Effect of thyroliberin on the course of experimental candidosis in mice.

Thyroliberin (TRH) is one of the hormones, which affect immunologic processes. This hormone was studied in experimental subacute candidosis in mice. BALB/c males were given intraperitoneally single dose of Candida albicans cells (1 x 10(7) to 1 x 10(9) cfu of strain no. 244-33 ATCC). The animals from the experimental groups were injected subcutaneously, after 24 h from inoculation, dose of 10 microg TRH in 0.2 ml 0.9% NaCl, seven times at 24 h intervals. The control animals were given respectively 0.2 ml of physiologic NaCl solution. We have found that the examined hormone significantly decreases mortality in these animals (LD50 C. albicans for mice treated with TRH was three times higher than that in the control groups), prolongs mean survival time for mice and decreases the intensity of fungal invasion of the animal organs.

Comparison of the effect of Ascaris trypsin inhibitor in various periods of mouse pregnancy.

Trypsin inhibitor isolated from Ascaris suum and injected into pregnant BALB/c mice (five times, in doses: 300 or 400 mg/kg/day) in various periods of pregnancy (early and late organogenesis) disturbed the development of fetuses. The nature and intensity of prenatal disturbances are determined by the inhibitor dose and time of injection. It has been found that administration of the inhibitor from 5-th until 9-th day of gestation did not delay or prevent implantation, but caused a high rate of intrauterine deaths and also specific congenital malformations (exnencephaly and hydrocephalus). Additionally, other types of defects were noted in fetuses after injection of the inhibitor between 8-th and 12-th day of pregnancy (cleft palate, fusion of ribs). Independent of the time of injection during gestation the inhibitor exhibited embriotoxic effects (e.g. decreased the number of live fetuses per litter and mean fetal weight).

Preliminary evaluation of maternotoxic effect of Ascaris alpha-chymotrypsin inhibitor in mice.

Administration intraperitoneally of the Ascaris alpha-chymotrypsin inhibitor (40-300 mg/kg/day) at a late stage of organogenesis (8-12 days of gestation) disturbed course of mouse pregnancy. The low doses of alpha-chymotrypsin inhibitor (40-80 mg/kg/day) significantly decreased the number of live fetuses per litter, increased the number of fetal resorptions. The symptoms of maternal toxicity that occurred after administration of the highest doses of the inhibitor (80-300 mg/kg/day) to pregnant mice included: decreased body weight gain as compared to control, vaginal hemorrhage, intrauterine resorption of litters, abortions, altered behaviour of animals immediately after injection and death. There is a linear interrelationship between the logarithm of the doses of the inhibitor and mortality of pregnant mice. The DL50 value of the inhibitor for female was 116 mg/kg/day (confidence interval: 95.5-140.0 mg/kg/day).

Disturbances of mouse pregnancy after injection of Ascaris homogenate during early organogenesis.

Administration of the Ascaris tegumental homogenate (0.6-1.2 g of Ascaris proteins/kg/day) at a early stage of organogenesis (5-9 days of pregnancy) had a harmful effect upon the developing mouse fetuses. It has been found that injection of the homogenate did not delay or prevent implantation, but causes a high rate of intrauterine deaths. The Ascaris homogenate significantly decreased the number of live fetuses per litter, increased the frequency of litter resorption, produced a delay in bone formation and induced pathological changes of fetal organs and tissues. The congenital malformations were noted in fetuses after injection of higher doses of Ascaris homogenate (exencephaly, craniomeningocele and internal hydrocephalus). No malformations were noted in control groups and after injection of minimum dose of the homogenate. The symptoms that occurred after administration of the tegumental homogenate to pregnant mice included: decreased body weight gain (p<0.001) as compared to controls, vaginal hemorrhage, intrauterine resorption of litter and mortality. These signs suggest that the Ascaris homogenate causes maternal toxicity.

[Teratogenic action of alpha-chymotrypsin inhibitor of Ascaris lumbricoides in mice]. / Dzialanie teratogeniczne inhibitora alfa-chymotrypsyny Ascaris lumbricoides u myszy.

During investigations of biological activity of proteolysis inhibitors from Ascaris lumbricoides, teratogenic action of alfa-chymotrypsin inhibitor (ICH) was evaluated. The inhibitor was obtained by a method of Roli and Pudles and was applied parenterally at 8-12 day of pregnancy to BALB/c mice in doses of 20-80 mg/kg of mice per 24 hours. Control groups received respectively 1 cm3 of 0.9% NaCl or 80 mg of bovine albumin. Normal status of development of internal organs in 19-days old fetuses was evaluated by a method of Wilson and Dyban and of their skeletons according to Dawson. It was found that character and exacerbation of prenatal disturbances of mice development is conditioned by the ICH dose. Teratogenic action of ICH was apparent in fetuses after application to mice of 60 and 80 mg. Most frequent developmental defects were: cleft palate, brain hernia, fusion of ribs and curvature of spine. No defects were noted in control groups. Lower doses of ICH exhibited only embryotoxic effect.

[The effect of Ascaris lumbricoides suis and its trypsin inhibitor on the chick embryo]. / Dzialanie homogenatu Ascaris lumbricoides suis oraz jej inhibitora trypsyny na zarodek kury.

It has been found that tegument homogenate of Ascaris lumbricoides suis and also trypsin inhibitor isolated from it induce the Leghorn chick embryos mortality when injected into their yolk sac on 4th, 8th or 13th day of incubation. The trypsin inhibitor is one of important components of Ascaris homogenate causing mortality. There is linear interrelationship between the logarithm of dose of homogenate or trypsin inhibitor and the mortality of chickens in %. A significant decrease of mean mass of chicks injected with Ascaris homogenate or trypsin inhibitor in comparison with control groups was observed. There was more frequent occurrence of developmental abnormalities and pathological changes in groups of hatched chicks which received Ascaris homogenate or inhibitor.

Proteolysis inhibitors from Ascaris lumbricoides: fact or fiction?

The results of our own 25 years investigations on biological activity of proteolytic inhibitors of Ascaris lumbricoides with the help of various experimental models were discussed. As it results from these studies alpha-chymotrypsin and trypsin inhibitors from A. lumbricoides are not fiction but are substances with significant biological activity, which may be important in regulation of the host-parasite system as well as parasite pathogenic factor.

[Studies of compounds with potential antiparasitic action. VIII. New oxime ethers in the 1-thiochromone system]. / Badania zwiazków o potencjalnym dzialaniu przeciwpasozytniczym. VIII. Nowe etery oksymów w ukladzie 1-tiochromonu.

The 50% antitrichomonal 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 degrees C, 24 hr) was calculated with the aid of regression equation. All examined ethers show in vitro a marked antitrichomonal 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 clotrimazole. The strongest complex antitrichomonal and mycostatic effect-comparable to ornidazole or clotrimazole - shows the new derivative N,N-diethylaminoethyl oxime of 1-tioflavone (compound II), which is fairly toxic for mammal.