Kinetics and Mechanism of Hydrolysis of Benzimidazolylcarbamates

Synthesis of new 2-aminobenzimidazole-1-carbamates was accomplished by carbamoylation of 2-aminobenzimidazole using different substituted phenyl chloroformates. The aqueous hydrolysis of the new compounds was examined in the pH range 1-13 at 25 oC. The evaluated kinetic parameters led to the conclusion that up to pH 4 reaction proceeds by a bimolecular attack of water to the N-protonated substrate. This is the first time this behavior is described for carbamates, and can be ascribed to the higher basicity of the benzimidazolyl moiety when compared with the carbonyl oxygen. For higher values of pH, the results are consistent with a BAc2 mechanism with nucleophilic catalysis, but while between pH 4 and pH 7 water acts as the nucleophile, for pH> 7 the hydroxide ion is the acting species

Propagação da figueira 'Roxo de Valinhos' por alporquia Propagation of the fig tree 'Roxo de Valinhos' by air layering

O objetivo do presente trabalho foi estudar a posição do ramo associada a diferentes ferimentos, substratos e concentrações de ácido indolbutírico (AIB) no enraizamento de alporques de figueira 'Roxo de Valinhos'. No primeiro experimento, foram realizados alporques na porção basal, mediana e apical dos ramos, no início do mês de março. No preparo dos alporques, foram realizados diferentes ferimentos: anel inteiro (anéis de três cm de comprimento), dois cortes (cortes paralelos de três cm de comprimento e um cm de largura), um corte (corte de três cm de comprimento e um cm de largura) e a testemunha com ausência de corte. Em seguida, colocou-se, no local do tratamento, substrato à base de casca de pínus umedecido, envolvendo-se com plástico transparente e amarrando-se nas extremidades, para evitar a perda de umidade. Passados 50 dias, os alporques foram removidos para a avaliação da porcentagem de alporques calejados, enraizados e o número médio de raízes. Em seguida, foram transplantados para leito de areia umedecido sob telado constituído de sombrite com 50% de luminosidade. Passados 30 dias, foram mensurados a porcentagem de alporques vivos e brotados, e o número médio de brotos. No segundo experimento, os alporques foram realizados no mês de abril, na porção mediana dos ramos, sem ferimento, aplicando-se no local, diferentes concentrações de AIB (0; 1.000; 2.000 e 3.000 mg L-1) e, em seguida, foram envolvidos pelos seguintes substratos: casca de pínus umedecido, esfagno umedecido e a mistura de ambos na proporção 1:1 v/v. Passados 60 dias, os alporques foram removidos para a mensuração da porcentagem de alporques calejados, enraizados e o número médio de raízes. Concluiu-se que os alporques devem ser realizados na porção mediana dos ramos, ausentes de ferimento, tratados com 1.000 mg L-1 de AIB e envolvidos com substrato à base de casca de pínus.<br>The objective of the present work was to study the position of the branch associated to different wounds, substrates and concentrations of indolbutyric acid (IBA) in the rooting of air layering in 'Roxo de Valinhos' fig tree. In the first experiment, air layering was accomplished in the basal, medium portion and apical of the branches in the beginning of the month of March. In the prepare the air layering, different wounds were accomplished: whole ring (rings of three cm of length), two cuts (parallel cuts of three cm of length and a cm of width), a cut (measuring three cm of length and one cm of width) and the witness cut absence. Soon after, it was placed in the place of the treatment, substrate of humidified pinus, wrapped up with transparent plastic and being tied in the extremities, to avoid the humidity loss. After 50 days, the air layering was removed for the evaluation of the percentage of case-hardened and rooted layers and the medium number of roots. Soon after, they were transplanted for bed of sand humidified under nursery constituted of sombrite with 50% of brightness. After 30 days, it was evaluated the percentage of alive, air layering sprouted and the medium number of sprouts. In the second experiment, the air layering was accomplished in the month of April, in the medium portion of the branches, without wound, being applied in the place, different concentrations of IBA (0, 1000, 2000 and 3000 mg L-1) and soon after, they were involved by the following substrate: humidified pinus, humidified sphagnum and the mixture in the proportion 1:1 v/ v. After 60 days, the air layering was removed for the evaluated of the percentage of case-hardened and rooted layers and the medium number of roots. It was concluded that the air layering should be accomplished in the medium portion of the branches, absent of wound, agreements with 1000 mg L-1 of IBA and involved with pinus substrate

Mechanical ventilation in patients with cardiogenic pulmonary edema : a sub-analysis of the LUNG SAFE study

Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality. Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model. From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59-78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57-77] vs 74 [64-80] years, p < 0.001) and had lower driving (12 [8-16] vs 15 [11-17] cmHO, p < 0.001), plateau (20 [15-23] vs 22 [19-26] cmHO, p < 0.001) and peak (21 [17-27] vs 26 [20-32] cmHO, p < 0.001) pressures. Latent mixture analysis of patients receiving invasive mechanical ventilation on ICU day 1 revealed a subgroup ventilated with high pressures with lower probability of being discharged alive from the ICU (hazard ratio [HR] 0.79 [95% confidence interval 0.60-1.05], p = 0.103) and increased hospital mortality (HR 1.65 [1.16-2.36], p = 0.005). In a marginal structural model, driving pressures in the first week (HR 1.12 [1.06-1.18], p < 0.001) and tidal volume after day 7 (HR 0.69 [0.52-0.93], p = 0.015) were related to survival. Higher airway pressures in invasively ventilated patients with CPE are related to mortality. These patients may be exposed to an increased risk of ventilator-induced lung injury. Trial registration Clinicaltrials.gov NCT02010073

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

International audienceBackground: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk.Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels.Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43.Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)