Zidovudine pharmacokinetics during pregnancy.

As the indications for zidovudine (ZDV) treatment in human immunodeficiency virus-infected individuals expand, we anticipate an increased use of this drug during pregnancy. We report pharmacokinetics data from a patient studied both in the third trimester and intrapartum. ZDV peak-plasma levels and serum half-lives were comparable to nonpregnant adults. High concentrations of ZDV and its glucuronide metabolite were found in umbilical cord blood and in amniotic fluid.     

Fluorescence immunohistochemistry and confocal scanning laser microscopy

We have developed a reliable technique for labeling and examining neural structures in soft tissues associated with articular joints and have tested it in human wrist joints under various specimen-related conditions. The labeling protocol employs an immunohistochemical process with a panneuronal marker (PGP 9.5) as the primary antibody and Alexa Fluor 488 as the fluorescing secondary antibody. Imaging was done using a confocal laser scanning microscope, which produced exceptionally detailed three-dimensional images of nerve endings and transiting nerve fibers from thick sections of wrist joint ligaments obtained from human cadavers. The protocol provided a practical postmortem window for specimen acquisition and processing without significant apparent worsening of image quality. The images produced are resistant to fading with repeated exposure to a fluorescent light source, which gives many opportunities for observation. Background staining is minimal, producing high contrast labeling of target tissues, which, in turn, enhances image analysis.     

Preoptic LH-RH and somatostatin in the rat median eminence. An experimental light and electron microscopic immunocytochemical study

Glass microknife lesions and immunocytochemistry were used to evaluate luteinizing hormone-releasing hormone (LH-RH)- and somatostatin (SS)-immunoreactive pathways from the preoptic region to the rat median eminence. Cuts were so placed that axons of more caudally located neurons in the periventricular hypothalamic areas were spared. Light and EM observations of LH-RH-immunostained preparations indicated that following the midline periventricular cuts the density of LH-RH labelled axons and axon terminals in the ME appeared similar to that of nonlesioned animals. Following bilateral lateral hypothalamic cuts placed between the preoptic area and the ME, LH-RH immunostaining in the ME was markedly reduced. This provides evidence that the preponderance of LH-RH axons originating from the preoptic area reach the ME by a lateral hypothalamic route. In contrast to the LH-RH findings, midline lesions made using the same coordinates caused a noticeable reduction in SS immunostaining in the accurate nucleus and ME. There was either no change or only minimal change after the lateral cut. Somatostatin axons arising from the preoptic periventricular nucleus take a periventricular route and contribute to median eminence innervation, but much less extensively than the more caudally located somatostatin neurons in the hypothalamic periventricular nucleus [19].     

Pharmacokinetics, skin absorption, stability, blood partition, and protein binding of AS 2-006A, a new wound healing agent

After intravenous administration of AS 2-006A, 20, 50, and 90 mg/kg, to rats, the pharmacokinetic parameters, terminal half-life (69.8-86. 6 min), mean residence time (56.2-75.2 min), apparent volume of distribution at steady state (809-1040 mL/kg), and total body clearance (11.4-11.9 mL/min/kg), were dose-independent. After topical application of 0.5 or 1% AS 2-006A ointment, 300 mg, to abraded rat skin, the absorbed amounts were dose (0.5 and 1%) and time (30, 60, 120, 240, 360 and 480 min)-independent; the value was approximately 20%. The tissue-to-plasma ratios of AS 2-006A were greater than unity in all rat tissues studied, except in the muscle and large intestine. AS 2-006A was stable for up to 24 h incubation in rat plasma, and human plasma and urine; however, it seemed not to be stable in rat urine; the disappearance rate constant was 0.0218/h. AS 2-006A reached equilibrium fast between plasma and blood cells, and the equilibrium plasma/blood cells partition ratios were independent of the initial rabbit blood concentrations of AS 2-006A, 10, 20, and 50 microg/mL; the mean values were in the range of 2.38-2.75 for three rabbit blood. The protein binding of AS 2-006A to rat plasma was high, as the drug was under detection limit in the filtrate at the plasma concentrations of the drug, ranging from 7.21 to 228 microg/mL.     

Plasticity of catecholaminergic terminals in rat paraventricular hypothalamic nucleus after 6-hydroxydopamine lesion: an emphasis on bouton sizes and synaptic frequency

Catecholaminergic (CA) nerve terminals in the paraventricular hypothalamic nucleus (PVN) of adult rats were studied at 4, 21, 56 and 180 days after a single injection of 6-hydroxydopamine (6-OHDA) neurotoxin into the right lateral ventricle of the brain. We previously described and quantified the extent of CA terminal sprouting in the PVN after 6-OHDA lesions. For this communication we studied parameters, specifically the bouton sizes and the synaptic frequencies of CA terminals during the renewal process, and evaluated how changes of these parameters are related to axonal sprouting. The CA boutons were identifiable in the electron microscope by exhibiting small granular vesicles (SGVs) after central administration of 5-hydroxydopamine (5-OHDA) marker. The marked CA boutons were measured and further categorized according to whether or not they were associated with distinct synaptic specializations at various post-lesion stages. The average sizes of CA boutons were strikingly similar in their diameters (1.0 micron) for both control and experimental tissues. However, CA boutons larger than 2.1 micron were rare and seen more often in the experimental tissues with 6-OHDA lesion and were sustained up to 180 days after lesions. Catecholaminergic profiles with ultrastructural features of growth cones were also seen in the PVN following the 6-OHDA lesions, indicating that there is growth activity in the PVN after 6-OHDA lesion. There were 33% of CA boutons in the PVN from the control tissues that appeared to have synaptic contacts.(ABSTRACT TRUNCATED AT 250 WORDS)