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Biomedical subjects

H Hüller

Publications and source records attributed to H Hüller.

At least 19 recordsLinked to original sources

Cloning, expression, and characterization of a chitinase gene from the Antarctic psychrotolerant bacterium Vibrio sp. strain Fi:7.

A marine psychrotolerant bacterium from the Antarctic Ocean showing high chitinolytic activity on chitin agar at 5 degrees C was isolated. The sequencing of the 16S rRNA indicates taxonomic affiliation of the isolate Fi:7 to the genus Vibrio. By chitinase activity screening of a genomic DNA library of Vibrio sp. strain Fi:7 in Escherichia coli, three chitinolytic clones could be isolated. Sequencing revealed, for two of these clones, the same open reading frame of 2,189 nt corresponding to a protein of 79.4 kDa. The deduced amino acid sequence of the open reading frame showed homology of 82% to the chitinase ChiA from Vibrio harveyi. The chitinase of isolate Fi:7 contains a signal peptide of 26 amino acids. Sequence alignment with known chitinases showed that the enzyme has a chitin-binding domain and a catalytic domain typical of other bacterial chitinases. The chitinase ChiA of isolate Fi:7 was overexpressed in E. coli BL21(DE3) and purified by anion-exchange and hydrophobic interaction chromatography. Maximal enzymatic activity was observed at a temperature of 35 degrees C and pH 8. Activity of the chitinase at 5 degrees C was 40% of that observed at 35 degrees C. Among the main cations contained in seawater, i.e., Na+, K+, Ca2+, and Mg2+, the enzymatic activity of ChiA could be enhanced twofold by the addition of Ca2+.

Adaptation, Physiological↗

[Results of conversion from conventional immunosuppressive therapy to cyclosporin A in complications following kidney transplantation].

In 41 patients suffering from complications late after kidney transplantation the conventional immunosuppression was converted to Cyclosporin A. A complete normalization was obtained in the case of acquired immunoglobulin G deficiency and in persistent leukocytopenia. 6 patients suffering from life-threatening bacterial infections did survive after conversion with functioning allograft and 8 out of 9 late rejections were reversible. Conversion may be necessary in chronic hepatopathy and chronic rejection. A conversion to cyclosporin A is recommended because of control of complications in 78% (46/59) of the recipients.

Adolescent↗

Effect of methotrexate on the pharmacokinetics and renal excretion of cisplatin.

The kinetics of platinum in plasma and erythrocytes, and its renal excretion, have been examined in five patients with non-small cell carcinoma of the lung, after treatment with cisplatin 50 mg/m2 (Platidiame) and, three weeks later, a combination of 50 mg/m2 cisplatin and 40 mg/m2 methotrexate. The patients were given 0.9% saline 1 l 1 h prior to drug application. Plasma platinum elimination was biphasic with a short initial phase (t1/2 alpha 10-31 min) and a long beta-phase (t1/2 beta 65-91 h). With the exception of increased AUC values in all five patients 0-8 h after the injection, no significant change in the kinetics of platinum in plasma was found after coadministration of methotrexate. In four of the five patients renal platinum excretion was reduced in the first 6 h after administration of methotrexate. The renal clearance of platinum was 50% lower in those four patients 0-3 h after the injection. With the exception of one patient, no signs of nephrotoxicity were observed after combined drug administration. Other toxic effects were mild and showed no increase after the initial administration of methotrexate.

Adult↗

Pharmacokinetics of adriamycin, adriamycinol, and antipyrine in patients with moderate tumor involvement of the liver.

The pharmacokinetics of adriamycin, its metabolite adriamycinol, and antipyrine were studied in 17 patients with moderate tumor involvement of the liver and compared to that of 19 tumor patients with normal liver function (Preiss et al. 1985). The individual liver function parameters deviated from normal by a factor ranging from 2.5 to 12.2. The t1/2 alpha and t1/2 beta, the AUC (corrected for body weight and dose) and the total body clearance (CL, corrected for body weight) of adriamycin did not differ significantly between the two groups of patients. Likewise, there was no difference in the kinetic parameters of antipyrine between the two groups. Unlike adriamycin and antipyrine, adriamycinol was found to have a significantly longer t1/2term (60.5 vs 28.3 h, P less than 0.001), an increased AUC (3.00 vs 1.43 h/ug per ml, P less than 0.02), and a higher AUCadriamycinol/AUCadriamycin ratio (0.94 vs 0.52, P less than 0.02) in patients with moderate tumor involvement of the liver. The CL, the AUC, and t1/2 beta of adriamycin correlated significantly (P less than 0.001 and P less than 0.01) with the corresponding kinetic parameters of antipyrine, but not with the usual liver function parameters. No correlation could be found between the kinetic parameters of adriamycinol and those of antipyrine.

Adult↗

Capillary blood, dried on filter paper, as sample for monitoring cyclosporin A concentrations.

For monitoring the immunosuppressive drug cyclosporin A by radioimmunoassay (Sandoz Ltd.) we propose a simple method of sampling in which 20 microL of capillary blood is dried on filter paper. Patients can collect their own samples and mail or bring them to the laboratory. Results for such samples, and their variability, correspond to those for conventional methods of sampling (collection of venous or capillary blood into buffer). Capillary blood can be stored on paper at room temperature for more than four weeks with no effect on assay results.

Blood Chemical Analysis↗

[Pharmacokinetics of dihydralazine following intravenous administration in laboratory animals].

Comparative pharmacokinetic studies with high i.v. doses of dihydralazine (1, 5 and 7.5 mg/kg-1, respectively) were performed in rats, rabbits, and dogs. 1 was distributed in rabbits and dogs in two phases with half lives of 0.25-0.4 min and 1.0-2.0 min. The terminal slope was species dependent. The relative clearance values decreased in the order rabbit, rat, dog. High tissue concentrations were observed in rabbits and dogs in parenchymatous organs and endothelium (aorta). Skeletal and heart muscles belonged to the central compartment. The biliary excretion was low in rabbits. Dogs accumulated the drug in bile (bile/serum-ratios = 19-390). Maximally 5% of the given dose were excreted in rabbits with the 12-h-urine.

Animals↗

The influence of the acetylator phenotype for the clinical use of dihydralazine.

Dihydralazine is a substrate of the human N-acetyltransferase. Therefore the acetylator phenotype could influence the pharmacodynamic response of dihydralazine and/or side effects of this drug. In this study it could be shown that: among patients with dihydralazine incompatibility slow acetylators preponderated; the risk of early side effects was higher in females than in males; and the ratio of fast/slow acetylators was higher in dihydralazine treated patients than in patients treated with other antihypertensives. Dihydralazine should be given very cautiously to female hypertonic patients that are slow acetylators.

Acetylation↗

Plasma pharmacokinetics of adriamycin and antipyrine and its relation to the therapeutic and toxic effects.

After a simultaneous administration of adriamycin and antipyrine to 19 tumor patients, the plasma kinetics of both drugs, the therapeutic effect and the reaction to white blood cells were determined. Antipyrine was given orally at a dose of 875 mg, whereas adriamycin was administered by means of intravenous infusion for 20 min at 60 mg/m2. This application was repeated in eight patients after three weeks. Nine patients had a normal liver function. In ten patients, slight increases were found in individual liver function parameters. All patients were free from metastases of the liver and had bilirubin levels within the normal range. Antipyrine followed an open one-compartment model, whereas adriamycin followed an open two-compartment model. In the mean, t1/2 el and Cl tot of antipyrine were found to be 16.1 h and 32.9 ml/min, t1/2 beta and Cl tot of adriamycin were 23.1 h and 877 ml/min. For antipyrine and adriamycin, these parameters varied interindividually by the factors 2.8 and 3.1, respectively. No correlations were found between the liver function parameters, and the kinetic elimination parameters and the areas under the curves of both drugs. However, significant positive correlations were found to exist between t1/2 el antipyrine and t1/2 beta adriamycin and between the areas under the curves of the two drugs. A relationship between the AUC adriamycinol/AUC adriamycin ratio (which was 0.52 in the mean) and the antipyrine elimination rate did not exist. As compared to 12 persons with no response or progression, the seven patients with partial or complete response had a significantly higher AUC and a significantly lower Cl tot of adriamycin. As compared to the patients with elimination half-life values of less than 20 h, five patients with antipyrine elimination half-life values of more than 20 h had a significantly longer adriamycin elimination beta-phase and a stronger depressive effect on the white blood cells. The results obtained suggest that the antipyrine kinetics in patients with normal or slightly impaired liver function is a useful parameter for an assessment of the depression of white blood cells and the dose adjustment for adriamycin.

Administration, Oral↗