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  • 1
    ISSN: 1432-0428
    Keywords: NOD mouse ; insulin ; diabetes ; prevention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Early intensive insulin treatment is thought to improve subsequent Beta-cell function in Type 1 (insulin-dependent) diabetic patients. Prophylactic insulin administration also reduced diabetes incidence in diabetes-prone animals. To study the mechanisms by which these effects occur, we tested the ability of insulin therapy in the model of non-obese-diabetic mice, to prevent the penetration of committed T cells into the islets and subsequent Beta-cell destruction. Sublethally irradiated non-obese-diabetic males of 8 weeks of age were adoptively transferred with splenocytes from diabetic donors and treated with the maximum tolerable dosage of fast-acting insulin (0.5 U, twice daily) until 30 days after cell transfer. Diabetes incidence was compared to control animals injected with the same concentration of insulin diluent. After one month of treatment, the cumulative diabetes frequency was significantly less within the insulin-treated group (4 of 15, 26.6%) than in the control group (15 of 18, 83.3%; p 〈0.01). Pancreatic histological analysis of insulin-treated animals revealed a lower severity of insulitis and Beta-cell necrosis and a higher percentage of normal islets (46.6±10% vs 2.3±2%, p 〈 0.01), including five (33%) mice with no lesions. Immunoperoxydase staining of pancreatic sections indicated similar insulin and ganglioside staining of Beta cells from insulin-treated mice and control animals. Insulin-treated mice had comparable pancreatic insulin content to normal mice. Flow cytometry analysis of spleen cell populations indicated that insulin increased the number of Thy1,2+ and Lyt-2+ T cells. Although an effect at the Beta cell level cannot be definitely excluded, several lines of evidence suggest that insulin may influence the capacity of effector T cells to invade the islets and cause Beta-cell destruction. These effects may have potential interest for future immunointervention trials in Type 1 diabetic patients of recent onset.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Glutamate decarboxylase ; Type 1 (insulin-dependent) diabetes mellitus ; islet cell autoantibody ; prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalence of glutamic acid decarboxylase autoantibodies was determined with an immunotrapping enzyme activity assay in newly-diagnosed Type 1 (insulin-dependent) diabetic patients as well as in first-degree relatives using rat brain homogenate as a source of glutamate decarboxylase. Twenty-six out of 86 islet-cell cytoplasmic autoantibody positive and one out of 24 islet cell autoantibody negative patients of recent onset, had autoantibodies to glutamate decarboxylase above the upper 99% confidence limit obtained from 89 control sera. Among 27 islet cell autoantibody positive relatives including 19 siblings and 8 parents, antibodies to glutamate decarboxylase were found in 8 of 9 (89%) relatives and 7 of 8 (87.5%) siblings with islet cell autoantibody titres above 20 JDF units, in 1 of 19 (5.2%) relatives with islet cell autoantibody titres between 2 and 5 JDF units, in 2 of 263 (0.7%) siblings and 1 of 139 parents without islet cell autoantibodies. In first-degree relatives, high titre islet cell autoantibodies and autoantibodies to glutamate decarboxylase were tightly associated (X2=182, p=0.0001). None of the relatives with low genetic risk (n=64), i.e. HLA-different to the diabetic proband, was found to be antibody positive. Antibodies to glutamate decarboxylase were present only in those relatives sharing at least one haplotype with the diabetic proband, including two islet cell autoantibody negative but HLA-identical siblings. Autoantibodies to glutamate decarboxylase were present in 7 of 9 (77%) relatives who developed the disease, including one islet cell autoantibody negative sibling. Altogether, the simultaneous presence of autoantibodies to glutamate decarboxylase and high titre islet cell autoantibody increases the positive predictive value for the disease from 66% to 75%. This study indicates therefore that autoantibodies to glutamate decarboxylase detected by an immunotrapping enzyme activity assay are additional predictive markers for future development of Type 1 diabetes and should be now prospectively studied in high risk individuals as well as other autoantibodies to Beta-cell autoantigens.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 46 (1994), S. 477-478 
    ISSN: 1432-1041
    Keywords: Theophylline ; flumequine ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The kinetics of a single i. v. dose of theophylline given either alone or with flumequine was studied in eight healthy volunteers. No statistically significant differences were observed in the pharmacokinetic parameters of theophylline (volume of distribution, elimination half-life, AUC, plasma clearance) following the two treatments. Pretreatment for 5 days with oral flumequine (400 mg, three times daily) had no significant effect on the disposition of a single i. v. dose of theophylline in healthy volunteers.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: Moclobemide ; food interaction ; tyramine pressor test ; exercise ; monoamine oxidase inhibitor ; blood pressure ; dietary interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An open study was carried out to examine the effect of moclobemide, a new antidepressant reversible inhibitor of MAO-A, on the pressor response induced by oral tyramine added to meals of different lipid and protein composition, and to correlate the blood pressure increase in the tyramine test with that obtained during an exercise test. Eight healthy volunteers of both sexes participated in the study. A tyramine sensitivity and an exercise test were performed beforehand. Subjects were included if, under fasting condition, their systolic blood pressure (SBP) increased by more than 30 mmHg after administration of 400 or 600 mg tyramine. Exercise tests were performed to determine the grade of effort that corresponded to a rise in SBP of 30 mmHg. Subjects received moclobemide 600 mg/d. Starting on Day 7, each subject consumed a standardized meal (52 g lipids, 43 g proteins, 86 g carbohydrates) just before taking moclobemide. Tyramine was added to these meals in daily increasing doses of 50, 100, 150 ... mg until an increase in SBP 〉 30 mmHg was obtained. On moclobemide treatment, an average dose of 250 mg tyramine (range 150-400 mg) increased SBP by 36.6 mmHg. The time to reach peak SBP was longer (175 min) than in the fasting condition before the trial (40.6 min). The administration of the same dose of tyramine both during a protein-rich (75 g proteins, 85 g lipids, 90 g carbohydrates) and lipid-rich (110 g lipids, 55 g proteins, 100 g carbohydrates) meal significantly reduced the average increase in SBP to 21 mmHg, but did not significantly modify the time of appearance of the peak SBP In the exercise test, an increase in SBP of 30 mmHg was produced by the low load of about 100 W. During moclobemide treatment, oral doses of tyramine considerably larger than the amounts present in normal meals did not increase SBP by more than the effort exerted during every day life. Concomitant administration of a large quantity of lipids significantly reduced the pressor response.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Surgical and radiologic anatomy 1 (1978), S. 189-197 
    ISSN: 1279-8517
    Keywords: pancreas ; pancreatectomy ; portal system ; hepatic artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Résumé Les diverses techniques de la DPC doivent exploiter le dispositif anatomique en tenant compte avant tout: - de la disposition du péritoine résultant des remaniements survenus au cours du développement embryologique, - des rapports du pancréas avec le tronc veineux mésentérico-portal et ses affluents, - de la disposition des artères du pancréas et des viscères voisins qui appartiennent à un système d'irrigation régionale présentant de nombreuses variations, - des modalités du drainage lymphatique de la tête du pancréas, éventuellement. Une application chirurgicale est proposée à partir de ces principales bases antomiques.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 224 (1981), S. 503-506 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Electroanalytical Chemistry 70 (1976), S. 65-72 
    ISSN: 0368-1874
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Electroanalytical Chemistry 127 (1981), S. 169-177 
    ISSN: 0368-1874
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 338 (1985), S. 171-178 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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