Methodology for application of supramolecular fenbendazole against helminthosis of ruminants

The purpose of the research is developing a methodology for application of the supramolecular complex of fenbendazole (SMCF) against helminthosis in ruminants.The SMCF was obtained by the method of mechanochemical technology with polyvinylpyrrolidone (PVP) in a ratio of 1 : 10 in a balling drum. The drug was produced in plastic cans of 2, 4 and 8 kg and stored in its original packaging in dry, nonresidential area. The SMCF was used against gastrointestinal strongylatosis, dictyocaulosis and monieziosis of sheep and goats at a dose of 20 mg/kg (2 mg/kg for the active substance). The methodology provides a brief chemical characteristic of the SMCF, summarizes its mode of action, and describes toxicological properties, which gives an idea of the drug in general. The procedure is described for preparing the drug for use on animals, both individually and in a group. Reasoned recommendations are given on the timing for animal slaughter, and the use of milk after treating cows

Кумулятивные свойства и субхроническая токсичность супрамолекулярного комплекса фенбендазола

The purpose of the research is to study the cumulative effect and subchronic toxicity of supramolecular complex of fenbendazole (SMCF).Materials and methods. The cumulative effect of SMCF was studied on 20 outbred white rats weighing 180 g that were divided into experimental and control groups of 10 animals each. SMCF was administered intragastrically to rats of the experimental groups for 24 days at the dose of 2000 mg/kg (1/10 of the previously established single LD50 (20000 mg/kg)) on the first day, then the dose was increased by 1.5 times every four day. The main criterion for evaluation of the results was the death of animals; we also observed the overall condition and behavior of rats. Subchronic toxicity was studied on 40 male white rats weighing 220–240 g. The animals were divided into 4 equal groups. The drug was administered daily to rats of the 1st, 2nd and 3rd experimental groups intragastrically using the doses of 1/5 (4000 mg/kg), 1/10 (2000 mg/ kg) and 1/20 (1000 mg/kg) of LD50 (20000 mg/kg) respectively for 7 days. The control group received 1% starch paste in an appropriate volume throughout the experiment. During the experiment, we observed physical signs and behavior of animals, food and water consumption; weight gains of animals on the 1st, 3rd, 5th and 7th days of the experiment. After the drug administration, animals were sacrificed by cervical dislocation. The laboratory examinations for hematological parameters and biochemical parameters were performed after treatment. Samples of organs (liver, heart, lungs, kidneys, spleen) were taken during necropsy to calculate mass coefficients and to make macroscopic examinations.Results and discussion. We found that the SMCF did not have any cumulative properties. The overall condition and behavior of rats was within the physiological range; animals consumed food and water and showed no signs of intoxication after oral administration of SMCF at doses of 1/5, 1/10 and 1/20 of LD50 for 7 days. The drug did not have influence on weight gains of animals. Hematological and biochemical parameters did not undergo significant changes and were comparable with the parameters of the control group. The mass coefficients of the internal organs did not differ statistically in experimental and control groups of rats. Цель исследований – изучить кумулятивные свойства и субхроническую токсичность супрамолекулярного комплекса фенбендазола (СМКФ).Материалы и методы. Кумулятивные свойства СМКФ изучали на 20 беспородных белых крысах живой массой 180 г, которых разделили на опытную и контрольную группы по 10 животных в каждой. СМКФ вводили крысам опытной группы внутрижелудочно в течение 24 сут: в первый день в дозе 2000 мг/кг (1/10 от ранее установленной однократной ЛД50 (20000 мг/кг)), затем дозу увеличивали в 1,5 раза через каждые четыре дня. Основным критерием оценки результатов является гибель животных; также учитывали общее состояние и поведение крыс. Субхроническую токсичность изучали на 40 белых крысах-самцах массой тела 220–240 г. Животных разделили на 4 равные группы. Препарат вводили крысам 1, 2 и 3-й опытных групп в дозах соответственно 1/5 (4000 мг/кг), 1/10 (2000 мг/кг) и 1/20 (1000 мг/кг) от ЛД50 (20000 мг/кг) в течение 7 сут ежедневно внутрижелудочно с помощью зонда. Контрольная группа на протяжении всего опыта получала 1 %-ный крахмальный клейстер в соответствующих объемах. В течение опыта проводили наблюдение за общим состоянием и поведением животных, приемом корма и воды; учитывали прирост массы тела животных на 1, 3, 5 и 7-е сутки опыта. После окончания введения препаратов животных подвергали эвтаназии методом декапитации. Отбирали пробы крови для определения основных гематологических и биохимических показателей; после вскрытия отбирали образцы внутренних органов (печени, сердца, легких, почек, селезенки) для определения массовых коэффициентов и макроскопических исследований.Результаты и обсуждение. Установлено, что СМКФ не обладает кумулятивными свойствами. При пероральном введении СМКФ в дозах 1/5, 1/10 и 1/20 от ЛД50 крысам в течение 7 сут общее состояние и поведение животных было в пределах физиологической нормы; крысы активно принимали корм и воду, признаки интоксикации отсутствовали; введение препарата не оказывало существенного влияния на прирост массы тела животных. Гематологические и биохимические показатели крови не подвергались значительным изменениям и были сравнимы с показателями контрольной группы животных. Массовые коэффициенты внутренних органов достоверно не отличались у крыс опытных и контрольной группы.

Evaluation of the efficacy of benzimidazole anthelmintics against different stages of gastrointestinal nematodes of young cattle

The purpose of the research is to study the efficacy of benzimidazole anthelmintics against different development stages of gastrointestinal nematodes of young cattle.Materials and methods. The efficacy of benzimidazole drugs against early development stages of gastrointestinal nematodes was evaluated on 58 male calves aged 12–18 months spontaneously infected with gastrointestinal strongylates on the Moscow Region farms contaminated by nematode parasites. The animals were weighed, numbered and divided into experimental and control groups of 7–10 animals each. The male calves from different experimental groups were orally administered Panacur, Febtal, Fenbendazole (substance), Alben, Alvet, Valbazen, Closalben and Albendazole 10% powder once at a dose of 7.5 mg/kg for the active substance. The control animals did not receive the drug. The drug efficacy was recorded in the experiments of the "control test" type based on the coproovoscopic examination results by the flotation method using a VIGIS counting chamber, and on the results of helminthological dissections of the digestive tract of 3–5 animals from each group. The drug efficacy was recorded as per the Guidelines Approved by the World Association for the Advancement of Veterinary Parasitology (1995). The results were processed statistically using the Microsoft Excel computer tool.Results and discussion. We established the 94.4–97.2% efficacy of the drugs based on benzimidazoles, namely, Panacur, Febtal, Alben, Alvet, Valbazen and Closalben in therapeutic doses against imaginal gastrointestinal strongylates and 44.2–69.2% activity against nematode larvae

Methodology for the quantitative determination of fenbendazole and its metabolites in organs and tissues of animals by high performance liquid chromatography with tandem mass spectrometry detection

The purpose of the research is to develop a methodology for the quantitative determination of fenbendazole (FBZ) and its metabolites in organs and tissues of sheep by high performance liquid chromatography tandem mass-spectrometry (HPLC-MS/MS).Materials and methods. The method for determining of FBZ and its metabolites after the administration of the supramolecular complex of fenbendazole was validated in accordance with international guidelines for the following indicators: linearity, recovery, specificity, precision, accuracy, limits of quantitative and qualitative determination.Results and discussion. The method of quantitative analysis of FBZ and its metabolites sulfone and sulfoxide in the body of sheep after the administration of the supramolecular complex has been adapted. The proposed method has a linear relationship (R > 0.99) in the range of 5–1000 ng / g and has shown a good reproducibility and accuracy

Методика по применению супрамолекулярного фенбендазола при гельминтозах жвачных животных

The purpose of the research is developing a methodology for application of the supramolecular complex of fenbendazole (SMCF) against helminthosis in ruminants.The SMCF was obtained by the method of mechanochemical technology with polyvinylpyrrolidone (PVP) in a ratio of 1 : 10 in a balling drum. The drug was produced in plastic cans of 2, 4 and 8 kg and stored in its original packaging in dry, nonresidential area. The SMCF was used against gastrointestinal strongylatosis, dictyocaulosis and monieziosis of sheep and goats at a dose of 20 mg/kg (2 mg/kg for the active substance). The methodology provides a brief chemical characteristic of the SMCF, summarizes its mode of action, and describes toxicological properties, which gives an idea of the drug in general. The procedure is described for preparing the drug for use on animals, both individually and in a group. Reasoned recommendations are given on the timing for animal slaughter, and the use of milk after treating cows.Цель исследований: разработать методику по применению супрамолекулярного комплекса фенбендазола (СМКФ) при гельминтозах жвачных животных.СМКФ получали методом механохимической технологии с поливинилпирролидоном (ПВП) в соотношении 1 : 10 в барабане шаровой мельницы. Выпускали препарат в пластмассовых канистрах емкостью 2, 4 и 8 кг. Хранили препарат в заводской упаковке в сухом, нежилом помещении. СМКФ применяли при стронгилятозах пищеварительного тракта, диктиокаулезе, мониезиозе овец и коз в дозе 20 мг/кг (2 мг/кг по ДВ). В методике приведена краткая химическая характеристика СМКФ, приведен механизм его действия, описаны токсикологические свойства, что, в целом, дает представление о препарате. Описана процедура подготовки препарата для применения на животных как индивидуально, так и групповым методом. Приведены обоснованные рекомендации по срокам убоя животных и использования молока после обработки коров

Optimal schemes for the use of anthelmintics at gastrointestinal strongylatosis of young cattle

The purpose of the research is to study the rational terms for the use of anthelmintics in case of gastrointestinal strongylatoses of young cattle in Nonchernozem zone of the Russian Federation.Materials and methods. The timing of the onset of re-isolation of nematode eggs with feces of cattle after the use of some anthelmintics was determined on 50 black-motley calves weighing 117–130 kg, spontaneously infected with gastrointestinal strongylates. The optimal schemes for the use of anthelmintics in case of gastrointestinal strongylatosis of young cattle were studied on 109 calves of the first year of grazing in the pasture period of 2010. After numbering, the animals were weighed and divided into experimental and control groups. Each group was divided into two subgroups of 15–17 heads. Animals of all groups from May 3 to October 10, 2018 were grazed together in one herd on a pasture where cattle infected with strongylates had previously grazed. Levamisole from the group of imidothiazoles, Alben from the group of benzimidazoles and Aversect-2 from the group of macrocyclic lactones were tested. The drugs were used in therapeutic doses: levamisole at a dose of 7.5 mg/kg by AS intramuscularly, Alben at a dose of 7.5 mg/kg with concentrated feed, and Aversect-2 at a dose of 0.2 mg/kg subcutaneously once. Levamisole was administered to the animals of the first group on the 6th, 10th and 14th weeks of grazing, and to the animals of the second group - on the 6th and 10th weeks of grazing. Alben was used on young cattle of the third group on the 6th, 11th and 16th weeks, and on the animals of the fourth group - on the 6th and 11th weeks of grazing. Aversect-2 was administered to cattle of the fifth group at the 6th, 13th and 20th weeks of grazing, and to the animals of the sixth group – at the 6th and 13th weeks. Animals of the 7th group did not receive the drug and served as control. Fecal samples were taken from animals of all groups on a monthly basis and investigated by a quantitative method in order to detect eggs of gastrointestinal strongylate. The results obtained were statistically processed using the computer program Microsoft Excel.Results and discussion. Tests of drugs for gastrointestinal strongylatoses of young cattle showed different persistence of anthelmintic action. After deworming the animals, single eggs of strongylate in their faeces were again detected 4 weeks after the administration of Levamisole, 5 weeks after the administration of Alben, and 7 weeks after the administration of Aversect-2. The most rational scheme for deworming young cattle with gastrointestinal strongylatoses is the use of Aversect-2 on the 6th and 19th weeks of grazing

Modifcation of anthelmintic drugs by nanotechnology (review)

The purpose of the research is to analyze and summarize the literature data and the results of our own studies on the use of drug delivery systems and methods for increasing the solubility and efcacy of anthelmintic drugs.Helminthoses are one of the most important problems in veterinary medicine and animal husbandry, not only due to the pathological effects, but also due to the spread of anthelmintic resistance. Since the development of new anthelmintic substances takes many years and investment, some strategies are currently focused on modifying existing drugs to increase their efcacy, reduce side effects and overcome anthelmintic resistance. Literature data analysis on various methods and means of increasing the solubility and efcacy of anthelmintic drugs was carried out and the prospects for their use, including using modern nanotechnological methods of drug delivery were given

Effect of digitalization on unemployment among the elderly population in EAEU countries

Objective: to identify current trends in the labor market under digitalization and the growing risks and global instability in the world and national markets in the EAEU countries.Methods: panel data analysis models, graphical method, least squares method, generalized feasible least squares method.Results: the data of the EAEU countries from 2016 to 2020 show the synchronization of unemployment indicators; a slight increase in the share of unemployed aged 55 and older in all countries except Russia; a decrease in value added produced within the “Information and Communication” type of activity, with the exception of Kazakhstan; during the pandemic, a decrease in the integral indicator of unemployment and the number of unemployed aged 55 and older was found under the influence of the gross value added within the “Information and Communication” type of activity, as well as a decrease in unemployment among elder citizens under the influence of the share of the population using the Internet.Scientific novelty: the current trends of unemployment are reflected, under digitalization and the growing risks and global instability in the world and national markets in the EAEU countries.Practical significance: the main conclusions of the article can be an argument in favor of the competitive advantages of the older population in the labor market under digitalization and uncertainty of economy

Efficiency of Fenbendazole on the Basis of Nanosized Supramolecular Delivery Systems with Polyvinyl Pyrrolidone and Dioctylsulphosuccinate Sodium in the Cases of Helminthosis

The purpose of the research is to study the efficiency of fenbendazole on the basis of nanosized supramolecular delivery systems with polyvinyl pyrrolidone and dioctylsulphosuccinate sodium in the cases of helminthosis in animals.Materials and methods. Experiments were conducted on 120 mice experimentally infected by Trichinella spiralis, Hymenolepis nana and on sheep experimentally infected by gastro-intestinal eelworms (120 animals) and by moniezias (60 animals). In each case of helminthosis animals from different groups (10 animals in each) were given fenbendazole supramolecular complex with polyvinyl pyrrolidone and dioctylsulphosuccinate sodium orally at the single dose of 3.0, 2.0 and 1.0 mg/kg on AS compared to background drug fenbendazole at a dose of 2.0 mg/kg. Group of animals, which did not receive a drug was a control. Drug efficiency calculated according to the results of mice enterotomy and data of coproovoscopic studies of sheep by flotation technique before and in 15 days after drug administration.Results and discussion. Fenbendazole supramolecular complex with polyvinyl pyrrolidone and dioctylsulphosuccinate sodium at the doses of 3.0, 2.0 and 1.0 on AS showed 100, 100 and 87.7 % of efficiency against T. spiralis, 100, 100, 91.14% against H. nana, 100, 97.7 and 94.0% against gastro-intestinal eelworms and 100, 92.44 and 44.26% against Moniezia expansa, respectively while efficiency of background drug – fenbendazole substance was 23.0–26.3%

СПЕКТР АНТИГЕЛЬМИНТНОЙ АКТИВНОСТИ СУПРАМОЛЕКУЛЯРНОГО КОМПЛЕКСА ФЕНБЕНДАЗОЛА С АРАБИНОГАЛАКТАНОМ

Objective of research - to study the biological activity of supramolecular complex of fenbendazole with arabinogalactan against helminthoses of sheep considering spectrum of action. Materials and methods. Anthelmintic activity of supramolecular complex of fenbendazole with arabinogalactan (SMCF) was studied in sheep farms of the Moscow and Samara regions, which were infected with helminthoses. The experiments were made in 2014-2015 in the period of the maximal infection of animals. 386 younger sheep were used in experiments, including 50 sheep spontaneously infected with Dictyocaulus filaria , 48 - Nematodirus spp ., 52 - other gastrointestinal strongylata, 47 - Fasciola hepatica , 49 - Dicrocoelium lanceatum , 42 - Strongyloides sp ., 44 - Trichocephalus spp ., 54 - Moniezia spp . All the animals in each case of helminthoses were divided into 6 equal groups of 7-10 sheep each by the principle of analogs. SMCF was administered orally in the form of 10 % powder at the dose of 1,0; 2,0 and 3,0 mg/kg of active substance once to the sheep of the first, second and third groups. Animals of the fourth and fifth groups received the basic drug - fenbendazole at the doses respectively 1,0 and 7,5 mg/kg of bw except for the cases of fasciolosis and dicroceliasis when SMCF was administered at the doses of 15,0; 7,5 and 5,0 mg/kg and fenbendazole - at the dose of 5,0 and 15,0 mg/kg. The control group did not receive the drug. The efficacy of SMCF was evaluated by the results of larvaovoscopic researches of feces by Berman's method in case of dictyocaulosis, a flotation method in case of other helminthoses before and in 15-18 days after treatment. The efficacy of SMCF was evaluated in «control test» with calculation of middle amount of eggs/larva of helminths in 1 g of feces. Results and discussion. The spectrum of anthelmintic action and the therapeutic dose of SMCF with arabinogalactan, received by mechanochemical technology were studied and defined in experiments on 386 sheep, spontaneously infected with different species of helminths. SMCF showed maximum efficiency (96-100 %) in a dose of 3,0 mg/kg of active substance against main helminthoses and in a dose of 15,0 mg/kg - against dicroceliasis and fasciolosis. The efficacy of SMCF was in 2-3 times higher than activity of fenbendazole substance.Цель исследования - изучение биологической активности супрамолекулярного комплекса фенбендазола с арабиногалактаном при гельминтозах овец с учетом спектра действия. Материалы и методы. Антигельминтную активность супрамолекулярного комплекса фенбендазола с арабиногалактаном (СМКФ) изучали в овцеводческих хозяйствах Московской и Самарской областей, неблагополучных по гельминтозам. Опыты проводили в 2014-2015 гг. в период максимальной инвазированности животных. В опытах использовали 386 голов молодняка овец, в том числе спонтанно инвазированных диктиокаулами 50 гол., нематодирусами 48 гол., другими видами желудочно-кишечных стронгилят 52 гол., фасциолами 47 гол., дикроцелиями 49 гол., стронгилоидами 42 гол., трихоцефалами 44 гол., мониезиями 54 гол. При каждом гельминтозе животных по принципу аналогов разделяли на 6 равноценных групп по 7-10 овец в каждой. Животным первой, второй и третьей групп вводили СМКФ в форме 10%-ного порошка однократно перорально в дозе соответственно 1,0; 2,0 и 3,0 мг/кг по ДВ. Овцы четвертой и пятой групп получали базовый препарат - фенбендазол в дозах соответственно 1,0 и 7,5 мг/кг за исключением, когда СМКФ при фасциолезе и дикроцелиозе назначали в дозах 15,0; 7,5 и 5,0 мг/кг, а фенбендазол - в дозах 6,0 и 15,0 мг/кг. Животные контрольной группы препарат не получали. Эффективность СМКФ учитывали по результатам ларвоовоскопических исследований фекалий методом Бермана при диктиокаулезе, методом флотации при других гельминтозах до и через 15-18 сут после дегельминтизации. Учет активности препаратов проводили по типу «контрольный тест» с расчетом среднего числа обнаруженных личинок и/или яиц гельминтов. Результаты и обсуждение. В опытах на 386 овцах, спонтанно инвазированных различными видами гельминтов, изучен спектр антигельминтного действия и установлена терапевтическая доза СМКФ с арабиногалактаном, полученного по механохимической технологии. СМКФ показал максимальную эффективность (96-100 %) при основных гельминтозах в дозе 3,0 мг/кг по ДВ, а при дикроцелиозе и фасциолезе - в дозе 15,0 мг/кг по ДВ. Эффективность СМКФ оказалась в 2-3 раза выше активности субстанции фенбендазола