scholarly journals EXPERIMENTAL MODELS OF THE HYPOTHYROIDISM

2021 ◽  
Vol 29 (1) ◽  
pp. 69-76
Author(s):  
Aleksey M. Chaulin ◽  
Julia V. Grigorieva ◽  
Galina N. Suvorova

Hypothyroidism is a systemic chronic disease that occurs as a result of a deficiency of thyroid hormones (thyroid hormones): triiodothyronine and tetraiodothyronine (thyroxine). Targets of thyroid hormones are almost all organs and tissues of the human body, which explains the variety of clinical manifestations that occur when these hormones are deficient. Recently, basic research through the use of experimental models has become more relevant and allowed us to obtain a number of new morphological and functional changes that occur in hypothyroidism. This review discusses the main experimental models of hypothyroidism: surgical, radioactive, dietary, anti-thyroid administration and genetics’ model. The main principle of the surgical model of hypothyroidism is to remove the thyroid gland. The radioactive model is based on the introduction of a radioactive isotope of iodine to laboratory animals. The dietary model is based on the use of a special diet with a limited amount of iodine. The drug model is based on the introduction of antithyroid drugs - methylimidazole and propylthiouracil. The principle of the genetic model consists in special genetic manipulations with the genome of laboratory animals. The advantages and disadvantages of each model are discussed. The use of sophisticated equipment has brought specialists closer to a more complete and holistic understanding of the morphological and functional manifestations of hypothyroidism. Researching of experimental models is an important tool in relation to the studying of the mechanisms underlying hypothyroidism and, as a result, in improving prevention and treatment-diagnostic strategies.

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Aleksey M. Chaulin ◽  
Julia V. Grigorieva ◽  
Galina N. Suvorova ◽  
Dmitry V. Duplyakov

Hypothyroidism is one of the most common pathological conditions in modern clinical practice. Due to the fact that the targets of thyroid hormones are virtually all organs and tissues, the morphological and clinical manifestations arising with a deficiency of thyroid hormones are quite diverse. Experimental models of hypothyroidism in laboratory animals are widely used for preclinical study of the fundamental pathophysiological mechanisms underlying hypothyroidism, as well as for assessing the effectiveness of treatment-and-prophylactic effects. Currently, several groups of effective models of hypothyroidism have been developed: dietary, surgical, medicamentous, genetic, radioactive and immunological. Each of the specified models is based on different principles, has advantages and disadvantages, and can be used depending on the goals and objectives of the experiment. In this review, we will consistently consider hypothyroidism modeling methods and indicate some promising areas of their use in cardiology.


2020 ◽  
Vol 10 (4) ◽  
pp. 48-55
Author(s):  
Aleksey Chaulin ◽  
Julia Grigoryeva ◽  
Nikolay Svechkov ◽  
Galina Suvorova

The purpose of our paper is to discuss principles and techniques of experimental modeling of hypothyroidism in laboratory animals, as well as reviewing advantages and disadvantages of experimental models. Materials and methods. Comparative analysis of contemporary international biological and medical publications in PubMed/MEDLINE and Embase databases; analysis of contemporary national scientific sources using Google Scholar database. Results. To date, there are six basic principles of experimental modeling of hypothyroidism, i.e.: dietary, drug, surgical, immunological, radioisotope, genetic. Each of the techniques can be used for simulation of the main conditions for hypothyroidism development. Dietary modeling stands for the iodine intake restriction because iodine is an indispensable component in thyroid hormones synthesis. Drug modeling means the use of antithyroid drugs that block thyroid hormones synthesis. Surgical modeling principle involves thyroidectomy. The principle of immunological modeling of hypothyroidism consists in administration of immunosuppressants to animal body. The principle of radioisotope modeling of hypothyroidism lies in acting with a radioactive isotope of iodine on animal body. Genetic modeling principle leads to stimulation of gene mutations in laboratory animals to encode the thyroid hormones formation or their receptors, and results in appearance of the transcription factors responsible for development of the thyroid gland. Conclusion. Hypothyroidism is a very common pathological condition affecting many organs and tissues. Thus, employment of the hypothyroidism experimental models to study fundamental pathophysiological and pathomorphological processes represents a scientific and research topic of immediate interest. Each of the hypothyroidism modeling principles is specific, and provides for simulation of particular conditions needed for hypothyroidism development in laboratory animals. Taking into consideration numerous beneficial effects of thyroid hormones upon almost all organs and tissues of human body, it is noteworthy that experimental models of hypothyroidism shall be highly sought after by researchers practicing in all medical specialties.


2010 ◽  
pp. 633-644 ◽  
Author(s):  
Y Wang ◽  
U Wisloff ◽  
OJ Kemi

Exercise training-induced cardiac hypertrophy occurs following a program of aerobic endurance exercise training and it is considered as a physiologically beneficial adaptation. To investigate the underlying biology of physiological hypertrophy, we rely on robust experimental models of exercise training in laboratory animals that mimic the training response in humans. A number of experimental strategies have been established, such as treadmill and voluntary wheel running and swim training models that all associate with cardiac growth. These approaches have been applied to numerous animal models with various backgrounds. However, important differences exist between these experimental approaches, which may affect the interpretation of the results. Here, we review the various approaches that have been used to experimentally study exercise training-induced cardiac hypertrophy; including the advantages and disadvantages of the various models.


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).


2020 ◽  
Vol 10 (4) ◽  
pp. 56-62
Author(s):  
Antonina Pronina ◽  
Galina Suvorova ◽  
Aleksey Chaulin ◽  
Julia Grigoryeva ◽  
Dmitry Rusakov ◽  
...  

Purpose: To consider the basic principles and methods of experimental modeling of hypogonadism in laboratory animals, to define the main benefits and drawbacks of each separate method in hypogonadism modeling. Materials and methods: We analyzed modern foreign and domestic literature using the following databases: PubMed / Medline, Embase, Google Scholar. Results: Presently, there are three main principles of modeling hypogonadism: surgical, genetic, and pharmacological. The principle of surgical modeling of hypogonadism is based on the removal of the gonads, or on the temporary imposition of a suture on the distal section of the spermatic cord, which leads to occlusion of the testicular artery that feeds the gonads. The principle of genetic modeling of hypogonadism is to induce mutations in the genes encoding the most important regulatory molecules, in particular kisspeptin, neurokinin B, and their receptors in laboratory animals. The principle of pharmacological modeling of hypogonadism is based on the administration of streptozocin to laboratory animals, which has a toxic effect on the gonads and pancreas. Conclusion: Hypogonadism represents a very common pathological condition that affects many organs and tissues. Therefore, the use of experimental models of hypogonadism to study fundamental pathophysiological and pathomorphological processes is a relevant research area. Each principle of hypogonadism modeling is unique in its own way, exhibits advantages and disadvantages, and allows the creation of specific conditions necessary for the development of hypogonadism in laboratory animals. Taking into account the numerous beneficial effects of testosterone on many cells and tissues of the human body, it becomes obvious that experimental models of hypogonadism can be in demand for many medical spheres.


2021 ◽  
Vol 8 (4) ◽  
pp. 485-494
Author(s):  
Sergey V. Vissarionov ◽  
Timofey S. Rybinskikh ◽  
Marat S. Asadulaev ◽  
Nikita O. Khusainov

Background. Spinal cord injuries have diverse characteristics and associated traumatic changes; they are known as the most severe injuries of locomotorium. The creation of an optimal experimental model of spinal cord injuries using experimental animals, which would have similar changes in humans, is important to assess and analyze the pathological processes, as well as to develop complex treatment methods. Aim. This study aimed to analyze various experimental models of spinal cord injury using laboratory animals by assessing its advantages and disadvantages for further research and implementation in clinical practice. Materials and methods. A literature review was performed on the capabilities of experimental models of traumatic spinal cord injury in laboratory animals. A literature search was carried out using databases of PubMed, Science Direct, E-library, and Google Scholar for the period from 1981 to 2019; the keywords are shown below. In total, 105 foreign and 37 domestic articles were identified, 59 articles were analyzed after exclusion, and 75% of studies were published in the last 20 years. Results. The review of available experimental options of spinal cord injury in laboratory animals revealed that a generally accepted universal model is not yet established. The experimental animal models had characteristics that do not correspond to the same parameters in an actual clinical situation. Besides, some difficulties were encountered in the estimation of pathological processes of experimental animals, translations with clinical changes, and interpretations of achieved functional results in experimental animals, which complicated the application in clinical practice. Conclusion. Development of experimental models of spinal cord injury that can consider multifactorial aspects of the trauma process, including its biomechanics and time factor, is necessary.


2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Yuejia Ding ◽  
Yuan Wang ◽  
Qiujin Jia ◽  
Xiaoling Wang ◽  
Yanmin Lu ◽  
...  

Myocardial fibrosis is characterized by excessive deposition of myocardial interstitial collagen, abnormal distribution, and excessive proliferation of fibroblasts. According to the researches in recent years, myocardial fibrosis, as the pathological basis of various cardiovascular diseases, has been proven to be a core determinant in ventricular remodeling. Pressure load is one of the causes of myocardial fibrosis. In experimental models of pressure-overload-induced myocardial fibrosis, significant increase in left ventricular parameters such as interventricular septal thickness and left ventricular posterior wall thickness and the decrease of ejection fraction are some of the manifestations of cardiac damage. These morphological and functional changes have a serious impact on the maintenance of physiological functions. Therefore, establishing a suitable myocardial fibrosis model is the basis of its pathogenesis research. This paper will discuss the methods of establishing myocardial fibrosis model and compare the advantages and disadvantages of the models in order to provide a strong basis for establishing a myocardial fibrosis model.


2021 ◽  
Vol 66 (2) ◽  
pp. 103-111
Author(s):  
N. V. Petrova ◽  
K. K. Ganina ◽  
S. A. Tarasov

Due to the new coronavirus infection pandemic, the global scientific community has been forced to change the direction of the most research, focusing on vaccine development as well as the search for new antiviral drugs to treat COVID-19. The choice of experimental models, timeframe and approaches for evaluating drugs and vaccines under development is crucial for the development of effective measures to prevent and control this disease.The purpose of this review was to summarize the relevant data concerning the susceptibility of laboratory animals to SARS-CoV-2. This paper describes the most virus-susceptible animal species that can be used to reproduce coronavirus infection, stressing the main advantages and disadvantages of each of them.According to the latest data, small rodents (Rodentia) and non-human primates (Strepsirrhini) are commonly used in the scientific community to model coronavirus infection. The viral load in the upper and lower parts of the respiratory system, clinical symptoms of infection (weight loss, body temperature and general health status), pathomorphological picture in target organs and the production of antibodies after infection are considered to the main markers of pathology. Despite the vast amount of data, none of the described models of SARS-CoV-2 infection may be considered a gold standard, since they do not reproduce all spectrum of morphological and pathogenetic mechanisms of infection, and do not fully reflect the clinical picture observed in patients in human population.Based on the analyzed literature data, we suppose that Syrian hamster (Mesocricetus auratus) and mice (Muridae) expressing the angiotensin converting enzyme receptor 2 (ACE2) are the most suitable animal species for their use in experiments with SARS-CoV-2 infection. The development of neutralizing antibodies makes it possible to evaluate the efficacy of vaccines, while the course and severity of symptoms infection makes the use of mice and hamsters especially popular for screening pharmacological substances with antiviral mechanism of action, when their administration can prevent or slow the disease progression.


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.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 506
Author(s):  
Loris Zamai

The article describes the rationale for the administration of zinc-chelating agents in COVID-19 patients. In a previous work I have highlighted that the binding of the SARS-CoV spike proteins to the zinc-metalloprotease ACE2 has been shown to induce ACE2 shedding by activating the zinc-metalloprotease ADAM17, which ultimately leads to systemic upregulation of ACE2 activity. Moreover, based on experimental models, it was also shown the detrimental effect of the excessive systemic activity of ACE2 through its downstream pathways, which leads to “clinical” manifestations resembling COVID-19. In this regard, strong upregulation of circulating ACE2 activity was recently reported in COVID-19 patients, thus supporting the previous hypothesis that COVID-19 may derive from upregulation of ACE2 activity. Based on this, a reasonable hypothesis of using inhibitors that curb the upregulation of both ACE2 and ADAM17 zinc-metalloprotease activities and consequent positive feedback-loops (initially triggered by SARS-CoV-2 and subsequently sustained independently on viral trigger) is proposed as therapy for COVID-19. In particular, zinc-chelating agents such as citrate and ethylenediaminetetraacetic acid (EDTA) alone or in combination are expected to act in protecting from COVID-19 at different levels thanks to their both anticoagulant properties and inhibitory activity on zinc-metalloproteases. Several arguments are presented in support of this hypothesis and based on the current knowledge of both beneficial/harmful effects and cost/effectiveness, the use of chelating agents in the prevention and therapy of COVID-19 is proposed. In this regard, clinical trials (currently absent) employing citrate/EDTA in COVID-19 are urgently needed in order to shed more light on the efficacy of zinc chelators against SARS-CoV-2 infection in vivo.


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