Multiple steroid hormone levels in depressed patients and normal controls before and after exogenous ACTH

Forty depressed patients and 36 age- and sex-matched controls were given 250 μg ACTH_1–24 by bolus. Plasma steroid hormone levels were measured prior to and 60 min after ACTH administration. The depressed patients had significantly greater cortisol (F), 11-deoxycortisol (S), androstenedione (AD), and 17-hydroxyprogesterone (17-OHP) responses (delta; p<0.05) and a marginally greater 11β-hydroxyandrostenedione (11β-OHAD) response (delta; p=0.091) than the controls. There was no significant difference in the corticosterone (B) response between the two groups.

With the exception of 11β-OHAD, all the steroid hormones were significantly negatively correlated with age in the controls, but only S and AD marginally demonstrated this relationship in the depressed patients. F, S, AD, 17-OHP, and B, but not 11β-OHAD, were significantly positively correlated with each other in the controls, but only F was significantly correlated with AD in the depressed patients. These data suggest that the hypercortisolemia found in some depressed patients involves increased precursor and metabolite levels both at baseline and in response to exogenous ACTH, compared to controls. Furthermore, variability in these precursors is greater in depressed patients, and their relationship to age is lost. These findings are consistent with the hypothesis that adrenal products other than cortisol also could be related to affective symptoms.     

Attenuation of insulin-induced drinking by beta-adrenoceptor antagonists.

Insulin-induced drinking (IID) in male Wistar rats, evoked by administering 5 U/kg of crystalline porcine insulin i.p., was significantly decreased by propranolol (0.1 and 0.5 mg/kg s.c.) after 1 and 2 h. The blood glucose of rats treated with a much higher dose of propranolol (10 mg/kg body weight) and insulin did not differ from that of rats treated solely with insulin after 30 and 120 min. Atenolol (0.5 mg/kg s.c.) caused a reduction in IID after 1 and 2h. Butoxamine (1 mg/kg s.c.) also reduced IID after 1 and 2h, and at 0.5 mg/kg after 1h. The alpha-blocker, phenoxybenzamine (10 mg/kg s.c.), had the opposite effect, stimulating IID after 2h. There is no direct evidence that insulin activated the sympathetic system at the doses used in these experiments. Nevertheless, the results reported here seem to be compatible with the involvement of the sympathetic system in IID, possible through the renin-angiotensin system.     

Complex interactions in Parkinson's disease: a two-phased approach.

The identification of pathogenic mutations in the three genes alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) has elucidated the ubiquitin proteasome system (UPS) and its potential role as a causal pathway in Parkinson's disease (PD). In addition, polymorphisms of these three genes have been shown to be independently associated with PD. In a sample of 298 unrelated PD cases and 185 controls, we applied a two-phased approach of recursive partitioning and logistic regression analyses to explore complex interactions. For women only, we observed an epistatic interaction of UCHL1 and alpha-synuclein genotypes with significant effects on PD risk (odds ratio = 2.42; P = 0.003). Our findings are consistent with the hypothesis that PD is a multigenic disorder of the UPS.     

Long-term result of guided nerve regeneration with an inert microporous polytetrafluoroethylene conduit

Thedevelopmentinmicrosurgicaltechniqueshasgreatlyimprovednervefunctionalrecovery .However ,owingtotheinabilitytocoaptateandsuturethousandsofnervefiberstotheirfunctionallysimilarnervefibersandinaccuratesutureofthenervestumps ,regeneratednervefiberspartiallylosethechancetoselectivelyregrowintotheirtargetendoneurialtubes,1 4whichresultsinaninevitablemismatchofmotorandsensorynervefibers .Thus,thecontact guidance basedmicrosurgicalnerverepairhasfailedtoachieveconsistentsatisfactoryfunctionalrecover…     

Reduced Serum Theophylline Concentrations after Discontinuation of Azithromycin: Evidence for an Unusual Interaction

A 68-year-old man receiving long-term therapy with oral sustained-release theophylline 450 mg twice/day was admitted to the hospital after failing treatment with azithromycin for an acute exacerbation of obstructive lung disease. Peak serum theophylline concentration was 20 μg/ml (normal 10–20 μg/ml). Azithromycin was discontinued and the theophylline dosage reduced by 33%. The subsequent 80% decrease in serum theophylline to 4.6 μg/ml was unexpectedly large. Two rechallenges produced similar transient depressions of serum theophylline concentrations after withdrawal of azithromycin, suggesting an interaction. Withdrawal of azithromycin may leave an increased number of active enzyme sites available as the drug is cleared from the system. In some circumstances, it may be useful for pharmacokinetic interaction studies to continue measuring concentrations after the suspected interacting agent is stopped.     

Folding of the conserved domain but not of flanking regions in the integrin β2 subunit requires association with the α subunit

We have used immunoprecipitation with mAbs to probe folding during biosynthesis of the β₂ integrin subunit of lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) before and after association with the α_L subunit. An evolutionarily conserved region is present in the β₂ subunit between amino acid residues 102 and 344. mAbs to one subregion before the conserved region, and two subregions after the conserved domain, immunoprecipitated both the unassociated β′₂ precursor and mature α_L/β₂ complex, suggesting portions of these subregions are folded before association with α_L. An activating mAb to the C-terminal cysteine-rich region, KIM127, preferentially bound to the unassociated β subunit, suggesting that it may bind to an epitope that is in an αβ interface in unactivated LFA-1. By contrast, mAbs to five different epitopes in the conserved region did not react with unassociated β′₂ precursor, suggesting that this region folds after α_L association and is intimately associated with the α_L subunit in the α_L/β₂ complex. mAbs to two different epitopes that involve the border between the conserved region and the C-terminal segment, were fully or partially reactive with the β′₂ precursor, suggesting that this region is partially folded before association with α_L. The findings suggest that the conserved region is a distinct folding and hence structural unit, and is intimately associated with the α subunit.