Solubilization and biochemical characterization of the melatonin deacetylase from Xenopus laevis retina

Melatonin deacetylase, an enzyme activity recently discovered in the Xenopus laevis retina, regulates local melatonin levels. The deacetylase occurs in retina, retinal pigment epithelium, and skin, all sites of melatonin action, and is widely distributed among vertebrates. We have solubilized the enzyme from Xenopus retina and pigment epithelium using nonionic detergents, and have developed a specific enzyme assay. We have characterized the enzyme and now report that the deacetylase is relatively specific for melatonin and is inhibited by the melatonin precursor N-acetylserotonin and the product of the deacetylase, 5-methoxytryptamine. Inhibition of deacetylase activity by eserine (physostigmine) suggests a relationship between deacetylase and cholinesterase activities. However, among a variety of cholinesterase inhibitors tested, only eserine inhibits the deacetylase. Furthermore, eserine is much less potent as an inhibitor of the deacetylase than the cholinesterases, and purified cholinesterases failed to deacetylate melatonin. We also show that melatonin deacetylase and aryl acylamidase (an enzyme related to cholinesterases) activities are differentially extractable from Xenopus ocular tissues, and that they exhibit different pH optima and inhibition profiles. Our results provide an initial characterization of the Xenopus retinal melatonin deacetylase, and indicate that deacetylase activity is distinct from cholinesterase and aryl acylamidase activities.     

Epidemiology of hepatitis C and G in sporadic and familial porphyria cutanea tarda

From 1995 to 1997, we prospectively evaluated the prevalence of hepatitis C virus (HCV) RNA in 124 patients with porphyria cutanea tarda (PCT) from Northern France (83 sporadic and 41 familial PCT). Serum samples were analyzed for ferritin, transaminases, HCV antibodies, and HCV RNA. In addition, genotyping of HCV and searches for HCV infection risk factors (blood transfusion, iv drug abuse, and surgical intervention) were performed. Twenty-six of 124 patients (21%; 95% CI: 13.9-28) were positive for serum HCV antibodies. All of them were also positive for HCV RNA. The prevalence of HCV infection was higher in the sporadic PCT group (26.5%, 22 out of 83) than in the familial PCT group (9.7%, 4 out of 41). Risk factors for hepatitis C infection were found to be significantly increased in the HCV-positive group when compared with the HCV-negative PCT group. In all HCV-positive patients with a risk factor, the suspected date of exposure to the virus always preceded the clinical onset of PCT. The HCV genotype pattern in PCT patients was similar to that observed in nonporphyric HCV patients in western European countries. Serum ferritin level was increased in both HCV-positive and HCV-negative porphyric patients. Transaminase levels were significantly higher in HCV-infected PCT patients. Sixty-seven out of 124 patients were retrospectively studied for hepatitis G virus (HGV) infection. Six of these 67 patients (8.9%; 95% CI: 2.1-15.8) were positive for HGV RNA. None of the six HGV-infected patients were positive for HCV RNA. The HGV-infected patients did not differ statistically from those without HGV infection with regard to age, ferritin, transaminase levels, and PCT treatment. These results support the view that sporadic cases of HGV infection may occur frequently. This study of a large cohort of HCV and PCT patients further documents an increasing gradient in HCV prevalence from northern to southern Europe, and shows that HCV infection acts as a triggering factor of PCT. Finally, the HGV prevalence found in the PCT patients was comparable with that found in French blood donors, suggesting that HGV is not a PCT triggering factor.     

Exchange and oxidation of CO on O-predosed Rh---Al2O3 and Rh---CeO2 catalysts

Exchange and oxidation of C¹⁶O were investigated at 450°C on ¹⁸O-predosed Rh and Pt catalysts supported on A1₂O₃, CeO₂ and CeO₂-Al₂O₃. In all cases, a rapid exchange of C¹⁶O with the surface can be observed. CO oxidation leads to C¹⁶O₂, C¹⁶O¹⁸O and C¹⁸O₂. Significant formation of C¹⁶O₂ is due to the relatively high ¹⁶O coverage in reaction resulting from the C¹⁶O exchange and from an exchange between O surface species and ¹⁶O internal atoms. Hydrogen is also formed via a water-gas shift reaction (CO + surface OH) in higher proportion on CeO₂-containing catalysts than on A1₂O₃. Chlorine inhibits all the reactions (exchange, oxidation and WGS) and particularly the internal exchange.     

Age-related changes in cognitive ERPs of attenuation

The purpose of this article is to deliberate the moral and legal dilemma entailed in the weapon of the labour strike as a pressure tactic on the Israeli Finance Ministry regarding job slots, budgets and, in effect, violating the collective agreement signed by the nurses and impairing patients' treatment, as opposed to refraining from striking and suffering the heavy burden of work, the lack of trained personnel, low wages, and the inability to give patients proper, high quality treatment.     

Hydrogen peroxide in exhaled air is increased in stable asthmatic children

Exhaled air condensate provides a noninvasive means of obtaining samples from the lower respiratory tract. Hydrogen peroxide (H2O2) in exhaled air has been proposed as a marker of airway inflammation. We hypothesized that in stable asthmatic children the H2O2 concentration in exhaled air condensate may be elevated as a result of airway inflammation. In a cross-sectional study, 66 allergic asthmatic children (of whom, 41 were treated with inhaled steroids) and 21 healthy controls exhaled through a cold trap. The resulting condensate was examined fluorimetrically for the presence of H2O2. All subjects were clinically stable, nonsmokers, without infection. The median H2O2 level in the exhaled air condensate of the asthmatic patients was significantly higher than in healthy controls (0.60 and 0.15 micromol, respectively; p<0.05), largely because of high values in the stable asthmatic children who did not use anti-inflammatory treatment (0.8 micromol; p<0.01 compared to controls). We conclude that hydrogen peroxide is elevated in exhaled air condensate of children with stable asthma, and may reflect airway inflammation.     

Pharmacokinetics of dolasetron after oral and intravenous administration of dolasetron mesylate in healthy volunteers and patients with hepatic dysfunction

In previous studies, dolasetron was shown to have both renal and hepatic elimination mechanisms. This study was conducted to determine the impact of varying degrees of hepatic dysfunction on the pharmacokinetics and safety of dolasetron and its reduced metabolites. Seventeen adults were studied: six healthy volunteers (group I), seven patients with mild hepatic impairment (Child-Pugh class A; group II), and four patients with moderate to severe hepatic impairment (Child-Pugh class B or C1; group III). Single 150-mg doses of dolasetron mesylate were administered intravenously and orally, with a 7-day washout period separating treatments. After intravenous administration, no differences were observed between healthy volunteers and patients with hepatic impairment in maximum plasma concentration (Cmax), areas under the plasma concentration-time curve (AUC), or elimination half-life (t1/2) of intact dolasetron. No significant differences were found in Cmax, AUC, or apparent clearance (C(lapp)) of hydrodolasetron, the primary metabolite of dolasetron. The mean t1/2 increased from 6.87 hours in group I to 11.69 hours in group III. After oral administration, C(lapp) of hydrodolasetron decreased by 42%, and Cmax increased by 18% in patients with moderate to severe hepatic impairment. There were less changes in patients with mildly hepatic impairment. Total percentage of dose excreted as metabolites was similar for healthy volunteers and patients with hepatic impairment, although urinary metabolite profiles differed slightly. Dolasetron was well tolerated and there were no apparent differences in adverse effects between groups or treatments. Because hepatic impairment did not influence Cl(app) of hydrodolasetron after intravenous administration, and the range of plasma concentrations of hydrodolasetron after oral administration was not different from those observed in healthy volunteers, dosage adjustments are not recommended for patients with hepatic disease and normal renal function.     

Procollagen propeptide and pyridinium cross-links as markers of type I collagen turnover: sex- and age-related changes in healthy children

The correlations among age, gender, body size parameters, and type I collagen metabolism were evaluated in 183 healthy infants, aged 8.5-27.5 months. Collagen formation was assessed by measuring serum type I collagen carboxy-terminal propeptide, and degradation was determined by urinary pyridinoline and deoxypyridinoline (measured by high performance liquid chromatography) and cross-linked N- and C-terminal telopeptides of type I collagen (measured by NTx and CrossLaps assays). A new RIA specific for deoxypyridinoline was also evaluated. The results provide reference values at 10 months and 2 yr of age, including cross-linked C-terminal telopeptides (1492 +/- 685 and 1510 +/- 446 in boys; 1705 +/- 612 and 1849 +/- 611 micrograms/mmol creatinine in girls; mean +/- 1 SD). There was a good correlation between the high performance liquid chromatography and RIA data for deoxypyridinoline, showing that the RIA method is suitable for use in healthy children. Some correlations were found among peptide-bound cross-links, serum type I collagen carboxy-terminal propeptide, and the anthropometric parameters, suggesting that these peptides reflect bone resorption and also overall body type I collagen. Finally, there were age- and sex-related differences in the urinary excretion of the collagen degradation markers, suggesting that, unlike boys, girls maintain a high degree of collagen degradation up to the age of 24 months despite a decrease in their rate of collagen formation.