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Vaginal Tritrichomonas foetus infection in mice as an in vivo model for drug development against Trichomonas vaginalis
No full textTrichomonas vaginalis is the causative agent of the common sexually transmitted disease, trichomoniasis, which affects more than a hundred million people worldwide. Metronidazole and tinidazole, agents belonging to the 5-nitroheterocyclic class of antimicrobials, are most often used to treat infection, but increased resistance has been reported and adverse effects of the drug can be significant. Consequently, an urgent need exists for the development of novel drug entities against trichomoniasis. Critical for antimicrobial drug development is the demonstration of in vivo efficacy. Murine models of vaginal T. vaginalis infection are often not reliable, while infections with the related bovine pathogen, Tritrichomonas foetus, tend to be more robust, although susceptibility to different antimicrobials might differ from T. vaginalis. Here, we explored the utility of T. foetus infection as a surrogate model for drug development against T. vaginalis. Four different T. foetus strains caused robust vaginal infection in young mice, while none of four diverse T. vaginalis strains did. Comparison of drug susceptibility profiles revealed that T. foetus and T. vaginalis were similarly susceptible to a range of 5-nitroheterocyclic and gold(I) compounds. By comparison, proteasome inhibitors were 10- to 15-fold less active against T. foetus than T. vaginalis, although one of the proteasome inhibitors, bortezomib, had low micromolar activity or better against multiple strains of both trichomonads. Different strains of T. foetus were used to demonstrate the utility of the murine vaginal infection models for in vivo efficacy testing, including for bortezomib and a gold(I) compound. The differences in susceptibility to proteasome inhibitors may be partially explained by differences in the proteasome subunit sequences between the two trichomonads, although the functional relevance of the proteasome was similar in both organisms. These findings indicate that T. foetus can serve as a reliable surrogate model for T. vaginalis in vitro and in murine infections in vivo, but caution must be exercised for specific drug classes with targets, such as the proteasome, that may display genetic divergence between the trichomonads
Social choice and topology a case of pure and applied mathematics
No full textAbstractThe existence of a social choice model on a preference space P is a topological, even homotopical problem. It has been solved 50 years ago, under different terminology, by the author and, a little later, jointly with T. Ganea and P.J. Hilton. P must be an H-space and either contractible or homotopy equivalent to a product of Eilenberg-MacLane spaces over the rationals
Lake water level increase during spring affects the breeding success of bream Abramis brama (L.)
No full textProbst WN, Stoll S, Peters L, Fischer P, Eckmann R. Lake water level increase during spring affects the breeding success of bream Abramis brama (L.). HYDROBIOLOGIA. 2009;632(1):211-224.In Lake Constance Eurasian bream Abramis brama (L.) spawn in very shallow littoral areas by the beginning of May. They attach their adhesive eggs to pebble and cobble substratum at less than 40 cm depth. Increasing water levels before spawning inundate bare substratum to which bream eggs may attach better than to deeper substratum covered by epilithon. Consequently, the water level increase prior to spawning should determine the amount of pristine spawning substratum available to bream and thus influence their breeding success. To test this hypothesis, the influence of hydrology and climate on the abundance of age-0 bream was combined with results from field investigations on the egg survival and abundance of age-0 bream. A strong positive correlation between the mean water level increase during the spawning season of bream (April-May) and the abundance of juvenile bream was found. By contrast, the absolute water level during spawning and during the nursery stage in summer, the cumulative temperature during the egg, larval and juvenile stages and two North Atlantic Oscillation (NAO) indices did not affect the abundance of juvenile bream. The field investigations confirmed that bream eggs attach better to and have higher survival rates on bare substratum than on substratum with epilithon cover. Accordingly, eggs within a spawning habitat of bream were most abundant between 10 - 20 cm depth, where the epilithon cover was lower than at depths exceeding 30 cm. The results of this study confirm an adverse influence of epilithon cover on the attachment and subsequent survival of bream eggs and emphasize the importance of spring inundations for the successful breeding of bream
Drug Development Against the Major Diarrhea-Causing Parasites of the Small Intestine, Cryptosporidium and Giardia
No full textDrug Development Against the Major Diarrhea-Causing Parasites of the Small Intestine, Cryptosporidium and Giardia
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