Variation in the activities of late stage filaggrin processing enzymes, calpain-1 and bleomycin hydrolase, together with pyrrolidone carboxylic acid levels, corneocyte phenotypes and plasmin activities in non-sun-exposed and sun-exposed facial stratum corneum of different ethnicities

BACKGROUND: Knowledge of the ethnic differences and effects of photodamage on the relative amounts of natural moisturizing factor (NMF) together with filaggrin processing enzymes in facial stratum corneum is limited. Our aim was to characterize the activities of calpain-1 (C-1), bleomycin hydrolase (BH) and the levels of pyrrolidone carboxylic acid (PCA) as a marker for total NMF levels and to relate them to plasmin activities and corneocyte maturation. METHODS: Enzyme activities, PCA levels and corneocyte maturation were determined from facial tape strippings of photoexposed cheek and photoprotected post-auricular areas (PA) of healthy Caucasian (C), Black African (BA) and albino African (AA) female subjects living in South Africa. RESULTS: PCA concentration levels were of the order AA > BA > C subjects, and the highest activities of BH were present in the AA subjects. BH activities were greater on the photoexposed sites for the BA and C subjects, but they were only numerically elevated in the AA subjects. Photoprotected sites had an increase in C-1 activity in pigmented groups (C and BA), whereas in the AA subjects, the opposite was measured. Plasmin activities were greater on the cheek compared with the PA site for the AA and C subjects, but the activity was low in the BA subjects. In both test sites, the AA, but not the BA and C subjects, had smaller, parakeratotic and less mature corneocytes. CONCLUSION: Variation in PCA levels has been found for different ethnic groups in this study (AA > BA > C subjects). The values in the AA subjects are surprising as one might expect that the lack of pigmentation, and thereby increased photodamage, might lead to lower levels. Increased BH, but not C-1 activity, was observed in the AA subjects indicating that BH is associated with PCA production to a greater extent. Surprisingly, corneocyte maturation is still impaired with elevated PCA levels in AA subjects. The higher levels of plasmin and BH activities on the cheeks, especially for AA and C subjects, suggest that they can be used as markers for epidermal photodamage

Topical niacinamide enhances hydrophobicity and resilience of corneocyte envelopes on different facial locations

Age-related differences in maturation parameters of corneocyte envelopes (size, hydrophobicity and rigidity) were examined at several facial test sites in young and old female Caucasians. In addition, the effect of topically applied niacinamide on these parameters was evaluated in a 4-week placebo-controlled study

The importance of 12R-lipoxygenase and transglutaminase activities in the hydration-dependent ex vivo maturation of corneocyte envelopes

Background Terminally differentiated keratinocytes acquire corneocyte protein envelopes (CPE) complexed with corneocyte lipid envelopes (CLE). These two structural components of the corneocyte envelopes (CE) undergo maturation by gaining in hydrophobicity, rigidity and surface area. Linoleoyl acylceramides are processed by 12R‐lipoxygenase (12R‐LOX) and other enzymes before transglutaminase (TG) attaches ω‐hydroxyceramides to involucrin in the CPE. Concurrently, structural proteins are cross‐linked by TG that has been activated by cathepsin D (CathD). Objectives The primary aim of this work was to demonstrate the impact of relative humidity (RH) during ex vivo CE maturation. Low, optimal and high RH were selected to investigate the effect of protease inhibitors (PI) on CE maturation and TG activity; in addition, 12R‐LOX and CathD activity were measured at optimal RH. Finally, the effect of glycerol on ex vivo CE maturation was tested at low, optimal and high RH. Methods The first and ninth tape strip of photo‐exposed (PE) cheek and photo‐protected (PP) post auricular sites of healthy volunteers were selected. Ex vivo CE maturation was assessed via the Relative CE Maturity (RCEM) approach based on CE rigidity and hydrophobicity. The second and eighth tapes were exposed to RH in presence of inhibitors. Results Irrespective of tape stripping depth, CEs from PE samples attained CE rigidity to the same extent as mature CEs from the PP site, but such improvement was lacking for CE hydrophobicity. 70% RH was optimal for ex vivo CE maturation. The inhibition of 12R‐LOX activity resulted in enhanced CE rigidity which was reduced by the TG inhibitor. CE hydrophobicity remained unchanged during ex vivo maturation in the presence of TG or 12R‐LOX inhibition. CE hydrophobicity was enhanced in the presence of glycerol at 44% RH and 100% RH but not at 70% RH. Furthermore, TG activity was significantly diminished at 100% Rh compared to the commercial inhibitor LDN‐27219. However, a protease inhibitor mix reversed the negative effect of over hydration. Conclusion The study adds to the understanding of the roles of 12R‐LOX and TG activity in CE maturation, and gives further insight into the effect of glycerol on the SC

A fundamental investigation into aspects of the physiology and biochemistry of the stratum corneum in subjects with sensitive skin

BACKGROUND: Sensitive skin is a poorly understood skin condition. Defects in stratum corneum (SC) barrier function and/or extrasensory neuronal networks in the epidermis are believed to be involved in the problem. OBJECTIVES: This study aimed to unravel the relationships between bleomycin hydrolase (BH) and calpain-1 (C-1), pyrrolidone carboxylic acid (PCA) levels, corneocyte maturation, transglutaminase (TG) and plasmin activities on the cheeks of subjects with sensitive skin. METHODS: Forty-eight female Caucasian subjects, Fitzpatrick skin phototypes II-III, with self - perceived sensitive facial skin were assessed and underwent a capsaicin reactivity test. Expert grading of skin condition was conducted as well as measurement of transepidermal water loss (TEWL), skin capacitance, SC cohesion and SC integrity. BH, C-1 and plasmin activities were measured as well as PCA levels, plasmin and TG activity. Differential Nile red and involucrin immunostaining was performed to assess corneocyte maturation and size. RESULTS: 52% of the subjects reacted to capsaicin. There were no significant differences between the capsaicin-sensitive and non-capsaicin-sensitive subjects with reference to skin grading, TEWL, skin capacitance and SC cohesion. PCA levels and BH activity were lowest in the capsaicin-sensitive panel (p<0.05) and were correlated in non-capsaicin-sensitive subjects (r = 0.72). The activity of TG was significantly lower (48%) in the capsaicin-sensitive subjects (p<0.001) and their corneocytes were less mature and smaller (p ≤ 0.03). SC was estimated to be thinner (6.87 ± 0.28 vs. 8.68 ± 0.26 μm; p=0.001) in the capsaicin-sensitive subjects with a corresponding shorter SC path length (83.2± 4.4 μm and. 113.1 ± 4.5 μm; p=0.001). CONCLUSIONS: Despite the physiological similarities between the two groups of sensitive skin subjects, differences in their biochemistry were clearly evident. Lower levels of PCA, BH and TG activities together with a greater number of smaller and immature corneocytes indicate inferior SC maturation in the capsaicin-sensitive subjects. The reduced maturation of corneocytes and thinner SC likely contributes to a greater penetration of capsaicin and the associated increased skin sensitivity

The Presence of Essential and Non-Essential Stratum Corneum Proteases: The Vital Need for Protease Inhibitors

Dry skin is one of the most important concerns of consumers worldwide. Despite huge efforts over several decades, the personal care industry still does not offer complete solutions that satisfy the unmet needs of consumers for moisturizing treatments. The paucity of data for the underlying biochemical problems in and the effects of moisturizers on facial skin biology and physiology may partly explain this. Our recent color mapping studies based on bio-instrumental evaluations of skin capacitance and transepidermal water loss have revealed the complexity of facial skin. However, the biomolecular reasons for these subtle differences in the different zones of the face are unknown so far. As the maturation of the stratum corneum is vital for skin moisturization and optimal barrier function, we believe that the protease / proteaseinhibitor balance particularly of the plasminogen system may be key in these processes. Thus, our aim was to develop a specific dual plasmin and urokinase inhibitor for topical application to barrier-impaired skin and demonstrate its efficac

The African hind's (Cephalopholis taeniops, serranidae) use of artificial reefs off Sal Island (Cape Verde): a preliminary study based on acoustic telemetry

The African hind Cephalopholis taeniops (Valenciennes, 1828) is one of the most important commercial demersal species caught in the Cape Verde archipelago. The species is closely associated with hard substrate and is one of the main attractions for SCUBA divers. In January 2006 a former Soviet fishing vessel - the Kwarcit - was sunk off Santa Maria Bay (Sal Island). Young C. taeniops are commonly observed in this artificial reef (AR). In order to investigate the species' use of the AR, 4 specimens were captured and surgically implanted underwater with Vemco brand acoustic transmitters. The fish were monitored daily with an active telemetry receiver for one week after release. Simultaneously, an array of 3 passive VR2 / VR2W receivers was set for 63 days, registering data that allowed an analysis of spatial, daily and short term temporal activity patterns. The results showed site fidelity to the AR, with no migrations to the nearby natural reef. The method used allowed to register a consistent higher activity during daytime and a preference for the area opposite the dominant current

Spin dependent scattering of a domain-wall of controlled size

Magnetoresistance measurements in the CPP geometry have been performed on single electrodeposited Co nanowires exchange biased on one side by a sputtered amorphous GdCo layer. This geometry allows the stabilization of a single domain wall in the Co wire, the thickness of which can be controlled by an external magnetic field. Comparing magnetization, resistivity, and magnetoresistance studies of single Co nanowires, of GdCo layers, and of the coupled system, gives evidence for an additional contribution to the magnetoresistance when the domain wall is compressed by a magnetic field. This contribution is interpreted as the spin dependent scattering within the domain wall when the wall thickness becomes smaller than the spin diffusion length.Comment: 9 pages, 13 figure

Survival of Migrating Salmon Smolts in Large Rivers With and Without Dams

The mortality of salmon smolts during their migration out of freshwater and into the ocean has been difficult to measure. In the Columbia River, which has an extensive network of hydroelectric dams, the decline in abundance of adult salmon returning from the ocean since the late 1970s has been ascribed in large measure to the presence of the dams, although the completion of the hydropower system occurred at the same time as large-scale shifts in ocean climate, as measured by climate indices such as the Pacific Decadal Oscillation. We measured the survival of salmon smolts during their migration to sea using elements of the large-scale acoustic telemetry system, the Pacific Ocean Shelf Tracking (POST) array. Survival measurements using acoustic tags were comparable to those obtained independently using the Passive Integrated Transponder (PIT) tag system, which is operational at Columbia and Snake River dams. Because the technology underlying the POST array works in both freshwater and the ocean, it is therefore possible to extend the measurement of survival to large rivers lacking dams, such as the Fraser, and to also extend the measurement of survival to the lower Columbia River and estuary, where there are no dams. Of particular note, survival during the downstream migration of at least some endangered Columbia and Snake River Chinook and steelhead stocks appears to be as high or higher than that of the same species migrating out of the Fraser River in Canada, which lacks dams. Equally surprising, smolt survival during migration through the hydrosystem, when scaled by either the time or distance migrated, is higher than in the lower Columbia River and estuary where dams are absent. Our results raise important questions regarding the factors that are preventing the recovery of salmon stocks in the Columbia and the future health of stocks in the Fraser River

The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial

Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients