Characteristics of neonatal mortality in the State of Rio de Janeiro, Brazil, in the 1980''s: a spatio-temporal analysis

AIMS: To examine the population pharmacokinetics of lamotrigine in patients newly diagnosed with epilepsy and receiving oral lamotrigine monotherapy for up to 48 weeks. METHODS: The population consisted of 158 Caucasians and 5 Asians of whom 81 were males and 82 females. Age and weight ranged between 14 and 76 years and 41-107 kg, respectively. A one-compartment compartment model with first-order absorption and elimination was fitted to plasma lamotrigine concentration-time profiles from retrospective drug monitoring, using non-linear mixed effect modelling (NONMEM), with first-order estimation. Oral clearance (CLo), apparent volume of distribution (V/F) and absorption rate constant (Ka) were the main pharmacokinetic parameters. RESULTS: CLo was not significantly influenced by body weight, age, gender, oral contraceptives and dose. However, due to auto-induction CLo increased by 17.3% during the 48 weeks of therapy, from 1.94 to 2.28 l h(-1), and was 28.7% lower in Asians than Caucasian. The final magnitude in interpatient variability was 32%. The effect of the covariates weight, age, race and gender on V/F was examined and none was statistically significant. The final population estimate of V/F was 77.4 l with an interpatient variability of 34%. CONCLUSIONS: In view of the wide therapeutic margin of lamotrigine and the 21% residual variability in plasma concentrations, the modest significant effects of race and auto-induction on clearance are unlikely to be clinically significant and, thus, no dosage adjustment is warranted for these effects.     

Activity of aryl sulfatase A enzyme in patients with schizophrenic disorders

The effect of diazepam on locomotor activity was tested by measuring the number of crossings between two compartments of a toggle-floor box, in control mice (water drinking) and in mice receiving caffeine solution (0.5 g/I) instead of drinking water. In control mice, diazepam did not produce any significant change in total activity measured on the whole 60-min test, but animals showed phases of increased activity broken by periods of immobility. After chronic ingestion (18 days) of caffeine, doses of 0.5, 1 and 2 mg/kg ip diazepam significantly increased total locomotor activity. Caffeine slightly reduced diazepam-induced immobility and increased the frequency of crossings in active periods. Taken together, these two effects may explain the significant increase in total activity induced by diazepam in caffeine-treated mice. Mixed stimulatory-depressant action was also produced by 3 mg/kg diazepam, a dose that slightly decreased the total activity.     

Assignment of absolute stereochemistry to an insect pheromone by chiral amplification

We assessed the replicability of reliability and validity of a brief self-report disability scale, adapted from the Medical Outcomes Survey (short form), in a 15-center, cross-national, multilingual study of psychological illness among primary care patients (n = 5438). Across all 15 centers in the World Health Organization Collaborative Study of Psychological Problems in General Health Care, the reliability of the disability scale was high and individual items were responsive at similar levels of disability. Self-report disability was consistently correlated with disability in work role (including housework) as rated by interviewers according to the Groningen Social Disability Schedule, a semistructured method taking local norms into account. Disability as measured by the self-report questionnaire was also consistently correlated with depressive symptoms as measured by the General Health Questionnaire. At each center, the disability items formed a moderately to strongly hierarchical (Guttman-like) scale. These findings support the feasibility of using self-report disability scales in cross-national primary care research.     

Contributions of Microdialysis to New Alternative Therapeutics for Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a common complication of cirrhosis, of largely reversible impairment of brain function occurring in patients with acute or chronic liver failure or when the liver is bypassed by portosystemic shunts. The mechanisms causing this brain dysfunction are still largely unclear. The need to avoid complications caused by late diagnosis has attracted interest to understand the mechanisms underlying neuronal damage in order to find markers that will allow timely diagnosis and to propose new therapeutic alternatives to improve the care of patients. One of the experimental approaches to study HE is microdialysis; this technique allows evaluation of different chemical substances in several organs through the recollection of samples in specific places by semi-permeable membranes. In this review we will discuss the contributions of microdialysis in the understanding of the physiological alterations in human hepatic encephalopathy and experimental models and the studies to find novel alternative therapies for this disease.     

Oviposition Responses of Gravid Female <Emphasis Type="Italic">Culex quinquefasciatus</Emphasis> to Egg Rafts and Low Doses of Oviposition Pheromone Under Semifield Conditions

Semifield experiments were conducted to study the oviposition of gravid Culex quinquefasciatus females in response to one or 10 egg rafts, or 3.0 μg of synthetic oviposition pheromone, (-)-(5R,6S)-6-acetoxy-5-hexadecanolide, a dose equivalent to 10 egg rafts. These treatments were added to the small bowls filled with either hay infusion or water in a small (0.3-m spacing) or a large-square design (3.4-m spacing). Oviposition choice was more pronounced in the “small square” assays. Mean number of egg rafts laid in response to a single egg raft in an oviposition jar filled with hay infusion was significantly greater than with all other treatments. When the oviposition pheromone dose was increased from one to 10 rafts or when 3.0 μg synthetic oviposition pheromone were dispensed on a floating receptacle, synergistic effects were observed between the oviposition pheromone and the hay infusion at both distances. This study is the first demonstration that the amount in a single raft induces oviposition of gravid Cx. quinquefasciatus females under semi-natural conditions.