Antimethanogenic drugs and Heliotropium europaeum poisoning in penned sheep

1978 ◽  
Vol 29 (6) ◽  
pp. 1281 ◽  
Author(s):  
GW Lanigan ◽  
AL Payne ◽  
JE Peterson

Most sheep fed for prolonged periods on a ration containing 50% dried Heliotropium europaeum developed some of the clinical manifestations seen in field cases of pyrrolizidine alkaloidosis. Histologically demonstrated liver damage in the laboratory animals was comparatively mild, but the marked decline in their bromosulphophthalein (BSP) clearance rates indicated severe depletion of liver functional capacity. In sheep fed on H. europaeum for 13-week periods separated by 18-week rests, simultaneous oral administration of iodoform (16 mg twice daily) led to an increase from 33 to 55 weeks in the time required for death of half the susceptible sheep. Iodoform at levels of 32 mg and above twice daily proved hepatotoxic when given orally for several months. All susceptible sheep not given iodoform died following two periods of H. europaeum feeding, whereas three such periods were needed for iodoform-treated animals. It is concluded that iodoform prophylaxis may be a useful protective measure in the field for sheep exposed to H. europaeum grazing during a single season. Up to 20% of the sheep used survived ingestion of H. europaeum for the full experimental term; some of them sustained little or no decline in BSP clearance rate. This finding indicates that there are prospects for development of a pyrrolizidine-tolerant strain of sheep by selective breeding. Chloral hydrate proved unsatisfactory as a replacement for iodoform.

1972 ◽  
Vol 23 (6) ◽  
pp. 1085 ◽  
Author(s):  
GW Lanigan

Five halogenated methane analogues (bromoform, chloroform, iodoform, carbon tetrabromide, and carbon tetrachloride) have been shown to inhibit methane formation in the sheep's rumen as well as in rumen fluid in vitvo. On a molar basis the methane analogues were 100-200 times as effective as chloral hydrate in vitro, but in the rumen this difference was reduced by a factor of 10 with four of the compounds and to parity with chloral hydrate in the case of carbon tetrachloride. When rumen methanogenesis was inhibited by administration of chloral hydrate, bromoform, or iodoform, the time taken for metabolism of 2 g of Heliotropium europaeum alkaloids was reduced to 25-40% of that taken in animals not so treated. These results support the conclusion that inhibition of methanogenesis may be a useful protective measure for sheep ingesting plants which contain hepatotoxic pyrrolizidine alkaloids.


Author(s):  
E. K. Rakhmatullin ◽  
O. D. Sklyarov

Preclinical study of the drugs toxicity was analysed it allows predicting the safety of veterinary drugs in laboratory animals. The fundamental normative instruments in the field of preclinical study of drugs for veterinary medicine and animal husbandry are Order of the Ministry of Agriculture of the Russian Federation dated 06.03.2018 N 101 and GOST 33044-2014 Principles of Good Laboratory Practice. An important indicator of the preclinical study of the veterinary drugs is the determination (calculation) of median lethal dose value (lethal dose for half of the animals tested) or concentration (LD50 or LC50). Existing methods for determining this indicator make it possible at the initial study stage to determine the degree and class the drug of toxicity. Studying the symptoms of intoxication in the analysis of pharmacological substances one obtains significant information about the nature of the action of the future drug. The clinical manifestations of intoxication with damage to various organ systems are presented. As criteria for assessing the toxic effects of veterinary drugs it is recommended to determine LD50, cumulation coefficient, latitude index of therapeutic effects, dose level of toxic effects in the experiment which allows predicting the nature and degree of toxic effects of the drug even at the stage of preclinical veterinary drugs study.


1991 ◽  
Vol 74 (5) ◽  
pp. 857-861
Author(s):  
Philip P Sapienza ◽  
George J Ikeda ◽  
Patricia I Warr ◽  
Richard H Albert

Abstract The homogeneity of test substances in a carrier (animal feed) is a critical factor In conducting long-term feeding studies in laboratory animals. A method for determining the adequate amount of mixing to achieve homogeneity by a mixer of the type described has been determined when 2 distinctly different compounds are added to ground dog feed. Nicotinic acid and butylated hydroxyanlsole at a concentration of 1% were separately mixed with the dog feed for 15,30,45,60, and 120 min to determine optimum mixing time. Test portions were taken from 4 different sampling sites at each time period and analyzed in duplicate for the added substance. Four batches were prepared and the results were aggregated. Very little interbatch variability was observed. The variance of the average values from the 4 sampling sites at each time period was calculated and used as a simple, crude, but effective numerical quantity to monitor the approach to homogeneity of the mixture.


Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 795
Author(s):  
Sergei N. Shchelkunov ◽  
Stanislav N. Yakubitskiy ◽  
Alexander A. Sergeev ◽  
Alexei S. Kabanov ◽  
Tatiana V. Bauer ◽  
...  

The mass smallpox vaccination campaign has played a crucial role in smallpox eradication. Various strains of the vaccinia virus (VACV) were used as a live smallpox vaccine in different countries, their origin being unknown in most cases. The VACV strains differ in terms of pathogenicity exhibited upon inoculation of laboratory animals and reactogenicity exhibited upon vaccination of humans. Therefore, each generated strain or clonal variant of VACV needs to be thoroughly studied in in vivo systems. The clonal variant 14 of LIVP strain (LIVP-14) was the study object in this work. A comparative analysis of the virulence and immunogenicity of LIVP-14 inoculated intranasally (i.n.), intradermally (i.d.), or subcutaneously (s.c.) to BALB/c mice at doses of 108, 107, and 106 pfu was carried out. Adult mice exhibited the highest sensitivity to the i.n. administered LIVP-14 strain, although the infection was not lethal. The i.n. inoculated LIVP-14 replicated efficiently in the lungs. Furthermore, this virus was accumulated in the brain at relatively high concentrations. Significantly lower levels of LIVP-14 were detected in the liver, kidneys, and spleen of experimental animals. No clinical manifestations of the disease were observed after i.d. or s.c. injection of LIVP-14 to mice. After s.c. inoculation, the virus was detected only at the injection site, while it could disseminate to the liver and lungs when delivered via i.d. administration. A comparative analysis of the production of virus-specific antibodies by ELISA and PRNT revealed that the highest level of antibodies was induced in i.n. inoculated mice; a lower level of antibodies was observed after i.d. administration of the virus and the lowest level after s.c. injection. Even at the lowest studied dose (106 pfu), i.n. or i.d. administered LIVP-14 completely protected mice against infection with the cowpox virus at the lethal dose. Our findings imply that, according to the ratio between such characteristics as pathogenicity/immunogenicity/protectivity, i.d. injection is the optimal method of inoculation with the VACV LIVP-14 strain to ensure the safe formation of immune defense after vaccination against orthopoxviral infections.


2020 ◽  
pp. 51-57
Author(s):  
Lyudmila Mikhaylovna Kashkovskaya ◽  
Andrey Vladimirovich Balyshev ◽  
Vladimir Aleksandrovich Orobets ◽  
Ivan Aleksandrovich Fedorov

The common practice in the prevention and treatment of eimeriosis in chickens is the application of anticoccidial preparations. The parameters of acute toxicity of the anticoccidial preparations Decvycox in laboratory animals were studied. It was found out that the LD50 of Decvycox with oral administration to mice and rats exceeds doses of 6579 and 7222 mg/kg of animal weight, respectively. Thus, according to the generally accepted hygienic classification, Decvycox belongs to hazard class 4 - low-hazard substances.


Author(s):  
A.A. Martemyanova ◽  
◽  
A.L. Kochoyan ◽  
R.A. Kalyokin ◽  
A.M. Orlova ◽  
...  

The differences in clinical manifestations of oral administration of 40% ethanol (vodka) with carbonation compared with neat (non-carbonated) vodka were studied. It was found that when taking carbonated ethanol, both subjective and objective symptoms appear, which are absent when taking ethanol without carbonation. The symptoms of alcohol intoxication characteristic of ethanol, both with and without carbonation, persist longer when carbonated ethanol is ingested. The maximum heart rate values when taking ethanol with carbonation, recorded 4 hours after ingestion, were 18.4% higher relative to the baseline (the time of intake), and when taking ethanol without carbonation — by 9.6%. There was no significant difference in the change in blood pressure indicators when taking ethanol with and without carbonation.


2020 ◽  
Vol 175 ◽  
pp. 03002
Author(s):  
Elena Kuzminova ◽  
Marina Semenenko ◽  
Evgeny Dolgov ◽  
Serik Kanatbaev ◽  
Andrey Abramov

Currently, among chemical pollutants a significant danger to the health of animals and humans represent oxygen-containing nitrogen compounds nitrates and nitrites, which are widely used as mineral fertilizers. The article presents data on the study of chronic nitrate intoxication, reproduced in laboratory animals and its pharmacological correction with a complex of substances of phospholipid and polysaccharide nature. The introduction of sodium nitrate to non-linear rats for 30 days at a dose of 3.8 mg per animal leads to the development of intoxication in rats with dominant signs of liver damage. On this background, the use of the complex of beet fiber and rapeseed lecithin leads to a weakening of nitrate toxicosis, which is demonstrated by an increase in rats’ body weight, weakening of the clinical manifestations of intoxication, a decrease in cytolytic syndrome, intrahepatic cholestasis and impaired protein synthesis function of liver.


2020 ◽  
pp. 28-34
Author(s):  
В. Е. Милюков ◽  
Х. М. Шарифова

Цель - выявить закономерности морфофункциональных изменений в печени в динамике развития обтурационной острой тонкокишечной непроходимости (ОТКН). Материал и методы. Исследование выполнено на 18 взрослых беспородных собаках обоего пола массой 17-20 кг, у которых моделировали низкую ОТКН. Все научные эксперименты проведены в соответствии с руководящими документами, руководством по уходу и использованию лабораторных животных Национального института здравоохранения (National Institute of Health - NIH, Бетесда, США) и «Правилами проведения работ с экспериментальными животными», одобрены комитетом по этике Главного военного клинического госпиталя имени академика Н. Н. Бурденко Министерства обороны РФ и локальным комитетом по этике Первого МГМУ им. И. М. Сеченова. В гистологических препаратах, окрашенных гематоксилином - эозином, оценивали изменение площади сосудистого русла печени, определяли уровень содержания гликогена в печени по результатам количественной оценки продуктов ШИК-реакции и уровень содержания суммарных и цитоплазматических нуклеопротеидов по Эйнарсону. Результаты. С 3-х суток после формирования непроходимости отмечается уменьшение площади центральных вен в 3,15 раза по сравнению с нормой на фоне увеличения площади междольковых вен в 1,49 раза и междольковых артерий в 1,55 раза. Уровень гликогена и нуклеопротеидов на всех сроках эксперимента оставался сниженным. Выводы. При формировании ОТКН уже с 3-х суток, несмотря на отсутствие манифестирующих клинических проявлений острой кишечной непроходимости, отмечается изменение организации гемодинамики, свидетельствующее о формировании анастомотического гемодинамического пути, минующего внутрипеченочный. Это является основой уменьшения детоксицирующей функции, сопровождается энергетической и белковосинтетической дисфункцией печени и морфофункциональной основой развития синдрома полиорганной недостаточности (СПОН). Objective - to reveal the patterns of morpho-functional changes in the liver in the dynamics of the development of acute small bowel obstruction (ASBO) caused by obturation. Material and methods. The study was performed on 18 adult mongrel dogs of both sexes weighing 17-20 kg, in which low small bowel obstruction was modeled. All scientific experiments were conducted in accordance with the guidance documents, guidelines for the care and use of laboratory animals of the National Institute of Health (National Institute of Health - NIH, Bethesda, USA) and the «Rules for working with experimental animals», approved by the Ethics Committee for Federal State Institution «Main Military Clinical Hospital named after Academician N. N. Burdenko» of the Ministry of Defense of the Russian Federation and the local ethics committee of the I. M. Sechenov First Moscow State Medical University. On histological sections stained with hematoxylin and eosin, the change in the area of the vascular bed of the liver was evaluated, the glycogen content in the liver was determined by a quantitative evaluation of the products of the Schick reaction and the level of total and cytoplasmic nucleoprotein according to Einarsson. Results. From the 3 day after the formation of an obstruction, the central venous area decreased by 3.15 times compared with the norm, and the area of interlobular veins and arteries increased by 1.49 times and 1.55 times, respectively. The level of glycogen and nucleoproteins remained reduced throughout the experiment. Conclusions. In the formation of obturational ASBO, despite the absence of its clinical manifestations, a change in the organization of hemodynamics was noted since the 3 day of the operation. It indicated the formation of the anastomotic hemodynamic pathway, bypassing the liver, which is the basis for reducing the detoxification function of the liver. It was also accompanied by energy and protein-synthetical liver dysfunction, which is the morpho-functional basis for the development of multiple organ dysfunction syndrome (MODS).


2016 ◽  
Vol 3 (1) ◽  
pp. 114-118
Author(s):  
Глухарева ◽  
E. Glukhareva

Objective of research: to determine the toxicological properties of the preparation Cyflunit- Flock under acute experimental conditions at oral and subcutaneous administration routes to laboratory animals. Materials and methods: White outbred mice and white outbred rats of both genders were used for testing. Each dose of the preparation was tested on groups of males and females to identify the eventual sex differences in drug-responsiveness.In experiment on mice, animals were divided into 5 groups of 10 animals each.The medicine was given orally at the doses of 4350, 8700, 13050, 17400 and 21750 mg a.i./kg. In experiment on rats, 4 experimental male and 4 female groups were formed (6 animals in each). The drug was given orally at the doses of 17400 and 21750, 26100 and 30450 mg a.i./kg. While studying the acute cutaneous toxicity, Cyflunit- Flock was applied at the doses 870, 1740, 4350 and 8700 mg a.i./kgin 4 experimental groups of male and 4 groups of female rats of 6 animals each. Observations of general health status, behavior of animals, intoxication symptoms and eventual death of animals were conducted within 14 days. Results and discussion: LD50 of Cyflunit-Flockat oral administration to mice of both genders was 12180 mg/kg,at oral administration tomale rats - 22475 mg/kg, to female rats - 23925mg/kg. At cutaneous use of the preparation in rats, LD50 was more than 8700 mg/kg. Accordingtothestandardhygienicclassification, the preparation belongs to the 4thhazard class (low-hazard substances).


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