Role of the vitamin D3 pathway in healthy and diseased skin – facts, contradictions and hypotheses

Abstract: Irradiation of human keratinocytes with UVB (280–320 nm) in vitro and in vivo activates the metabolism of 7‐dehydrocholesterol to hormonally active calcitriol. The production of calcitriol in the skin strongly depends on the photosynthesis of vitamin D₃ which is biologically inactive in the first instance. Vitamin D₃ serves as the starting substrate for two subsequent enzymatic hydroxylation steps in epidermal keratinocytes. Both the amount of vitamin D₃ and the activity of anabolic and catabolic vitamin D hydroxylases determine the cutaneous level of calcitriol. The hormonally active metabolite of vitamin D₃ regulates a huge number of genes in keratinocytes, and thus acts in an autocrine and/or paracrine manner. This local pathway of vitamin D₃ is unique, but its relevance for healthy and diseased skin is widely unknown, yet. Experimental findings implicate several questions: ( 1 ) Is UVB‐induced formation of calcitriol involved in regulation of growth and differentaition of epidermal cells as well as immunological and skin protective processes? ( 2 ) What endogenous and exogenous factors including drugs affect the cutaneous vitamin D₃ pathway? From a therapeutical point of view, it has been known for a long time that topical application of calcitriol and its analogs can improve hyperproliferative skin diseases like psoriasis. In spite of many encouraging studies in recent years, the fields of the routinely therapeutical application of calcitriol or vitamin D analogs in dermatology (e.g. treatment of immunological, inflammatory, malignancies and infectious skin diseases) have not been intensified. Why is that?     

A study of a method for distribution analysis of skin color

Background/aims: The objective and quantitative assessment of the skin is important in medical and cosmeceutical research. Assessment of color is an important element for analyzing the surface of the skin, which is usually determined subjectively by a doctor or using color analysis devices. These devices, however, cannot provide correct color information because color is construed from the mean value of the observation region, and analysis of color distribution is impossible. The purpose of this paper is to develop an objective analysis method to permit skin color measurement of each pixel unit of an image and analyze the distribution of skin surface color. Methods: The Skin Color Distribution Analyzer (SCDA) is an analysis method newly developed at the Research Institute for Skin Image at Korea University. The SCDA system presented in this paper performed a novel form of quantitative and objective analysis of skin color distribution using each pixel color model parameter found in image wavelength information. In this paper, distribution analysis was conducted on normal skin and skin lesions and skin affected by artificially induced irritant contact dermatitis and pigmented nevous. The method selected a grade using a color model parameter. Twenty healthy Korean males participated in this study. A comparative study of the eight anatomical areas was performed, including the exposure and non‐exposure parts and the medial aspect and the lateral aspect of the forearm. A reliability test for the SCDA system was also conducted with a spectrometer (SPEC) using the color analysis method. Results: Each skin lesion was precisely segmented by grade and each parameter hada different statistical significance for results of analysis of distribution in pigmented nevous and the artificially induced irritant contact dermatitis. Parameters L^*, b^*, a^*, and EI showed salient traits. Showed resemble measured result in the SCDA system and the SPEC of normal skin. The exposed site, in comparison with the non‐exposed site, showed a notable difference in the L^* parameter and a significant statistical difference in the x and z parameters, except b^*. The comparison of the medial and lateral aspects of the forearm showed a notable difference in the L^* parameter and a significant statistical difference in the parameters except y and b^*. In the reliability test result using the SCDA system and the SPEC, the SCDA system was highly reliabile in terms of the CV value in all color model parameters. Conclusions: The color distribution analysis method using the SCDA system has revealed an aspect that the existent method of medical research has not shown, and is considered to be more reliable than other methods. This method can provide better study findings because it can be applied to other fields in addition to the medical science field and the ripple effect is thought to be bigger in other science field too.     

Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to FcɛRI

BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity.     

The role of Self-Defined Race/Ethnicity in Population Structure Control

Population-based association studies are powerful tools for the genetic mapping of complex diseases. However, this method is sensitive to potential confounding by population structure. While statistical methods that use genetic markers to detect and control for population structure have been the focus of current literature, the utility of self-defined race/ethnicity in controlling for population structure has been controversial. In this study of 1334 individuals, who self-identified as either African American, European American or Hispanic, we demonstrated that when the true underlying genetic structure and the self-defined racial/ethnic groups were roughly in agreement with each other, the self-defined race/ethnicity information was useful in the control of population structure.     

头皮电烧伤骨外露带毛发皮瓣修复

目的：探讨头皮电烧伤骨外露用头皮扩张皮瓣移植修复的临床效果。方法：采用早期扩创,保留部分坏死骨质,用邻近头皮扩张使带毛发的头皮面积扩大后移植覆盖创面,电性失活骨质在血循环良好的皮瓣覆盖下,为周边及基底健康骨质生长起到支架作用,皮瓣扩张到一定面积后移植到裸露骨质上,使其得以修复。结果：在治疗的9例中,除1例皮瓣边缘在1．5cm×1．5cm坏死外,其余皮瓣全部成活,未发生感染坏死,创面均一次性封闭。结论：头皮电烧伤骨外露扩张后皮瓣带毛发修复,可缩短创面愈合时间,外形较好,易掌握,效果较为满意。     

Granulomatous jellyfish dermatitis

The induction of a granulomatous inflammation by jellyfish toxins is rare. More typically, acute toxic and urticarial reactions are seen. An 11-year-old boy developed a striated urticarial erythema on the left cheek after contact with a gelatinous mass while swimming in the sea in Croatia. After initial erosion, a striated induration developed in the area of contact. Histological examination revealed a granulomatous inflammation with some eosinophils. While topical steroid-based antiinflammatory and antibacterial therapy over several weeks was not effective, topical therapy with tacrolimus 0.1% for two two-week treatment periods led to healing of the skin changes with a slight scar. There was no clinical recurrence after 5 month of follow-up.     

Developing Organ Offer and Acceptance Measures: When 'Good' Organs Are Turned Down

Turndowns of offers of deceased donor kidneys for transplantation can contribute to inefficiencies in the organ distribution system and inequality in access to donated organs. Match run data were obtained for 4967 'good' kidneys placed and transplanted in 2005 after fewer than 50 offers. These kidneys were not recovered from donation after cardiac death or expanded criteria donors, or from donors with a history of substance abuse. On average, these good kidneys were not accepted until after seven offers to candidates and after offers to 2.4 programs. Models for the likelihood of acceptance found several donor and candidate characteristics to be significantly related to acceptance rates (p < 0.05). After accounting for these variables, there remained 2- to 3-fold differences among transplant programs in acceptance rates. These models could be used to identify kidney transplant centers with exceptional acceptance practices. Several strategies might be employed to increase acceptance rates for good organs.