Developmental organization of neurophysin neurons in the human brain.

Neurophysin (NPH) was detected immunohistochemically in 34 human brains ranging in age from 10 weeks of gestation (wg) to 3 months postnatal. Weakly-stained NPH-immunoreactive (NPH-IR) cells were already aggregated in the lateral hypothalamus in the supraoptic nucleus at 10 wg, the first time point examined. From this time, there was a clear and consistent chronology in the first appearance of NPH-immunoreactivity in different cell groups progressing from the supraoptic nucleus at 10 wg to cells in the accessory NPH cell group at 13 wg, paraventricular nucleus at 14 wg, suprachiasmatic nucleus at 18 wg and various other well defined clusters in the basal forebrain at 18-20 wg. NPH-IR fibers were present in the hypothalamo-hypophyseal tract from 10 wg, and together with other available evidence, our findings suggest the presence of a potentially functional hypothalamohypophyseal system by the end of the first trimester. NPH staining patterns and orientations of cells suggest that NPH-IR cells originate from the region of the hypothalamic sulcus in a manner consistent with animal studies, and migrate to their settling areas before expressing NPH-immunoreactivity. In spite of the likelihood that most NPH-IR cells (with the probable exception of those in the suprachiasmatic nucleus) derive from a single primordium, the final organization of NPH-IR cells consists of many scattered groups, as seen in the late fetal period and mature brain. Developmental analysis provides further evidence that there is a high degree of conservation in the topographic organization of the numerous diverse NPH-IR cell groups in humans and other mammals, suggesting that the separation and organization of these groups may be of functional importance.

[Biochemical studies with oxitropium bromide. 2. Pharmacokinetics and metabolism in humans]. / Biochemische Untersuchungen mit Oxitropiumbromid. 2. Pharmakokinetik und Metabolismus im Menschen.

The present paper reports on the human pharmacokinetics of (8r)-6 beta, 7 beta-epoxy-8-ethyl-3 alpha-/(-)-tropoyloxy/-1 alpha H, 5 alpha H-tropanium bromide (oxitropium bromide, Ba 253 BR, Ventilat) after intravenous and oral administration as well as following inhalation. The 14C-labelled substance was used. The concentrations of radioactivity measured in the plasma after i.v. administration show a biphasic course, a rapid alpha phase and a terminal phase (t 1/2 = 1.5 h). Once the alpha phase has passed the radioactivity concentrations measured after i.v. administration of 1 mg are comparable with those after 20 mg administered orally. The concentration course after inhalation corresponds essentially to the course after oral administration of lower doses. The cumulative renal excretion of the radioactivity is 68-78% for i.v. administration, 13% for oral administration, and 10% for inhalation. 7% (i.v.), 77% (p.o.) and 88% (inhalation) is excreted in the faeces. Oxitropium bromide is rapidly hydrolysed after oral administration. As little as 4 h later only 2-3% of intact active ingredient is found, whereas there is 85% of the hydrolysed product in the urine. A similar distribution pattern is observed in urine samples taken later. Some other metabolites are also recorded in minimal quantities. After i.v. administration, too, the hydrolysed product is excreted as the main component.