A genome wide association study identifies new genes potentially associated with eyelid sagging

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10^‐10) and rs4746957 (P = 1.06 × 10^‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.     

Human melanocytes and melanoma cells constitutively express the Bcl-2 proto-oncogene in situ and in cell culture.

The Bcl-2 proto-oncogene regulates cell survival by antagonizing events that lead to apoptotic cell death and has been reported to be expressed in situ in lymphoid tissues, glandular epithelium, neurons, and basal epidermal cells. When we performed immunostaining on cryostat sections of normal skin, anti-Bcl-2 reactivity was confined to scattered dendritic cells in the basal epidermal layer. Double-staining experiments showed that the Bcl-2+ cells were positive for vimentin but negative for cytokeratins, CD1a, and CD45 antigens, excluding keratinocytes and Langerhans cells as possible candidates for constitutive Bcl-2 expression. Bcl-2+ epidermal cells also reacted with the monoclonal anti-melanocyte antibody NKI/beteb, and were absent from lesional skin in vitiligo, confirming that they represented epidermal melanocytes. Western blot analysis of cultured melanocytes and melanoma cell lines revealed a 26-kd protein specifically reacting with the anti-Bcl-2 monoclonal antibody. Immunostaining of pigmented lesions revealed strong expression of Bcl-2 by five of five nevocellular nevi and seven of seven melanomas. Our observations demonstrate that, within normal human epidermis, melanocytes are the only cells that express Bcl-2 constitutively and that Bcl-2 is expressed in benign and malignant pigmented tumors of the skin in situ.     

Cutaneous elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxin

BACKGROUND: After exposure, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is excreted via the faeces, breast milk and epidermal lipids. OBJECTIVES: To determine to what extent TCDD is eliminated via the skin and to evaluate whethe cutaneous elimination can be accelerated by the application of petrolatum. METHODS: In two patients severely intoxicated with TCDD, material obtained from the skin surface and, in one patient, cerumen and the content of epithelial cysts, was analysed for TCDD. RESULTS: The TCDD concentration in the initial blood sample taken was 144 000 pg g(-1) blood fa in patient 1, and 26 000 pg g(-1) blood fat in patient 2. Six months later, when the skin tests were performed, the blood TCDD levels had decreased to 80 900 and 16 100 pg g(-1) blood fat, respectively. In the two samples of pooled cyst contents from patient 1, TCDD levels of 34 400 an 18 600 pg g(-1) fat were found. A cerumen sample contained TCDD at 20 500 pg g(-1) fat. In the material collected from the skin surface we observed a linear increase of the amount of TCD measured per test field with time, indicating a continuous elimination of TCDD via the skin. Th daily amount of TCDD eliminated via the skin was 1.51 pg cm(-2) in patient 1 and 0.57 pg cm(-2) in patient 2. Application of petrolatum led to a twofold increase in the amount of TCDD measured in patient 1, but had no significant effect in patient 2. CONCLUSIONS: In our patients, elimination of TCDD via the skin, most probably through desquamating scales, represented 1-2% of the overall daily TCDD elimination rate, with regard to the body surface and when calculated on the basis of the half-life of TCDD at the time of the skin test. If a more typical overall elimination half-life of 7 years is used as the basis for the calculatio the skin would account for 9% (patient 1) and 15% (patient 2) of the overall elimination. Although we observed an increase in TCDD in material derived from the skin surface of up to 100% after application of petrolatum in patient 1, such an approach appears not to be a feasible means to increase elimination. Owing to the small amount of TCDD measured in skin-surface material, as well as in the cyst contents and cerumen obtained from one patient, contamination of the environment and other persons appears highly unlikely.     

Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: clinical and laboratory effects

A variety of health effects have been attributed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but little information is available on the course of a verified high-level TCDD intoxication. In this paper we describe two cases of heavy intoxication with TCDD and present a 2-year follow-up including clinical, biochemical, hematologic, endocrine, and immunologic parameters monitored in two women, 30 and 27 years of age, who suffered from chloracne due to TCDD intoxication of unknown origin. Patient 1, who had the highest TCDD level ever recorded in an individual (144,000 pg/g blood fat), developed severe generalized chloracne, whereas in the second patient, despite heavy intoxication (26,000 pg/g blood fat), only mild facial acne lesions occurred. Both patients initially experienced nonspecific gastrointestinal symptoms. In Patient 1 we observed a moderate elevation of blood lipids, leukocytosis, anemia, and secondary amenorrhoea. The laboratory parameters in Patient 2 were all normal. Despite the high TCDD levels, apart from chloracne, only few clinical and biochemical health effects were observed within the first 2 years after TCDD intoxication.     

Filaggrin genotype in ichthyosis vulgaris predicts abnormalities in epidermal structure and function

Although it is widely accepted that filaggrin (FLG) deficiency contributes to an abnormal barrier function in ichthyosis vulgaris and atopic dermatitis, the pathomechanism of how FLG deficiency provokes a barrier abnormality in humans is unknown. We report here that the presence of FLG mutations in Caucasians predicts dose-dependent alterations in epidermal permeability barrier function. Although FLG is an intracellular protein, the barrier abnormality occurred solely via a paracellular route in affected stratum corneum. Abnormal barrier function correlated with alterations in keratin filament organization (perinuclear retraction), impaired loading of lamellar body contents, followed by nonuniform extracellular distribution of secreted organelle contents, and abnormalities in lamellar bilayer architecture. In addition, we observed reductions in corneodesmosome density and tight junction protein expression. Thus, FLG deficiency provokes alterations in keratinocyte architecture that influence epidermal functions localizing to the extracellular matrix. These results clarify how FLG mutations impair epidermal permeability barrier function.     

Variations of skin biophysical properties after recreational swimming

Background/purpose: Sensations of itching and skin tightness are frequently reported after recreational swimming in pool water. Our objective was to measure the potential changes occurring at the skin surface under such conditions.
Methods: Nine women participated in this study, which consisted of two periods. During a 4-day control period, basal biophysical skin parameters were assessed every morning. On the first day, measurements were also performed in the afternoon. The second study period followed the same study design as for the control period, except that, on the first day, women swam for 1 h in a public pool, between the measurements performed in the morning and the afternoon. Skin capacitance, transepidermal water loss, skin temperature, skin pH and sebum casual level (SCL) were measured on facial and body sites.
Results: During the control period, biophysical skin parameters did not show significant variations. By contrast,      h after swimming, biophysical values showed significant changes for all test sites: skin pH increased, whereas skin capacitance and SCL decreased. Biophysical parameters returned to baseline values the day after swimming.
Conclusion: Our results demonstrate that recreational swimming leads to significant transient changes in skin surface properties of women with healthy skin.     

Beneficial effects of protease inhibitors on body composition and energy expenditure: a comparison between HIV-infected and AIDS patients

OBJECTIVES: (i) To investigate whether protease inhibitor (PI) (nelfinavir)-containing highly active antiretroviral therapy (HAART) affects body composition differently in HIV-infected and AIDS patients without wasting syndrome. (ii) To delineate the changes in resting energy expenditure (REE) under PI therapy, and to determine whether sustained reductions in HIV RNA would decrease REE. DESIGN: Prospective longitudinal cohort study with individually matched healthy controls. SETTING: Tertiary care centre at a University Hospital. METHODS: HIV-seropositive (n = 20) and AIDS patients (n = 17) with a plasma viral load of at least 10000 copies/ml and 37 healthy volunteers were enrolled. All participants were weight stable, free of acute opportunistic infections, and naive to PI therapy. Patients underwent testing of bioelectrical impedance analysis (BIA), indirect calorimetry and food intake, shortly before the initiation of HAART and 24 weeks thereafter. RESULTS: Both patient groups gained weight, body mass index (BMI), and fat-free mass (FFM) (P < 0.05 versus baseline), whereas only AIDS patients gained fat mass. Increases were more pronounced in the AIDS group. REE was elevated compared with corresponding controls at baseline, and decreased similarly in HIV and in AIDS patients during PI therapy (P < 0.05). The reduction in the viral burden preceded the decrease in REE by several weeks. CONCLUSION: Body composition and metabolic parameters improved during PI therapy in HIV-infected and AIDS patients without wasting. Although an early reduction in viral load as a result of HAART does not seem to influence REE directly, sustained viral load suppression may promote a decrease in energy expenditure.