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K Norpoth

Publications and source records attributed to K Norpoth.

At least 91 records · Page 5Linked to original sources
PubMed1979

Identification of S-(carboxymethyl)-L-cysteine and thiodiglycolic acid, urinary metabolites of 2,2'-bis-(chloroethyl)-ether in the rat.

S-(carboxymethyl)-L-cysteine (CMC) and thiodiglycollic acid (TGA) were identified by gas chromatographic-mass spectrometric measurements in the urine of rats after intraperitoneal injections of 2,2'-bis-(chloroethyl)-ether (BCEE). It is therefore probable that BCEE is O-dealkylated by a mixed-function oxidation. The hepatocarcinogenic effect of BCEE may be explained by the liberation of chloroacetaldehyde in vivo.

Animals↗
PubMed1977

[Dose-dependent effects on phenobarbital on microsomal liver enzymes of chicken embryos (author's transl)].

Levels of cytochrome P-450 and the activities of amino-pyrinedemethylase and p-nitrophenol-UDP-glucuronyltransferase were measured in homogenates and microsomes of 16 to 19 day old chicken embryos exposed in ovo to phenobarbital. The activities of glucose-6-phosphatase were measured on the 19th day of incubation. After the highest dose of 3 X 8 mg phenobarbital, cytochrome P-450 increased 3-6fold, aminopyrinedemethylase activity 7fold and the activity of p-nitrophenol-UDP-glucuronyltransferase 3fold. Glucose-6-phosphatase activity was not increased but decreased. Corresponding to the given dose of phenobarbital (3X3, 3X4, 3X6, 3X8 mg) into the yolk sac an increase in enzyme activity levels mentioned above could as a rule be demonstrated at the level of p less than 0.0025. Calculated microsomal protein amounted to 43.0+/-6.5 mg/g liver.

Aminopyrine N-Demethylase↗
PubMed1976

[Isolation and characterisation of two main metabolites of ifosfamide from human urine (author's transl)].

Two main metabolites of the cytostatic agent 1,3,2-oxazaphosphorine-3(2-chloroethyl)-2-[(2-chloroethyl)-amino]-tetrahydro-2-oxide (ifosfamidd as two different dechloroethylated derivatives. They both can also be derived from ifosfamide in vitro by means of KMnO4-oxidation. The metabolites are stable in organic solutions and they show no cytotoxic activity in biological test systems. In the urine of a patient treated with ifosfamide, nearly 50% of the applied dose were excreted as dechloroethylated derivatives. In the urine of other patients "carboxyifosfamide" was the main metabolite. It is assumed that the therapeutic effect of ifosfamide depends partially on whether side chain oxidation or ring oxidation is the predominant way of biotransformation.

Biotransformation↗
PubMed1976

Studies on the metabolism of isopnosphamide (NSC-109724) in man.

A method is described for the quantitative determination of cyclophosphamide, isophosphamide, and trophosphamide and their stable alkylating metabolites on thin-layer chromatography plates with the aid of 4-pyridinealdehydr-2-benzothiazolylhydrazone (PBH). The method requires only 0.01-0.02 ml of urine from patients treated with high doses of cyclophosphamide of isophosphamide, but a careful standarization is required by using reference substances. In the urine of patients treated with isophosphamide, the 4-carboxy derivative and two different dechloroethyl derivatives resulting from side-chain oxidation are the predominant metabolites determined, next to isophosphamide. Side-chain oxidation may be prevalent. Determination of isophosphamide and its stable alkylating metabolites in the urine of 25 patients shows that the ratio of unchanged isophosphamide to its metabolites varies widely. The mean value of the total amount of PBH-reactive compounds exceeded 50% of the given dose, whereas less than 1% was found to be converted to urine metabolites which release acrolein.

Alkylating Agents↗
PubMed1976

[Detection of alkylating air pollutants (author's transl)].

Occupational toxicological observations made during the last few years have shown that the respiratory intake of certain alkylating compounds entails a major carcinogenic risk even at concentrations below 1 ppm. Such inhalation carcinogens can also stem from photochemical and spontaneous chemical reactions in the atmosphere and not merely from direct emissions. For the examination of air samples for alkylating activities simple colorimetric test methods are available. Some of them must be considerably modified and matched to the reaction of the various alkylating compounds. In this manner colour reactions of, in part, high selectivity are obtained: thus, for example, carcinogenic alpha halogen ether can be detected in concentrations of 10 ng/ml test solution. By the use of sensitive colorimetric methods of analysis it was possible to fractionate the alkylating activity found in the exhaust gases of automobiles. It is now possible to enrich certain compounds, which react positively to the colour test, and to purify them for further chemical characterization.

Air Pollutants↗
PubMed1975

Side chain oxidation of ifosfamide in man.

Ifosfamide as well as its stable alkylating metabolites namely carboxy-Ifosfamide and two dechloroethylated compounds were determined in the urine of a patient with progredient lung carcinoma who had been treated with 6 g of the drug. Quantitative measurements were carried out using a colorimetric procedure which consists of TL-spectrophotometric determinations on sheets which had previously been sprayed with 4-pyridinaldehyde-2-benzothiazolylhydrazone. In the case investigated the Ifosfamide was found to have been converted largely into two dechloroethylated compounds (48%) and only a small portion of carboxy-Ifosfamide (2.2%).

Alkylation↗
PubMed1975

Plaque development by vaccinia-viruses on the chicken chorio-allantois under the influence of cyclophosphamide.

The development of Vaccinia-virus plaques on the chorioallantois of embryonated eggs was studied under the influence of active cyclophosphamide metabolites. The viruses were inoculated on the 9th or the 13th incubation day. Cyclophosphamide was injected in doses of 62.5--500 mug in 0.2 ml NaCl into the yolk sac either 7 hrs after the virus inoculation or 3, 6, or 9 hrs in advance. The plaque development was not influenced when cyclophosphamide was given after the virus inoculation. But in treating the embryos before the infection a decrease dependent on the dose in the number of embryos with recognizable plaques occurred. This decrease was more marked with cyclophosphamide treatment 6 or 9 hrs, than with cyclophosphamide treatment 3 hrs before the virus inoculation. When the embryos were inoculated on the 13th day and treated with cyclophosphamide 9 hrs in advance, the mean effective dose was 316 mug/egg. The range of effective doses corresponds with that of the inhibitory effective doses of cyclophosphamide on transplantation tumors grown on the chorio-allantois of embryonated eggs.

Allantois↗
PubMed1975

[Quantitative determination of cyclophosphamide, ifosfamide, and trofosfamide and their stable metabolites on TLC-plates with the aid of 4-pyridine-aldehyde-2-benzothiazolyl-hydrazone (PBH) (author's transl)].

Cyclophosphamide, ifosfamide, and trofosfamide can be analysed quantitatively together with their stable alkylating urine metabolites on TL-plates by means of the PBH-reagent (4-pyridine-aldehyde-2-benzothiazolyl-hydrazone). The method requires only 0.01 ml urine, but a careful standardisation is necessary by using reference substances. The minimum measurable amounts are between 0.25 and 0.5 mug. In the urines of rat and man the carboxy derivatives and the dechloroethyl derivatives, respectively, resulting from side chain oxidation, are predominant next to cyclophosphamide, ifosfamide, or trofosfamide, respectively. Side chain oxidation can be prevalent, as we have found in some patients treated with ifosfamide. The method described allows not only the calculation of time functions for the excretion of PBH-reactive substances but also in vitro investigations of the chemokinetic properties of cyclophosphamide derivatives under physiological conditions.

Animals↗