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  • 1
    Electronic Resource
    Electronic Resource
    Toxicological evaluation of imipramine in combination with adriamycin and strophanthin (1977)
    Springer
    Inflammation research 7 (1977), S. 341-346 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic oral administration of imipramine to rats caused characteristic changes of the electrocardiogram (ECG), i.e. prolongation of the PR interval, widening of the QRS complex, and increase in T-wave voltage. The cardiotoxic anthracycline antibiotic adriamycin induced dose-dependent widening of the QRS complex. This effect on intraventricular conduction was not enhanced in rats receiving both drugs. The high adriamycin dose (5×4 mg/kg) abolished imipramine-induced prolongation of the PR interval and T-wave elevation. This was not seen with the low adriamycin dose (20×1 mg/kg). Imipramine prolonged survival time of rats treated with toxic doses of adriamycin, but enhanced growth retardation in animals receiving the low adriamycin dose. Chronic treatment with increasing doses of strophanthin induced significant flattening of the T wave in rats with and without imipramine therapy, but did not influence the changes of the ECG or body weight gain caused by imipramine. It is concluded that the combined use of imipramine and adriamycin or strophanthin did not lead to a serious enhancement of the toxicity of the tricyclic antidepressant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01969566
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  • 2
    Electronic Resource
    Electronic Resource
    Modification of adriamycin toxicity in rats fed a high fat diet (1977)
    Springer
    Inflammation research 7 (1977), S. 163-170 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats fed a diet containing a high percentage of butter, cholesterol, cholic acid and propyl thiouracil (HFD) showed weight loss and developed hyperlipidemia, marked fatty in filtration of the liver, moderate elevation of SGPT, degenerative changes of the heart muscle, bradycardia, alterations of the QRS complex in the electrocardiogram, and initial hemoconcentration followed by moderate anemia. Treatment with adriamycin (18×1 mg/kg i.p.) resulted in significant augmentation of the cardiotoxic effects of this drug demonstrated by electrocardiographic measurements and myocardial histopathology. Adriamycin-induced atrophy of the lymphatic tissue was seen only in rats fed HFD and not in animals receiving ground chow. Adriamycin levels in the heart after single i.p. injection were higher in rats receiving HFD. This effect was present already after 10 days on HFD. At this time histopathological liver changes were present and SGPT was elevated. It is concluded that the increase in adriamycin toxicity is, at least in part, due to diminished excretion by the liver. These experimental findings are in accordance with clinical observations which have identified liver disease as one of the important risk factors for the development of adriamycin cardiomyopathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01964915
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  • 3
    Electronic Resource
    Electronic Resource
    Toxicological effects of Evans blue and Congo red on blood platelets (1974)
    Springer
    Inflammation research 4 (1974), S. 173-180 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The addition of 2 diazo dyes Evans blue (EB) and Congo red (CR) to human platelet-rich plasma caused platelet aggregation at final concentrations of 6.5×10−4 mmole/ml and 1.35×10−3 mmole/ml respectively. After dilution of the platelet-rich plasma with isotonic saline lower dye concentrations were necessary to cause aggregation. With gel filtrated platelets suspended in protein-free medium aggregation was induced with minute quantities of the dyes. Addition of bovine serum albumin markedly reduced the aggregating effect of the 2 substances. During slow i.v. infusion of the dyes into guinea-pigs platelet aggregates appeared in the blood and total platelet counts decreased. From the experimental results and the dye concentrations obtained when the two reagents are used in man, safety factors could be calculated. It was concluded that single i.v. injections of EB for the determination of blood volume is a safe procedure. The i.v. administration of CR in amyloidosis, however, represents a considerable hazard, particularly in hypalbuminemic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01970259
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  • 4
    Electronic Resource
    Electronic Resource
    Effects of seven anthracyclin antibiotics on electrocardiogram and mitochondrial function of rat hearts (1975)
    Springer
    Inflammation research 5 (1975), S. 383-393 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Daunomycin, adriamycin and 5 semisynthetic anthracycline antibiotics inhibited oxygen consumption or ATP production of rat heart mitochondria in vitro. The no-effect levels varied depending on the substrate used and ranged from 1 nmole to 800 nmole per mg mitochondrial protein. Mitochondrial functions were also studied in hearts of rats treated with repeated i.p. injections of the 7 antibiotics. Decrease in oxygen consumption without change in ATP production was observed with adriamycin and NSC-149584. Daunomycin, NSC-164011, NSC-143496 NSC-143114 affected primarily ATP production. The most potent compounds were daunomycin and adriamycin which damaged mitochondrial funciton at cumultive doses of approximately 10mg/kg. ECGs were monitored in groups of equally treated rats. Cardiotoxicity manifested itself by progressive widening of the QRS complex often followed by the development of a S-wave trough. The most toxic compounds also induced intraventricular block, bradycardia and heart failure. The development of the ECG changes showed a good correlation with the impairment of mitochondiral function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02205248
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  • 5
    Electronic Resource
    Electronic Resource
    DNA repair processes in germ cells demonstrated in ejaculated sperms of rabbits treated with methyl methane sulfonate (1978)
    Springer
    Archives of toxicology 40 (1978), S. 37-43 
    Details
    ISSN: 1432-0738
    Keywords: Methyl methane sulfonate ; DNA repair ; Mutagenicity ; Unscheduled DNA synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male rabbits were treated with a single i.v. injection of 22.5 mg/kg methyl methane sulfonate (MMS). 0–24 h later [3H]-thymidine was injected in both testicles. Incorporation of the isotope in germ cell DNA was demonstrated in ejaculated sperms. In controls labeled sperms were demonstrated first on day 40–43. These cells were in the preleptotene spermatocyte phase at the time of [3H]-thymidine injection. In rabbits treated with MMS significant radioactivity occurred in sperms collected from day 19 onwards. These cells were in late spermatocyte and early spermatid phase of maturation when [3H]-thymidine was injected. Incorporation of thymidine in these cell populations is interpreted as an expression of unscheduled DNA synthesis, a repair process initiated after chemical damage of germ cell DNA by MMS. The usefulness of the rabbit test system within the framework of conventional mutagenicity screening tests is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00353277
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  • 6
    Electronic Resource
    Electronic Resource
    LD50 versus acute toxicity (1982)
    Springer
    Archives of toxicology 51 (1982), S. 183-186 
    Details
    ISSN: 1432-0738
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions Based on today's extensive experience on acute toxicity testing of chemical substances, and on the outcome of specific studies (Schütz and Fuchs 1982; Müller and Kley 1982; Lorke in preparation; Günzel et al. in preparation), it is now possible to conduct acute toxicity studies with the sacrifice of fewer animals and even to increase at the same time, the quality of the data obtained. Whereas for drugs, data on acute toxicity usually represents only part of the information available, for other chemical substances, acute toxicity may be the only data available, thus asking for more extensive examination of the animals used 'for this kind of study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00348850
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  • 7
    Electronic Resource
    Electronic Resource
    Application of fine-needle aspiration biopsy for the diagnosis of dysplastic and neoplastic liver cell changes induced by N-nitrosomorpholine in rats (1979)
    Springer
    Archives of toxicology 42 (1979), S. 225-238 
    Details
    ISSN: 1432-0738
    Keywords: Fine-needle aspiration biopsy ; N-nitrosomorpholine ; Hepatocarcinogenesis ; γ-Glutamyl transpeptidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male rats were treated with the hepatocarcinogen, N-nitrosomorpholine (NNM, 10 mg ad 100 ml drinking water) for 19 weeks. Repeated fine-needle aspiration biopsies of the liver were performed percutaneously. Cytomorpho-logic and cytochemical criteria were used for the characterization of dysplastic and carcinoma cells. The alterations seen in the smears were correlated with histopathologic findings in the punctured liver lobes. Cells showing type I dysplasia were recognized in smears obtained from day 7 on. They corresponded to the swollen, glycogen-free cells developing in zone 3 of the Rappaport acinus during the early treatment phases. In later stages type II dysplastic cells were observed in smears. This coincided with the development of neoplastic nodules seen in histopathologic preparations. Carcinoma cells were recognized first after 15 weeks. Marked γ-glutamyl transpeptidase (γ-GT) activity could be demon-strated cytochemically in biopsy smears and biochemically in biopsy homogenates during the early phases of NNM-treatment. Simultaneously, a rise in γ-GT activity was also observed in the serum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00334836
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  • 8
    Electronic Resource
    Electronic Resource
    Impact of toxicological regulations on modern society Preface (1979)
    Springer
    Archives of toxicology 43 (1979), S. 1-1 
    Details
    ISSN: 1432-0738
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00695867
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  • 9
    Electronic Resource
    Electronic Resource
    Mutagenicity testing of pharmaceuticals: Present status (1980)
    Springer
    Archives of toxicology 46 (1980), S. 1-7 
    Details
    ISSN: 1432-0738
    Keywords: Mutagenicity testing ; Guidelines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An international conference was held in Paris from March 12 to 14, 1980, to discuss the proposed guidelines on testing of medicinal products for their mutagenic potential, issued in April 1979 by the Committee on Proprietary Medicinal Products in Brussels. This introductory paper describes the goals of the conference and an appraisal of the discussions held at this meeting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00361240
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  • 10
    Electronic Resource
    Electronic Resource
    Quantitative analysis of rat activity in the home cage by infrared monitoring. Application to the acute toxicity testing of acetanilide and phenylmercuric acetate (1989)
    Springer
    Archives of toxicology 63 (1989), S. 85-96 
    Details
    ISSN: 1432-0738
    Keywords: Motor activity ; Toxicological screening ; Acetanilide ; Phenylmercuric acetate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A new method for continuous in-cage monitoring of the activity of rats using passive sensors to detect the animals' infrared emissions, and its usefulness for toxicological screening tests is described. In order to obtain baseline values for toxicological tests, the differences between day and night activity, adaptation to changing day/night rhythm, the effects of handling the animals (measurement of body weight, food and water consumption) and the effect on activity patterns of the female estrus cycle were investigated. In two separate experiments, single doses of acetanilide and phenylmercuric acetate were administered. Passive infrared monitoring of motor activity proved to be a sensitive and discriminating method suitable for quantitative and qualitative assessment of acute toxic effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316429
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