Effect of aclidinium bromide on exacerbations in patients with moderate-to-severe COPD: a pooled analysis of five phase III, randomized, placebo-controlled studies

We investigated the effect of the long-acting muscarinic antagonist aclidinium bromide on chronic obstructive pulmonary disease (COPD) exacerbations by pooling data from five randomized, placebo-controlled, parallel-group Phase III studies of 3–6 months’ duration. Data were pooled from the aclidinium 400 μg twice-daily (BID) and placebo arms (N = 2,521) and stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) group (A, B, C and D). Results showed that fewer patients experienced ≥1 exacerbation with aclidinium (any severity: 12.5%; moderate to severe: 10.9%) compared with placebo (any severity: 15.7%; moderate to severe: 13.3%) and the odds of experiencing ≥1 exacerbation of any severity were reduced in patients receiving aclidinium (odds ratio = 0.78, p = 0.039). Furthermore, aclidinium reduced the rate of exacerbations compared with placebo (any severity: rate ratio = 0.79, p = 0.026; moderate to severe: 0.80, p = 0.044). The time to first exacerbation of any severity was delayed with aclidinium compared with placebo (hazard ratio = 0.79, p = 0.026) and there was a numerical delay in time to first moderate-to-severe exacerbation. Finally, the effects of aclidinium on exacerbations versus placebo were greater in patients in GOLD Groups B and D; however, it is of note that only 10.7% of patients were classified in Group A or C. In summary, the results indicate that aclidinium 400 μg BID reduces the frequency of COPD exacerbations compared with placebo and that these effects are greater in symptomatic patients

Simultaneous determination of clobutinol hydrochloride and doxylamine succinate from syrups by RP HPLC using a new stationary phase containing embedded urea polar groups

A new, simple, fast, reproducible and sensitive reversed phase HPLC method, using a new stationary phase containing embedded urea polar groups, has been developed and validated for the simultaneous determination of clobutinol hydrochloride (CLO) and doxylamine succinate (DOX) in syrups. The determination was carried out on a C8 urea column (125 mm x 3.9 mm i.d., 5 µm particle size) synthetized at the Liquid Chomatography Laboratory (LabCrom) of the Chemistry Institute of Unicamp. The mobile phase consisted of a mixture of acetonitrile:methanol:phosphate buffer (pH 2.5) in the gradient mode. The diode array detector (DAD) was operated at 230 nm for CLO and 262 nm for DOX. The method showed adequate precision, with relative standard deviations (RSD) less than 1%. The presence of the excipients did not interfere in the results of the analysis. Accuracy was determined by adding standards of the drugs to a placebo and good recovery values were obtained. The analytical curves were linear (r² 0.9999 for CLO and 0.9998 for DOX) over a wide concentration range (2.4-336 µg mL-1 for CLO and 2.3-63 µg mL-1 for DOX). The solutions were stable for at least 72 hours at room temperature. The criteria for validation using the ICH guidelines were fulfilled.<br>Um novo método simples, fácil e reprodutível, de fase reversa para CLAE, usando uma fase estacionária contendo um grupo polar, uréia, embutido, foi desenvolvido e validado para determinação simultânea de cloridrato de clobutinol (CLO) e succinato de doxilamina (DOX) em xarope. A determinação foi realizada em uma coluna C8 uréia (125 mm x 3,9 mm d.i., 5 µm tamanho de partícula) sintetizada em nosso laboratório (LabCrom). A fase móvel consistiu de mistura de acetonitrila:metanol:tampão fosfato pH 2,5, em eluição por gradiente. O detector por arranjos de diodo (DAD) foi utilizado a 230 nm para CLO e a 262 nm para DOX. O método apresentou precisão adequada, com desvio padrão relativo menor que 1%. A presença de excipientes não interferiu nos resultados obtidos. A exatidão foi realizada pela adição dos padrões dos fármacos ao placebo e valores de recuperação aceitáveis foram obtidos. As curvas analíticas mostraram-se lineares (r² 0,9999 para CLO e 0,9998 para DOX) em uma ampla faixa de concentração (2,4-336 µg mL-1 para CLO e 2,3-63 µg mL-1 para DOX). A solução padrão foi estável por 72 horas a temperatura ambiente. Os parâmetros de validação foram realizados conforme o guia ICH

Associations of FASN gene polymorphisms with economical traits in Nellore cattle (Bos primigenius indicus)

The aim of this study was to identify molecular markers to be applied to marker-assisted selection. Three SNPs of the FASN gene were studied. PCR-RFLP was used for genotyping. The SNPs g.17924A > G, g.17860C > T and g.15603A > G all in the FASN gene were genotyped using the enzymes MscI, DdeI and Hae III, respectively. The animals were raised in extensive systems and belong to three lines selected for growth as part of the Selection Program of Zebu and Caracu Breeds, So Paulo, Brazil. Allele and genotype frequencies were compared between selection lines using the Genepop 3.4. Associations between polymorphisms and the traits studied were evaluated using the PROC MIXED procedure of the SAS/STAT 9.1.3. The G and C alleles were the most frequent alleles of the g.15603A > G and g.17860C > T loci, respectively. The g.17924A > G locus showed no polymorphism in the population studied. Allele and genotype frequencies differed significantly between the NeT line and the NeC and NeS lines. The g.15603A > G polymorphism tended to exert an additive effect on rump fat thickness and male yearling height. For g.17860C > T, an additive effect on male yearling height was observed. Genotype combination analysis revealed a significant effect on loin eye area. Although this study provided evidence of an association between the FASN gene and some traits, more detailed analyses are needed to obtain more efficient molecular markers.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Potential Health Benefits of Anthocyanins in Oxidative Stress Related Disorders

Anthocyanins are naturally occurring water-soluble plant pigments belonging to the flavonoids chemical class. The red, blue and purple colours of leaves, flowers and fruits of plants confirm that they are rich sources of anthocyanins. Many in vivo and in vitro studies reveal that anthocyanins have different health beneficial effects such as antioxidant, antidiabetic, anti-inflammatory, anti-obesity, antihypertensive and anticancer properties. Major benefits of anthocyanin administration are owing to their potent anti-inflammatory and antioxidant activities. Recent investigations have revealed that anti-inflammatory activities of anthocyanins follow the inhibitory pathways of NFкB-mediated decline of inflammatory cytokines production. Inhibition of the anti-inflammatory pathways also influences the modulation of arteriolar disorders and cardiovascular complications due to anthocyanin administration. Moreover, anthocyanins improve diabetes, obesity and cancer pathology by inhibiting NF-кB-mediated inflammatory pathways. However, considerable variations in activities do exist among structurally diverse anthocyanins. This review appraises the recent literature regarding the health benefits of anthocyanins and their molecular mechanisms in various oxidative stress related pathophysiological conditions