Stereologic study of Purkinje cells in mice after early exposure to phenobarbital

The present investigation was designed to study the dendritic tree of the Purkinje cells surviving after prenatal (Pre B) or neonatal (Neo B) exposure to phenobarbital (PhB). Prenatal exposure in mice was accomplished transplacentally by feeding the pregnant mother 3 g PhB/kg milled food on getation days 9 to 18. Neonatal exposure was conducted directly by injecting the neonates daily (50 mg PhB/kg) on postnatal days 2 to 21. Brains were removed at 14, 21, and 50 days of age. They were cut in the sagittal plane and prepared according to the Golgi method for analysis of the Purkinje cells dendrites. A few brains of 50-day-old Neo B and controls were cut and stained with hemotoxylin and eosin for the assessment of number of Purkinje cells. Neonatal PhB exposure caused 9% reduction in the number of dendritic spines per millimeter at age 14 and 21 days. This deficit was only transient as it disappeared by day 50. However, when the injection dose was reduced to 40 mg PhB/kg the deficits persisted to day 50. Possibly, selection against the most affected individuals accounted for the lesser effect of the higher dose. Prenatal PhB exposure had no long-lasting effect on the dendritic spines. No deficit in the area of the dendritic tree or the number of branches of all orders could be detected in any of the PhB-treated groups studied. Early PhB administration which had severe effects on the neuronal number, had a relatively small effect on the dendrites of the surviving Purkinje cells. Unlike some milder insults, it did not decrease the ratio of granule cells: Purkinje cells, and it is possible that the dendritic effects were dependent on changes in this ratio.     

Decreased cerebrospinal fluid levels of neutral and basic amino acids in patients with Parkinson''s disease

We measured the CSF levels of 21, and the plasma levels of 26, amino acids in 31 patients with Parkinson's disease (PD) and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had lower CSF levels of taurine, alanine, valine, leucine, isoleucine, ethanolamine, citrulline, ornithine, lysine, histidine, arginine, and alpha-aminobutyric acid. PD patients not treated with levodopa or with dopamine agonists had higher CSF tyrosine and phenylalanine levels than those not treated with these drugs and also than controls. PD patients had higher plasma levels of phosphoserine, threonine, methionine, tyrosine, sarcosine and -aminoadipic acid, and lower plasma levels of valine, leucine, and tryptophan, than controls. The CSF/plasma ratio of many of these amino acids was significantly lower in PD patients than those of controls, suggesting that PD patients might have a dysfunction in the transport of neutral and basic amino acids across the blood–brain barrier.     

Comparative biochemical and pharmacological characterization of a novel,NOP receptor selective hexapeptide,Ac-RYYRIR-ol

Nociceptin/orphanin FQ (N/OFQ) is an endogenous neuropeptide, which is widely distributed in central and peripheral nervous system. Some N/OFQ sequence unrelated hexapeptides can effectively bind to the N/OFQ peptide (NOP) receptor and they were used as template for structure-activity studies that lead to discovery of the new NOP selective ligands. In the present study, the pharmacological profile of the novel hexapeptide Ac-RYYRIR-ol was investigated using various in vitro assays including receptor binding and G-protein activation in rat brain membranes, mouse and rat vas deferens, guinea pig ileum, mouse colon and Ca²⁺ mobilization assay in chinese hamster ovary (CHO) cells co-expressing the human recombinant NOP receptor and the C-terminally modified Gα_qi5 protein. In rat brain membranes Ac-RYYRIR-ol displaced both [³H]nociceptin/OFQ and [³H]Ac-RYYRIK-ol with high affinity (pK_i 9.35 and 8.81, respectively) and stimulated [³⁵S]GTPγS binding showing however lower maximal effects than N/OFQ (α = 0.28). The stimulatory effect of Ac-RYYRIR-ol was antagonized by the selective NOP receptor antagonist UFP-101. In the electrically stimulated mouse vas deferens Ac-RYYRIR-ol displayed negligible agonist activity while antagonizing in a competitive manner (pA₂ 7.99) the inhibitory effects of N/OFQ. Similar results were obtained in the rat vas deferens. In the mouse colon Ac-RYYRIR-ol produced concentration dependent contractile effects with similar potency and maximal effects as N/OFQ. Finally, in the Ca²⁺ mobilization assay performed with CHO-hNOP-Gα_qi5 cells Ac-RYYRIR-ol displayed lower potency and maximal effects (α = 0.87) compared with N/OFQ. In conclusion, the novel NOP receptor selective hexapeptide Ac-RYYRIR-ol has been shown to have fine selectivity, high potency, furthermore agonist and antagonist effects toward the NOP receptors were measured in various assays; this is likely due to its partial agonist pharmacological activity.     

In vitro activity of rosoxacin against Haemophilus influenzae

The in vitro activity of rosoxacin was compared to that of ampicillin, cefoxitin, chloramphenicol, and rifampin, against 94 clinical isolates of Haemophilus influenzae. The results indicated that rosoxacin had significantly better in vitro activity against H. influenzae than the other antibiotics evaluated in this study. In addition, rosoxacin was an effective antimicrobial agent against isolates of H. influenzae that were resistant to ampicillin due to beta-lactamase production.     

Association between A218C polymorphism of the tryptophan-hydroxylase-1 gene,harm avoidance and binge eating behavior in bulimia nervosa

Genes involved in serotonin transmission are likely involved in the biological predisposition to bulimia nervosa. We investigated whether the A218C polymorphism of the tryptophan-hydroxylase-1 gene was associated to bulimia nervosa and/or to some phenotypic aspects of the disorder. One hundred eighty Caucasian women (91 patients with bulimia nervosa and 89 healthy controls) were enrolled into the study. They underwent a blood sample collection for A218C polymorphism of the tryptophan-hydroxylase-1 genotyping and a clinical evaluation assessing comorbidity for Axis I and II psychiatric disorders, harm avoidance personality dimension and bulimic symptoms. The distribution of both tryptophan-hydroxylase-1 A218C genotypes and alleles did not significantly differ between patients and controls. Bulimic women with the AA genotype exhibited a more severe binge eating behavior and higher harm avoidance scores than those with CC genotype. These findings support the idea that tryptophan-hydroxylase-1 A218C polymorphism does not play a part in the genetic susceptibility to bulimia nervosa, but it seems to be involved in predisposing bulimic patients to a more disturbed eating behavior and higher harm avoidance.