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Biomedical subjects

W Raether

Publications and source records attributed to W Raether.

At least 55 records · Page 3Linked to original sources
PubMed1984

Action of a new floxacrine derivative (S 82 5455) on asexual stages of Plasmodium berghei: a light and electron microscopical study.

The floxacrine derivative S 82 5455, 7-chloro-1-( 4N - methylpiperazino -1N-imino)-10-hydroxy-1, 2, 3, 4-tetrahydro-3-(4-trifluoromethylphenyl)-9(10 H)- acridone , shows a high activity against blood induced infection of a drug-sensitive line of Plasmodium berghei in mice and rats. The dosis curativa minima/ dosis tolerata maxima values against the drug-sensitive P. berghei strain ascertained in the '28-day test' in mice, were 1.56 (X 5)/400 (X 1) mg/kg after the oral route 3.12(X 5)/400(X 1) mg/kg after the subcutaneous (sc) route. Morphological changes in erythrocytic stages of P. berghei following a single oral/sc dose of 25 and 50 mg/kg respectively in rats were at first swollen lacunes of the endoplasmic reticulum and extremely enlarged mitochondrion (6 h after treatment), then an apparent vacuolisation of the cytoplasm and pyknosis of the nucleus, as well as distinctly enlarged perinuclear space and later marked fissuring of the cytoplasm. After 23 h most of the parasites were destroyed by disruption of their pellicle. The majority of the degenerate parasites were situated outside of the apparently ruptured host cell. The remnants of damaged parasites and host cells disappeared completely from smears 96 h after treatment at all oral and sc doses used.

Acridines↗
PubMed1983

The action of polyether ionophorous antibiotics (monensin, salinomycin, lasalocid) on developmental stages of Eimeria tenella (Coccidia, Sporozoa) in vivo and in vitro: study by light and electron microscopy.

The effect of three polyether antibiotics (monensin, salinomycin, lasalocid) on developmental stages of Eimeria tenella (Coccidia, Sporozoa) was studied in vivo and in vitro by means of light and electron microscopy. It was found that these three drugs act against free merozoites, which are destroyed by bursting of the cell border (i.e. pellicle), endoplasmic reticulum and internal organelles even after very short exposure times (20 min) in media containing 1 ppm, 10 ppm or 100 ppm of these drugs. Sporozoites, however, survived these drug concentrations during an exposure time of 30 min (this would be sufficient to penetrate host cells and start development). Intracellular stages, which were situated in a parasitophorous vacuole within an intact host cell, were not attacked, apparently because these drugs are almost incapable of penetrating host cells. On the other hand, parasites (such as differentiated schizonts, gamonts) located within degenerating host cells showed slight disintegration, which did not necessarily led to their death. From these results it becomes clear why these polyether antibiotics have to be fed daily. Doses of 70 ppm salinomycin, 125 ppm monensin and 125 ppm lasalocid were found to bring about an equivalent protective effect against an infection with 40,000 Eimeria tenella oocysts.

Animals↗
PubMed1983

The activity of fexinidazole (HOE 239) against experimental infections with Trypanosoma cruzi, trichomonads and Entamoeba histolytica.

A new 5-nitroimidazole compound, 1-methyl-2-(4-methylthiophenoxymethyl)-5-nitroimidazole: fexinidazole, HOE 239, was found to be highly active against experimental infections with Trypanosoma cruzi, Tritrichomonas foetus, Trichomonas vaginalis and Entamoeba histolytica. It was slightly superior to benznidazole and nifurtimox in suppressing parasitaemia in mice infected with T. cruzi. It also eradicated the parasites from infected mice after a prolonged treatment period. The order of activity of some standard 5-nitroimidazoles obtained on the basis of several mouse or hamster infections with trichomonads and E. histolytica, respectively, was: fexinidazole greater than tinidazole and ornidazole greater than metronidazole greater than nitrimidazine (nimorazole), except that ornidazole had an amoebicidal effect close to that of fexinidazole. The principal metabolites, the sulphoxide and the sulphone were as active as the parent compound against T. cruzi, trichomonads and E. histolytica infections in mice and hamsters, respectively. The general tolerability of fexinidazole in rodents, rabbits and dogs is good and there is a wide range between the effective and maximum tolerated dose. Some side effects, such as anaemia and reduction of body weight occurred in rats and dogs at high dose levels following prolonged administration (90-day test). Structure-activity relationships of various 5-nitroimidazoles substituted in the 2-position, pharmacokinetic properties and metabolism of the experimental compound, as well as its foetal and perinatal tolerance, are discussed.

Animals↗
PubMed1981

[Microbiological laboratory studies with ciclopiroxolamine (author's transl)].

A survey is given on the microbiological laboratory results obtained up to date with 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone, 2-aminoethanol salt (ciclopiroxolamine, Cic, Hoe 296, Batrafen). The activity spectrum of the drug on fungi, bacteria and other organisms is described. Various properties by which Cic differs from commercial antimycotics are mentioned. They concern the great uniformity of MICs in pathogenic fungi, their consistency under various test conditions, the importance of the nutrient medium for the level of in vitro activity, and the steepness of dose-response curves. In addition, previously described properties of Cic are summarized, including findings on its mode of action in fungi, its effect in model mycoses, and its high efficacy in hornified skin types. The relevance of laboratory findings for therapy is discussed.

Antifungal Agents↗
PubMed1981

Suppressive and causal prophylactic activity of floxacrine in various avian malaria models.

Floxacrine, a 7-chloro-10-hydroxy-3(4-trifluoromethylphenyl)-3, 4-dihydroacridine-1,9-(2H, 10H)-dione and various standard malarials were found to be distinctly less active against avian malaria parasites than against rodent or nonhuman primate malaria parasites. Especially the suppressive action against asexual stages of P. gallinaceum, P. praecox and P. cathemerium was markedly reduced in comparison with that ascertained in mice infected with P. berghei. Similar results were observed in sporozoite-induced infections of P. gallinaceum and P. cathemerium respectively. Expressed as quotient of calculated causal prophylactic activity (CPD50) floxacrine was 42 and pyrimethamine 54 times more active against P. berghei yoelii than P. gallinaceum. The blood schizontocidal effect of floxacrine proved superior to that of mefloquine, chloroquine and mepacrine, whereas the causal prophylactic activity was slightly inferior to that of pyrimethamine but superior to that of primaquine. In vitro floxacrine revealed no effect against sporozoites of P. gallinaceum even at concentrations of 100 mcg/ml.

Acridines↗
PubMed1980

10-Hydroxy-3,4-dihydroacridine-1,9(2H,10H)-diones, a new group of malaricidal and coccidiostatic compounds.

2-Nitrobenzaldehydes and 1,3-cyclohexanediones condense in a mixture of hydrochloric acid and glacial acetic acid to 10-hydroxy-3,4-dihydroacridine-1,9(2H,10H)-diones. Many compounds of this group reveal a pronounced coccidiostatic and malaricidal effect in vivo even against drug-resistant malaria parasites. Synthesis and chemotherapeutic results as well as structure-activity relationships are described.

Acridines↗
PubMed1979

[Fine-structure changes in Toxoplasma gondii trophozoites after deep-freezing with dimethyl sulphoxide (author's transl)].

The changes observed in trophozoites of Toxoplasma gondii after deep-freeze preservation were examined by electron microscopy. Toxoplasmas (strain BK) from peritoneal exudate of infected NMRI mice were supended in Ringer's solution, deep-frozen in liquid nitrogen with 5% dimethylsulphoxide (DMSO), and compared after thawing with control samples with and without the addition of DMSO. Slight structural changes such as widening of endoplasmic reticulum, formation of fissures in the cytoplasm, and loosening of chromatin were only observed in some of the free toxoplasmas of the DMSO control. Among the deep-frozen parasites, about 1/5 of the free stages showed no or only slight morphological changes. In contrast to this, almost all intracellular forms found in macrophages showed lesions. The most remarkable change was a partial destruction of the inner cell membrane complex. The outflow of ribosome-containing protoplasm with ballon-like swelling of the outer elementary membrane was observed as a consequence of this frequent lesion. The outflow of protoplasm induced a drastic decrease in the electronic density of the whole cytoplasm. Other characteristic degenerative signs were vacuolation of cytoplasm up to formation of great optically empty spaces, widening of the perinuclear space, swelling of mitochondria, disintegration of rhoptria, micronemata, and Golgi zone, coarse-plaque loosening, and displacement of electron-dense areas of the nucleus up to disintegration with maintenance of the karyoplasm. In some almost completely disintegrated trophozoites, enlarged mitochondria with remarkable electronic density were observed. Apart from the cell membrane, the conoid was the longest-persisting organelle. The alterations observed after deep-freezing permit the conclusion that the free cells, which were only slightly impaired or not at all, remained infective.

Animals↗
PubMed1979

Antimalarial activity of Floxacrine (HOE 991) I. Studies on blood schizontocidal action of Floxacrine against Plasmodium berghei, P. vinckei and P. cynomolgi.

Floxacrine (HOE 991), 7-chloro-10-hydroxy-3-(4-trifluoromethylphenyl)3,4-dihydroacridine-1,9-(2H, 10H) dion, shows a high level of antimalarial action against blood-induced infection of drug-sensitive and drug-resistant lines of Plasmodium berghei in mice, rats and Syrian hamsters. The drug is also a potent blood schizontocide against drug-sensitive P. vinckei strains in rodents and P. cynomolgi in rhesus monkeys. The CD50/CD90 values against the drug-sensitive P. berghei strain ascertained in the '28-day test' in mice were 4.3/6.7 mg/kg after the oral route and 1.7/3.6 mg/kg after the subcutaneous (sc) route. In the 'two- and four-day test' the ED50 against sensitive P. vinckei was 0.7 mg/kg in both mice and rats. A moderate prophylactic effect could be demonstrated after the sc route probably due to a 'depot effect' of the water-insoluble active principle. Floxacrine was also highly active against P. berghei-lines which were resistant to chloroquine, mepacrine, dihydrofolate reductase inhibitors, sulfadoxine and dapsone. Resistance to HOE 991 could be developed in P. berghei and P. cynomolgi when the compound was used alone and administered repeatedly in subcurative doses. The antimalarial activity of the compound was not influenced by p-aminobenzoic acid or folic acid supplements in diets. Structural changes induced by floxacrine on pigment cytoplasm and nucleus in erythrocytic stages of P. berghei differed in some aspects from those of mepacrine and chloroquine. It is therefore assumed that the mode of action of floxacrine differs from that of the known antimalarial drugs. The general tolerance of the compound in rodents and rhesus monkeys is good and there is a wide range between the effective and maximum tolerated doses. Floxacrine was also effective at 100 ppm against pathogen Eimeria species in chickens, at 1000 mg/kg orally against Fasciola hepatica in rats and at 300-800 mg/kg orally against Heterakis spumosa in rats.

4-Aminobenzoic Acid↗
PubMed1979

Chemotherapeutically active anthraquinones. I. Aminoanthraquinones.

Basically substituted 2,6-diacetaminoanthraquinones proved to have an interesting in vivo effect against Entameba histolytica, but this effect was markedly exceeded by that of the series of the 2,6-diamidinoanthraquinones. A number of compounds of this series revealed a significantly stronger extraintestinal effect in the golden hamster than the standard amebicides metronidazole and tinidazole, but they were not superior to these compounds in their trichomonacidal effect, which was in general only a moderate one. In both substance classes, the amebicidal effect was confined to 2,6-disubstitution. Variations of the anthraquinone system resulted in a loss of activity. The structure-activity relationships are discussed.

Amebicides↗
PubMed1978

[Invasion of erythrocytes by toxoplasma gondii (author's transl)].

The in vitro-invasion of mouse erythrocytes by Toxoplasma gondii could be detected and analysed by electron microscopy. The sequence of events observed during erythrocyte invasion led to the assumption of an actively penetrating parasite into the non-phagocytic host cell.

Animals↗
PubMed1978

Action of p-(4-amidino-phenoxy)-benzaldehyde-p-amidino-phenylhydrazone dihydrochloride on Leishmania donovani infections in the golden hamster.

The chemotherapeutic effect of a new diamidine, HOE 668, the p-(4-amidino-phenoxy)-benzaldehyde-p-amidino-phenylhydrazone dihydrochloride, was compared with that of known anti-leishmanial drugs in golden hamsters infected with Leishmania donovani. The effect of HOE 668 against visceral leishmaniasis proved superior to that of pentamidine isethionate and the pentavalent antimonial drugs, sodium stibogluconate and N-methylglucamine antimoniate. However, HOE 668 can be used only experimentally because of its toxicity. Its very good anti-leishmanial action qualifies HOE 668 as a standard compound in screening tests.

Amidines↗
PubMed1978

Chemotherapeutically acitve nitro compounds. 4. 5-Nitroimidazoles (Part III).

More than 100 1-methyl-5-nitroimidazoles substituted in the 2-position via an oxymethyl group were synthesized and their structure-activity relationship toward various protozoa was investigated. Among the derivatives substituted with an aromatic radical there are most of the compounds which are highly effective against trichomonads; 9 preparations are superior to tinidazole and 29 are superior to metronidazole in mice infected with Trichomonas fetus, and 9 compounds exhibit a better effect than metronidazole in golden hamsters intrahepatically infected with Entamoeba histolytica. In the same series one dialkylamino-acetamide derivative shows excellent trypanocidal activity in the NMRI mouse, but this effect is limited to Trypanosoma brucei; 12 preparations developed a trypanocidal effect only after relatively high doses; their range of efficacy included Trypanosoma cruzi, among others, after repeated treatment. Of the carboxyl acid, carbamic acid and sulphonic acid esters synthesized only the already known group of carbamic acid esters possesses a pronounced antiprotozoal effect. Among the preparations substituted with a heterocyclic radical some of the pyridine derivatives proved to have distinct trichomonacidal activity. The influence of the type of substitution and the stability of the C-X bond in 2-substituted 5-nitroimidazoles of all compounds synthesized so far (I--III, 4th report) are discussed in 2 tables.

Animals↗