RESUMO
The pharmacological action of vitamin E on the mechanical activity of isolated guinea pig colonic smooth muscle was examined in normoxic and hypoxic conditions. In hypoxia, but not normoxia, alpha-tocopherol (1-160 microM) evoked rapid concentration-dependent contractions from the colon. This was also seen with other members of the vitamin E family, and potency measurements gave EC(50) values (microM) of 10.6 +/- 0.9 for D-alpha-tocopherol, 6.0 +/- 1.2 for D-beta-tocopherol, 7.5 +/- 0.7 for D-gamma-tocopherol, and 6.1 +/- 1.5 for D-delta-tocopherol. This order of potency for the components of the vitamin differs from previously studied bioassay systems and from their antioxidant activity. A range of potent natural and synthetic antioxidants was not active in this system. Compounds with structural similarities to the side chain of vitamin E produced similar stimulatory responses and some, like phytol, were more potent than the vitamin (EC(50): 1.0 +/- 0.2 microM), whereas ring structures related to the vitamin, like Trolox C, antagonized the stimulant responses in a concentration-dependent manner. Therefore, this model system measures, directly, vitamin E-induced responses through a mechanism that does not appear to be related to the known antioxidant capacity of these agents.
Assuntos
Antioxidantes/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , alfa-Tocoferol/farmacologia , Animais , Antioxidantes/química , Ácido Ascórbico/farmacologia , Cromanos/farmacologia , Colo Transverso/efeitos dos fármacos , Colo Transverso/fisiologia , Relação Dose-Resposta a Droga , Feminino , Cobaias , Hipóxia , Técnicas In Vitro , Contração Isométrica/efeitos dos fármacos , Masculino , Metacrilatos/farmacologia , Músculo Liso/fisiologia , Fitol/farmacologia , Pirogalol/farmacologia , Relação Quantitativa Estrutura-Atividade , Estereoisomerismo , Temperatura , Terpenos/química , Terpenos/farmacologia , alfa-Tocoferol/químicaRESUMO
The introduction of clinical care pathways into one acute hospital trust provided the opportunity to investigate reasons why doctors behave the way they do, and to identify receptive and non-receptive factors for change. A multi-method research strategy was used to obtain primary data, both quantitative and qualitative material, namely responses to a questionnaire and interviews. The questionnaire was distributed to 70 consultants from a variety of medical and surgical specialties, and 42 questionnaires were returned (60 per cent response rate). Reports some of the findings and shows that consultant behaviour and the factors that influence that behaviour are affected by their own characteristics, specifically age and specialty, although all specialties agreed that non-financial incentives would influence their behaviour. Characteristics of opinion leaders were also found to be specialty-specific in their degree of influence. Concludes that the multi-method research approach was effective in identifying factors which influence consultant behaviour, and further studies should be carried out in this area.