Experimental Modeling Of Hypothyroidism: Principles, Methods, Several Advanced Research Directions In Cardiology

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.

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EXPERIMENTAL MODELS OF THE HYPOTHYROIDISM

MORPHOLOGICAL NEWSLETTER ◽

10.20340/mv-mn.2021.29(1).69-76 ◽

2021 ◽

Vol 29 (1) ◽

pp. 69-76

Author(s):

Aleksey M. Chaulin ◽

Julia V. Grigorieva ◽

Galina N. Suvorova

Keyword(s):

Thyroid Hormones ◽

Genetic Model ◽

Clinical Manifestations ◽

Experimental Models ◽

Laboratory Animals ◽

Antithyroid Drugs ◽

Diagnostic Strategies ◽

Functional Changes ◽

Advantages And Disadvantages ◽

Holistic Understanding

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.

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Fundamental principles and techniques of experimental modeling of hypothyroidism: a literature review

Archiv Euromedica ◽

10.35630/2199-885x/2020/10/4.11 ◽

2020 ◽

Vol 10 (4) ◽

pp. 48-55

Author(s):

Aleksey Chaulin ◽

Julia Grigoryeva ◽

Nikolay Svechkov ◽

Galina Suvorova

Keyword(s):

Thyroid Hormones ◽

Pathological Condition ◽

Gene Mutations ◽

Experimental Models ◽

Experimental Modeling ◽

Laboratory Animals ◽

Antithyroid Drugs ◽

Medical Specialties ◽

Animal Body ◽

Advantages And Disadvantages

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.

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PRECLINICAL STUDY OF THE VETERINARY DRUGS TOXICITY

Vestnik of the Russian agricultural science ◽

10.30850/vrsn/2019/5/61-64 ◽

1970 ◽

pp. 61-64

Author(s):

E. K. Rakhmatullin ◽

O. D. Sklyarov

Keyword(s):

Lethal Dose ◽

Clinical Manifestations ◽

Preclinical Study ◽

Veterinary Drugs ◽

Toxic Effects ◽

Laboratory Animals ◽

Therapeutic Effects ◽

Significant Information ◽

Important Indicator ◽

Organ Systems

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.

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Animal models in the study of exercise-induced cardiac hypertrophy

Physiological Research ◽

10.33549/physiolres.931928 ◽

2010 ◽

pp. 633-644 ◽

Cited By ~ 1

Author(s):

Y Wang ◽

U Wisloff ◽

OJ Kemi

Keyword(s):

Animal Models ◽

Exercise Training ◽

Cardiac Hypertrophy ◽

Wheel Running ◽

Experimental Models ◽

Laboratory Animals ◽

Training Models ◽

Advantages And Disadvantages ◽

Experimental Approaches ◽

Exercise Induced

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.

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BASIC PRINCIPLES AND METHODS OF MODELING HYPOGONADISM: A LITERATURE REVIEW

Archiv Euromedica ◽

10.35630/2199-885x/2020/10/4.12 ◽

2020 ◽

Vol 10 (4) ◽

pp. 56-62

Author(s):

Antonina Pronina ◽

Galina Suvorova ◽

Aleksey Chaulin ◽

Julia Grigoryeva ◽

Dmitry Rusakov ◽

...

Keyword(s):

Pathological Condition ◽

Research Area ◽

Experimental Models ◽

Laboratory Animals ◽

Basic Principles ◽

Domestic Literature ◽

Beneficial Effects ◽

Advantages And Disadvantages ◽

Genes Encoding ◽

Distal Section

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.

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Modeling spinal cord injuries: advantages and disadvantages

Pediatric Traumatology Orthopaedics and Reconstructive Surgery ◽

10.17816/ptors34638 ◽

2021 ◽

Vol 8 (4) ◽

pp. 485-494

Author(s):

Sergey V. Vissarionov ◽

Timofey S. Rybinskikh ◽

Marat S. Asadulaev ◽

Nikita O. Khusainov

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Clinical Practice ◽

Spinal Cord Injuries ◽

Experimental Models ◽

Laboratory Animals ◽

Severe Injuries ◽

Experimental Animals ◽

Advantages And Disadvantages ◽

Cord Injury

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.

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Susceptibility of animal species to experimental SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) infection

Voprosy Virusologii ◽

10.36233/0507-4088-47 ◽

2021 ◽

Vol 66 (2) ◽

pp. 103-111

Author(s):

N. V. Petrova ◽

K. K. Ganina ◽

S. A. Tarasov

Keyword(s):

Neutralizing Antibodies ◽

Scientific Community ◽

Animal Species ◽

Vaccine Development ◽

Clinical Symptoms ◽

Experimental Models ◽

Laboratory Animals ◽

Susceptible Animal ◽

Advantages And Disadvantages ◽

Coronavirus Infection

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.

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Upregulation of the Renin–Angiotensin System Pathways and SARS-CoV-2 Infection: The Rationale for the Administration of Zinc-Chelating Agents in COVID-19 Patients

Cells ◽

10.3390/cells10030506 ◽

2021 ◽

Vol 10 (3) ◽

pp. 506

Author(s):

Loris Zamai

Keyword(s):

Chelating Agents ◽

Ethylenediaminetetraacetic Acid ◽

Current Knowledge ◽

Clinical Manifestations ◽

Renin Angiotensin System ◽

Experimental Models ◽

Zinc Metalloprotease ◽

Previous Hypothesis ◽

Zinc Metalloproteases

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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CD4+ CD25+ Foxp3+ Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

Infection and Immunity ◽

10.1128/iai.00578-10 ◽

2010 ◽

Vol 78 (11) ◽

pp. 4763-4772 ◽

Cited By ~ 55

Author(s):

Raquel M. Gonçalves ◽

Karina C. Salmazi ◽

Bianca A. N. Santos ◽

Melissa S. Bastos ◽

Sandra C. Rocha ◽

...

Keyword(s):

Dendritic Cells ◽

Parasite Species ◽

Inflammatory Responses ◽

Clinical Symptoms ◽

Clinical Manifestations ◽

Surface Expression ◽

Interleukin 10 ◽

Treg Cells ◽

Experimental Models ◽

Necrosis Factor Alpha

ABSTRACT Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4+ CD25+ Foxp3+ Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123+), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-α) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and long-lasting protective immunity to malaria.

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COLLOID CYSTS OF THE THIRD VENTRICLE: A REVIEW OF SIXTEEN CASES

10.36106/ijsr/0102258 ◽

2021 ◽

pp. 62-64

Author(s):

Y Srinivas Rao ◽

Hemal Chheda ◽

Ch Surendra ◽

M V Vijayasekhar ◽

K Satya Varaprasad

Keyword(s):

Benign Lesion ◽

Third Ventricle ◽

Clinical Manifestations ◽

Colloid Cyst ◽

Surgical Approaches ◽

Imaging Features ◽

Complete Excision ◽

Advantages And Disadvantages ◽

The Third ◽

Colloid Cysts

BACKGROUND : Colloid cysts are one of the rare brain tumours and are mostly located in the anterosuperior portion of the third ventricle, between the fornix and surround of Foramen of Monroe. OBJECTIVES: Ÿ 1.To review the demographic information & analyse clinical manifestations of patients presenting with colloid cyst of third ventricle. Ÿ 2.To analyze the advantages and disadvantages of various surgical approaches Ÿ 3.To assess the surgical outcome in colloid cyst patients operated by any method. MATERIALS AND METHODS: A retrospective study was performed on 16 patients who presented with a colloid cyst and underwent surgery at the Department of Neurosurgery, King George Hospital, Andhra Medical College between 2013-2018. They were evaluated based on clinical ndings and imaging features, surgical approaches used for resection and their outcomes. RESULTS: Sixteen cases of colloid cyst of the third ventricle were operated upon between 2013-2018. There were seven male and nine female patients with their ages varying between 9 and 62 years old. Nine patients were operated on by using a transcortical trans-ventricular approach, four using the anterior trans-callosal approach and, three patients by using an endoscopic approach. In all patients, complete excision of the lesions was achieved. CONCLUSION: Colloid cysts, though benign, present surgical challenges because of its deep midline location. Complete excision of the colloid cyst carries an excellent prognosis. Surgery is a safe and effective treatment option for this benign lesion.

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