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Widely introduced parasitic control programs rely heavily on the use of synthetic or semi-synthetic antiparasitic compounds. The ineffectiveness of these therapies and growing drug resistance of nematodes leads researchers to search for new alternative methods to combat parasites. One proposal is to use the medicinal properties of herbs that have been used in medicine and veterinary practice for a longer period. The research of activity of plant extracts and their fractions are increasingly important to develop therapies that improve the health of humans and also animals. Anthelmintic properties of plant compounds may be used in an environment where invasive forms of parasites develop. At this stage different compounds can affect the growth and development of parasites, such as inhibiting the molting process. Knowledge of the development of nematodes is still incomplete. On account of the simple structure and transparent body of the nematode, Caenorhabditis elegans is a model species to study many phenomena. Development of the nematode (parasitic and free-living) is strictly programmed. Apoptosis is one of the major mechanisms involved in nematode development. The main apoptotic pathway proteins are CED-3, CED-4 (pro-apoptotic) and CED-9 (anti-apoptotic). Changes in the levels of these proteins may alter the course of organogenesis leading to adverse phenotypic effects. Saponins are compounds commonly occurring in the plant kingdom (both in edible plants and herbs). The mechanism of the action of triterpenoidsaponins per cell is not fully understood. They show numerous properties such as immunomodulatory, antiviral, cytotoxic, or antitumor. Particularly derivatives of oleanolic acid and ursolic acid exhibit a variety of pharmacological properties without toxic side-effects. Due to their characteristics active plant compounds, mainly derivatives of pentacyclictriterpenoids, are a potential source of anticancer, cytotoxic and anthelmintic new generation substances. These may affect the development of the parasite to regulate apoptosis. The discovery of the manner in which saponins are involved in apoptosis can be the first step toward the development a new drug for parasite diseases.
Автор провел экспериементальное исследование токсического влияния адипата фисфата пиперазина на организмы 48 серебристых и голубых лисиц (песцов) применяя главным образом анатомопатологическое вскрытие. Животные были разделены на 2 группы. I группа получала в пище 10 дней ежедневно по 0,5 г соответствующего препарата, а I! по 1,5 г. Установлено, что адипат или фосфат пиперазина применяемые ежедневно 10 дней по 0,5 г не вызывают у лисиц побочных вредных последствий, но в тех же условиях при дозировке по 1,5 г у животных появляются деструктивные изменения в печени и в почках (паренхиматозная дегенерация, жировая инфильтрация и маленькие некротические очаги), клеточные инфильтраты и большая гиперемия этих органов. Установлено тоже гиперемию легких, поджелудочной железы и селезенки, а также острое, иной раз геморрогическое, воспаление слизистой оболочки пищеварительного тракта, а особенно тонких кишек. Кроме того в течение последних 2 лет подвержено дегельминтизации около 1200 серебристых и 60 платиновых лисиц а также ок 1400 песцов, применяя адипат пиперазина в дозировке 0,1 /кг ж.в., двухкратно с трехдневными интервалами. Взрослые лисицы и их мелодеж были дегельминтизированы 2 раза в год. Никаких вредных последствий не установлено.
By the modification of chemical structure of some drugs the series of ether compounds with potential anti-trichomoniasis and anti-fungial action were received.
The trichomonacidal activity in vitro of 6 new derivatives of theirs containing amine and halogenaryloalkyl groups in comparison with metronidazole, ornidazole and tinidazole has been examined. For all the examined compounds curves of action were obtained after 30 min. and lethal concentrations for 50% population (CL₅₀) of three strains of T. vaginalis used for experiments were calculated. The trichomonacidal action of the following compounds was especialy strong: 2-/1-methylpiperazin-4-yl/ethyl-4-chlorbenzhydryl ether dihydrochloride and 2-/1-benzylperhydro-1,4-diazepin-4-yl/ethyl 2,4-dichlorbenzyl ether dihydrochloride. The trichomonacidal action of these compounds was several times stronger than that of metronidazole and tinidazole.
The 50% trichomonocidal concentration of 7 examined ethers (T. vaginalis strain N° 1/86, Roiron medium, safranine staining, 30 min.) was estimated by means of dose-response curve. The minimal mycostatic concentration (Candida albicans L-45, Geotrichum candidum; 3% Sabouraud agar, 37°C, 24 hr) was calculated with the aid of regression equation. All examined ethers show in vitro a marked trichomonocidal effect comparable with activity of ornidazole or phenol. Mycostatic activity of new compounds is many times higher than activity of phenol, but considerably lower than that of klotrimazole. The strongest complex trichomonoddal and mycostatic effect-comparable to ornidazole or klotrimazole - shows the new derivative N,N-diethylaminoethyl oxime of 1-tioflavone (compound II), which is fairly toxic for mammal.
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