Impact of cessation of smoking on the course of ulcerative colitis.

OBJECTIVES: The incidence and severity of ulcerative colitis (UC) are higher in nonsmokers than in smokers. The natural course of UC in smokers who stop smoking is not known. The aim of this study was to determine the impact of cessation of smoking on the course of UC among the cohort of patients regularly seen at our institution. METHODS: The severity of UC, as judged by the occurrence of flare-ups and the need for systemic steroids, immunosuppressive drugs and colectomy, was determined in 32 patients with UC who stopped smoking after the diagnosis of UC. We compared the period after cessation of smoking (7-yr mean follow-up) with the period between the onset of the disease and the cessation of smoking (9-yr mean duration). The course of UC in this group was compared with that of 32 nonsmokers and 32 continuing smokers matched for sex, age, and age at onset. RESULTS: In patients who quit, cessation of smoking was followed by an increase in the rate of years with active disease (p < 0.01), years with hospitalization (p < 0.05) and years with major medical therapy (oral steroids, intravenous steroids, and azathioprine, p < 0.01). After cessation of smoking, the rate of years with immunosuppressive therapy was significantly greater in ex-smokers and nonsmokers than in continuing smokers (p < 0.01). The risk of colectomy in ex-smokers after smoking cessation was similar to that of nonsmokers and continuing smokers. CONCLUSIONS: In smokers with UC who stop smoking, the severity of the disease increases after smoking cessation, with an increase in the disease activity and the need for hospital admission and major medical therapy. In addition, the need for azathioprine therapy becomes similar to that of nonsmokers.

Dose response of laboratory markers to alcohol consumption in a general population.

The dose response to alcohol use of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and their combination (gamma-CDT) was studied in an age- and gender-stratified, random sample from Finland in 1997. A linear association with a threshold between alcohol consumption and the three markers was observed. Body mass index was negatively associated with CDT and positively with GGT Age was positively associated with GGT and gamma-CDT In conclusion, CDT appears to be an early phase marker of alcohol consumption. The combined marker, gamma-CDT, was less associated with factors such as body mass index but more strongly correlated with alcohol consumption than were the two markers separately.

Enhanced clinical utility of gamma-CDT in a general population.

BACKGROUND: The use of a combination of markers to detect excessive alcohol consumption has been reported to provide better sensitivity in the diagnosis of alcohol abuse than single markers. However, the optimal combination of markers for the diagnosis of alcohol abuse has not yet been found. The aim of this study was to compare the diagnostic value of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) to discriminate among heavy drinkers (>280 g/week), moderate drinkers (105-280 g/week), and light drinkers (<105 g/week). Their mathematical combination, named gamma-CDT, which has been found to be a strong marker of alcohol abuse in a former study, was also evaluated. METHODS: The study was conducted in a group of 6962 subjects (3974 males and 2988 females), between the ages of 25 and 74 years, who participated in a large cross-sectional risk factor survey carried out in five geographic areas in Finland. In each study area, an age- and gender-stratified random sample was drawn from the general population. Sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic curves were used to evaluate the performance of CDT, GGT, and gamma-CDT. RESULTS: For both sexes, the combined marker had the highest specificity (95%) and sensitivity in detecting heavy drinkers. In all cases, gamma-CDT had the highest area under ROC plots. Our results also showed that GGT and CDT have similar, and rather low, sensitivity but high specificity in a general population. CONCLUSIONS: Compared with single markers, a significant improvement of sensitivity was obtained when the combination of both markers was used, especially in females.

Affinity labeling of the catalytic and AMP allosteric sites of 3-hydroxy-3-methylglutaryl-coenzyme A reductase kinase by 5'-p-fluorosulfonylbenzoyladenosine.

The nucleotide analogue 5'-p-fluorosulfonylbenzoyladenosine (FSBA) reacts irreversibly with rat liver cytosolic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase kinase, causing a rapid loss of the AMP activation capacity and a slower inactivation of the catalytic activity. The rate constant for loss of AMP activation is about 10 times higher (kappa 1 = 0.112 min-1) than the rate constant of inactivation (kappa 2 = 0.0106 min-1). There is a good correspondence between the time-dependent inactivation of reductase kinase and the time-dependent incorporation of 5'-p-sulfonylbenzoyl[14C]adenosine ([14C]SBA). An average of 1.65 mol of reagent/mol of enzyme subunit is bound when reductase kinase is completely inactivated. The time-dependent incorporation is consistent with the postulate that covalent reaction of 1 mol of SBA/mol of subunit causes complete loss of AMP activation, whereas reaction of another mole of SBA/mol of subunit would lead to total inactivation. Protection against inactivation by the reagent is provided by the addition of Mg2+, AMP, Mg-ATP, or Mg-AMP to the incubation mixtures. In contrast, addition of ATP, 2'-AMP, or 3'-AMP has no effect on the rate constants. Mg-ATP protects preferentially the catalytic site against inactivation, whereas Mg-AMP at low concentration protects preferentially the allosteric site. Mg-ADP affords less protection than Mg-AMP to the allosteric site when both nucleotides are present at a concentration of 50 microM with 7.5 mM Mg2+. Experiments done with [14C]FSBA in the presence of some protectants have shown that a close correlation exists between the pattern of protection observed and the binding of [14C]SBA. The postulate is that there exists a catalytic site and an allosteric site in the reductase kinase subunit and that Mg-AMP is the main allosteric activator of the enzyme.

Allosteric activation of rat liver microsomal [hydroxymethylglutaryl-CoA reductase (NADPH)]kinase by nucleoside phosphates.

Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase kinase activity is enhanced about 5 fold by 2 mM of either AMP or ADP. Activation constants, Ka, for AMP and ADP are 17 microM and 430 microM respectively, showing that AMP is a more potent activator than ADP. This property is expressed by increasing not only the rate of reductase inactivation but also the rate of reductase phosphorylation from [gamma-32P]ATP. GTP can replace ATP as substrate of reductase kinase but GMP and GDP cannot replace AMP as activators. Kinetic studies show that ATP can only act as a substrate. Nucleoside mono or diphosphates and nucleoside triphosphates, thus, appear to bind to different sites on microsomal HMG-CoA reductase kinase. Nucleoside mono or diphosphates act as allosteric activators of reductase kinase. The adenosyl moiety and the unaltered phosphate ester at the 5' position are two essential features of the activator molecule. Phosphorylation of reductase either by microsomal or cytosolic AMP-activated reductase kinase produces an 80% inactivation, with a concomitant incorporation of 0.8 mol of 32P per mol of reductase (Mr 55,000). In both cases exhaustive tryptic digestion of 32P-labeled HMG-CoA reductase, which had been denatured in 2M urea, yields two major phosphopeptides, the phosphoryl group being bound to serine residues.

Activation of rat liver cytosolic 3-hydroxy-3-methylglutaryl coenzyme A reductase kinase by adenosine 5'-monophosphate.

Inactivation of 3-hydroxy-3-methylglutaryl Coenzyme A reductase by reductase kinase and ATP-Mg needs either ADP or 5'-AMP as cofactors. 5'-AMP is a more potent activator of cytosolic reductase kinase than ADP. This capacity is expressed by increasing not only the rate of reductase inactivation, but also the rate of reductase phosphorylation from [gamma-32P]ATP. Activation constants, Ka, for 5'-AMP and ADP are 20 microM and 420 microM respectively. Neither 3'-AMP nor 2'-AMP activate reductase kinase. Other nucleoside monophosphates like UMP, CMP and GMP cannot replace 5'-AMP as activators of reductase kinase.

[Eugregarines from Caraboidea Coleoptera. New data and species. (author's transl)]. / Eugrégarines parasites de Coléoptères Carabiques. Données et Espèces nouvelles.

In this work, we describe some new species of Eugregarines parasites from Caraboidea: Ramicephalus nebriae and Ramicephalus rostratus from Nebria lafresnayei Serville; Ramicephalus cecheni from Cechenus (Iniopachys) pyrenaeus Serville; Ancyrophora penetreti from Penetretus rufipennis Dejean; Ancryophora hispani from Chrysocarabus (Chrysotribax) hispanus Fabr.; Gregarina peloris from Pelor (Iberozabrus) obesus Serville; Gregarina dichirotrichi from Dichirotrichus pallidus Dejean. We complete the life-cycle of Gregarina ophoni Tuz. Arm., 1951 and confirm his classification in the genus Gregarina. We have found this parasite in a new host, Ophonus similis Dejean.