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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: This study analyzed the effects of acute systemic treatment with buthionine sulfoximine (BSO), a synthesis inhibitor of the antioxidant reduced glutathione (GSH), on dopaminergic neurons of the murine nigrostriatal pathway. Part 1 of the study established a dose-response curve and the temporal pattern of GSH loss and recovery in the substantia nigra and striatum following acute BSO treatment. Part 2 of the study determined the effect of acute BSO treatment on the morphology and biochemistry of nigrostriatal neurons. We found that decreases in GSH levels had profound morphological effects, including decreased catecholamine fluorescence per cell, increased levels of lipid peroxidation and lipofuscin accumulation, and increased numbers of dystrophic axons in dopaminergic neurons of the nigrostriatal pathway. However, no measurable effects were observed in biochemical levels of either dopamine or its metabolites. These changes mimic those that have been reported to occur in the nigrostriatal system of rodents with advancing age. Our data suggest that reduction of GSH via BSO treatment results in the same types of nigrostriatal degenerative effects that occur during the aging process and consequently is a good model system for examining the role of GSH in protecting this area of the brain against the harmful effects of age-related oxidative stress.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 648 (1992), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Type I diabetes ; diabetic nephropathy ; incidence ; prevalence ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A follow-up of 1475 Type 1 (insulin-dependent) diabetic patients diagnosed before 1953 (815 males, 660 females) and before the age of 31 years was conducted. All patients were seen at the Steno Memorial Hospital and were referred from all parts of Denmark; 91 (6%) could not be traced. The rest (94%) were followed until death or for at least 25 years; 249 (17%) were followed for 〉40 years. Clinical diabetic nephropathy developed in 531 (41%) of the 1303 patients in whom sufficient information was available regarding proteinuria. Other causes of proteinuria were found in 3%, and 57% did not develop persistent proteinuria. The prevalence of diabetic nephropathy was 21% after 20–25 years of diabetes duration followed by a decline to 10% after 40 years. Two incidence peaks of the onset of proteinuria were seen, one after 16 and another after 32 years duration of diabetes. Incidence increased steeply 10 years after onset of diabetes and was low after 35 years duration. The cumulative incidence was 45% after 40 years of diabetes. A male preponderance was seen among patients with nephropathy. A significant difference in the pattern of annual incidence rates of diabetic nephropathy was seen, when groups with onset of diabetes before 1933, between 1933–1942, and 1943–1952, respectively, were compared. An association between daily insulin requirement and nephropathy incidence was found. Patients with nephropathy had a much poorer survival than those without proteinuria; 40 years after onset of diabetes, only 10% of patients who developed nephropathy were alive, whereas 〉70% of patients who did not develop nephropathy survived. Uraemia was the cause of death in 66% of the patients with nephropathy; 7 years after the onset of persistent proteinuria, 49% of the patients had died. It is concluded that diabetic nephropathy is the major life threatening complication in Type I diabetes of juvenile onset.
    Type of Medium: Electronic Resource
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