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  • 1
    ISSN: 1432-1238
    Keywords: Key words Cytokines ; Euthyroid sick syndrome ; Non-thyroidal illness ; Hypothalamo-pituitary-adrenal axis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine whether cytokine release or activation of the hypothalamo-pituitary-adrenal (HPA) axis is predominantly involved in the development of the euthyroid sick syndrome (ESS). Design: Prospective observational study. Setting: Intensive care unit at a tertiary care medical center in Germany. Patients: Nine patients with sepsis of different causes and eight patients with acute myocardial infarction. Interventions: None. Measurements and results: Immediately on admission and on day 7 the following parameters were determined: total thyroxine (T4), free thyroxine (FT4), total triiodothyronine (T3), thyrotropin (TSH), interleukin-1β (IL-1β), interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), serum cortisol and plasma adrenocorticotropin (ACTH). On admission, concentrations of all thyroid hormones and TSH were significantly lower in septic patients compared to non-septic patients, whereas all cytokines except IL-2 were significantly elevated in the sepsis group. By contrast, there was no difference in serum cortisol and plasma ACTH levels between the two groups. On day 7, T4 and T3 were still lower in the septic group, whereas IL-1β, sIL-2R and IL-6 were still elevated. Again, no differences were found with regard to cortisol and ACTH levels. Conclusions: Euthyroid sick syndrome occurs very early during the course of septic diseases. Significantly decreased levels of total T4, FT4, T3 and TSH in septic patients suggest central suppression of TSH as well as inhibition of thyroid hormone release in ESS. The HPA axis is activated in septic patients and in non-septic patients and does not contribute to the development of ESS.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: tolbutamide ; antipyrine ; selective inhibition ; metabolite formation ; pharmacokinetics ; drug interaction ; sulphaphenazole ; cimetidine ; primaquine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of sulphaphenazole, cimetidine and primaquine on the disposition of antipyrine and tolbutamide in healthy volunteers have been investigated. The model substrates were administered simultaneously in order more clearly to define any selective effects of the potential inhibitors. Sulphaphenazole produced a significant increase in the half-life of tolbutamide (7.10 to 21.50 h) and a correponding decrease in its clearance (0.260 to 0.084 ml·min−1·kg−1). Clearance to hydroxytolbutamide (OHTOL) and carboxytolbutamide (COOHTOL) was also significantly decreased. In contrast, sulphaphenazole had no effect on the disposition of antipyrine. Administration of cimetidine did not significantly alter the disposition of either model drug. However, a 1.6-times higher dose of cimetidine did increase the half lives both of tolbutamide and antipyrine (6.21 to 9.04 h and 14.2 to 19.2 h, respectively) and decrease their clearance (0.226 to 0.148 and 0.50 to 0.31 ml·min−1 kg−1, respectively). Clearance to OHTOL and hydroxymethylantipyrine (HMA) was reduced. A single dose of primaquine had no demonstrable effect on tolbutamide disposition whereas the half-life of antipyrine was increased (12.1 to 15.0 h) and its clearance decreased (0.63 to 0.38 ml·min−1·kg−1). The partial clearance to HMA, 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) was also significantly reduced. The two main inferences are first, that tolbutamide and antipyrine are metabolished by different forms of cytochrome P-450, and second that a battery of model substrates is needed to investigate the inhibitory effects of a drug in man.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: rifampicin ; rifabutin ; microsomal enzyme induction ; healthy volunteers ; antimicrobial agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine. The urinary excretion of 6-β-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-β-hydroxycortisol, but the magnitude of the effects was signifiantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 261-265 
    ISSN: 1432-1041
    Keywords: Frusemide ; probenecid ; phenprocoumon ; anticoagulant ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of phenprocoumon with and without co-administration of frusemide and probenecid in two groups of 17 healthy volunteers. Frusemide 40 mg b.i.d. for 7 days did not interact with phenprocoumon to a significant extent. Probenecid 500 mg q.i.d. for 7 days significantly accelerated the overall elimination of phenprocoumon, as indicated by a decrease in AUC from 295 to 157 μg · h · ml−1, and a reduction in the fraction of the dose excreted by the kidneys. The data are consistent with inhibition of the glucronidation of phenprocoumon by probenecid. Its accelerated elimination may be a consequence of the increased formation of hydroxylated metabolites.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 203-204 
    ISSN: 1432-1041
    Keywords: Chlormethiazole ; hepatic monooxygenase activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Chlormethiazole is a strong inhibitor of cytochrome P-450-dependent monooxygenases in isolated human liver microsomes. To assess its effect in vivo, we measured the pharmacokinetic parameters of antipyrine (1.2 g orally) and tolbutamide (0.5 g i. v.) before and after administration of chlormethiazole 314 mg b. d. for 2 days to 8 healthy volunteers. The elimination of neither substance was affected, indicating that chlormethiazole did not inhibit in vivo the cytochrome P-450 isozymes responsible for the elimination of antipyrine and tolbutamide.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 563-568 
    ISSN: 1432-1041
    Keywords: nitrendipine ; pharmacokinetics ; hepatitis ; liver cirrhosis ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty one patients with liver disease (cirrhosis 11, chronic hepatitis 5 and acute hepatitis 5) and 6 healthy volunteers were given a single i.v. dose of nitrendipine 5 mg. Afterwords nitrendipine 20 mg once daily were administered orally for seven days. With the intravenous injection a significant increase in the AUC and elimination half-life of nitrendipine was found in patients with cirrhosis as compared to the normal volunteers. After chronic oral dosing, the area under the plasma concentration-time curve, AUC (0–24), was 94.5 ng ml−1 h and the plasma clearance CL was 1380.6 ml/min in the healthy controls; in patients with cirrhosis the AUC (0–24) h was significantly greater at 309.4 ng ml−1 h and CL had fallen to 686.6 ml/min. Considerable accumulation of nitrendipine was also found in the patients with chronic hepatitis. Nitrendipine could not be detected in urine from any of the subjects. Blood pressure and heart rate were not significantly influenced by the treatment in the various groups investigated. Antipyrine clearance in the patients with cirrhosis was correlated with the nitrendipine plasma clearance. Thus, accumulation of nitrendipine has been demonstrated in the patients with cirrhosis and chronic hepatitis.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 24 (1968), S. 1113-1114 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Zusammenfassung Nach Röntgenbestrahlung von polykristallinemdl-Valin bei Zimmertemperatur ergibt sich ein ESR-Spektrum ohne aufgelöste Hyperfeinstruktur. Erwärmt man die bestrahlte Substanz auf 353 °K, so zeigt das Spektrum mehrere gut aufgelöste Tripletts. Demnach ist die intermolekulare Radikalwanderung bei Zimmertemperatur noch nicht abgeschlossen, sondern erst nach weiterer Temperaturerhöhung.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 37 (1981), S. 1331-1332 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Lipopolysaccharides (LPS) from variousRhodopseudomonas andRhodospirillum species were tested for their radioprotective efficiency against X-irradiation and for their influence on the growth of spleen colony forming units (CFU-s) in mice. The LPS fromRhodopseudomonas gelatinosa Dr2 gave a high survival rate. It also favoured CFU-s formation and erythroid differentiation.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 202 (1964), S. 289-290 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Polycrystalline d,Z-methionine ('De-gussa5, Frankfurt/Main) with a bulk volume of 187 cm8/100 g was evacuated (〈 10-3 torr) in quartz-tubes and X-irradiated (180 kV, 20 m.amp, half-value layer: 0-90 mm copper, dose-rate: 450 r/min, dose: 100 kr.). Nearly 5 min later, after the electron spin ...
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 203 (1964), S. 859-860 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Polycrystalline native bovine serum albumin (Behring Werke, Marburg, Germany) with a bulk volume of 540 cm8/ 100 g was sealed under vacuum (〈 103 torr) and irradiated at room temperature. The electron spin resonance measurements were carried out under the same conditions. The irradiation with ...
    Type of Medium: Electronic Resource
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