The growing competition in Brazilian science: rites of passage, stress and burnout

Brazil's scientific community is under pressure. Each year there is an increase in its contribution to international science and in the number of students who are trained to do research and teach at an advanced level. Most of these activities are carried out in state and federal universities, but with government funding that has decreased by more than 70 percent since 1996. Interviews with graduate students, post-doctoral fellows and professors in one university department with a strong research tradition illustrate the level of stress engendered by the conflict between increasing competition and diminishing resources, and serve to underscore the negative effects on creativity and on the tendency to choose science as a career

The growing competition in Brazilian science: rites of passage, stress and burnout.

Brazil's scientific community is under pressure. Each year there is an increase in its contribution to international science and in the number of students who are trained to do research and teach at an advanced level. Most of these activities are carried out in state and federal universities, but with government funding that has decreased by more than 70% since 1996. Interviews with graduate students, post-doctoral fellows and professors in one university department with a strong research tradition illustrate the level of stress engendered by the conflict between increasing competition and diminishing resources, and serve to underscore the negative effects on creativity and on the tendency to choose science as a career.

Possible association between poor metabolism of mephenytoin and hepatotoxicity caused by Atrium, a fixed combination preparation containing phenobarbital, febarbamate and difebarbamate.

Drug hepatotoxicity is partially determined by genetic factors involved in drug metabolism, which may involve the debrisoquine oxidation polymorphism mediated by cytochrome (CYP) 2D6. The purpose of this study was to assess the relationship between drug hepatotoxicity and another genetic polymorphism of drug oxidation, namely that of S-mephenytoin metabolism mediated by CYP2CMP. Mephenytoin hydroxylation capacity was assessed by a hydroxylation index in 24 patients with drug-induced hepatitis and in 23 healthy controls. Hydroxylation index was calculated as the ratio of S-mephenytoin dose to the (0-10 h) urinary excretion of 4-hydroxymephenytoin after oral administration of 100 mg racemic mephenytoin. The test was performed following the patient's recovery. In three patients, hepatitis was related to Atrium, a drug containing phenobarbital, febarbamate and difebarbamate. The mean hydroxylation index (+/- SD) value in patients with Atrium hepatitis (12.4 +/- 8.3) was markedly higher than that found in healthy controls (1.8 +/- 0.4) or in patients with other drug-induced hepatitis (2.5 +/- 3.3). Mean hydroxylation index values were similar in the two latter groups. Considered individually, oxidation capacity was low (hydroxylation index > 9) in two of the three patients with Atrium hepatitis and intermediate (hydroxylation index between 4 and 9) in the third patient. In contrast, all 23 healthy subjects exhibited a high oxidation capacity (hydroxylation index < 4). In the 21 patients with other drug-induced hepatitis, oxidation capacity was high in 19 subjects, intermediate in one subject with chlorpromazine hepatitis, and low in one subject with dapsone hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Productivity versus promised results: one of the dilemmas of biotechnology in Brazil.

In 1983 a new funding program--PADCT ("Programa de Apoio ao Desenvolvimento Cientifico e Tecnológico")--was created in Brazil to stimulate the development of research projects related to what was established as technological priorities. In this paper 3 features of the Biotechnology/Health subprogram of PADCT were studied: a) to what extent productivity of the leaders of the research projects affected the way they were evaluated by the award panel, b) the conflict of interests that might result from the composition of the award panel, and c) the final impact of the program on science and technology. In our sample of 210 submitted projects, 62 were funded. The data suggest that the selection of projects did not ensure a better funding for the more productive research leaders. The presence on the award panel of at least one member from the same institution of a given project increased the chance of its approval but, after approval, it had no influence on the amount of funds granted. In a subsample of 21 scientists, support to 24 projects did not increase the productivity level and 4 products in a preliminary phase of development were reported. The issue of trying to solve problems in areas where there is no established scientific competence is discussed.

Productivity versus promised results: one of the dilemmas of biotechnology in Brazil

In 1983 a new funding program - PADACT ("Program de Apoio ao Desenvolvimento Científico") - was created in Brazil to stimulate the development of research projects related to what was established as technological priorities. In this paper 3 features of the Biotechnology/Health subprogram of PADCT were studied: a) to what extent productivity of the leaders of the research projects affected the way they were evaluated by the award panel, b) the conflict of interest that might result from the composition of the award panel, and c) the final impact of the program on science and technology. In our sample of 210 submitted projects, 62 were funded. The data suggest that the selection of projects did not ensure a better funding for the more productive research leaders. The presence on the award panel of at least one member from the same institution of a given project increased the chance of its approval but, after approval, it had no influence on the amount of funds granted. In a subsample of 21 scientists, support to 24 projects did not increase the productivity level and 4 products in a preliminary phase of development were reported. The issue of trying to solve problems in areas where there is no established scientific competence is discussed

Nilutamide inhibits mephenytoin 4-hydroxylation in untreated male rats and in human liver microsomes.

1. The effects of nilutamide (an anti-androgen with a hydantoin moiety) on the 4-hydroxylation of mephenytoin were studied in rat liver microsomes. Nilutamide, at a concentration expected in human liver (100 microM) during prolonged administration of nilutamide, inhibited by 40% mephenytoin (0.3 mM) 4-hydroxylase activity in liver microsomes from untreated male rats, but not in microsomes from untreated female rats, or in microsomes from dexamethasone-treated male or female rats. 2. Administration to male rats of nilutamide, in doses (20 mg/kg i.p. twice daily) known to reproduce plasma concentrations observed in human therapeutics, decreased by 60% the 24 h urinary excretion of 4-hydroxymephenytoin after administration of mephenytoin (15 mg/kg oral). 3. Nilutamide (100 microM) markedly inhibited mephenytoin 4-hydroxylase activity in human liver microsomes. Inhibition kinetics were consistent with mixed inhibition. It is concluded that nilutamide inhibits mephenytoin 4-hydroxylase activity in untreated male rats and in human liver microsomes. It is suggested that inhibition is likely to occur in vivo in humans receiving therapeutic doses of nilutamide.