CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for steroid-dependent Crohn's disease: a randomized, double-blind, placebo-controlled trial

Background More than 50% of patients with Crohn's disease become either steroid resistant or dependent. Accordingly, development of new treatments for steroid-dependent Crohn's disease is a research priority. Aim To evaluate CDP571, a humanized antibody to tumour necrosis factor-α, for the treatment of steroid-dependent Crohn's disease. Methods Patients with steroid-dependent Crohn's disease (n = 271) were enrolled in a 36-week, double-blind, placebo-controlled trial. Steroid dependence was defined as use of prednisolone or prednisone (15–40 mg/day) or budesonide (9 mg/day) for ≥8 weeks, a previous failed attempt to decrease or discontinue steroids within 8 weeks of screening, and a Crohn's Disease Activity Index score of ≤150 points. Patients were randomized to receive intravenous CDP571 10 mg/kg or placebo 8-weekly through to week 32. Steroids were then tapered using a defined schedule. The primary efficacy endpoint was the percentage of patients with steroid sparing, defined as discontinuation of steroid therapy without a disease flare (Crohn's Disease Activity Index score ≥220 points) at week 36. Results Steroid sparing occurred in 53 of 181 (29.3%) CDP571 patients and 33 of 90 (36.7%) placebo patients (P = 0.24). Adverse events occurred at similar frequencies in both treatment groups. Conclusions CDP571 was ineffective for sparing steroids in patients with steroid-dependent Crohn's disease. CDP571 was well tolerated.

40Ar/39Ar dating of Mn-iron ore of the Sapecado Mine, Qadrilatero Ferrifero, Brazil

The SW region of Amazonian craton presents policyclic evolution between 1.80-1.00 Ga and is comprised of the Rio Negro-Juruena, Rondoniana and Sunsas Provinces. The evolution of this region has being characterized by four orogens: Alto Jauru (1.79-1.74 Ga), Cachoeirinha (1.58-1.52 Ga), Suíte Santa Helena (1.45-1.42 Ga) e Sunsas/Aguapeí (1.0-0.9 Ga). The Alto Jauru orogen consists of TTG gneissic associations, greenstone sequences and intrusive granitoids origined in volcanic arc setting. Eight 40Ar/39Ar step-heating analyses were carried out in minerals (biotiteand hornblende) to investigate the thermal history and crustal evolution of this region. From the Alto Jauru orogen was sampled the gneiss banded and two biotite grains provide large dispersion of apparent ages, suggesting heterogenity in reservoir of the argon. Apparent age diagram yielded integrated ages of 1472 ± 6 Ma, interpreted as minimum ages of regional cooling episode. Three analyses of hornblende present ages varing from 1310 to 1400 Ma, possibly because smaller grain size become more susceptible to argon loss. 40Ar/39Ar step-heating methodology applied on biotite of pyroclastic tuff (U-Pb age about 1758 ± 7 Ma) presented integrated age of 1507 ± 7 Ma. The results found for this terrane demonstrated a geochronological correlation with metamorphic process linked Cachoeirinha orogen. Biotite and hornblende grains separates from granite and a tonalite origined during Cachoeirinha orogen were analyzed and the apparent age diagrams indicated well-defined plateau ages of 1520-1540 Ma. Biotite grains from a granitic sample were analized, and integrated ages about 1526 ± 2 Ma were obtained due argon loss in the initial steps. Thermochronologic history of SW region Amazonian craton is coherent with regional policyclic events and 40Ar/39Ar ages here presented probably correspond to regional cooling period of Cachoeirinha orogen.