B-Scanning assessment of the anti-inflammatory activity of methylprednisolone aceponate on experimentally induced allergic reactions

Background The inhibitory activity of methylprednisolone aceponate (MPA) on experimentally induced allergic reactions was assessed by an echographic method employing a B-scanner and a dedicated software, and compared to the effects of corticosteroids of known potency. Material and methods Experimental lesions, which were induced by patch testing 12 sensitized subjects with 5% nickel sulfate (pet.), were treated with two medications of different steroids (clobetasol propionate, fluocinolone acetonide, clobetasone butyrate, and methylprednisolone aceponate), performed 16 and 40 h after the application of the nickel patch tests. Clinical and echographic evaluations were carried out at the beginning of the experiment, and 64 hours after the induction of the reactions, Values of skin thickness and of extension of hypo-reflecting dermal areas were determined by image processing on echographic recordings. Results Rank order of the potency of the tested corticostcroids, as evaluated by echography, was the same as the one obtained by visual scoring. MPA proved to be less effective than clobetasol propionate, more effective than clobetasone butyrate. and equally as effective as fluocinolone acetonide. Conclusion This experiment indicated MPA can be considered a potent steroid.     

Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes in atopic dermatitis. Implications for sustained dendritic cell activation in the skin.

Lesional skin of atopic dermatitis (AD) harbors high numbers of dendritic cells with enhanced stimulatory capacity for T lymphocytes. In this study, lesional AD skin was shown to stain heavily in both epidermal and dermal compartments for GM-CSF, a cytokine crucial to dendritic cell functions. Keratinocyte cultures established from uninvolved skin of AD patients exhibited markedly increased spontaneous and PMA-stimulated release of GM-CSF compared with keratinocytes from nonatopic controls. Correspondingly, keratinocytes from AD patients showed higher constitutive as well as PMA-induced GM-CSF gene expression. Larger amounts of GM-CSF were produced by AD keratinocytes, also in response to IL-1alpha, but not after stimulation with LPS, lipoteichoic acid, or staphylococcal enterotoxin B. Hydrocortisone reduced GM-CSF gene expression and protein release in both atopic and control keratinocytes. Supernatants from atopic keratinocytes were able to strongly stimulate PBMC proliferation in a GM-CSF-dependent manner. Moreover, conditioned medium from PMA-treated AD keratinocytes, together with exogenous IL-4, could support phenotypical and functional maturation of peripheral blood precursors into dendritic cells. Enhanced production of GM-CSF by keratinocytes may contribute relevantly to the establishment and chronicity of AD lesions, in particular to the increased number, sustained activation, and enhanced antigen-presenting functions of dendritic cells.     

Cell adhesion to silicon substrata: characterization by means of optical and acoustic cytometric techniques

The adhesion and growth of cells on silicon dioxide substrata are analysed. The adhesion of human red blood cells to silicon dioxide layers of different depth and doping compares well with that to glass. Rat pheochromocytoma cells also grow on the same substrata. The adhesion of these two biological systems is characterized at the microscopic level by using the quite new technique of scanning reflection acoustic microscopy. Possible future developments towards the functional coupling of living cells to microelectronic integrated circuits are briefly discussed.     

CLinical Experience Acquired with Raptiva® (CLEAR) trial in patients with moderate‐to‐severe plaque psoriasis: results from extended treatment in an international,Phase III,placebo‐controlled trial

Background: The 12‐week, double‐blind, placebo‐controlled, first‐treatment (FT) CLEAR trial period demonstrated the efficacy/safety of efalizumab in moderate‐to‐severe plaque psoriasis, including refractory or contraindicated patients unsuitable for other systemic treatments. This study assessed the efficacy/safety of open‐label extended treatment (up to 24 weeks' continuous treatment) in patients not achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI‐75) at week 12 of the FT period. Time to relapse after treatment cessation, and efficacy/safety of 12 weeks' open‐label re‐treatment in patients achieving PASI‐75 at week 12 FT were also assessed. Patients and methods: Patients with PASI‐75 at week 12 FT were observed without treatment until relapse, then re‐treated with open‐label efalizumab (1.0 mg/kg/week for 12 weeks). Others received open‐label extended treatment without intervening observation. Results: Among efalizumab‐treated patients (n = 308) who had < 75% PASI improvement at week 12 FT, extended treatment led to PASI‐75 in 26.6%. Among patients with between ≥ 50 and < 75% PASI improvement at week 12 FT (n = 118), 47.5% improved to PASI‐75 with extended treatment. Forpatients achieving PASI‐75 at week 12 FT (n = 164), median time to relapse was 58 days. Re‐treatment after relapse led to mean PASI improvement of 62.3% from study baseline (n = 145). Safety results were consistent with pre‐vious studies, with no new safety concerns. Conclusions: These results demonstrate additional benefit of continuing efali‐zumab. Re‐treatment re‐established disease control in patients with PASI‐75 who relapsed following treatment cessation. The safety profile remained consistent with that seen at 12 weeks.     

Barriers and facilitators to diabetes self-management in a primary care setting – Patient perspectives

Background

Diabetes self-management (DSM) is a key element in the overall management of type-2 diabetes (T2DM). Identifying barriers and facilitators to DSM and addressing them is a critical step in achieving improved health outcomes in this population.