Topical Therapy

The primary goal of this study was to determine if atopy is a risk factor for keratoconus. Other potential risk factors were also studied and included age, sex, race, eye rubbing, mitral valve prolapse, handedness, collagen vascular disease, ocular trauma, pigmentary retinopathy, Marfan's syndrome, Down's syndrome, and a history of contact lens wear. A case-control study was designed (n=120) with incident cases assembled from the years 1985-99. Controls were chosen from the same person-time experience as cases and were picked from a source population with multiple outcomes ensuring that none was knowingly related to any of the potential exposures being studied. Atopy was defined based on the UK working group 1994 definition (at least 4/6 criteria = complete, 3/6 criteria = incomplete, and at least 1/6 criteria = partial). Keratoconus was defined based on clinical criteria and previously published I-S values. Multiple logistic regression was used in the analysis to obtain the odds ratios as the measure of association. In the univariate associations, there was an association between keratoconus and atopy as well as eye rubbing and family history of keratoconus. However, in the multivariate analysis, only eye rubbing was still a significant predictor of keratoconus (odds ratio = 6.31 p = 0.001). This study supports the hypothesis that the most significant cause of keratoconus is eye rubbing. Atopy may contribute to keratoconus but most probably via eye rubbing associated with the itch of atopy. No other variable measured was significantly associated with the aetiology of keratoconus.

Alternative splicing of the human glucocorticoid receptor (hGR) pre-mRNA generates two highly homologous isoforms, termed hGR alpha and hGR beta. hGR alpha is a ligand-activated transcription factor which, in the hormone-bound state, modulates the expression of glucocorticoid-responsive genes by binding to specific glucocorticoid response element (GRE) DNA sequences. In contrast, hGR beta does not bind glucocorticoids and is transcriptionally inactive. We demonstrate here that hGR beta is able to inhibit the effects of hormone-activated hGR alpha on a glucocorticoid-responsive reporter gene in a concentration-dependent manner. [3H]-Dexamethasone binding studies indicate that hGR beta does not alter the affinity of hGR alpha for its hormonal ligand. The presence of hGR beta in nuclear extracts and its ability to bind to a radiolabeled GRE oligonucleotide suggest that its inhibitory effect may be due to competition for GRE target sites. Reverse transcription-PCR analysis shows expression of hGR beta mRNA in multiple human tissues. These results indicate that hGR beta may be a physiologically and pathophysiologically relevant endogenous inhibitor of glucocorticoid action, which may participate in defining the sensitivity of target tissues to glucocorticoids. They also underline the importance of distinguishing between the two receptor isoforms in all future studies of hGR function and the need to revisit old data.

Coated titanium dioxide (TiO 2 ) microparticles are commonly used as UV filter substances in commercial sunscreen products. The penetration of these microparticles into the horny layer and the orifice of the hair follicle was investigated. The distribution of the microparticles in the horny layer was analyzed using the method of tape stripping in combination with spectroscopic measurements. Deeper layers of the stratum corneum were devoid of TiO 2 even after repetitive application of sunscreen preparation when analyzing interfollicular areas. Only in the areas of the pilosebaceous orifices could microparticles be identified. The penetration of TiO 2 was investigated in histological skin sections. A biopsy was taken from a skin area from which the horny layer had been removed by tape stripping. In isolated areas, a penetration of coated TiO 2 into the open part of the follicle was observed. The amount of TiO 2 found in a given follicle was less than 1% of the applied total amount of sunscreens. A penetration of microparticles into viable skin tissue could not be detected.