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Biomedical subjects

D Ullrich

Publications and source records attributed to D Ullrich.

At least 55 records · Page 3Linked to original sources

Glucuronide formation of various drugs in liver microsomes and in isolated hepatocytes from phenobarbital- and 3-methylcholanthrene-treated rats.

Various substrates of rat liver microsomal UDP-glucuronosyltransferase were classified in vitro as preferred substrates of either 3-methylcholanthrene- or phenobarbital-inducible enzyme forms. Microsomal UDP-glucuronosyltransferase activities towards a third group of substrates (including oestrone, phenolphthalein, paracetamol and oxazepam) are not markedly altered by treatment with either 3-methylcholanthrene or phenobarbital. Some substrates of the 3-methylcholanthrene- and phenobarbital-inducible enzyme activities were selected to evaluate the importance of multiple enzyme forms for glucuronide formation in the intact cell. The metabolism of these compounds was compared in isolated hepatocytes from untreated controls and from rats treated with 3-methylcholanthrene (MC-hepatocytes) or phenobarbital (PB-hepatocytes). Glucuronidation of 1-naphthol and 3-hydroxybenzo[a]pyrene was chiefly enhanced in MC-hepatocytes (greater than 2-fold), whereas glucuronidation of chloramphenicol and bilirubin was chiefly enhanced in PB-hepatocytes. These observations are in agreement with differential induction of UDP-glucuronosyltransferase activities in vitro suggesting that, besides other factors such as cofactor supply, physiological activators, etc., the levels of the multiple enzyme forms are critically determining glucuronide formation in the intact cell.

Animals↗

Intralobular distribution of UDP-glucuronosyltransferase in livers from untreated, 3-methylcholanthrene- and phenobarbital-treated rats.

A 3-methylcholanthrene-inducible enzyme form of UDP-glucuronosyltransferase has been localized within the liver lobule both immunohistochemically and enzymatically in microdissected centrilobular and periportal liver tissue. Livers of untreated, 3-methylcholanthrene- and phenobarbital-treated rats have been compared. The enzyme was detected in hepatocytes throughout the liver. However both immunohistochemical determination of the enzyme level and biochemical determination of its activity towards 1-naphthol revealed a heterogeneous distribution of the enzyme. In untreated controls and 3-methylcholanthrene-treated rats both enzyme activity and histochemical staining was highest in centrilobular hepatocytes. However, after phenobarbital-treatment enzyme staining and activity was highest in periportal hepatocytes, suggesting that the differentially inducible enzyme activities may be localized in different zones of the liver lobule. The results demonstrate that the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase is preferentially expressed in centrilobular hepatocytes.

Animals↗

Immunohistochemical and biochemical detection of uridine-diphosphate-glucuronyltransferase (UDP-GT) activity in putative preneoplastic liver foci.

Preneoplastic liver foci were produced in female Wistar rats by the administration of 2-acetylaminofluorene (0.03% w/w) in the diet for 174 days. Increased UDP-glucuronyltransferase (UDP-GT) could be visualized immunohistochemically in the same focal areas which were ATPase-negative and gamma-glutamyltranspeptidase-positive. Immunohistochemical detection was possible using rabbit anti-UDP-GT and peroxidase-labeled swine anti-rabbit immunoglobulins. The results of immunohistochemistry were substantiated by enzyme determination in microdissected material. UDP-GT activity was 5-fold higher in focal areas in comparison with the surrounding liver tissue. Increased UDP-GT activity in conjunction with the altered pattern of other drug-metabolizing enzymes is consistent with increased resistance of preneoplastic cells to the cytotoxicity of carcinogens. Immunohistochemical detection of UDP-GT may provide a new marker for preneoplastic lesions which, in conjunction with other markers, may prove useful in analyzing the various stages of liver carcinogenesis and the remodeling of preneoplastic lesions after cessation of carcinogenic stimuli.

2-Acetylaminofluorene↗

[Initial results with urine cytology in gynecologic tumors].

60 cytologic examinations were done of urine of 29 patients with gynecologic tumors. Material and methods are basically different from the usual cytology. Urinary cytology was a repeatable procedure without risk in the prediagnostic of gynecologic tumors in the field of the bladder. It completes cystocopy and is likely looking for recurrencies.

Cystoscopy↗

Activating and inactivating reactions controlling 2-naphthylamine mutagenicity.

Factors controlling 2-naphthylamine mutagenicity were studied using the Ames test. 1) Both rat liver microsomes and cytosolic proteins were required for generation of mutagenic metabolites. 2) 1-Hydroxy-2-naphthylamine, the major metabolite of 2-naphthylamine, was not mutagenic but cytotoxic to bacteria. 3) Ascorbic acid, reduced glutathione and conjugation reactions, such as glucuronidation, were strongly inhibiting 2-naphthylamine mutagenicity. 4) When isolated hepatocytes were used as the activating system mutagenic metabolites could not be detected. However cytotoxicity was detectable at doses of 2-naphthylamine greater than 0.2 mumol/10(6) cells. The results suggest that the formation of genotoxic metabolites of 2-naphthylamine is largely prevented in the intact, non-dividing rat hepatocyte.

2-Naphthylamine↗

[The effect of lacquer coatings on indoor air quality using as example radiator lacquers].

Examination of the air of a redecorated office room revealed the lacquer used to paint the radiators as one of the possible reasons for complaints by persons working in that room. The dry lacquer was found to contain solvent residues and considerable amounts of aldehydes (from propanol to n-nonanal), in particular of n-hexanal. In model studies, the details of aldehyde formation have been elucidated. An electric radiator was painted twice with special radiator lacquer, allowed to dry for 3 days and placed into a 1 m3 glass cube. The cube was continuously purged with clean air, simulating air exchange rates of 0.6 and 0.15 per hour. During the experiment, air samples were taken at intervals of several days and analyzed by gas chromatography. The temperature of the radiator was varied between 40 and 60 degrees C. In addition to the different aldehydes which appeared in the air of the cube each at concentrations of up to the mg/m3 range, remarkable concentrations of the corresponding carboxylic acids were found. In analogy to the aldehyde series with a predominance of n-hexanal, there was a maximum concentration of 50 mg/m3 of n-hexanoic acid in the air of the cube. Taking as an example n-butyric acid, which has an odour threshold value of appr. 4 micrograms/m3, the values measured in the cube were used to calculate the corresponding indoor air concentration in a room of 50 m3 with an air exchange rate of 0.6 per hour. It was found that even after a 4-weeks operation of such a radiator, the odour threshold value was surpassed by a factor of 3. By using other types of lacquers (e.g. water-soluble lacquers), the occurrence of such aldehydes and carboxylic acids in indoor air can be largely prevented.

Air Pollutants↗

[The influence of age and weight on the normal oral glucose tolerance (author's transl)].

The individual influence of age and weight on the normal glucose tolerance after an oral glucose load of 50 g was investigated in 332 test subjects (231 male + 101 female) presenting a healthy metabolism. The results show that, even within the range of normal glucose tolerance, the relative weight (age factor eliminated) exerts an influence both on the fasting blood sugar and on the 1 h-value (p less than or equal to 0.01), in women even on the 2 h-value (p less than or equal to 0.05) ("plain" glucose tolerance--weight correlation). The influence of the age factor (weight eliminated) on the normal glucose tolerance can only be demonstrated in the 1 h-value of men as sole value (p less than or equal to 0.01). Here it even slightly exceeds the influence of the weight factor ("plain" glucose tolerance--age correlation). Apart from this value, however, it can be stated that, within the normal glucose tolerance of both male and female subjects, the weight factor is of greater importance than the age factor. With increasing weight the sugar levels progressively approach the upper limit of the norm. Perhaps this is already the forefield to future secondary arteriopathies.

Age Factors↗