Change in Japanese medical education has been accelerating over the last 10 years. Historically, clinical departments in each medical school played a crucial role, but reports in the mass media tried to refute the feudal 'ikyoku-koza' system with a number of malpractice cases, inappropriate patient-doctor communication, etc. At that time policies by the Ministries of Education and Health (rationalized in 2001) independently became more influential in medical education. In particular the network of governmental medical schools has been restructured, merged and privatized since 2001. In the 1990s several private medical schools developed distinctive curricula including problem-based learning (PBL), the objective structured clinical examination (OSCE) and introduction to clinical medicine (ICM). The curriculum for clinical medicine is still a critical issue and will be a major challenge for the management of each medical school. The effectiveness of the National Model Curriculum consisting of more than 1200 objectives might be questionable but the National Common Achievement Test (CAT) will make a strong impact on the preclinical curriculum. In the future each medical school should adopt an outcome-based education system to close the loop of curriculum development. An evaluation system based on the entire medical school or curriculum will be the key to successful education.
Margosa oil (MO), a fatty acid-rich extract of the seeds of the neem tree and a reported cause of Reye's syndrome, has been used in the induction of an experimental model of Reye's syndrome in rats. It has been reported that MO causes a decrease in in vivo mitochondrial enzyme activity similar to that seen in Reye's syndrome. We have attempted to uncover some of the biochemical mechanisms of MO's toxicity by examining its effect in vitro on isolated rat liver mitochondria. Male rat liver mitochondria were isolated by centrifugation; oxygen uptake, reduced forms of cytochrome b, c + c1, a + a3, and flavoprotein, intramitochondrial concentrations of acetyl coA, acid-soluble coA, acid-insoluble coA, and ATP content were measured after incubation with and without MO. Our results reveal that MO is a mitochondrial uncoupler. State 4 respiration was increased while the respiratory control ratio was decreased. The intramitochondrial content of ATP was also decreased. There were substantial changes in the reduction of the respiratory chain components after incubation of mitochondria with MO. This decelerative effect on mitochondrial electron transport was alleviated by the addition of coenzyme Q and/or carnitine. These effects of MO on mitochondrial respiration may be due to changes in fatty acid metabolism caused by MO as MO caused a shift in the proportion of acid-soluble or acid-insoluble coA esters. Supplementary therapy with L-carnitine and coenzyme Q may be useful in the management of MO-induced Reye's syndrome.