The influences of dexamethasone levels on the predictive value of the DST for unipolar major depression and the relationships between post-dexamethasone cortisol and ACTH levels

To investigate the relationships between dexamethasone (DEX) and post-DEX cortisol and adrenocorticotropic hormone (ACTH) levels, the authors measured DEX at 8.00 a.m. and post-DEX cortisol and ACTH levels at 8.00 a.m. and 4.00 p.m. in 72 depressed patients categorized according to DSM-III. Cortisol non-suppressors exhibited significantly (P = 0.0006) decreased levels of DEX compared to suppressors. DEX levels at 8.00 a.m. explained 21.1% of the variance in the post-DEX cortisol values at 8.00 a.m. and 34.5% of those at 4.00 p.m. DEX levels were not significantly different among minor depressives (300.40, 309.00), major depressives without melancholia (296.X2) or with melancholia and/or psychotic features (296.X3, 296.X4). In the latter the post-DEX cortisol was significantly increased compared to all other depressives and these differences remained significant even after adjusting for the variations in DEX (by means of regression analysis). Also the diagnostic performance of the post-DEX cortisol values for major depression with associated features versus minor depression was not substantially affected when the DEX levels were accounted for. ACTH levels after DEX were shown to correlate significantly (P less than 0.05) and negatively with DEX. Although post-DEX ACTH levels did not differ among the DSM-III diagnostic categories, cortisol non-suppressors averaged significantly (P = 0.0004) higher ACTH levels than suppressors.     

Tissue distribution of amiodarone and desethylamiodarone in rats after multiple intraperitoneal administration of various amiodarone dosages

Tissue distribution of amiodarone (Cordarone) and desethylamiodarone in the rat was studied after repeated intraperitoneal administration of the drug. Tissue and serum concentrations of amiodarone and desethylamiodarone were determined by high-performance liquid chromatography. The levels of amiodarone and desethylamiodarone in serum and tissues obtained after repeated intraperitoneal application of doses varying from 25 mg to 200 mg/kg show that the accumulation of amiodarone and desethylamiodarone in the rat is dose-dependent and both drugs are preferentially distributed in decreasing order in adipose tissue, lung, liver, kidney and thyroid gland. The penetration of the drug and its metabolite into brain was poor and with all the applied dosages brain levels were considerably lower than the corresponding serum levels. Desethylamiodarone serum and tissue concentrations were substantially lower than the corresponding amiodarone concentrations and varied from 1 to 48% (mean 15%) depending on the dosage used and the kind of tissue. The amiodarone tissue/serum concentration ratios were exceptionally high in adipose tissue (1,000-4,000) and moderate to high in the other tissues except brain (5-90), and indicate an extensive distribution of the drug with fat as a reservoir with a large storage capacity. The levels of amiodarone and desethylamiodarone, obtained with 50 mg/kg and 100 mg/kg dosages, showed in function of time clearly an increase in serum and tissues. The observed amiodarone tissue/serum ratios in function of time revealed no further significant increase (p less than or equal to 0.05) after 3 injections over a 6-day period, indicating the attainment of "steady-state".(ABSTRACT TRUNCATED AT 250 WORDS)     

Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes

We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus–infected patients. We studied the relationship between KIR–human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4–003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4–003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.     

Effect of vaccination against Mycoplasma hyopneumoniae in pig herds with an all-in/all-out production system

A multi-site field study was conducted to evaluate an inactivated Mycoplasma hyopneumoniae (Mh) vaccine in 14 pig herds infected by Mh and practising an all-in/all-out production system. In each herd, a vaccinated and control group of 250 pigs each were compared during the growing/finishing period with respect to performance parameters (major variables) and by means of clinical, serological and pathological parameters (ancillary variables). Mh vaccination significantly (P < 0.05) improved daily weight gain (+22 g), feed conversion ratio (-0.07), medication costs (-0.476 ECU/pig) (1 ECU = US$1.0269542), prevalence of pneumonia lesions (-14%) and severity of pneumonia lesions (-3%). Mortality rate, severity of coughing and carcass quality were not significantly influenced by Mh vaccination. Serological results of Mh and other respiratory pathogens are presented and discussed. A cost-benefit analysis based on significantly improved performance parameters demonstrated that Mh vaccination was economically attractive as it resulted in an increase of the net return to labour with 1.300 ECU per finishing pig sold. The sensitivity of the economic benefit was illustrated towards fluctuations in pig finishing prices.     

Effects of a low-intensity worksite-based nutrition intervention

Male employees from four local worksites were recruited to participate in a short-term and low-intensity nutrition intervention which focused on promoting low-fat dietary habits. The sites were randomized to control conditions or to the intervention programme that consisted of an individualized health risk appraisal, group sessions, mass media activities and environmental changes. Participants were seen before and three months after intervention to measure blood lipids, nutrition knowledge and dietary changes. Eighty-three per cent of all eligible subjects were screened (n = 770) and follow-up measures were obtained for 82%. The score for nutrition knowledge improved significantly in the intervention group. There was also a net reduction in the intake of total calories and in the percentage of energy from total fat. Reported intake of carbohydrates and proteins increased. For all employees assessed, there were no changes in mean total cholesterol level or fatty acid composition. Only among participants with hypercholesterolemia was a significant reduction in blood cholesterol observed. This low-intensity intervention programme achieved some self-reported dietary changes and was successful (at least in part because statistical regression needs to be considered) in obtaining a more short-term beneficial cholesterol level in employees at higher cardiovascular risk.     

High-performance liquid-chromatographic-atmospheric-pressure chemical-ionization ion-trap mass-spectrometric identification of isomeric C6-hydroxy and C20-hydroxy metabolites of methylprednisolone in the urine of patients receiving high-dose pulse therapy

Fourteen metabolites of methylprednisolone have been analysed by gradient-elution high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The compounds were separated on a Cp Spherisorb 5 microm ODS column connected to a guard column packed with pellicular reversed phase. The mobile phase was an acetonitrile- 1.0% aqueous acetic acid gradient at a flow rate of 1.5 mL min(-1) The analysis gave a complete picture of parent drug, prodrugs and metabolites, and the alpha/beta stereochemistry was resolved. The short (1-2 h) elimination half-life of methylprednisolone is explained by extensive metabolism. The overall picture of the metabolic pathways of methylprednisolone is apparently simple-reduction of the C20 carbonyl group and further oxidation of the C20,C21 side chain (into C21COOH and C20COOH), in competition with or in addition to oxidation at the C6 position.