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  • 1
    ISSN: 0003-9861
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Diabetic control ; urine ; glycopeptides ; affinity chromatography ; non-enzymatic glycosylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relationship between improvement in diabetic control and changes in levels of glycosylated urinary peptides was investigated. Eight poorly controlled Type 1 (insulin-dependent) diabetic patients were studied as optimal metabolic control was achieved. Mean daily blood glucose values and weekly haemoglobin A1 levels were determined simultaneously. Urinary glycosylated peptide levels fell 50% in 15 days, compared with 23 days for haemoglobin A1. Levels of glycosylated urinary peptides were sensitive to increased mean blood glucose concentrations of 9.72 mmol/l and increased linearly up to 20.0 mmol/l (r=0.98) when compared with mean blood glucose levels obtained 8–9 days earlier. A similar correlation was found with haemoglobin A1 levels. Levels of glycosylated urinary peptides before and after optimal control were compared, and a decrease of 40% was observed (pre-control: 269±44 μmol/day, optimal control: 162±45 μmol/day, mean±SEM). The lag time between the fall in mean blood glucose level and the parallel fall in glycosylated urinary peptides was 8–9 days, suggesting that measurement of these compounds may become a useful clinical laboratory technique for monitoring short-term integrated glycaemia in diabetic patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1463
    Keywords: Keywords: Oxidative stress ; diabetes ; aging ; advanced glycation endproducts ; lipid peroxidation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Many approaches have been undertaken to understand Alzheimer's disease (AD) but the heterogeneity of the etiologic factors makes it difficult to define the clincally most important factor determining the onset and progression of the disease. However, there is increasing evidence that the previously so-called "secondary factors" such as a disturbed glucose metabolism, oxidative stress and formation of "advanced glycation endproducts" (AGEs) and their interaction in a vicious cycle are also important for the onset and progression of AD. AGEs are protein modifications that contribute to the formation of the histopathological and biochemical hallmarks of AD: amyloid plaques, neurofibrillary tangles and activated microglia. Oxidative modifications are formed by a complex cascade of dehydration, oxidation and cyclisation reactions, subsequent to a non-enzymatic reaction of sugars with amino groups of proteins. Accumulation of AGE-crosslinked proteins throughout life is a general phenomenon of ageing. However, AGEs are more than just markers of ageing since they can also exert adverse biologic effects on tissues and cells, including the activation of intracellular signal transduction pathways, leading to the upregulation of cytokine and free radical production (oxidative stress). Oxidative stress is involved in various divergent events leading to cell damage, including an increase in membrane rigidity, DNA strand breaks and an impairment in glucose uptake. In addition, other age-related metabolic changes such as depletion of antioxidants or decreased energy production by a disturbed glucose metabolism diminish the ability of the cell to cope with the effects of radical-induced membrane, protein and DNA damage. With our improving understanding of the molecular basis for the clinical symptoms of dementia, it is hoped that the elucidation of the etiologic causes, particularly the positive feedback loops involving radical damage and a reduced glucose metabolism, will help to develop novel "neuroprotective" treatment strategies able to interrupt this vicious cycle of oxidative stress and energy shortage in AD.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The secretions of interleukin 1 (IL-1), tumour necrosis factor α (TNF), and prostaglandin E2 (PGE2) of low-dose E. coli lipopolysaccharide (LPSJ-stimulated human monocytes (Mø) were investigated in an endotoxin (ET)-free milieu (〈1.6 pg LPS/ml). Human Mø cultures from nine healthy men were stimulated with 0, 12.5–500, and 250,000 pg LPS/ml as measured by a very sensitive Limulus test. The IL-1 activity was tested by the mouse costimulatory thymocyte (LAF) assay, which was thoroughly standardized and characterized (interassay variation 22–24%, intra-assay variation 3–7%). Spontaneous Mø secretions of IL-1, TNF, and PGE2 were negligible, but 12.5 pg LPS/ml significantly stimulated the secretions of these Mø products and the monokine responses to 500 and 250,000 pg LPS/ml were almost in the same range. It was demonstrated that the secretions of IL-1-TNF and TNF-PGE2 were strongly correlated. Pronounced interindividual differences in LPS responsiveness were demonstrated, and two low-responders, one of whom was HLA-DR 1,2-positive, were identified. Three first-degree relatives of the DR1.2-positive low-responder had similar low responses. Furthermore. Mø cultures were prepared weekly for 4 weeks from four HLA-DR different men and the only DR2.2 homozygous individual had low monokine responses. In conclusion, stable interindividual differences in in vitro monokine and PGE2 secretions of LPS-stimulated Mø were demonstrated. It is suggested that HLA-DR2-positive individuals may be low responders.
    Type of Medium: Electronic Resource
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