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Biomedical subjects

F Leuschner

Publications and source records attributed to F Leuschner.

At least 37 records · Page 2Linked to original sources
PubMed1977

[Toxicological investigation of reproterol (author's transl)].

Only slight toxicity of 7-(3-[2-(3,5-dihydroxyphenyl-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol, Bronchospasmin) was shown in the examination of acute, subacute and chronic trials on various animal species with different modes of application. Slight side-effects noted with high toxically active dosages correspond with those of other well-known beta-sympathicomimetics. No influence on the pre-,peri- and postnatal development could be proven with doses tolerated by the parent animals.

Abnormalities, Drug-Induced↗
PubMed1977

[Toxicological study on piprozoline (author's transl)].

The compatibility of ethyl (Z)-(3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (piprozoline, Gö 919, Probilin) was tested orally in rats and intragastrically in dogs for 6 months. Moreover, the effect of the substance was studied on pregnant rats and rabbits and their foetuses after intragastric administration and on the fertility and breeding capacity of rats after oral application. In the course of the chronic experiments, in the highest dosage group of rats a slight sedation and a decrease of body weight gain and food intake could be observed. The female animals showed an enlargement of the adrenal glands. A small hyperemesis was noted in the highest dosage group of dogs. Subtoxic doses applied to rats and rabbits during gestation did not induce malformations in the newborns. Even treatment with large doses did not influence fertility and breeding capacity.

Animals↗
PubMed1977

[Toxicological studies on Etozolin (author's transl)].

The tolerance of ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene)acetate (etozolin, Gö 687, Elkapin) has been investigated over 18 months after oral administration in rats and over 1i months after intragastric application in dogs. Further the influence of the compound on pregnant animals and their fetuses after intragastric application has been investigated in rats and rabbits. The investigation of the influence on fertility and breeding capacity as well as on the peri- and postnatal development was carried out in rats after peroral administration. In the course of the chronic experiments a dose related increase of the excretion of fluid and electrolytes was observed. Side-effects, which mainly occurred during the last weeks of the experiment in the highest dosage group, were most probably due to the exhaustion of the fluid and especially of the electrolyte reserves of the animals. The experiments in rats and rabbits did not yield any findings indicating teratogenic properties. Fertility and breeding capacity were likewise not influenced by etozolin. An influence on the peri- and postnatal development could be demonstrated only in the toxic dose range.

Administration, Oral↗
PubMed1976

[The anti-hyperlipemic and anti-atherogenic effect of "essential" phospholipids: a pharmacologic trial].

To prove antilipemic and antiatherogenic effectiveness several animal species were given "essential" phospholipids (EPL) during different experimental procedures. The following actions were studied: 1. Effect of EPL-substance after prophylactic and therapeutic oral administration (dosage: 50, 150, 450 mg/kg bodyweight daily) in rats with acute and subacute hypelipemia induced by triton. 2. Effect of EPL-substance after prophylactic and therapeutic oral administration (dosage: 50, 150, 450, 1800 mg/kg bodyweight daily) in rats with dietetic hypercholesterolemia. 3. Effect of EPL-substance after daily oral administration (dosage: 50, 150, 450 mg/kg bodyweight) on the development of coronary and aortic atherosclerosis and various biochemical parameters in cholesterol-fed cockerels. 4. Effect of EPL-substance after dialy oral administration (dosage: 50, 150, 450 mg/kg bodyweight) on subacute triton-hyperlipemia in mini pigs. Triton-administration causes a greater or smaller increase in all parameters of the lipid metabolism measured. EPL treatment decreases these parameters during therapeutic and prophylactic administration in some cases even reaching normal values. The effect was clearly dose-dependent. EPL inhibit the increase in total lipids in dietetic hypercholesterolemia during therapeutic as well as during prophylactic administration. The effect was clearly dose-dependent in all doses, being statistically significant at the highest dosage level. In cockerels EPL were effective at all dose levels in counteracting the development of coronary atherosclerosis while the effect in atherosclerosis of aorta was less distinct. Except for non-esterified fatty acids, EPL reduced all biochemical parameters measured.

Animals↗
PubMed1976

[Toxicological investigations of the combination sulfamoxole/trimethoprim, a new broad-spectrum chemotherapeutic (author's transl)].

The chemotherapeutically effective 5:1 combination N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (trimethoprim) (CN 3123, Nevin, Supristol) was investigated to determine any evidence of toxicological potentiation or new toxic signs. It was found that CN 3123 had a very low acute toxicity when administered orally to mice, rats and dogs (oral LD50: mouse greater than 12 000 mg/kg; rat greater than 14 000 mg/kg; dog greater than 1000 mg/kg body weight). The combination was also tolerated by rats and dogs in repeated doses administered over a period of 4 or 26 weeks, that greatly exceeded the therapeutic dose. The only change observed occurred in the thyroid, which in all doses administered exhibited a dose-related increase in weight accompanied by histological changes indicating an activation of thyroid function and a hypersecretion of basophilic thyrotropic cells in the anterior lobe of the pituitary. Six weeks after discontinuation of treatment this condition showed a tendency to reversibility or had already returned to normal. In dogs there was a dose-related increase in iodine uptake by the thyroid and a decrease in serum thyroxine over a period of 6 months under the highest dosage of CN 3123 administered. Whereas the thyroid changes observed under the combination could be reproduced with sulfamoxole, no effect on thyroid weight was observed in rats and dogs in the subacute toxicity phase of a comparative investigation with trimethoprim. Moreover, trimethoprim did not increase the effect of sulfamoxole on the thyroid gland. The effect of sulfamoxole on the thyroid is discussed in detail with a review of the literature. It can be characterized as species-specific for sulfonamides in mice, rats, rabbits and dogs but not in monkeys or in man and appears to be caused by the inhibition of the organic binding of iodine in the thyroid, whereby the predisposing factors must vary considerably from species to species. The thyroid hypertrophy observed is due to the activation of the regulatory cycle via the anterior lobe of the pituitary. The following systemic changes occurred after 600 mg CN 3123/kg, a lethal-toxic dosage and the highest administered in the study: reduced body weight, decreased food consumption leading to cachexia, slightly increased SGPT and alkaline phosphatase, slight thrombocyte depression, enlargement and increased fatty degeneration of the liver, occurrence of necrotic areas in the liver, hemosiderin accumulation in Kupffer's cells, and an increase of reticular cells in the spleen. The acute toxicity of CN 3123 and all major functional and histological changes under repeated administration were due exclusively to sulfamoxole. The combination sulfamoxole/trimethoprim gives no indication of toxicological potentiation or new toxic signs.

Animals↗
PubMed1976

[Investigations on the effect of the combination sulfamoxole/trimethoprim on fertility and fetal development in rats and rabbits (author's tranls)].

The chemotherapeutically active combination of N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (trimethoprim) in a dose ratio of 5:1 (CN 3123, Nevin, Supristol) was investigated, with respect to teratogenicity, effects on fertility and reproduction and influence on peri- and post-natal development. Experiments with the combination and partly with the single substances were done on Sprague-Dawly and Wistar rats and on rabbits (New Zealand White). With regard to the known effects of trimethoprim in this field--fetal malformations typical of those caused by folic acid antagonists--it was to clarify whether or not potentiation phenomena or new toxic effects occur with the combination. The results were as follows: 1. CN 3123 is teratogenically and fetotoxically active when given in very high doses to pregnant rats and rabbits during the critical phase of organogenesis (day 8-15 of pregnancy in rats, day 8-14 in rabbits). There were malformations, decrease in the number of pups and an increase in the number of absorption sites. Litter size and litter weight were reduced. The malformations observed were cleft palates, rarely cleft lips, micrognathies and shortening of limbs. Doses up to 180 mg/kg CN 3123, corresponding to more than tenfold the daily maintenance dose in man, were without any effects on all parameters observed. Toxic effects were observed in Sprague-Dawley rats at a dose level of 420 mg/kg and in Wistar rats with 600 mg/kg, corresponding to the effects seen following 100 mg/kg of trimethoprim alone. Sulfamoxole in the corresponding dose of 500 mg/kg caused no embryotoxic effects in the rat. In rabbits 600 mg/kg CN 3123 induced no malformations but increased fetal loss. Therefore it can be concluded, that the teratogenic and fetotoxic effects seen with high doses of CN 3123 are due to the amount of trimethoprim in the combination. The observed effects with the combination are quantitatively related to those seen with trimethoprim. 2. CN 3123 in high doses which are teratogenic also provoked a reduction of growth of the animals. Food consumption and weight gain were reduced in dams with 420 and 600 mg/kg CN 3123. In this dose range the pup weights and the weight gain of the offspring of dams with continued dosing during lactation were also reduced. Variation rate including retardations was increased. The depressing effect of CN 3123 in high doses on food consumption and weight gain is known from long-term toxicological studies previously described [7]. 3. CN 3123 even with high doses has no effects on the fertility of male and female rats. The number of corpora lutea and implantations and also the pregnancy rate were unaffected when either the female or the male rats used for mating had been treated. There was also no influence on mating activity of the male animals treated. 4. According to the results of the fertility study with treatment of the male rats for a period of ten weeks or more there were no signs of mutagenic effects due to CN 3123.

Abnormalities, Drug-Induced↗
PubMed1975

Testing of cigarette smoke inhalation for teratogenicity in rats.

The effect of cigarette smoke inhalation on the developing rat embryo was studied. Female rats were exposed to smoke prior to and after mating at miximal tolerated doses. Male rats were ezposed to smoke to prior to mating to investigate the influence upon sperm. On the 21st day of gestation pregnant females of all groups were killed and implantations, litter sizes, foetal resorptions and abortion, foetal weight and length recorded: no significant differences were observed for these parameters between smoke-exposed and control animals. Total maternal wight gain during gestation was lower for smoke-exposed animals than for non-smoke-exposed animals. Examination of foetuses stained according to the method of Frohberg and Oettle resulted in normal variation in the skeletal development in smoke-exposed and control groups as well as in placebo groups. No skeletal malformations could be found.

Animals↗
PubMed1975

[Structure-activity relationships in the diuretic xipamide (4-chloro-5-sulfamoyl-2', 6' -salicyloxylidide)].

The synthesis of various derivatives of 4-chlorosalicylic acid substituted in position 5 is described. The evaluation of their diuretic potency on the rat showed 4-chloro-5-sulfamoyl-2,6-salicyloxylidide (BE 1293, xipamide, Aquaphor) as the most effective one. The normal urinary volume is increased tenfold by a oral dose of 100 mg/kg body weight. All changes in the molecular structure of xipamide, even acetylation, the introduction of a second sulfamoyl group or the exchange of the sulfonic group for the carbonyl group, lead to a decrease in activity.

Acetylation↗
PubMed1975

[Pharmacological and toxicological properties of the saluretic xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide)].

Xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide, Aquaphor), a new compound is a derivate of salicylic acid with marked sodium and water excreting potency. Its effect is dosage dependent. Dosages as low as 0.001 mg/kg p.o. in rats and 0.04 mg/kg p.o. in dogs lead to a statistically significant increase of sodium and water excretion. Potassium excretion was less affected and showed to be rather constant in a dosage range between 0.01 and 10.0 mg/kg. In rats a maximum of sodium and water excretion could be reached by a dose of 200 mg/kg duration of action in rats was approximately 10 h. In dogs a statistically significant sodium and chloride excretion could be detected after oral application of 0.04 mg/kg. Xipamide increased diuresis started with an oral dose of 0.1 mg/kg. Intravenous application of xipamide in a dose of 0.2 mg/kg in dogs accompanied by permanent infusion of 5 per cent mannit solution clearly showed the diuretic profile of the substance: increased diuresis started within 40 min. A peak was reached within 40-60 min post injectionem. Then excretion decreased slowly. Even 120 min post injectionem a diuretic action could be detected. Diuresis and sodium excretion could be demonstrated in rats with experimentally predamaged kidneys and with steroid dependent sodium retention. As could be demonstrated in hypertensive rats xipamide had a hypotensive effect, normotensive rats were not affected. In animal studies xipamide was excellently tolerated. The therapeutic range of the substance was high in single doses as well as when the drug administered over 6 weeks.

Animals↗
PubMed1975

[The saluretic effect of xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylilide) in normal subjects].

The diuretic and saluretic effectiveness of xipamide (4-chloro-5-sulfamoyl-2',6'-salicyloxylidide, Aquaphor) is determined and compared to those of chlortalidone and furosemid in normal subjects. The substance is revealed as a potent diuretic agent. In the range of 0.035--0.750 mg/kg body weight the dose-response curve of orally administered xipamide for the increase of excretion of urine, sodium and potassium ion and chloride during 24 h is described. Observing the renal activity over a period of 3 days after a single administration the duration of action is found to be up to 24 h with its maximum within the first 12 h. In the following 2 days the degree of the physiological rebound effect depends on the preceding saluretic effect and thus on the given dose. The pattern of ion-excretion (Na

Administration, Oral↗