Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde : results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis

Introduction: Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. Objective: To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Methods: Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Results: Administration of L-cysteine increased MTCA (p <.0004) and decreased gastric acetaldehyde concentrations by 68% (p <.0001). The peak L-cysteine level was 7552 +/- 2687 mu mol/L at 40 min and peak MTCA level 196 +/- 98 mu mol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. Conclusions: After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.Peer reviewe

Application of LC-MS/MS for environmental analysis

Vätskekromatografi kopplad till masspektrometri blivit en populär metod inom många vetenskapsområden för kvantitativ och kvalitativ analys av organiska föreningar. Inom miljökemin används metoden för analys av vattenlösliga föreningar i främst den akvatiska miljön. Min avhandling behandlar tre användningsområden för denna analysmetod. 1)Analys av läkemedelsrester i miljön. Läkemedel är biologiskt aktiva föreningar och förekomsten av dem och deras nedbrytningsprodukter har väckt stort intresse inom ekotoxikologi och andra miljövetenskaper. I avhandlingen har jag utvecklat en förenklat metod för analys av antibiotika i vattenprov och för att bestämma möjliga nedbrytningsvägar för ett antal olika läkemedel, undersöktes floden Rakkolanjoki i östra Finland. Floden innehåller en hög halt av renat avloppsvatten som härstammar från en enda källa. Koncentrationsmätningar vid olika årstider gav möjligheten att bestämma sannolika nedbrytningsvägar. 2) Analys av narkotika i avloppsvatten. En ny metod för uppskattandet av narkotika konsumtionen i ett väldefinierat geografiskt område som har framlagts under de senaste åren är analys av narkotika rester i avloppsvatten. Inom avhandlingen utfördes analys på prov av vatten från Åbo och Helsingfors och arbetet utgjorde en del av ett större europeisk samarbetsprojekt där konsumtionsmönster jämfördes. 3) Analys Av TBT. En metod för analys av TBT utvecklades. Metoden användes för att mäta TBT halten i sediment, och dess överföring från den akvatiska till den terrestriska miljön via myggor och dess larver. Larverna upptar TBT som ligger i bottensediment och överför sedan föreningen till den terrestriska miljön i vuxenstadiet som myggor

Hydrophobization of marble pore surfaces using a total immersion treatment method - Product selection and optimization of concentration and treatment time

International audienceSix products containing either fluorosurfactants or fluorinated polymers have been evaluated for hydrophobization of marble stones by a total immersion method. Successful hydrophobization was verified by water contact angle and capillary absorption measurements before and after intentional UV degradation of the outmost modified layer. Optimization of treatment time and solution concentration concluded that for the best performing product, Capstone FS-63, a 24h immersion in a 10 vol% aqueous solution was required to obtain marble stones fully protected toward water absorption. The presented surface modifications could significantly increase the product lifespan of a variety of marble products

Pharmacodynamic and pharmacokinetic profile of SM-1, a triple-drug combination to increase total sleep time

OBJECTIVE: The primary objective was to characterize the pharmacokinetics and pharmacodynamics of SM-1 after administration of a single oral dose to healthy volunteers in a placebo-controlled double-blind trial of daytime sedation. Secondary objectives were to determine the onset, duration, and offset of the sedative effects using subjective and objective measures of sedation. Safety and tolerability of SM-1 were also investigated. METHODS: Males and females 18-45 years of age received SM-1, a combination drug product comprised of diphenhydramine, zolpidem (delayed release), and lorazepam (delayed release). The pharmacokinetic profile of each drug was determined from blood samples. Sedative effects were assessed by visual analog scale, digit symbol substitution test, memory test, and quantitative electroencephalography. RESULTS: Similar number and severity of adverse events were observed following administration of SM-1 and placebo. Onset of sedation, as determined by subjective, performance, and electroencephalography measures, occurred 0.5-1 hr postdose, lasting about 7-7.5 hr. Plasma concentration curves for the two delayed-release components were altered compared with published data for unmodified drugs. Exposure values obtained with the combination product were in good agreement with published values of the drugs given individually. CONCLUSIONS: SM-1 was well tolerated and has pharmacologic activity starting within an hour of ingestion, lasting approximately 7-8 hr. Sedative activity was seen with subjective, psychomotor, and electroencephalography assays

Comparing illicit drug use in 19 European cities through sewage analysis

The analysis of sewage for urinary biomarkers of illicit drugs is a promising and complementary approach for estimating the use of these substances in the general population. For the first time, this approach was simultaneously applied in 19 European cities, making it possible to directly compare illicit drug loads in Europe over a 1-week period. An inter-laboratory comparison study was performed to evaluate the analytical performance of the participating laboratories. Raw 24-hour composite sewage samples were collected from 19 European cities during a single week in March 2011 and analyzed for the urinary biomarkers of cocaine, amphetamine, ecstasy, methamphetamine and cannabis using in-house optimized and validated analytical methods. The load of each substance used in each city was back-calculated from the measured concentrations. The data show distinct temporal and spatial patterns in drug use across Europe. Cocaine use was higher in Western and Central Europe and lower in Northern and Eastern Europe. The extrapolated total daily use of cocaine in Europe during the study period was equivalent to 356 kg/day. High per capita ecstasy loads were observed in Dutch cities, as well as in Antwerp and London. In general, cocaine and ecstasy loads were significantly elevated during the weekend compared to weekdays. Per-capita loads of methamphetamine were highest in Helsinki and Turku, Oslo and Budweis, while the per capita loads of cannabis were similar throughout Europe. This study shows that a standardized analysis for illicit drug urinary biomarkers in sewage can be applied to estimate and compare the use of these substances at local and international scales. This approach has the potential to deliver important information on drug markets (supply indicator)