Charles Universtity Pharmaceutical Faculty in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Jitka Karásková Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Natural compounds isolated from plants at the Faculty of Pharmacy in Hradec Králové as potential inhibitors of aldo-ketoreductase 1A1 (AKR1A1) Aldo-keto reductase 1A1 is an enzyme belonging to the aldo-keto reductase superfamily. It is a monomeric, cytosolic enzyme that is able to reduce carbonyl groups within a wide range of substrates. The enzyme is expressed in almost every tissue in the body, most represented in hepatocytes, renal cells and salivary glands, where it contributes to the reduction of endogenous substrates and the first phase of biotransformation of xenobiotics. AKR1A1 catalyzes NADPH-dependent reduction of aldehydes and ketones to their corresponding primary and secondary alcohols. Enzyme substrates include, for example, mevalonate; anthracycline antibiotics doxorubicin or daunorubicin; some pro-carcinogens that are activated by the reaction into carcinogens, such as: trans- dihydrodiol metabolites of polycyclic aromatic hydrocarbons. Generally, it is involved in the metabolism of lipids and carbohydrates that contain an aldehyde function. The increased expression and activity of AKR1A1 has been...

Objective: Adolescence is a period of crucial neuropsychological development. Executive control functions (ECF) develop during adolescence and are constructs involving the planning, initiation, and regula¬tion of goal-directed behaviour. ECFs include impulse control critical for behavioural regulation. Training approaches for improving inhibitory control (IC) and impulsivity in young people (YP) are in their infancy, although some positive effects have been found in adults. This research aimed to test the hypothesis that IC intervention would improve IC and impulsivity (direct, near and far-transfer effects) and improve behavioural-control (mid and far-transfer effects) in YP. Methods: Six healthy YP, aged 11-16 years, attending mainstream education, participated in this single-case, multiple-baseline experimental design. The participants completed assessments at three phase-change points and completed continuous measures of their own impulsivity and behaviour goals. Each participant completed a baseline and intervention phase of differing randomised lengths within the 20 day study. The data were analysed visually using non-parametric tests of difference, randomisations tests and indices of reliable change. Results: IC and impulsivity were not observed to improve with intervention based on direct and far-transfer effects and limited improvement was observed based on near-transfer effects. Overall, behavioural control was not observed to improve with intervention based on near and far-training effects, but limited improvements were observed for some individual participants. Conclusion: The intervention was not observed to be effective in reducing IC or improving behavioural control overall, with very limited effects found in individual cases, which are discussed in directions for future research.

Addendum attached to back facing leaves. Includes bibliographical references (leaves 172-199). The findings establish leukemia inhibitory factor, and possibly oncostatin M, as new members of a small but growing class of cytokines produced in an intracellularly active form and also suggest that the production of alternate transcripts and intercellularly-retained proteins may be a common and important feature of cytokines of the IL-6 and other families.

This experiment studied relapse by assessing the separate/combined effects of two instigators: alcohol cues and stress on the salience of alcohol/gambling target stimuli and inhibitory control in twelve male problem gamblers and twelve male comorbid drinker-gamblers. Our study day consisted of two test sessions. Subjects received alcohol (non-alcoholic beer) and/or stress (uncontrollable noise) in a counterbalanced method. Hypotheses were tested using computer-based tasks, including the modified Stroop, gambling-word Shift Task, and the conventional and modified Stop-Signal Tasks. Stimuli with incentive value divert attention (i.e., are salient) selectively based on their clinical relevance to the subject and the nature of the instigating factor – stress (expected negative reinforcement) vs. anticipation of alcohol (expected positive reinforcement). Results suggest that alcohol cues and stress have differing effects on incentive salience, and disinhibit behaviour in both pathological populations. These findings have the potential to facilitate treatment and improve understanding for relapse prevention in these subjects.

This experiment studied relapse by assessing the separate/combined effects of two instigators: alcohol cues and stress on the salience of alcohol/gambling target stimuli and inhibitory control in twelve male problem gamblers and twelve male comorbid drinker-gamblers. Our study day consisted of two test sessions. Subjects received alcohol (non-alcoholic beer) and/or stress (uncontrollable noise) in a counterbalanced method. Hypotheses were tested using computer-based tasks, including the modified Stroop, gambling-word Shift Task, and the conventional and modified Stop-Signal Tasks. Stimuli with incentive value divert attention (i.e., are salient) selectively based on their clinical relevance to the subject and the nature of the instigating factor – stress (expected negative reinforcement) vs. anticipation of alcohol (expected positive reinforcement). Results suggest that alcohol cues and stress have differing effects on incentive salience, and disinhibit behaviour in both pathological populations. These findings have the potential to facilitate treatment and improve understanding for relapse prevention in these subjects.

Thesis (Ph. D.)--Ohio State University, 2009. / Title from first page of PDF file. Includes vita. Includes bibliographical references (p. 119-139).

Addendum attached to back facing leaves. / Includes bibliographical references (leaves 172-199). / 199 leaves, 5 photographic plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The findings establish leukemia inhibitory factor, and possibly oncostatin M, as new members of a small but growing class of cytokines produced in an intracellularly active form and also suggest that the production of alternate transcripts and intercellularly-retained proteins may be a common and important feature of cytokines of the IL-6 and other families. / Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 2000

Thesis (Ph.D.) -- University of Adelaide, Dept. of Biochemistry, 2000. / Addendum attached to back facing leaves. Includes bibliographical references (leaves 172-199).

Novel gene, named TILIr ( TIL Ixodes ricinus), that encoded yet unknown protein with TIL domain characteristic to proteins that belong to trypsin inhibitors family was discovered and isolated from hard tick Ixodes ricinus. Two isoforms of novel gene were identified and studied in this project. As the result of this study recombinant TILIr protein was produced in bacterial expression system and analysis of its functional characteristics was conducted. The protein belonging to family of trypsin inhibitors represent a potential candidate for anti-tick vaccine component.

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