Neurobehavioral toxicity study of dibutyl phthalate on rats following in utero and lactational exposure.

To investigate the neurobehavioral effects of dibutyl phthalate (DBP), an important endocrine disruptor known for reproductive toxicity, on rodent offspring following in utero and lactational exposure, pregnant Wistar rats were treated with DBP (0, 0.037, 0.111, 0.333 and 1% in the diet) from gestation day (GD) 6 to postnatal day (PND) 28, and selected developmental and neurobehavioral parameters of the offspring were measured. There were no significant effects of DBP on body weight gain of the dams during GD 6-20 or on the pups' ages of pinna detachment, incisor eruption or eye opening. Exposure to 1% DBP prolonged gestation period, decreased body weight in both male and female pups, depressed surface righting (PND 7) in male pups, shortened forepaw grip time (PND 10), enhanced spatial learning and reference memory (PND 35) in male pups. Exposure to 0.037% DBP also shortened forepaw grip time (PND 10), but inhibited spatial learning and reference memory in male pups. Sex x treatment effects were found in forepaw grip time (PND 10), spatial learning and reference memory, and the male pups appeared to be more susceptible than the females. However, all levels of DBP exposure did not significantly alter surface righting (PND 4), air righting (PND 16), negative geotaxis (PND 4 or 7), cliff avoidance (PND 7) or open field behavior (PND 28) in either sex. Overall, the dose level of DBP in the present study produced a few adverse effects on the neurobehavioral parameters, and it may alter cognitive abilities of the male rodent.

[Effects of butyl benzyl phthalate on neurobehavioral development of rats].

OBJECTIVE: To study the effects of butyl benzyl phthalate on neurobehavioral development of rats. METHODS: Levels of 0 (control), 0.05%, 0.25%, and 0.75% butyl benzyl phthalate (BBP) was given in the diet from 4 weeks of age of female F0 generation to 6 weeks of age of F1 generation in Wistar rats, including the period of the female F0 generation's mating, gestation and lactation and the F1 generation's growth and development. Selected parameters of neurobehavioral development were observed in F1 generation. RESULTS: (1)For the male F(1) generation, surface righting at postnatal (PND) 4 th day was significantly delayed in the low-dose group (P < 0.05) (scoring: 56 vs 61), cliff avoidance at PND 7 was significantly depressed in the high-dose group (P < 0.05) (scoring: 41), air righting at PND 14 was significantly depressed in all treatment groups (P < 0.05). In open field test, low- and high-dose groups moved more than control group (P < 0.05). In Morris water maze test, the escape latency was significantly delayed in the low-dose group at the 5th day of the 5 days' place navigation task (P < 0.05). (2) For the female F1 generation, there were no differences among groups in any parameter in the experiment (P > 0.05). CONCLUSION: BBP may affect the neurobehavioral development only in male rats in the F1 generation.

Steps towards preventive HIV treatment in Fujian, China: problems identified via an assessment of initial antiretroviral therapy provision.

BACKGROUND: At the end of 2009, a total of 501 AIDS patients were receiving antiretroviral therapy (ART) in Fujian Province in China, yet there were no assessments to determine treatment efficacy and HIV-1 preventive potency under the current health care delivery system. METHODS: During the period of 2005-2009, we assessed the outcomes of initial ART by following up 381 patients for 12 months in Fujian Province. CD4⁺ T-lymphocyte (CD4) count, plasma viral load (VL), and patient characteristics were analysed. The results were compared between 4 groups divided by the baseline CD4 values at the 25, 50 (median), and 75 percentiles. FINDINGS: Over three-quarters of the subjects reported heterosexual contact as the probable route of transmission. After 12 months of ART, CD4 recovery varied between the 4 groups (P < 0.001), but VL sharply declined regardless of the baseline CD4 count (P = 0.136). Although this VL decline indicates the potency of ART as an HIV-1 prevention tool, the time between positive diagnosis and ART initiation suggests serious delay in both diagnosis and treatment; the medians of periods for the lowest and highest baseline CD4 quartiles were 1.2 and 9.6 months, respectively. CONCLUSION: Current limitations in VL determination make it difficult to assess the efficacy of initial ART, and delays in diagnosis and treatment suggest that subjects contributed to HIV-1 transmission while they were not receiving ART. The current National Free ART scheme does not provide free treatment for sexually transmitted infection (STI), and there is no link between ART and the STI care delivery system. This may interfere with the HIV-1 preventive potency of ART. We highly recommend establishing a collaborating mechanism with STI care, strengthening the VL determination system, and promoting HIV tests and early ART initiation.

High-dose dibutyl phthalate improves performance of F1 generation male rats in spatial learning and increases hippocampal BDNF expression independent on p-CREB immunocontent.

Dibutyl phthalate (DBP), an important representative of endocrine disrupting chemical, is suspected of affecting the cognitive function of humans and animals. In this study, effects of DBP on maze performance in male rats were evaluated by spatial learning tasks; the effects of DBP on the expression of brain-derived neurotrophic factor (BDNF) were also analyzed in both mRNA and mature protein levels in the hippocampus, with intent to investigate the possible mechanism underlying the behavioral findings. Pregnant Wistar rats were treated orally by gavage with 0, 25, 75, 225 and 675mgDBP/kgBW/day from gestational day (GD) 6 to postnatal day (PND) 21, and then the weaned offspring continued receiving the same treatment till PND 28. We found that male pups treated with high-dose DBP showed enhancement in spatial acquisition in a Morris water maze during PNDs 30-33, and displayed better retention of spatial memory in a probe trial after a reverse trail during PNDs 60-62. Real-time PCR and western blotting analysis of the hippocampus from DBP-treated male rats on PND 21 revealed an increase in BDNF expression, compared to the vehicle-matched control. BDNF variant III, a transcription promoted by active CREB (i.e. p-CREB), as well as the immunocontent of p-CREB, was scarcely altered by the treatment. Our results suggest that developmental treatment with high-dose DBP improves spatial memory in male rats, and this effect may be related to an increase in BDNF expression in the hippocampus in a p-CREB independent route.