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Biomedical subjects

E Vogel

Publications and source records attributed to E Vogel.

At least 91 records · Page 5Linked to original sources
PubMed1981

Predictors of duodenal ulcer healing and relapse.

Predictors of duodenal ulcer healing and relapse were examined in a population known to have a high healing incidence. Two double-blind prospective studies were performed in 134 patients over 4 wk and in 66 patients over 1 yr, respectively. Short-term treatment consisted either of cimetidine 1 g/day, pirenzepine 75 mg/day, or placebo. In a multiple stepwise linear regression analysis the following factors proved to increase healing incidence in decreasing order of importance: female sex, moderate alcohol consumption, abstinence from smoking, young age, and cimetidine treatment. The following factors had no influence on duodenal ulcer healing: number and total area of peptic lesions, concomitant disease, relatives with duodenal ulcer, duration of duodenal ulcer disease, and status as a migrant worker. In the long-term study, treatment consisted either of cimetidine 400 mg at bedtime, pirenzepine 30 mg at bedtime, or placebo. Cimetidine prevented ulcer relapse. Smoking favored duodenal ulcer relapse in the placebo group, but not in the cimetidine and pirenzepine group. For all the other factors no statistically significant effect was found. It is concluded that in a population with high spontaneous healing incidence (a) factors other than drug treatment such as sex, alcohol intake, smoking, and age are at least as important predictors of the outcome of short-term treatment as the drug treatment itself; (b) moderate alcohol intake might favor ulcer healing; (c) the unfavorable effect of smoking on ulcer relapse is overcome by low-dose, long-term, antisecretory treatment.

Adult↗
PubMed1980

Biotransformation and spectral interaction of xenobiotics with subcellular fractions from Drosophila melanogaster.

Several rapid bioassays are in use to detect, by means of mutagenicity, the formation of reactive metabolites from foreign compounds during their metabolism in the organism. Of these bioassays, the fruitfly Drosophila melanogaster was investigated with respect to its capacity to biotransform xenobiotics. By spectral analysis it was shown that in microsomal preparations of Drosophila the cytochromes P-450 and b5 are present. Microsomes appeared to possess aryl hydrocarbon hydroxylase and epoxide hydratase activities, while post-microsomal supernatants were able to conjugate appropriate compounds with glutathione and phosphate. As yet, glucosyl- and sulfotransferase activities can not be detected. The activities are compared to similar activities in rat liver.

Animals↗
PubMed1980

Genetical relationship between resistance to insecticides and procarcinogens in two Drosophila populations.

Two Drosophila populations, one resistant and the other susceptible to several insecticides, were examined for response to several alkaryltriazenes (2,4,6-Cl3-PDMT; 3-PyDMT; 3-PyDET) and to DMN, DEN and AM. Hikone R (HR) males developed relative resistance to both mutation induction and cell killing by the triazenes, whereas Berlin K (BK) males showed increased tolerance to DMN, DEN, and AM. When F1 hybrid males from the two strains were treated with 2,4,6-Cl3-PDMT, the yield of recessive lethal mutations in the heterozygotes was nearly half of that found in homozygotes from the susceptible strain Berlin K. These findings indicate that in Drosophila metabolism of procarcinogens is controlled by multiple-gene systems located on several chromosomes. An extremely divergent response of the two genotypes was found following treatment with 3-PyDET; this triazene acts as a potent mutagen in BK males but is hardly mutagenic when tested in strain HR.

Animals↗
PubMed1979

The relation between reaction kinetics and mutagenic action of mono-functional alkylating agents in higher eukaryotic systems. I. Recessive lethal mutations and translocations in Drosophila.

The relationship in Drosophila males between chemical reaction pattern of mono-functional alkylating agents (AA), described in terms of primary alkylation pattern with DNA and proteins as well as the Swain--Scott s factor, and their biological effectiveness were investigated. The agents chosen for comparative analysis were the nitrosamides ENU and MNU, the methanesulfonic esters iPMS, EMS and MMS, the dialkylsulfate DMS, and the nitrosamines DEN and DMN. Parameters of their biological activity were mortality (LC50) of treated adult males, induction in post-meiotic stages of X-chromosomal recessive lethal mutations and 2--3 translocations after either adult feeding or injection. Induced frequencies of recessive lethals, determined for each AA with a range of concentrations, served as biological dosimeter for interaction with target DNA in the germ line. The results are interpreted as indicating for these AA a causal connection between the pattern of primary alkylation of DNA and the quality of genetic damage observed. 1. The agent with the lowest s value, ENU, and its pendant DEN, failed to produce translocations at mutation frequencies that reached 44% for ENU. The highest chromosome-breaking activity was attributed to AA with high s, MMS and DMS. For MMS, the proportions of translocations (T) to mutations (M) approximately reached a 1 : 1 ratio in stored spermatozoa, at a recessive-lethal frequency of 14%. Ability to break chromosomes, as indicated by the T : M ratios, decreased in the sequence MMS greater than or equal to DMS, MNU greater than DMN greater than EMS greater than iPMS greater than ENU = DEN. 2. Nearly the reversed sequence in relative mutagenci effectivenss was obtained when the (directly acting) AA were arranged on the basis of their CM4/LC50 ratios (CM4, the exposure condition producing 4% recessive lethals after injection): ENU greater than EMS greater than iPMS, MNU greater than MMS = DMS. 3. Among the AA, EMS had a somewhat unique position, in that it was slightly less effective in the translocation test, and also less cytotoxic but more mutagenic in the recessive-lethal test than one would expect from its s value. This is taken as an indication of the influence on biological effectiveness of factors other than the s value, e.g. methylation versus ethylation and the lipid/water partition ratio. An example of the latter was also provided by DMS which, although having the same s as MMS, with its 5-fold higher lipid/water partition ratio, was more toxic than MMS. 4. For those AA that were clearly active in the translocation tests--MMS, DMS, MNU, DMN and EMS--delayed formation of exchanges was observed. Only in 17 out of 555 translocation tests with positive response translocations were already found in progeny from unstored spermatozoa. Consequently, it was concluded that performance of storage experiments in Drosophila is an absolute necessity for the detection of this type of rearrangement by AA. 5...

Alkylating Agents↗
PubMed1979

The relation between reaction kinetics and mutagenic action of mono-functional alkylating agents in higher eukaryotic systems. II. Total and partial sex-chromosome loss in Drosophila.

In Drosophila the connection between primary alkylation pattern and genetic activity of 8 mono-functional alkylating agents (AA)--ENU, DEN, iPMS, MNU, DMN, EMS, MMS and DMS--was investigated in spermatozoa and spermatids of treated R 1 (2), y B/BS Y y+ males. The induction of ring-X loss, Y-chromosome loss, and Y-rearrangements served as parameters of their effectiveness to produce chromosomal aberrations. (1) The ability to cause chromosomal losses decreased in the sequence MMS = DMS greater than MNU = DMN greater than EMS greater than iPMS greater than ENU = DEN. This ranking is consistent with the sequence in effectiveness in producing translocations. (2) The low frequencies of Y-chromosome rearrangements made any meaningful comparison between the AA impossible. The diagnostic value of such tests is poor, because even at toxic concentrations large numbers of offspring must be scored to obtain statistically significant effects. (3) With MNU, DMN, EMS, MMS and DMS, a time-dependent increase in the frequencies of ring-X losses ("storage effect") was found. (4) A stage-by-stage comparison revealed a differential response of spermatozoa and spermatids to these AA. Mature spermatozoa tended to be more resistant to the induction of breaks by MNU, DMN, EMS and MMS. (5) A general observation with all the AA was a reduced rate in survival of X-bearing sperm after treatment with mutagen. There was, however, no apparent quantitative relationship between the shift in the sex ratios observed and the yield of chromosomal aberrations. It is concluded that differences between these AA in their selectivity to numerous nucleophiles of DNA, as expressed by their s values, account for most of the diversity in their genetic effectiveness. The significance for genetic activity of other parameters than the s value appeared from the lower activity of EMS relative to MNU, indicating that methylation was more effective than ethylation in breaking chromosomes.

Alkylating Agents↗
PubMed1978

[Epidemiology of duodenal ulcer (author's transl)].

The epidemiology of peptic ulcer was investigated in 1105 endoscopy patients in a Zurich city hospital and in a random nongastroenterological hospital population. A raised susceptibility for duodenal ulcer was found in young, mainly unskilled, foreign labourers. There was no raised susceptibility in female foreign workers who also suffered less often from gastric ulcer than Swiss women. A tendency to ulceration in certain other diseases previously incriminated and in alcohol and nicotine consumers was not observed. A connection between susceptibility to ulceration and migration is assumed.

Adult↗
PubMed1978

Absence of mutagenicity of praziquantel, a new, effective, anti-schistosomal drug, in bacteria, yeasts, insects and mammalian cells.

Praziquantel (Embay 8440, Droncit) a new, effective anti-schistosomal drug, was tested in various short-term assays that have shown a predictive value for the detection of potential carcinogens. Indicator organisms S. typhimurium strains, S. pombe, S. cerevisiae, cultured V79 Chinese hamster cells or human heteroploid cells and Drosophila melanogaster were treated with Praziquantel. The induction of reverse and forward mutations, mitotic gene conversions, X-linked recessive lethals, sister-chromatid exchanges and unscheduled DNA-repair synthesis was scored; rodent-liver microsome-, cell- and host-mediated assays were also performed. Hycanthone, another schistosomicide was included as a positive control. The absence of a genetic activity of Praziquantel uniformly observed in such a battery of tests (i) confirms the assumption that the anti-schistosomal effectiveness of this drug is not related to the mutagenic activity and (ii) should encourage the implementation of extended clinical and field trials.

Animals↗
PubMed1977

The mutational spectrum of procarbazine in Drosophila melanogaster.

The antineoplastic agent Procarbazine was tested for the induction of genetic damage in Drosophila melanogaster. The compound was administered to adult males by oral application. The following types of genetic damage were measured: (1) sex-linked recessive lethals; (2) dominant lethals; (3) total and partial sex-chromosome loss; and (4) translocations. Procarbazine is highly mutagenic in causing recessive lethal mutations in all stages of spermatogenesis. In sperm a clear-cut concentration-effect relationship is not apparent, but in spermatids such a relationship is obtained for mutation induction at low levels of procarbazine exposure, while at high concentrations the induction of recessive lethals is not a function of concentration. A low induction of total sex-chromosome loss (X,Y) and dominant lethals was observed in metabolically active germ cells (spermatids), but procarbazine failed to produce well-defined breakage events, such as partial sex-chromosome loss (YL,YS) and II-III translocations. The results obtained in Drosophila melanogaster are discussed and compared with the mutational pattern reported in the mouse after procarbazine treatment.

Administration, Oral↗
PubMed1977

Vinyl chloride mutagenesis in Drosophila melanogaster.

In inhalation experiments, Drosophila males were exposed to vinyl chloride at concentrations of 200, 850, 10,000 30,000 or 50,000 ppm for 2 days, and to 30 or 850 ppm for 17 days. VCM was mutagenic in the recessive-lethal test both after short-term and long-term exposures. The lowest effective concentration (LEC) was 850 ppm after 2 day exposure, and this value could be lowered to 30 ppm by prolonging the exposure time to 17 days. With the concentration levels tested, the mutation frequency increased with concentrations and reached a plateau at 10,000 ppm. This indicates a substrate saturation effect. In contrast with the recessive lethal assay, negative results were obtained when tests on dominant lethals, translocations, entire and partial sex-chromosome loss were carried out with VCM at 30,000 ppm for 2 days. This finding of a false negative seems a logical consequence of the observed saturation effect, and strengthens the concept that there exist two effective concentrations for point mutations vs the induction of chromosome breakage events. Vinyl chloride monomer provides another example to support our view that chromosome breakage is not a reliable measure of mutagenic activity.

Animals↗