6 research outputs found
Aquaporin and Vascular Diseases
Aquaporins (AQP) are family of water channels found in several epithelial and endothelial cells, whose recent identification has provided insights into water transport in several tissues, including the central nervous system (CNS). Since brain edema continues to be the main cause of death from several CNS diseases, such as stroke, much of the interest in AQPs and their functional contribution to the water balance is due to their possible role in clearing edema water from the brain and in managing hydrocephalus and benign intracranial hypertension, suggesting that they could be targets for future treatments of various brain conditions, particularly vascular diseases. AQPs also seem to be involved in cell migration, and a mechanism of AQP-facilitated cell migration has been proposed where local osmotic gradients created at the tip of the lamellipodium drive water influx, facilitating lamellipodial extension and cell migration. AQP-facilitated cell migration was also detected in tumour cells, suggesting that it may have an important role in tumour angiogenesis and spread, and accounting for AQP expression in many tumour cell types and for correlations found between AQP expression and tumour stage in some tumours
The Antiinflammatory Cytokine Interleukin-13 is not Detectable in the Circulation of Multiple Sclerosis Patients and is not Inducible by Interferon-β 1b Treatment, that Neither Modifies its ex vivo Secretion from Peripheral Blood Mononuclear Cells
Distribution of congenital melanocytic naevi and congenital naevus-like naevi in a survey of 3406 Italian schoolchildren.
Background Scanty information is available on the prevalence of congenital melanocytic naevi (CMN) and congenital naevus-like naevi (CNLN), particularly the small ones.Objectives To estimate the prevalence of CMN/CNLN in Italian schoolchildren, and to assess variations according to potential risk factors for melanoma.Methods We conducted a survey in 13 Italian areas on 3406 schoolchildren aged 12-17 years. Children were examined by dermatologists who assessed pigmentary traits and made a count of small (6-15 mm in diameter) and medium/large (> 15 mm) CMN/CNLN on 19 anatomical areas.Results Overall, 592 children (17.4%) had one or more CMN/CNLN. Prevalence of small CMN/CNLN was 16.1%, and that of medium/large CMN/CNLN was 1.8%. There was no difference between age groups and sexes. CMN/CNLN were more frequent in children with a higher number of common melanocytic naevi (multivariate odds ratio, OR = 7.1 for the highest vs. the lowest quartile), consistent in small (OR = 7.2) and medium/large CMN/CNLN (OR = 6.0). Family history of malignant melanoma (OR = 1.4) and personal history of diabetes (OR = 4.4) appeared to be directly, and sun exposure inversely associated with CMN/CNLN. No relation was evident between CMN/CNLN and pigmentary traits, anthropometric characteristics, dietary habits, freckles, sunburns, sunscreen use or history of selected diseases.Conclusions The association with family history of melanoma, the strong association with acquired melanocytic naevi, and the lack of association with pigmentary traits and sunburns suggest that CMN/CNLN may act as an independent risk marker for subjects at increased risk for cutaneous melanoma later in life
Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study
Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II\ue2\u80\u93IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56\uc2\ub76 [SEM 4\uc2\ub75] vs 68\uc2\ub73 [4\uc2\ub75]; rank-based treatment difference \ue2\u88\u9211\uc2\ub77, 95% CI \ue2\u88\u9224\uc2\ub73 to 0\uc2\ub796; p=0\uc2\ub70698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals