Background: High oxidative stress, which is caused by smoking, can alter omega-3 fatty acid concentrations. Since omega-3 fatty acids play a role in dopaminergic neurotransmission related to dependence, it is important to understand their effects on nicotine dependence. Methods: This research comprised 2 studies. The first one consisted of a cross-sectional evaluation, in which the levels of the most important omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were compared between smokers and non-smokers in a sample of 171 individuals; of them, 120 were smokers and 51 were non-smokers. The other study was a clinical, double-blind, randomized, placebo controlled, in which 63 smokers received daily treatment with capsules of fish oil (a source of omega-3/3 g/day) or mineral oil (used as placebo, also 3 g/day), taken 3 times a day for 90 days. Each fish oil capsules contained approximately 210.99 mg EPA and 129.84 mg of DHA. The outcome was evaluated by means of psychometric and biological measures as well as self-reports of tobacco use. The evaluations were carried out at the beginning of treatment and once a month thereafter (total of 4 times). Outcomes: The omega-3 fatty acid lipid profile showed that smokers present lower concentrations of DHA. After treatment, the omega-3 group showed a significant reduction in their levels of dependence. Interpretation: Smokers showed lower peripheral levels of omega-3, and treatment with the most important omega-3 fatty acids brought about a reduction in nicotine dependence.

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The results suggest that the C677T and A1298C polymorphisms of the MTHFR gene are not related to homocysteine levels in Brazilian patients with TS, despite the differential distribution of the mutated allele C (A1298C) in these patients. Further studies are needed to investigate the possible genetic interaction with homocysteine levels in TS.

RESUMOTelarca precoce, desenvolvimento mamário antes dos 8 anos de idade, apresenta dois picos de incidência, nos dois primeiros anos de vida e após os 6 anos de idade. Uma menina de 4,75 anos apresentou-se com telarca associada à ingestão excessiva de fitoestrógenos. O desenvolvimento puberal M2P1-2, os níveis hormonais e o US pélvico eram compatíveis com puberdade precoce periférica. Durante o seguimento, observou-se ingestão diária de alimentos baseados em soja (> 40 mg fitoestróge-nos/dia). Soja contém fitoestrógenos, principalmente genisteína e daidzeí-na. Embora menos potentes do que o estradiol, sua concentração pode ser 13.000 a 22.000 vezes maior em crianças alimentadas somente com fórmulas baseadas em soja. Os pais foram aconselhados a reduzir para uma vez na semana o seu fornecimento na dieta. O desenvolvimento puberal cessou em M2-3P1 e a paciente, com 8,66 anos, continua a desenvolver-se com idades óssea e cronológica equivalentes. Questões relacionadas à segurança alimentar, principalmente de alimentos baseados em soja, permanecem sem respostas precisas. Embora sejam conhecidas as etiologias da puberdade precoce não progressiva e da telarca prematura, neste caso esteve fortemente relacionada à ingestão excessiva de soja e de outros alimentos ricos em fitoestrógenos que poderiam ter desencadeado a telarca atuando como desreguladores endócrinos. Precocious thelarche is the breast development before 8 years of age with two peaks of incidence during the first two years of life and after 6 years of age. A 4.75-year-old girl presented with thelarche associated to an excessive intake of phytoestrogens (phye). Tanner development B2P1-2, hormonal levels and pelvic US were compatible with peripheral precocious puberty. During follow-up, a daily intake of soy-based foods was observed (> 40 mg phye/day). Soy is rich in phytoestrogens, mainly genistein and daidzein. Although phye are less strong than estradiol, its concentration could be from 13,000 to 22,000 times stronger in children fed only by soybased formulas. Parents were advised and soy intake was reduced to once a week. Progression of pubertal development ceased at B2-3P1. The patient, now 8.66 years old, keeps growing with similar bone and chronological ages. Some questions related to industrial food security, mainly the soy-based food, remain without precise answer. Although it is well known the entity of non-progressive precocious puberty and premature thelarche, pubertal development in this case was strongly related to excessive daily intake of soy and other phye-rich food that could trigger puberty as endocrine disruptor. (Arq Bras Endocrinol Metab 2007;51/3:500-503)

Busulfan is given in the conditioning regimens preceding hematopoietic stem cell transplantation (HSCT), and plasma levels can be monitored. A targeted, individualized systemic exposure (SE) dose can be achieved by calculating the area under the plasma concentration versus time curve (AUC). The objective of this study was to determine a cutoff value for safety for the AUC for busulfan plasma levels in patients undergoing HSCT. A total of 149 consecutive HSCT patients were studied. After an oral test dose of busulfan, we set target doses of 4000, 5000, or 6000 µMol ⋅ min/day, and analyzed the AUC of oral or intravenous Bu. These patients were compared with 53 historical control subjects who had received myeloablative conditioning regimen without busulfan pharmacokinetic monitoring. Using a test dose and the administration route had no impact on the sinusoidal obstructive syndrome (SOS) incidence, transplant-related mortality or 1-year overall survival. However, patients receiving busulfan at doses set up at AUC > 5000 had an increased risk to develop SOS after HSCT (hazard ratio 3.39, p ¼ 0.034, 95% CI 1.09-10.52). Adjusting the busulfan dose according to SE levels target dose during conditioning is associated with lower rates of oral severe mucositis and SOS. A cutoff of 5000 µMol ⋅ min is safe and does not impair survival. K E Y W O R D S acute toxicity, busulfan, hepatic sinusoidal obstructive syndrome, pharmacokinetics Multicenter study conducted in São Paulo, Brazil.