Control of neuronal nitric oxide synthase and brain-derived neurotrophic factor levels by GABA-A receptors in the developing rat cortex.

Gamma-aminobutyric acid (GABA) plays an important morphogenetic role, acting through GABA-A receptors, which are depolarizing in the developing rat brain. Other molecules with major morphogenetic roles are the nitric oxide free radical (NO(.)) and brain-derived neurotrophic factor (BDNF), both of which are involved in the control of synaptic plasticity and apoptosis. In the present work, we investigated the effect of GABA-A receptor activation on neuronal NO(.) synthase (nNOS) and BDNF immunoreactivity in the developing cortex of 5-day-old rats. We also determined the effect of GABA-A receptor activation on phosphorylated cAMP-response element binding protein (pCREB) immunoreactivity in an effort to elucidate the molecular mechanisms involved. Our results show that activation of GABA-A receptors leads to increased numbers of nNOS, BDNF and pCREB, as well as nNOS-pCREB and BDNF-pCREB doubly immunopositive cells. This effect is abolished when L-type Ca(2+) channels are blocked. These results indicate that the following mechanism could be operating: depolarization following GABA-A receptor activation leads to opening of L-type voltage-gated calcium channels, resulting in an increased Ca(2+) influx, which in turn leads to phosphorylation and, thus, activation, of the transcription factor CREB; the phosphorylated CREB can then induce BDNF, as well as nNOS.

Genetic detection of bladder cancer by microsatellite analysis of p16, RB1 and p53 tumor suppressor genes.

PURPOSE: We investigated the incidence of genetic alterations in urine specimens from patients with bladder cancer. MATERIALS AND METHODS: A total of 28 cytological urine specimens were assessed for microsatellite alternations, and 15 microsatellite markers were located on p53, RB1 and p16 regions. In 15 patients DNA from tumor specimens was also available. RESULTS: Loss of heterozygosity was detected in 26 of 28 patients (93%) in at least 1 microsatellite marker. Allelic losses were found in 18 patients (64%) for the p16 locus, in 8 (29%) for the RB1 locus and in 17 (61%) for the p53 region. In contrast, no microsatellite alterations were found in the normal group without evidence of bladder cancer. In 11 cases genetic alterations in the cytological urine specimens were not detectable in the corresponding tumor specimen, suggesting heterogeneity of bladder cancer. CONCLUSIONS: The detection of loss of heterozygosity in cytological urine specimens may be a prognostic indicator of early detection of bladder cancer. Our results suggest that microsatellite analysis of urine specimens represents a novel, potentially useful, noninvasive clinical tool to detect bladder cancer.

Spontaneous gastric perforation in premature twins.

Two pairs of identical and non-identical premature neonates proceeding from twin pregnancies were operated on for spontaneous gastric perforation. The newborns in our case, one girl and one boy two different pregnancies were delivered by emergency cesarean section. Their gestational ages were 30 and 32 weeks, and their birth weight 1400 and 2100 g, respectively. Both of the neonates were being treated in the Neonatal Intensive Care Unit when the perforations were diagnosed. They presented clinically abrupt symptoms of abdominal distension and pneumoperitoneum. The sites of the ruptures were located at the anterior gastric wall near the gastroesophageal junction. The sibling twins were consequently also observed very carefully and fortunately they did not develop any similar clinical symptoms. All four twins were finally discharged from the hospital in good condition.

Solitary crossed renal ectopia.

A case of a solitary crossed renal ectopia in a 45-year-old male patient with a simple renal bruise during traffic accident is presented. A brief review of the literature and the embryogenesis of this extremely rare congenital anomaly are discussed.