Luteinizing hormone sensitivity to naloxone in maturing male chimpanzees.

We have systematically investigated the involvement of endogenous opioids in gonadotropin secretion during primate sexual maturation by examining LH/FSH responses to gonadotropin-releasing hormone (GnRH) and changes in LH secretion during infusions of saline or naloxone, an opiate antagonist, in ten male chimpanzees between one and nine years of age. Animals were anesthetized with ketamine (10 mg/kg) and injected or infused IV with GnRH, naloxone or saline. Circulating levels of serum LH were elevated to the same extent (approximately 400%) in response to GnRH (100 micrograms) in animals 1-5 years old (juvenile) and in animals 6-9 years old (pubertal). No differences were noted between the two groups in GnRH-stimulated levels of serum FSH. During treatment with naloxone (0.14 mg/kg bolus followed by 0.2 mg/kg/h maintenance infusion for 3 h), serum LH levels in pubertal animals were significantly (p less than 0.05) elevated by as much as 95% over LH levels found during treatment with saline. Juvenile animals, on the other hand, failed to demonstrate significant increases in serum LH following naloxone at the doses tested. A strong correlation (r = .84) was found between circulating testosterone and serum LH levels during naloxone treatment. These data indicate that opioid inhibition of LH secretion can be reversed by naloxone only when puberty is reached in chimpanzees and suggest an alteration in opioid regulation of GnRH near the time of puberty. The strong correlation between testosterone levels and LH responses to naloxone suggests that steroids may participate in the maturation of opioid control of LH during puberty of nonhuman primates.     

3β-Hydroxysteroid Dehydrogenase/Isomerase and Aromatase Activity in Primary Cultures of Developing Zebra Finch Telencephalon: Dehydroepiandrosterone as Substrate for Synthesis of Androstenedione and Estrogens

3β-hydroxysteroid dehydrogenase/Δ⁵−Δ⁴isomerase (3β-HSD) activity was measured in primary dissociated cell cultures prepared from telencephalons of developing zebra finches. 3β-HSD activity was confirmed after cultures were incubated with [7-³H]pregneno- lone (Preg) or (1,2,6,7-³H-) dehydroepiandrosterone (DHEA) and³H-progesterone (Prog) and³H-androstenedione (AE) were detected in the medium. Product identity was confirmed by recrystallizations and by HPLC analysis. When DHEA was used as substrate,³H-estradiol and³H-estrone were also detected in the culture medium, presumably derived from the aromatization of³H-AE or³H-T produced from³H-DHEA. To test this idea, cultures were incubated with³H-DHEA together with radioinert AE or with fadrozole HCl, a potent and specific aromatase inhibitor. In the presence of radioinert AE,³H-AE increased but metabolites of³H-AE decreased in the media; in the presence of fadrozole,³H-estrogens decreased but³H-AE and its androgenic metabolite³H-5β-androstanedione increased. These data demonstrate 3β-HSD activity in the songbird brain. The presence of Prog and estradiol in these cultures suggest that Preg and DHEA can potentially serve as substrates for the ultimate formation of active sex steroids in the songbird telencephalon.     

Inherited Neurodegenerative Disorders Caused by CAG/Polyglutamine Tract Expansions: Symposium Introduction

At the beginning of this decade, the American Association of Neurology decided that the 1990's should be labelled "the decade of the brain" for expected advances in our understanding of neurological disorders and neuroscience. By the end of this decade, clinicians and researchers who work in the field of inherited neurological disorders might well remember the 1990's as "the decade of the trinucleotide repeat". At the time of writing this introduction, eleven inherited neurological disorders have been found to be caused by expansions of trinucleotide repeats, and a twelfth trinucleotide repeat expansion mutation has been identified (6), although the gene containing this mutant triplet repeat has not been cloned to our knowledge (Table 1).     

Effect of positioning on oxygenation in single-lung transplant recipients.

BACKGROUND: Many benefits and adverse effects of positioning are related to changes in ventilation and perfusion. A number of unique factors related to the allograft make the effects of positioning difficult to determine in single-lung transplant recipients. OBJECTIVES: To determine the effect of 3 body positions (supine, lateral with allograft lung down, and lateral with native lung down) on oxygenation and blood flow in single-lung transplant recipients in the 24 hours immediately after surgery. METHODS: A quasi-experimental repeated-measures design with stratified assignment to 1 of 3 different sequencing patterns for turning group was used to study 15 transplant recipients, 9 with emphysema and 6 with fibrosis. Oxygenation, ventilation, and blood flow measures (heart rate, blood pressure) were assessed after each turn. The effect of ischemic reperfusion injury was also explored. RESULTS: The oxygenation, ventilation, and bloodflow variables did not differ significantly across group, diagnosis, or time. Oxygenation variables measured when the allograft lung was dependent did not differ significantly from such measurements obtained when the native lung was dependent. CONCLUSIONS: No single position maximizes oxygenation in the immediate postoperative period in single-lung transplant recipients. Although a single standard protocol for positioning cannot be supported, the study does support the idea that transplant recipients can be safely turned in the immediate postoperative period without compromising oxygenation or hemodynamic status.