Objectives: To investigate whether docosahexaenoic acid (DHA) supplementation was able to ameliorate attention-deficit/ hyperactivity disorder(AD/HD) symptoms in AD/HD children. Design and subjects: A placebo-controlled double-blind study with 40 AD/HD (including eight AD/HD-suspected) children of 6-12 y of age who were mostly without medication. Subjects of a DHA group (n ¼ 20) took active foods containing fish oil (fermented soybean milk, bread rolls and steamed bread; 3.6 g DHA/week from these foods) for 2 months, whereas those of a control group (n ¼ 20) took indistinguishable control foods without fish oil. The following items were measured at the start and end of the study: (1) attention deficit, hyperactivity and impulsivity (AD/HD-related symptoms according to DSM-IV criteria); (2) aggression assessed by both parents and teachers; (3) visual perception (finding symbols out of a table); (4) visual and auditory short-term memory; (5) development of visual-motor integration; (6) continuous performance; (7) impatience. Results: Changes in tests 1, 2, 3, 5 and 7 over time did not significantly differ between the two groups. However, visual shortterm memory and errors of commission (continuous performance) significantly improved in the control group compared with the changes over time in the DHA group (P ¼ 0.02 and 0.001, respectively). Recalculation without AD/HD-suspected subjects (n ¼ 4 each group) showed similar P-values with regard to both measures. Conclusion: DHA supplementation did not improve AD/HD-related symptoms. Treatment of ADHD with fatty acids deserves further investigation, but careful attention should be paid as to which fatty acid(s) is used.

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(2014) The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial. J Hum Nutr Diet. 27 (Suppl. 2), 284-291 doi:10.1111/jhn.12090 AbstractBackground: Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed behavioural disorder of childhood, affecting 3-5% of school-age children. The present study investigated whether the supplementation of soy-derived phosphatidylserine (PS), a naturally occurring phospholipid, improves ADHD symptoms in children. Methods: Thirty six children, aged 4-14 years, who had not previously received any drug treatment related to ADHD, received placebo (n = 17) or 200 mg day -1 PS (n = 19) for 2 months in a randomised, double-blind

BackgroundSince both the antibacterial effects and common adverse effects of colistin are concentration-dependent, determination of the most appropriate dosage regimen and administration method for colistin therapy is essential to ensure its efficacy and safety. We aimed to establish a rapid and simple high-performance liquid chromatography (HPLC)-based system for the clinical determination of colistin serum concentrations.MethodsExtraction using a solid-phase C18 cartridge, derivatisation with 9-fluorenylmethyl chloroformate, and elution with a short reversed-phase Cl8 column effectively separated colistin from an internal standard. The HPLC apparatus and conditions were as follows: analytical column, Hydrosphere C18; sample injection volume, 50 μL; column temperature, 40 °C; detector, Shimadzu RF-5300 fluorescence spectrophotometer (excitation wavelength, 260 nm; emission wavelength, 315 nm); mobile phase, acetonitrile/tetrahydrofuran/distilled water (50,14,20, v/v/v); flow-rate, 1.6 mL/min.ResultsThe calibration curves obtained for colistin were linear in the concentration range of 0.10–8.0 μg/mL. The regression equation was y = 0.6496× − 0.0141 (r2 = 0.9999). The limit of detection was ~ 0.025 μg/mL, and the assay intra- and inter-day precisions were 0.87–3.74% and 1.97–6.17%, respectively. The analytical peaks of colistin A, colistin B, and the internal standard were resolved with adequate peak symmetries, and their retention times were approximately 8.2, 6.8, and 5.4 min, respectively. Furthermore, the assay was successfully applied to quantify the plasma colistin levels of a haemodialysis patient.ConclusionThe assay is a simple, rapid, accurate, selective, clinically applicable HPLC-based method for the quantification of colistin in human plasma.

We recently reported 'The effect of docosahexaenoic acidcontaining food administration on symptoms of attentiondeficit/hyperactivity disorder-a placebo-controlled doubleblind study ' (Hirayama et al, 2003). In that study, aggression of AD/HD schoolchildren was rated with our original questionnaire to their parents and teachers, and counted only when both of them gave the same assessment, like the method of AD/HD-related symptoms criteria of DSM-IV. However, the method of counting only when both of them agreed had a possibility that this method might lose detection power. Besides, there were only two questions about aggression in that study. Actually, we could not find any intergroup differences in aggression/hostility in that study. Here, we recalculated aggression as the sum of separate scores of both parents and teachers. Figure 1 shows the results of recalculations. In the DHA group, where subjects ate DHA-rich foods for 2 months, aggression was significantly reduced with significant differences from the control group with baseline as covariate. There was a discrepancy in the rating by parents and by teachers; the effect of active foods on hostility (question 1) was more appreciated by parents than by teachers, and the effect on physical aggression (question 2) was more appreciated by teachers than by parents. This was why recalculations of the sum of separately assessed scores were able to detect significant intergroup differences as shown in Figure 1. Although DHA-containing foods did not improve AD/HD-related symptoms (Hirayama et al, 2003), this effect of DHA on aggression, which we have already reported in healthy young adults (Hamazaki et al, 1996), may improve human relationships of AD/HD children both in school and in home, and, therefore, needs further investigation.

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Hepatotoxicity associated with administration of voriconazole (VRCZ) is a major treatment-related adverse event and in some cases requires discontinuation of therapy. This study aimed to investigate the clinical course and risk factors for VRCZ-induced hepatotoxicity. Demographic and laboratory data were retrieved retrospectively from the medical records of 66 Japanese patients who underwent VRCZ treatment. VRCZ-induced hepatotoxicity was defined as an abnormal increase in liver function tests. VRCZ-induced hepatotoxicity was observed in 30 patients (45％), with 11 (37％) of these patients needing to discontinue the drug. Most of the events were observed within 1 to 2 weeks after the first dose of VRCZ. Of the liver function tests, an abnormal increase in γ-glutamyl transferase tended to occur earlier than changes in the other tests (ie, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin). Multiple logistic regression analysis showed that the trough concentration of VRCZ was a risk factor for hepatotoxicity (adjusted odds ratio = 2.89, 95％CI 1.49-5.59, P = 0.002). Based on this result, a VRCZ trough concentration < 4 μg/mL was considered to be the target for minimizing the risk of developing hepatotoxicity. After discontinuation of VRCZ in patients who developed hepatotoxicity, every liver enzyme abnormality improved within approximately 1 week.In conclusion, this study shows that VRCZ-induced hepatotoxicity may occur early after the initiation of VRCZ therapy. We therefore recommend appropriate adjustments of the starting dose and frequent liver function tests in patients treated with VRCZ, especially during the first 2 weeks.

Linezolid is used as a first-line treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections. We aimed to analyze the clinical courses of patients who received linezolid therapy in order to determine the most appropriate point for assessing the validity of linezolid therapy and identify predictors of the clinical outcomes of linezolid therapy for early stage MRSA infections. We retrospectively retrieved demographic and laboratory data from the medical records of 123 patients who underwent linezolid therapy for proven MRSA infections. We compared the post-linezolid therapy clinical courses of the clinical success and clinical failure groups, and the most appropriate point for assessing the validity of linezolid therapy was investigated. Clinical success was achieved in 99 patients. The maximum body temperature of the clinical success group was significantly lower than that of the clinical failure group at 3, 5, and 7 days after the initiation of linezolid therapy. In conclusion, we suggest that patients＇ maximum body temperature and CRP levels should be carefully monitored for at least 3-4 days to assess the effects of linezolid against early stage MRSA infections; however, they should be monitored for 7 days in patients without the above-mentioned risk factors for late-appearing linezolid effects in order to obtain more accurate information about the outcomes of such treatment.