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).

The effect of Ascaris trypsin inhibitor on proteolytic activity of lungs and kidneys of guinea pig with larval ascariosis and after ascarid homogenate administration.

Trypsin inhibitor, isolated from Ascaris suum tegument reduces in vitro proteolytic activity (pH 7) of lungs and kidneys post-nuclear fractions of guinea pigs with larval ascariosis, pigs after subcutaneous ascarid homogenate administration as well as the activity in control groups. The comparative analysis of effect curves of trypsin inhibitor on the organ proteases revealed stronger reduction of the activity of post-nuclear lung proteases in ascariosis and of kidneys proteases after the injection of Ascaris homogenate than the inhibition of the fractions activity from respective control groups.

[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.

Further studies on the properties of bile acids. I. Bile acid-induced changes of the action of drugs acting on the autonomic nervous system on the heart and blood vessels.

The action of certain drugs on the autonomic system was studied under the influence of bile acids: 3,12-dihydroxycholanic acid (deoxycholic), 3,7,12-trihydroxycholanic acid (cholic), and 3,7,12-triketocholanic acid (dehydrocholic). The experiments were carried out on rat heart in vivo and on isolated rat vessel preparation. It was shown that bile acids reduced the stimulating effect of isoprenaline on rat heart and the relaxing effect on the blood vessels. An inversion of the effects of adrenaline and noradrenaline on the rat heart was observed, and an enhancement of the vasoconstrictor effect of these substances. Under the conditions of this experiment an inversion was noted of the action of acetylcholine on the heart and blood vessels.

[Effect of proteolysis inhibitors from Ascaris lumbricoides on the coagulation and fibrinolysis of human plasma]. / Die Einwirkung von Inhibitoren der Proteolyse aus Ascaris lumbricoides auf die Gerinnung und Fibrinolyse des Menschenplasmas.

By means of the method of ROLA & PUDLES modified by the authors the effect of trypsin and chymotrypsin inhibitors isolated from body walls of Ascaris lumbricoides on coagulation and fibrinolysis of human plasma in vitro was studied. The effect of both Ascaris inhibitors on coagulation phases I and II, the inhibition of thromboplastin and thrombin generations (thromboelastography, prothrombin and thrombin times) and the fibrinogenesis retardation of human plasma (time of lysis of euglobulin clot, time of clot fibrinolysis activated by streptokinase) were found. "The stairs phenomenon" was observed on thromboelastographic curves. The plasmin activity in an active form as well as its formation from plasminogen by streptokinase activation were reduced by chymotrypsin and trypsin Ascaris inhibitors alike.

L-aspartate of erythromycin A cyclic 11,12-carbonate, a new semisynthetic erythromycin derivative.

Erythromycin A cyclic 11,12-carbonate, a compound with high antibacterial activity, forms with L-aspartic acid a salt possessing valuable properties as a potential chemotherapeutic agent. The L-aspartate of erythromycin A cyclic 11,12-carbonate exhibits strong anti-bacterial activity, especially against Gram-positive bacteria and shows low toxicity. The serum and the lung tissue levels of the discussed salt after a single dose administration to a rat were measured in comparison with those of erythromycin, its L-aspartate, erythromycin cyclic 11,12-carbonate and its L-glutamate. The new erythromycin derivative showed definitely superior characteristics to those of the other substances tested. The activity of the L-aspartate of erythromycin A cyclic 11,12-carbonate in chemotherapy of experimental staphylococcal infection and experimental pneumococcal bronchopneumonia in mice is superior to that of the parent carbonate and erythromycin itself.