Application of liquid chromatography-tandem mass spectrometry to the analysis of benzodiazepines in blood

6 CHARLTON MILL,CHARLTON,, CHICHESTER,, W SUSSEX, ENGLAND, PO18 0H

The formation and stability of imidazolidinone adducts from acetaldehyde and model peptides - A kinetic study with implications for protein modification in alcohol abuse

The kinetics of the reaction of acetaldehyde (AcH) with the alpha-amino group of several di- and tripeptides to form 2-methylimidazolidin-4-one adducts were determined at pH 7,4, 37 degrees C, using reverse phase HPLC to separate peptides from adducts. The imidazoridin-4-one structure of the adducts was confirmed by C-13 NMR spectroscopy. The reaction of val-gly-gly with AcH was shown to follow second-order kinetics over a wide range of concentrations of both reactants, with k(2)=0.734+/-0.032 M(-1) min(-1). Under conditions similar to those in the liver of an alcoholic during chronic ethanol oxidation ([AcH](o)=50-910 mu M; [free peptide or-amino groups](o)=1.5 mM), the reaction proceeded until effectively all of the AcH had been consumed. The side chain of the N-terminal amino acid was shown not to have a marked effect on the rate of imidazolidinone formation. The decomposition of the imidazolidinone adduct of val-gly-gly and AcH was observed at 60-100 degrees C. Extrapolation of an Arrhenius plot to 37 degrees C provided an estimate of k(obs) of 0.002 h(-1) (t(1/2)similar to 14 days). Based on these kinetic studies, it is concluded that imidazolidinone adducts of AcH with proteins may be present in the liver and, possibly, in the blood of alcoholics

Metabolic and Endocrine Profiles in Sick Neonatal Foals Are Related to Survival

peer reviewedBACKGROUND: Sick neonatal foals suffer from a variety of endocrine and metabolic derangements that may be related to outcome. There are several hepatic and lipid metabolism blood markers that have never been assessed in neonatal foals. OBJECTIVES: Assess panel of endocrine and metabolic variables in group of sick and healthy neonatal foals in order to describe their relationship with diagnosis and survival. ANIMALS: All neonatal foals referred to Unitat Equina-Fundacio Hospital Clinic Veterinari during 3 consecutive foaling seasons and a group of healthy foals. METHODS: Observational prospective study. Blood samples were obtained on admission and, when possible, after 24-48 h of hospitalization and immediately before discharge or death. Measured variables were triglycerides, nonsterified fatty acids, glucose, creatinine, urea, gamma-glutamyltransferase, glutamate dehydrogenase (GLDH), insulin, cortisol, bile acids, and adrenocorticotropic hormone (ACTH). ACTH/cortisol and glucose/insulin ratios were calculated. RESULTS: Urea, creatinine, and cortisol had median concentrations in septic and nonseptic foals 2- to 8-fold higher than in the control group (P /= 2 of these variables were altered (P < .001), the foal had 32 times more risk of dying (OR, 31.7; 95% CI, 7.7-130.3). CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma creatinine, GLDH, and cortisol should be determined in sick newborn foals on admission because of their association with survival

Adrenocortical influences on free-operant avoidance behavior

Rats were conditioned to avoid shock on a free-operant avoidance schedule in which no exteroceptive stimulus signaled impending shock. Injections of adrenocorticotropic hormone (ACTH) or dexamethasone raised blood levels of glucocorticoids. These increases were accompanied by changes in avoidance performance: there was a higher frequency of long-duration interresponse times, a greater stability among them, and fewer short interresponse times, total responses, and shocks