[Comparative efficacy of original oil escazole and nemozole suspensions in albino mice with experimental trichinosis in the muscle phase of invasion].

The efficacy of original oil escazole and nemozole suspensions in albino mice in the muscle phase of T. spiralis invasion, which was detected by lifetime diagnosis of experimental trichinosis 6 days after initiation of treatment in a daily dose of 0.3 g/kg, was 100%. Under equal experimental conditions, the oil nemozole suspension showed high toxicity and caused death in 50% of the treated animals.

[THERAPEUTIC ACTIVITY OF MICRONIZED MEBENDAZOLE IN THE MUSCULAR PHASE OF EXPERIMENTAL TRICHINELLA SPIRALIS INVASION IN ALBINO MICE].

The incidence of trichinosis in Russia was 0.07 per 100,000 population in 2014, which was 2.9-fold higher than that in 2013. Two WHO recommended medications mebendazole and albendazole are now used to treat humari trichinosis. The drugs are active against only mature helminths and non-encysted muscle larvae. The original oil suspension of micronized mebendazole was.found to have 100% efficacy against trichinosis in albino mice in the late muscular phase (encysted larvae) of hyperinvasion after intensive therapy under lifetime diagnostic guidance during and after a treatment cycle. The lifetime diagnostic method used to evaluate the larvicidal activity of anti-trichinosis agents in animals with experimental trichinosis revealed the signs of viaility, established a trend for deatih of Trichinella larvae, and determined their destructive changes.

[EFFICACY OF A NEW MEBENDAZOLE FORMULATION FOR EXPERIMENTAL ECHINOCOCCUS GRANULOSUS LARVAL INVASION IN ALBINO MICE].

The problem of echinococcosis has acquired special urgency in Russia in the last 10 years. The dramatically worse epidemiological situation of echinococcosis in the country is suggested by just frequent cases of cystic echinococcosis in the indigenous population of Moscow and its region, including children. Currently, albendazole that is less toxic than mebendazole remains the drug of choice, However, some authors note that E. granulosus larval cysts are moresusceptible to mebendazole than to albendazole. Both drugs mainly show parasitological activity and have no larvicidal effect particularly in larval alveococcosis. Analysis of the results of chemotherapy, with a group of benzimidazole carbamates for echinococcosis in 6 clinical centers from 5 European countries (Italy, Bulgaria, Romania, Greece, and Turkey) over the past 30 years showed that the evaluation of therapeutic effectiveness was overestimated; thus, 40% of all parasitic larval cysts that were considered dead became active again after, 2 years after the treatment. The original oil micronized mebendazole suspension tested by us in albino mice with late-stage larval cystic echinococcosis showed the properties of a highly effective and safe systemic larvicide that caused prompt death in the entire parasite population in the treated animals even in extreme hyperinvasion when the baseline parasite weight was greater than the host's one.

[Efficacy of nocodazole et experimental invasion Echinococcus granulosus of white mice].

The therapeutic activity of subcutaneous and intraperitoneal nocodazole injections was studied in albino mice with experimental E. granulosus invasion. The animals were intraperitoneally infected with Echinococcus larval cysts (ELC) from a spontaneously inoculated sheep. Nocodazole aqueous suspension (NAS) was administered at the late stage of invasion in two experiments. In one experiment, the treatment was initiated 7.5 months after inoculation. The animals were given daily subcutaneous injections of gradually increasing daily doses (n = 32) from 5 to 20 mg/kg twice weekly for 4 months (the total active ingredient dose was 400 mg/kg). The mice were dissected 3 months after treatment termination. Their autopsy showed that all ELCs or their vast majority were dead in 17 (70.8%) of 24 NAS-treated mice. Among the completely cured mice, there were animals having dead ELCs amounting to 36.9% of the host's weight. In the other experiment, the mice received intraperitoneal treatment 11.5 months after inoculation. They were given NAS injections (n = 2-8) in the total active ingredient dose of 14-126 mg/kg for 4-32 days. The animals were dissected 12-14 months after inoculation. All the detected ELCs were ascertained to be dead in the mice that had received NAS in an active ingredient dose of 87-126 mg/kg and had been dissected 33-81 days after initiation of treatment. The damaging effect of NAS was accompanied by obvious ELC collapse (the ELC collapse index was 57.5-75.9% for all the cured animals).

[Comparative efficacy of albendazole and mebendazole oily suspensions in albino mice with experimental larval alveococcosis].

The comparative efficacy of albendazole and mebendazole oily suspensions (AOS and MOS) was studied in an experimental model of experimental larval alveococcosis in albino mice. The animals were intragastrically injected with the agents once daily for 40 days on day 35 after intraperitoneal inoculation with E. multilocularis acephalocysts. They were dissected 29 days after treatment termination (103 days following inoculation) and the rate of infestation and viability and the degree of maturity of developed alveococcosis larvocysts (AL) were determined. The AOS and MOS efficiency estimated by the mean mass of AL per animal was 83.3 and 98.1%, respectively; whereas the similar indicator calculated by one largest AL weight per animal found among all the animals in the compared groups was equal to 57.7 and 96.9%, respectively. Under the equal conditions of solubilization in vegetable oil, the biological activity and bioavailability of mebendazole were shown to increase to a much greater extent than those of albendazole. The findings suggest that the use of mebendazole is promising for designing new vegetable oil-based formulations of the agent.

[Study of the therapeutic activity of nocodazole on experimental models of larval alveococcosis].

The therapeutic activity of parenteral nocodazole was studied on four larval alveococcosis models: golden hamsters (Mesocricetus auratus), Djungarian hamsters (Phodopus sungorus campbelli Thomas), albino rats (Rattus rattus albus), and cotton rats (Sigmodon hispidus) at the late stage of E. multilocularis invasion. The agent (aqueous suspension) was intraperitoneally, intramuscularly, and subcutaneously injected in daily doses of 0.125-0.5 g/kg as 1-8 injections. Mebendazole was the drug of comparison. In the golden hamsters, one intraperitoneal nocodazole injection in daily doses of 0.25 and 0.5 g/kg caused death of all alveococcosis larvocysts whereas mebendazole 0.5 g/kg proved to be ineffective. In the Djungarian hamsters, one intraperitoneal nocodazole injection in a dose of 0.25 g/kg was fatal to alveococcosis larvocysts in 3 (75%) of the 4 animals. In the albino rats, nocodazole once administered intraperitoneally in a dose of 0.125 g/kg caused no death of all parasitic larvocysts, but inhibited their growth by 94.4%. The found alveococcus larvocysts were dead in all the cotton rats receiving nocodazole intramuscularly and subcutaneously 8 times in daily doses of 0.125 and 0.2 g/kg, respectively. Larvocystic death induced by nocodazole in animals with intensive invasion was accompanied by the high rate of collapse in larvocysts.

[Lifetime diagnosis of trichinosis in experimentally infected laboratory animals].

The authors propose a new method for lifetime diagnosis (LTD) of experimental invasion of Trichinella spiralis in migratory and muscular phases, which is based on thin-layer microscopy of minor samples of skeletal muscles (weighing 1-1.5 mg) on gradually increased impulse manual compression. The LTD method permits the monitoring of the most important follow-up qualitative and quantitative invasion parameters in each infected animal in normalcy and under the action of specific therapeutic and preventive agents (the onset and termination of a migratory phrase, the elimination time of intestinal Trichinella after infection, the number, sizes, morphological features, viability, and motor activity of nonincapsulated and incapsulated muscular Trichinella larvae of different age). The most important feature of LTD is its possibility of detecting and determining the viability of neonatal T. spiralis larvae. LTD enhances the informative value, reduces the costs of and makes experimental studies of the basic and applied problems of trichinosis shorter.

[Experimental model of activated Lamblia (Giardia) muris infection in albino mice].

Experimental L. muris infection was reproduced in 100% of the intact albino mice intragastrically given levomycin in an average total dose of 15.88-34.84 or 0.88-1.02 g/kg for 18-34 days. With levomycin administration, the intensity of giardiasis was 1121.6-8540.1 (mean 4830.9) thousand L. muris trophozoites per animal. The total number of trophozoites per animal decreased to 302.2-3481.4 (mean 1546.4) thousand and 28.1-324.0 (mean 109.4) thousand specimens 5-8 and 11-13 days after discontinuation of the antibiotic, respectively. The maximum number of L. muris trophozoites was observed in the proximal and middle portions of the murine small intestine during and after the administration oflevomycin. The highest isolation of cysts was seen 12-14 days after the initiation of administration of the antibiotic. Following 8-10 days of terminations of a course of levomycin therapy the native smear of animal feces showed no Lamblia cysts. In mice with activated infection, the isolation rate of Lamblia cysts was directly related to the intensity of intestinal infection with trophozoites of the parasite.

[The specific features of development of Echinococcus granulosus metacestode (exogenous blastogenesis) in man].

The paper describes a case of abnormal development of a parasitic cyst by the type characteristic of alveolar echinococcosis (exogenous blastogenesis) detected in a female patient operated on for echinococcus. The fact that the exogenous blastogenesis has been found allows the mechanism of a postoperative recurrence of human echinococcosis to be explained from basically new standpoints. A parasitological analysis of the punctates of cystic masses and cysts themselves, taken from patients operated on for cystic echinococcosis has revealed one of the signs of malignant exogenous proliferation of elements of a parasytic metacestode, namely, the development of acephalocysts from the germinative cells of the pedicle of protoscoleces. The capacity of cystic echinococcosis metacestodes for exogenous blastogenesis by the type of human alveolar echinococcosis is an early unknown species-specific feature of E. granulosus.

[Experimental grounds of a new concept of Opisthorchis felineus infection formation in a definitive host].

In the course of experiments in was found out that golden hamsters having the bilious duct operationally blocked display receptivity to the infection with the non-excysted Opisthorchis felineus metacercariae passed to the stomach. Excysted metacercariae injected to the system of the portal vein settle down in the bilious pathways of the liver and develop there up to the adult stage. In vitro, the metacercariae survive in the blood serum of the intact golden hamsters during one day. Based on the experiments, it is hypothesized that the early stage of O. felineus infection in the bilious duct of definitive hosts is performed by means of hematogenic migration of metacercariae through the portal veins system from the mucous layer of the alimentary tract of the host.

[Activity of the anthelmintic agent trichlorophen on the models of human helminthiasis]. / Aktivnost' otechestvennogo antigel'mintika trikhlofena na modeliakh gel'mintozov cheloveka.

Trials of trichlorophen have shown its high efficacy on models of cestode infections: hymenolepiasis (at the adult and cysticercoid stages of development on three types of animals: outbred albino mice, albino rats and golden hamsters), preimaginal echinococciasis alveolaris, larval alveolar echinococciasis (at the early stage of development of the parasite in experiments on cotton rats). The high nematodical activity of trichlorophen was first found on models of trichocephaliasis in DBA/2y mice, nippostrongyloidiasis (in in vitro experiments), and aspiculuriasis in outbred mice. The agent proved to be ineffective at the tissue developmental stage of Hymenolepsis nana (H. nana), the dwarf tapeworm, in albino mice, during experimental opisthorchiasis in golden hamsters. It showed a low efficacy in treating trichinosis in outbred albino mice. Unlike carbamatebenzimidazoles, trichlorophen was inactive at the tissue stage of H. nana; it exerted no effects on the eggs of a dwarf tapeworm in trichinosis. Trichlorophen was also inactive in treating experimental opisthorchiasis in golden hamsters.

[Experimental rationale for the use of medapec as the drug of choice in treating echinococcosis]. / Eksperimental'noe obosnovanie prigodnosti medapeka v kachestve preparata vybora dlia lecheniia ékhinokokkozov.

The dosage form of medamine-medapec was found to have a high antiechinococcal activity in experiments on laboratory animals. Its efficacy was shown in treating larval alveolar echinococciasis in mice and cotton rats with different doses and courses as compared with medamine and albendazole. It was ascertained that for its high larvicidal activity, medapec should be given to animals regularly during a day. The daily dose of the drug should be gradually increased. In complying with these conditions, the duration of effective courses of therapy drastically reduces.

[Developing of new anthelmintics. Evaluation of fluzamide on the new experimental models of intestinal cestode infections]. / Razrabotka novykh otechestvennykh antigel'mintikov. Otsenka terapevtitseskoi aktivnosti fluzamida na novykh éksperimental'nykh modeliakh kishechnykh tsestodozov.

The efficacy of the original drug fluzamide (a N,S-containing heterocycle derivative) was evaluated by primary screening on a modified model of monoinvasion with the luminal form of Echinococcus multilocularis and on an original model of intestinal mixed invasion of E. multilocularis and Hymenolepsis nana at the immature and mature stages of the parasites in golden hamsters when an experimental host was immunosuppressed with hydrocortisone. The efficacy of fluzamide in an oral dose of 0.3 g/kg against young E. multilocularis and H. nana (the duration of their invasion was 7 days) was 99.8-100%; that against adult cestodes of both species (their maximum age was 28 days) was 100%. The original method of simulation of intestinal cestodiases in laboratory rodents, which is based on the artificial transplantation of cestodes at the prepatent stage of development from the intestine of infected donors to the intestine of healthy recipients through the latter' stomach during drug immunosuppression, showed its high reliability. There is evidence that transplanted immature strobilar cestodes can survive in the stomach, get acclimated, and continue to develop in the recipients' small bowel up to the stage of formation of infective eggs.

[An improvement in a new method for the surgical treatment of echinococcosis]. / Sovershenstvovanie novogo sposoba khirurgicheskogo lecheniia ékhinokokkoza.

Parasitic cysts were intraoperatively treated with glycerol in 179 patients with echinococcosis at various sites and 3% hydrogen peroxide in 165 patients with hepatic echinococcosis. Experiments on 60 cotton rats experimentally infected with Echinococcus alveolaris and 156 albino mice with E. granulosus provided evidence for the surgical use of 80-100% glycerol or 3% hydrogen peroxide to treat the cysts. Intraoperative glycerol treatment of cysts in patients with complicated hepatic echinococcosis fails to normalize amino acid metabolism, as well as immunity even a year postoperatively. The glycerol method has no contraindications for pulmonary and hepatic echinococcosis. Hydrogen peroxide has a damaging effect on all germinal elements of both E. alveolaris and E. granulosus. The authors recommend that 3% hydrogen peroxide should be intraoperatively used for treatment of cysts. After surgery, there is a tendency for amino acid metabolism to become normal in such patients.

[Treatment of hydatid cysts' residual cavities (experimental and clinical study)]. / Obrabotka polosti kist pri gidatidnom ékhinokokkoze (éksperimental'no-klinicheskoe issledovanie).

Experimental series of 60 cotton rats and 150 white mice infected with echinococcus showed that 80-100% glycerin and 3% peroxide solution were effective scolicidal solutions for inactivation of the parasite. 344 patients have been operated on for hydatid disease with inactivation of the parasite by means of these scolicidal solutions. Glycerin during the surgical management of the hydatid cysts is effective and harmless in uncomplicated hydatid liver disease and any hydatid pulmonary cysts. Glycerin is contraindicated in complicated hydatid liver disease because of immunity disturbance. In complicated hydatid liver disease management of the hydatid cysts by 3% peroxide is effective and harmless. It is necessary to correct the hydatid liver disease patients' immunity in the preoperative and postoperative periods. Tactivin and antiechinococcus drug SK-1 are effective immunomodulators in hydatid liver disease.

[Homeopathic preparation Cheblin-CK-1 in the pathogenetic therapy of echinococcosis]. / Ispol'zovanie gomeopaticheskogo preparata Cheblin-CK-1 v patogeneticheskoi terapii ékhinokokkoza.

This study was experimental and clinical. The experiments were made on 80 cotton rats. The clinical study covered 289 patients operated on for echinococcosis. Earlier studies indicated that echinococcosis is accompanied by secondary immunodeficiency and amino acid metabolic disorders. The homeopathic drug Cheblin-CK-1 used normalized amino acid metabolism 40 days after treatment in these patients. The same properties were displayed by homeopathic drugs.

[Experimental echinococcosis and alveococcosis and a trial of the preparation SK-1]. / Eksperimental'nyi ékhinokokkoz i al'veokokkoz i ispytanie preparata SK-1.

In autobred albino mice, the maximum nonlethal dose of the agent CK-1 was established, which was 19.0 g/kg, the agent was nontoxic. Cotton rats aged 30-45 days were infected by alveococcosis from a donor rat. The methods and formulas developed by Mikhailitsin et al. were used during experiments and investigations. At the beginning of treatment, 5 rats were found to have a great deal of parasitic larvocysts (PL) 10 days after infection. Eight rats formed a control group, 8 were treated with CK-1 in a constantly increasing doses of 0.1, 0.26, and 0.34 g/kg for 3 weeks. Following 40 days of infection, the animals were anesthesized and CK-1 was ascertained to have a high antialveococcal activity: the index of suppressed PL growth was 90.23 to 92.74%. In 14 piglets aged 1 month, infected by echinococcosis strains and treated CK-1 in high doses, was established to cause echinococcal death. In 14 puppies, the agent was highly effective in strobular echinococcosis.

[The search for new antiparasitic agents. 17. The synthesis and study of the anti-echinococcal activity of the new preparation G-1697]. / Izyskanie novykh protivoparazitarnykh sredstv. 17. Sintez i izuchenie protivoékhinokokkovoi aktivnosti novogo preparata G-1697.

The paper describes the synthesis of the new agent G-1697 which is 4-[(benzo-2,1,3-thiadiazolyl-4)amino]-5, 6,7,8-tetrahydrobenzothieno [2,3-d] pyrimidine and the results of testing its acute toxicity and antiparasitic activity on a model of Echinococcus multilocularis invasion at the larval stage in cotton rats. The maximum nonlethal dose of G-1697 was 4.0 g/kg for outbred mice of both sexes whose weight was 14-16 g. Adult cotton rats (males) received the agent with their feed in increasing daily doses for 3 weeks continuously on days 8 to 28 after infection. The daily dose of its active ingredient varied from 0.03 to 0.35 g/kg and averaged 0.12 g/kg (the mean total dose per session was 2.47 g/kg). The baseline weight of parasitic larvocysts (PL) per animal averaged 0.28 g at the baseline. In the treated and control rats sacrificed 34 days following infection, the mean mass of PL per animal was 0.95 and 7.51 g, respectively. In the cotton rats treated with G-1697, the suppressed growth index calculated by three parameters (moderate, maximum, and minimum mass of PL in the animals of the comparable groups after treatment with regard to the similar baseline variables) was 90.8, 91.0 and 92.7, respectively, versus the controls. Among all PL found in each animal, its death was approximately 70-90% in the treated rats.