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?     

Comparison of three immunoassays for diagnosing sensitization to latex in children with spina bifida

As natural rubber latex (latex) has become more widespread in our environment, physicians have become increasingly aware of the problem of possible allergic reactions. Many fatal and near-fatal incidents have been reported (mainly during surgery) (1—3) and data has been published on groups frequently exposed to latex, such as patients with spina bifida (4—9), healthcare professionals (10—12) and occupationally exposed persons (13). The incidence of latex allergy in children seems to be increasing (14). Tests are therefore needed which can reliably detect sensitization to latex. Our aim was to compare the diagnostic accuracy of three commercial immunoassays for measuring specific IgE in serum to latex.     

Monitoring left ventricular dilation in mice with PET.

Molecular imaging by small-animal PET is an important noninvasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium, the serial assessment of LV volumes is important. By this, the presence of LV dilation as a sign of developing heart failure can be detected. Whereas PET is usually used to derive biochemical and molecular information, functional parameters such as ventricular volumes are generally measured using echocardiography or MRI. In this study, a novel method to monitor LV dilation in mice with PET is presented and evaluated using cardiac MRI. METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin). The volume enclosed by the 3-dimensional midmyocardial contour was calculated as a measure for LV volume for each mouse. Data were compared with ventricular volumes measured by MRI in the same animals. RESULTS: LV volumes obtained by PET and MRI correlated well (R = 0.89) for hearts with small and large left ventricles. In accordance with the hypothesis, the LV volumes were increased significantly for transgenic mice examined at an older age compared with those examined at a younger age (MRI: 160.5 +/- 25.7 microL vs. 114.7 +/- 15.2 microL [P = 0.012]; PET: 129.3 +/- 15.3 microL vs. 73.8 +/- 15.0 microL [P < 0.001], all values shown as mean +/- SD; for MRI, mean of end-diastolic and end-systolic volumes are given), whereas they did not for their wild-type littermates (MRI: 106.2 +/- 12.3 microL vs. 94.7 +/- 14.6 microL [P = 0.214]; PET: 82.6 +/- 20.9 microL vs. 65.0 +/- 16.9 microL [P = 0.185]). CONCLUSION: Evaluation and quantitation of LV dilation in both control and cardiomyopathic mice can be reliably and serially performed using small-animal PET and (18)F-FDG, yielding useful functional information in addition to metabolic data.     

Comparison of bronchial responsiveness to histamine in asthma, allergic rhinitis and allergic sensitization at the age of 7 years

BACKGROUND: Bronchial responsiveness (BR) to histamine or methacholin is a common finding in adult non-asthmatic patients with allergic rhinitis. OBJECTIVE: We tested whether BR is also present in children with a comparatively short history of allergic rhinitis in a paediatric cohort. METHODS: We performed pulmonary function tests and histamine challenges in a total of 654 children (age 7 years, participants of the German Multicenter Allergy Study) and compared PC20 FEV1 values in children with asthma, allergic rhinitis, asymptomatic allergic sensitization and non-atopic controls. RESULTS: Most pronounced BR to histamine was observed in allergic asthmatics (n = 28), irrespective of the presence or absence of allergic rhinitis. Furthermore, PC(20)FEV(1) values in non-asthmatic children with allergic rhinitis (n = 24) were not significantly different from those seen in asymptomatic atopic (n = 54) or non-atopic controls (n = 92). CONCLUSIONS: In contrast to adult study populations, 7-year-old non-asthmatic children with allergic rhinitis do not show a higher degree of BR than asymptomatic atopic or non-atopic controls. Therefore, secondary preventive measures in non-asthmatic children with allergic rhinitis (such as regular local anti-inflammatory therapy or specific immunotherapy) should be studied and applied more intensely to prevent bronchial hyper-responsiveness (BHR) and asthma in this high-risk group.     

Food allergy and non-allergic food hypersensitivity in children and adolescents

BACKGROUND: Previous studies have shown a 10-fold discrepancy of self-reported food-induced symptoms and physician-diagnosed food hypersensitivity. Little information is available on the prevalence of food hypersensitivity in unselected paediatric populations. No data were available for German children. OBJECTIVE: To study the perception of food-induced symptoms in the paediatric population, to investigate the allergens accused, to objectify patients' reports, and to identify subgroups at risk of having food-induced allergy (FA) or non-allergic food hypersensitivity (NAFH) reactions. METHODS: This paper presents the data of the paediatric group (0-17 years) of a representative, randomly sampled, cross-sectional population-based survey studying 13 300 inhabitants of the German capital city Berlin regarding food-related symptoms. Instruments included mailed questionnaires, structured telephone interviews, physical examination, skin-prick tests, specific serum IgE and standardized, controlled and blinded oral food challenges. RESULTS: Two thousand three hundred and fifty-four individuals were contacted by mailed questionnaire, 739 (31.4%) responses could be fully evaluated. Four hundred and fifty-five (61.5%) participants reported symptoms related to food ingestion, 284 (38.4%) affirmed reproducible symptoms in the standardized telephone interview. One hundred and eighty-four (24.8%) individuals were fully examined. Reproducible symptoms to food were found in 31 (4.2%) children and adolescents: 26 (3.5%) showed symptoms of FA and five (0.7%) of NAFH. The oral allergy syndrome was most often observed. Foods most commonly identified by oral challenges were apple, hazelnut, soy, kiwi, carrot and wheat. CONCLUSION: The perception of food-related symptoms is common among children and adolescents from the general population. Self-reports could be confirmed in around one out of 10 individuals, still resulting in 4.2% of proven clinical symptoms. However, most reactions were mild and mainly because of pollen-associated FA, while NAFH reactions were less common. Severe IgE-mediated FA was observed in individuals with pre-existing atopic disease, who should be fully investigated for clinically relevant FA.     

The effect of estrogens and dietary calcium deficiency on the extracellular matrix of articular cartilage in G?ttingen miniature pigs.

Clinical observations have suggested that estrogens are involved in the pathogenesis of postmenopausal osteoarthritis (OA). However, positive and negative associations between the incidence of OA and serum estrogen concentrations have been reported. In contrast to this, osteoporosis is regarded as a disease with a strong estrogen-dependent component. Moreover, there is an interaction between estrogen and calcium deficiency: calcium supplementation potentiates the effect of estrogen therapy. The present study was designed to investigate how estrogen deficiency affects the articular cartilage depending on calcium supply. The distribution of different types of glycosaminoglycans and collagens can be used as an indicator for extracellular matrix changes induced by estrogen deficiency. Different levels of dietary calcium were therefore fed to intact and ovariectomized G?ttingen miniature pigs for one year before articular cartilage was harvested. The histochemical staining for heavy sulfated glycosaminoglycans in the extracellular matrix of ovariectomized miniature pigs, especially of those fed with a low calcium diet, was stronger in comparison to intact animals. In intact animals type II-collagen was immunodetected in all zones of unmineralized and mineralized articular cartilage, while immunostaining for this protein was negative to weak in the deep radiated fiber zone of ovariectomized minipigs. These results suggest that the synthesis of heavy sulfated glycosaminoglycans and immunohistochemically detectable type II-collagen is possibly influenced by estrogen deficiency. In conclusion, under estrogen deficiency, the extracellular matrix of articular cartilage underwent similar changes to those observed in physiologically aging cartilage where keratan sulfate is increased as a heavy sulfated glycosaminoglycan.