription factors that drive differentiation. While STIM-mediated activation of Orai channels following store depletion is well defined, how TRPC channels are activated is less clear. Multiple modes of TRPC channel activation have been proposed, including 1) independent TRPC activation by STIM, 2) formation of Orai-TRPC-STIM complexes, and 3) the insertion of constitutively-active TRPC channels into the membrane during SOCE. To help distinguish between these models, we used high-resolution microscopy of intact keratinocyte (HaCaT) cells and immunogold transmission electron microscopy (TEM) of HaCaT plasma membrane sheets. Our data shows no evidence of significant insertion of Orai1 or TRPC subunits into the membrane during SOCE. Analysis of transmission electron microscopy data shows that during store-depletion and SOCE, Orai1 and TRPC subunits form separate membrane-localized clusters that migrate towards each other. This clustering of TRPC channel subunits in keratinocytes may support the formation of TRPC-STIM interactions at ER-plasma membrane junctions that are distinct from Orai-STIM junctions.

Store-operated calcium channels in skin.

The skin is a complex organ that acts as a protective layer against the external environment. It protects the internal tissues from harmful agents, dehydration, ultraviolet radiation and physical injury as well as conferring thermoregulatory control, sensation, immunological surveillance and various biochemical functions. The diverse cell types that make up the skin include 1) keratinocytes, which form the bulk of the protective outer layer; 2) melanocytes, which protect the body from ultraviolet radiation by secreting the pigment melanin; and 3) cells that form the secretory appendages: eccrine and apocrine sweat glands, and the sebaceous gland. Emerging evidence suggests that store-operated Ca2+ entry (SOCE), whereby depletion of intracellular Ca2+ stores triggers Ca2+ influx across the plasma membrane, is central to the normal physiology of these cells and thus skin function. Numerous skin pathologies including dermatitis, anhidrotic ectodermal dysplasia, hyperhidrosis, hair loss and cancer are now linked to dysfunction in SOCE proteins. Principal amongst these are the stromal interaction molecules (STIMs) that sense Ca2+ depletion and Orai channels that mediate Ca2+ influx. In this review, the roles of STIM, Orai and other store-operated channels are discussed in the context of keratinocyte differentiation, melanogenesis, and eccrine sweat secretion. We explore not only STIM1-Orai1 as drivers of SOCE, but also independent actions of STIM, and emerging signal cascades stemming from their activities. Roles are discussed for the elusive transient receptor potential canonical channel (TRPC) complex in keratinocytes, Orai channels in Ca2+-cyclic AMP signal crosstalk in melanocytes, and Orai isoforms in eccrine sweat gland secretion.

Human axillary skin condition is improved following incorporation of glycerol into the stratum corneum from an antiperspirant formulation.

The study objectives were to demonstrate that glycerol, when topically applied from a roll-on antiperspirant formulation, can be delivered directly to human skin ex vivo and the axillary stratum corneum (SC) in vivo, and to assess whether it improves the quality of the axillary skin barrier. Ex vivo human skin absorption of glycerol was measured following application of a roll-on antiperspirant formulation containing 4% 13C3-glycerol. Skin distribution of 13C3-glycerol over 24 h was assessed using gas chromatography-mass spectrometry. In vivo axillary SC penetration was measured by confocal Raman spectroscopy and multivariate curve-resolution software 1 h after topical application of a roll-on antiperspirant formulation containing 8% deuterated glycerol (d5-glycerol). A clinical study was conducted to determine the efficacy of a roll-on antiperspirant formulation containing 4% glycerol in reducing shaving-induced visual irritation and in increasing axillary-skin hydration. Ex vivo skin absorption studies indicated that the formulation delivered 13C3-glycerol into the SC at all timepoints over the 24-h period. In vivo Raman measurements (1 h after application) demonstrated that d5-glycerol was detectable to a depth of at least 10 µm in the axillary SC. Application of 4% glycerol from a roll-on antiperspirant formulation to the axilla was associated with significantly less visible irritation and greater skin hydration than observed with the control (glycerol-free) product. These studies demonstrate that glycerol, incorporated in a roll-on antiperspirant formulation, is delivered directly and rapidly to all depths of the axillary SC, and results in improvements in visible irritation and hydration in the axilla.

Web-based distributed data management in the childhood asthma research and education (CARE) network.

A well-designed distributed data management application provides an efficient, effective process to collect quality data in multicenter clinical trials. This paper describes the web-based clinical center data management application that was developed by the Data Coordinating Center of the Childhood Asthma Research and Education (CARE) Network. A series of modules was designed to allow the clinical staff at the remote clinical centers to enter clinical trial data, correct entry errors, respond to queries from the Data Coordinating Center, and submit data corrections for previously entered data to ultimately provide a clean and accurate dataset for analysis.