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  • 1
    Digitale Medien
    Digitale Medien
    Amsterdam : Elsevier
    Tetrahedron Letters 20 (1979), S. 4781-4782 
    ISSN: 0040-4039
    Quelle: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European archives of oto-rhino-laryngology and head & neck 219 (1978), S. 503-503 
    ISSN: 1434-4726
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 36 (1980), S. 78-79 
    ISSN: 1420-9071
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary Two new potent diabetogenic substances 4,5-dihydro-4,5-dihydroxyuric acid (1) and 5-hydroxy-pseudouric acid (2) have been found.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    ISSN: 1432-0428
    Schlagwort(e): Alloxan ; dehydrouramil ; 5-hydroxy-pseudouric acid ; diabetes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effects on islet morphology and blood glucose concentration of intravenous administration of alloxan to rats have been compared with those of two new diabetogenic agents, 5-hydroxy-pseudouric acid (5-HPUA) and dehydrouramil hydrate hydrochloride (DHU). Administration of alloxan (0.35 mmol/kg) caused a classical triphasic change in blood glucose characterised by initial hyperglycaemia, subsequent hypoglycaemia and a delayed persistent hyperglycaemia. In contrast, 5-HPUA and DHU elicited persistent hyperglycaemia as early as 30 min after administration. Morphological evidence for degranulation, pyknosis, necrosis and widening of pericapillary spaces was obtained with all three agents. However, both 5-HPUA and DHU elicit considerably more rapid and extensive changes than alloxan, with evidence for extensive pyknosis occurring as early as 15 min after administration of DHU and 5-HPUA compared with 24 h for alloxan. The more marked potency of DHU and 5-HPUA may be at least partially attributable to the greater stability of these agents compared with alloxan, since solutions of DHU or 5-HPUA kept for 15 min prior to administration retained full diabetogenic activity, whereas similar treatment of alloxan solution completely abolished its diabetogenic activity. Since both 5-HPUA and DHU are potential metabolites of uric acid, their marked diabetogenic potency raises the possibility of a role for uric acid metabolites in the pathogenesis of diabetes mellitus.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    ISSN: 1432-0428
    Schlagwort(e): Dehydrouramil hydrate hydrochloride ; alloxan ; diabetes ; islets of Langerhans ; insulin secretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Dehydrouramil hydrate hydrochloride (DHU) is an analogue of alloxan which retains the in vivo diabetogenic activity of alloxan but, in contrast to alloxan, is stable in aqueous media at physiological pH. Using rat islets of Langerhans, we have studied the acute effects of DHU on B cell function. Glucose-stimulated insulin release was markedly inhibited by DHU, the concentration of DHU giving 50% inhibition (I50) was 1 mmol/l; this was lowered to 0.5 mmol/1 when the islets were exposed to DHU for 5 min before elevation of glucose concentration. The basis for this change appeared to be a protective effect of glucose, since the inclusion of 3-0-methylglucose during pre-incubation with DHU also attenuated the subsequent inhibition of glucose-stimulated insulin release. The inhibitory effect on glucose-stimulated insulin release of a 5-min exposure to DHU persisted throughout a subsequent 120-min period in the absence of DHU. DHU also inhibited insulin release stimulated by mannose (20 mmol/l) or by 2-ketoisocaproate (20 mmol/l) with I50 of 1 and 0.5 mmol/l respectively. Concentrations of DHU up to 1 mmol/l had no significant effect on islet glucose oxidation or ATP content; 5 mmol/l DHU did not affect the rate of glucose oxidation, but lowered the ATP content by 30% without pre-incubation and by 60% in islets pre-incubated for 5 min with DHU before addition of glucose. Inhibitory effects of DHU were also found on rates of incorporation of [3H]-leucine into insulin plus proinsulin and into total islet protein; however, these parameters were less sensitive to DHU than was insulin release. These effects of DHU were similar to those of alloxan. These data suggest that DHU is an important new tool for studying the mechanism of action of B cell cytotoxic agents; in addition, the fact that DHU is a potential metabolite of uric acid could have relevance to the aetiology of diabetes mellitus.
    Materialart: Digitale Medien
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