Genistein induces phosphorylation of cAMP response element-binding protein in neonatal hypothalamus in vivo.

We investigated the effect of the phytoestrogen, genistein and 17beta-oestradiol on cAMP response element-binding protein (CREB) phosphorylation in the neonatal female rat hypothalamus in vivo using western blot analysis and immunohistochemistry. Although CREB expression was insensitive to the compounds we tested, administration of genistein and 17beta-oestradiol induced rapid CREB phosphorylation (< 15 min) in the hypothalamus and its level remained elevated at 4 h. Quantitative immunohistochemical analysis showed that genistein and 17beta-oestradiol had no effect on CREB phosphorylation in the magnocellular subdivision of paraventricular nucleus. By contrast, genistein induced a dose-dependent increase in CREB phosphorylation in the medial preoptic area (mPOA) and anteroventral periventricular nucleus (AVPV). Administration of 17beta-oestradiol also caused a rapid, dose-dependent increase in CREB phosphorylation in the hypothalamus, mPOA and AVPV. These results demonstrate that genistein induces oestrogen-like rapid action on CREB phosphorylation in the neonatal central nervous system in vivo.

Sex differences in oestrogen-induced p44/42 MAPK phosphorylation in the mouse brain in vivo.

In addition to the classical direct genomic mechanisms of action, oestrogen also exerts poorly understood, nonclassical effects on the signalling system in neurones. In the present study, we investigated whether sex differences exist in gonadectomy- and oestrogen-induced effects on p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in specific brain regions of mice. We demonstrate that MAPK immunoreactivity was not altered by gonadectomy or oestrogen treatment in either sex. However, we show that the level of phosphorylated MAPK (pMAPK) within the anteroventral periventricular nucleus (AVPV) was consistently higher in males than females irrespective of gonadal steroid hormone status. In addition, gonadectomy was found to decrease pMAPK immunoreactivity within the piriform cortex of males. Oestrogen increased pMAPK immunoreactivity in the medial preoptic area and AVPV of females, but failed to have the same effect in male mice. Overall, these results demonstrate a marked sex difference in oestrogen-induced alteration of MAPK phosphorylation in the brain in vivo.

Facilitation of spike-wave discharge activity by lipopolysaccharides in Wistar Albino Glaxo/Rijswijk rats.

In normal rats the proinflammatory cytokines like interleukin-1beta, interleukin-6, which are induced by bacterial lipopolysaccharides, are able to control thalamo-cortical excitability by exerting strong effects on physiological synchronization such as sleep and on pathological synchronization like that in epileptic discharges. To investigate whether proinflammatory cytokines or lipopolysaccharides could modulate absence seizures resulting from a very different generator mechanism than the already investigated bicuculline-, kindling- and kainate-induced seizures, we used a genetically epileptic Wistar Albino Glaxo/Rijswijk rat strain, which is spontaneously generating high voltage spike-wave discharges. Wistar Albino Glaxo/Rijswijk rats responded with an increase of the number of spike-wave discharges to lipopolysaccharide injection (from 10 microg/kg to 350 microg/kg). Repetitive administration of 350 microg/kg lipopolysaccharides daily for 5 days increased the number of spike-wave discharges on the first, second and third days but the number of spike-wave discharges returned to the control value on day 5, at the 5th injection of lipopolysaccharides, showing a tolerance to lipopolysaccharides. The lipopolysaccharide-induced increase in spike-wave discharges was not directly correlated with the elevation of the core body temperature, as it is in febrile seizures, although lipopolysaccharide induced prostaglandin and is clearly pyrogenic at the doses used. Indomethacin, the prostaglandin synthesis inhibitor, efficiently blocked lipopolysaccharide-induced enhancement of spike-wave discharge genesis suggesting that the spike-wave discharge facilitating effect of lipopolysaccharides involves induction of cyclooxygenase 2 and subsequent synthesis and actions of prostaglandin E2. Low dose (40 mg/kg, i.p.) of competitive N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid, and low dose of lipopolysaccharide (20 microg/kg) showed a synergistic interaction to increase the number of spike-wave discharges, whereas at supramaximal doses of lipopolysaccharide and the N-methyl-D-aspartate antagonist no synergy was present. The data reveal a functional connection between absence epileptic activity and lipopolysaccharide induction of prostaglandin synthesis and prostaglandin action and suggest some common cellular targets in epilepsy and lipopolysaccharide-induced inflammation.

[Maternal mortality estimation in France, according to a new method]. / Estimation de la mortalité maternelle en France: une nouvelle méthode.

OBJECTIVE: Ten years after implementation of maternal mortality monitoring in France, we established a new estimate of the current maternal mortality ratio (MMR) and revisited maternal death data collection. MATERIAL AND METHODS: Linkages were set up between female deaths and childbirths and between female deaths and causes of death. Information provided by confidential inquiries into maternal deaths carried out by the National Committee for maternal mortality study was added. The World Health Organization (WHO) definitions were used for maternal death and maternal mortality ratio. The study concerned deaths occurring in 1999. Results were compared with data from 1989. RESULTS: The official data showed 20% fewer maternal deaths than our inquiry. Estimated from our data, the MMR was 9 per 100000 live births in 1999. Direct obstetric causes were more often recorded than indirect causes. Hemorrhage was the leading obstetric cause of maternal death (21%). In comparison with the 1989-90 data, the underestimation of maternal deaths and maternal mortality ratios are improving (from 18 to 9 per 100000). CONCLUSION: These results, obtained while the mean maternal age at childbirth increased regularly, are interpreted as a sign of improvement in care. But the persistence of post partum hemorrhages as the leading cause of maternal death and the high rate of avoidable deaths, disclose important targets for further progress.

Severe bronchopulmonary dysplasia. Predictors of survival and outcome.

Predictors of survival and outcome were evaluated following severe bronchopulmonary dysplasia in 35 neonates, 15 of whom died during the initial hospitalization and four following discharge. There was no difference in the clinical characteristics between those infants who survived or died. The survival rate was 47 percent when the length of stay in the hospital was three months and was 17 percent when the length of stay was five months. The survival rate was 27 percent when the time receiving oxygen was three months. There were no survivors when the time receiving oxygen was longer than five months. Follow-up of 13 survivors revealed that four had neurologic sequelae, and two had severe retrolental fibroplasia. When comparing infants with a mean mental developmental index of less than 84 (n = 8) to those with more than 85 (n = 5) on the Bayley Scales of Infant Development, mean length of hospitalization was 125 days vs 72 days (p less than 0.05), and the time receiving oxygen was 84 days vs 46 days (p less than 0.05). When comparing infants with growth parameters below the 5th percentile (n = 4) to those above the 5th percentile (n = 9), the mean time receiving oxygen was 94 days compared to 58 days (p less than 0.05). Severe bronchopulmonary dysplasia is associated with a high mortality and morbidity, both in and beyond the neonatal period.