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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 40 (1991), S. 577-580 
    ISSN: 1432-1041
    Schlagwort(e): Nitecapone ; catechol-O-methyltransferase ; red blood cell COMT ; gastroduodenal COMT ; COMT inhibition
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of increasing single oral doses of the novel catechol-O-methyltransferase (COMT) inhibitor, nitecapone, on enzyme activity in red cells (RBC) and gastroduodenal COMT activity has been studied in healthy male volunteers. A dose-dependent decrease in RBC COMT activity was seen in all cases after 1 to 150 mg of the drug. The highest dose of 300 mg did not produce much more inhibition of COMT than 150 mg. The inhibition was not complete; at the highest doses the COMT activity was reduced by 50–60%. The effect and the duration of the inhibition in RBC COMT was strongly correlated with plasma nitecapone concentrations in the dose range up to 150 mg. RBC COMT activity recovered fully in 4 h after medication. Gastric mucosal COMT activity was several-fold higher than that in RBCs. It was also dose-dependently inhibited at the two doses (25 and 100 mg) studied. The inhibition of gastric and duodenal COMT was greater than that in RBCs. This also indicates that nitecapone is locally active in the gastroduodenal tract. The results confirm nitecapone as a potent COMT inhibitor in human tissues. New COMT inhibitors may provide a valuable approach to the treatment of Parkinson's disease in combination with L-dopa and dopa decarboxylase inhibitor therapy.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    New York, NY [u.a.] : Wiley-Blackwell
    Developmental Dynamics 199 (1994), S. 52-63 
    ISSN: 1058-8388
    Schlagwort(e): Embryonic myosin heavy chain ; Muscle injury ; Stretch ; Myoblast ; Nuclear domain ; Life and Medical Sciences ; Cell & Developmental Biology
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Medizin
    Notizen: This study examined whether satellite cells express an embryonic isoform of myosin upon fusion with hypertrophying muscle fibers. Anterior latissimus dorsi (ALD) muscle hypertrophy was induced in adult chickens by weighting one wing. One and 7 days of wing-weighting produced significant increases in ALD muscle wet weight and in the number of mature fibers expressing ventricular-like embryonic (V-EMB) myosin. V-EMB myosin expression could be an event during regeneration of fibers injured by overload or part of the hypertrophy process itself. Although there was an increase in both the number of damaged fibers and the number of mature fibers expressing embryonic myosin after wing-weighting, results from this study suggest that these two events were not necessarily related. The apparent health of fibers expressing V-EMB myosin and the lack of correlation between the numbers of damaged and V-EMB myosin positive fibers (r = 0.20) suggest that embryonic myosin expression in mature fibers was likely a feature of the hypertrophy process itself. The appearance of V-EMB myosin in mature fibers 1 day after wing-weighting suggests that the change in myosin expression did not involve satellite cells since 24 hr is too short a time to permit more than limited satellite cell fusion. The relationship between satellite cells and embryonic myosin expression was examined more closely by labeling dividing satellite cells and their progeny with 5-bromo-2-deoxyuridine, and then colocalizing labeled myofiber nuclei and embryonic myosin in consecutive transverse sections of hypertrophied ALD muscle. One week of wing-weighting resulted in marked increases in myofiber nuclear labeling index and myofiber nuclear density compared to contralateral control. V-EMB myosin was not expressed uniformly throughout individual fibers, but rather in discrete regions of varying length. Many V-EMB myosin positive regions had a higher labeled nuclear density than V-EMB myosin negative regions indicating that V-EMB myosin expression was associated with an accumulation of satellite cell progeny in a restricted area. However, it was also clear that satellite cell progeny were not the sole source of V-EMB myosin since labeled nuclei were completely absent from 41% of the V-EMB positive regions. Futhermore, the presence of new nuclei did not result in obligatory expression of embryonic myosin because many V-EMB negative regions had a high labeled nuclear density. Thus, recently incorporated nuclei arising by satellite cell division are implicated as one, but not the sole source of embryonic myosin in hypertrophying muscle. These observations suggest that the non-uniform pattern of embryonic myosin expression in hypertrophying muscle resulted from differences in nuclear activity, not necessarily the addition of new nuclei. © 1994 Wiley-Liss, Inc.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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