Complex estimation of thyroid gland state in tundra voles, inhabiting the natural radioactive polluted sites

Behow is presented the complex state of thyroid gland of tundra voles living in high level natural radioactivity conditions (Ukhta region of Komi Republic) by morphological and functional criteria. High sensitivity of thyroid gland under natural chronic irradiation of whole organism is noticed. The essential changes in the morphological structure and in the hormone level of the thyroid gland are found in animals, which live for a long time in the conditions of the radioactive pollution. It is determined, that the inside population processes influence on the structure and on the funcition of the thyroid gland.     

Extracorporeal biological perfusion of isolated canine thyroid glands

A model of extracorporeal biological perfusion of the isolated thyroid gland in dogs has been developed. The experiments on dogs were performed to analyse the functional state of the perfused gland. It has been shown that the functional state parameters in 6-hour perfusion were comparable to the control values. It is concluded that the model suggested creates physiologic conditions and can be employed as a model for studying the influence of various factors on the isolated thyroid gland, as well as for investigating problems related to thyroid gland transplantation.     

Morphological changes in the thyroid gland of rats during various phases of the estral cycle]

The functional state of the thyroid gland and the concentration of thyroid hormones in the peripheral blood were studied in 20 mature female albino rats during their estral cycle. Evaluation of the thyroid functional state was made according to data of histological, morphological (the diameter of folliculi, the height of the thyroid epithelium) and histochemical analysis (determination of NAD and NADP-dehydrogenase, succinatedehydrogenase, lactate dehydrogenase, peroxydase, acid and alkaline phosphatase) as well as biochemical determination of iodine bound with protein (IBP) in the blood plasma and investigation of the ratio of the parameters in question under conditions of the sex cycle. The cyclic changes of the morphological state of the thyroid gland attended by the phases of the estral cycle were revealed. The activation of the organ was observed in proestrus and estrus which was evidenced by high levels of activity of the enzymes under study, high concentration of IBP in the blood and increased height of thyreocytes. A decreased function of the thyroid parenchyma was observed at the period of metaestrus-diestrus.     

Models to study the pathogenesis of thyroid autoimmunity.

In vitro and in vivo models to study the pathogenesis of thyroid autoimmunity are reviewed. Animal models with experimentally induced or spontaneously developed autoimmune thyroid disease as well as transplantation models have been used extensively in these studies, but also the use of thyroid cell cultures from both humans and animals has contributed to the present state of knowledge. Cytokines may play a role in the pathogenic mechanism in thyroid autoimmunity. The major in vitro and in vivo effects of for example interleukin-1, tumour necrosis factor and gamma-interferon on differentiated thyroid cell functions are inhibitory. The advantage of using cell cultures has been the possibility of studying an influence on thyrocytes from a single agent individually, such as cytokines, hormones or growth factors. The disadvantage is that an organism is under the influence of a multitude of factors that can only be investigated in vivo in intact organisms. Both types of models have therefore been important in the understanding of thyroid autoimmunity.     

Morphofunctional characteristics of the thyroid gland in intact and partially sympathectomized rats of different age groups

The morphological and functional age-dependent changes have been studied in the thyroid gland of infantile (1-month-old), immature (2- and 3-month-old) and sexually mature (6-month-old) male rats. The decrease in thyroid functional activity with ageing was proved. Chemical sympathectomy (guanethidine at a dose of 15 mg/kg intramuscularly for 14 days after birth) was accompanied not only by morphological reconstruction of the thyroid tissue, but also (especially in 1-month-old rats) by a delay in transport-organic phase of iodine metabolism and a decline in thyroid hormone serum level. Later on, the compensatory hormonogenesis reinforcement occurs as a result of partial adrenergic innervation recovery.     

Comparative morphological analysis of peripheral endocrine glands in small mammals inhabiting areas with high levels of radioactive pollutants and exposed to chronic irradiation in laboratory experiments

The comparative study of cellular-tissue reactions in endocrine organs (thyroid and suprarenal glands, ovary) of rodents exposed to radiation in natural conditions (Radium station in Komi Republic and 30-km zone of Chernobyl APP) and experimental conditions modeling the chronic exposure has been conducted. There is evidence that chronic irradiation in low doses causes morphological disorders in different levels of structural organization (cellular-tissue, organism and population levels). The experimental results showed that observed variations in thyroid, suprarenal glands and ovary by morphometric parameters reflect the natural changes in their functional activity (within the physiological limits). These changes are directed at the homeostasis maintenance in changed conditions and have a compensatory and adaptation character. The effects of low dose radiation influence with combination of other agents may be amplified at the cellular-tissue reactions level. In comparison with experimental results, the natural conditions (high level of radioactivity with alpha- and beta-emitters, high natural radionuclides, toxic elements and extreme climatic factors) induce more expressed changes as a significant increasing of chromosomal and genes mutations in cells, destructive processes in organs of endocrine system and disorders of reproductive functions.     

Effect of weightlessness and artificial gravitation on thyroid gland morphology]

The investigation of the thyroid gland was carried out in Wistar rats, SPF colony 4.5--13 h and 25 days after a 18.5 days flight on board the space biosatellite "Cosmos-936". In animals subjected to weightlessness, moderate symptoms of the thyroid hypofunction were observed, statistically significant decrease in number and volume of the nuclei in calcitonin-secreting cells (C-cells) was especially pronounced during 4.5--9 h after landing. Similar but less pronounced changes were observed in C-cells of the rats subjected to artificial conditions of space flight, besides weightlessness. The similarity of the changes in the animals of both groups made it possible to connect the increasing amount of C-cells and the morphological symptoms of their functional inhibition with the effect of weightlessness and hypokinesia. During the space flight, the animals were kept under the conditions of artificial gravitation on board the biosatellite and therefore morphological peculiarities specific for the earth conditions were preserved in C-cells and the thyroid gland. Thus, it was concluded that artificial gravitation prevented the development of the thyroid changes which appeared under the influence of weightlessness.     

Relationship of biochemical and morphological changes in rat thyroid and proton spin-relaxation of the tissue water.

The effect was studied of biochemical and morphological changes induced by antithyroid substances (PTU, C10(-4)) on proton spin-relaxation properties of rat thyroid gland. It was found that thyroid stimulated by PTU (0.05%) or C10(-4) (1.0%) exhibit marked morphological changes (hyperplasia and epithelial hypertrophy) with alteration of the soluble iodoprotein pattern (content and composition.). Both relaxation times spin-lattice (T1) and spin-spin (T2) were increasing with the lenght of treatment with antithyroid drugs. Reversibility of the process was noted in accordance with biochemical and morphological data. The relaxation rate (formula: see text) for thyroid tissue water was in positive correlation with the suluble protein concentration and particularly with the TG content in the gland. There was no difference in relaxation times between normal thyroid and gland of rats treated chronically with excess iodide. The observed difference in T1 between normal glands and glands of PTU,-C10(-4)--treated rats was comparable with that found in cases of human thyroid cancer. This finding is of importance when the diagnostic potential of NMR in the detection of malignancy is considered. In conclusion, a strong correlation was found between microstructural and biochemical changes of the thyroid gland and proton magnetic relaxation of tissue water. The striking difference between the proton spin-relaxation times in normal and in goiter thyroid glands of rats suggests that pulsed NMR spectroscopy could be a method for evaluation of some disturbances in thyroid gland.     

Risk factors for rejection for morphological reasons of heart valves for transplantation

The study aim was to identify risk factors for morphological rejection of aortic and pulmonary valves for transplantation that could be used to optimize donor selection. The files of all Dutch heart valve donors, donating in a 2.5 years period, whose hearts were processed at Heart Valve Bank Rotterdam, were reviewed for all factors that could be relevant for valve rejection and related to outcome of morphological assessment of the valves. Valves were retrieved from 813 deceased Dutch donors, 24.1% also donating organs. For 797 aortic and 767 pulmonary valves, who met retrieval criteria, morphological assessment was done. 69.5% of aortic and 37.5% of pulmonary valves were considered unsuitable for transplantation at morphological assessment. Backward stepwise multivariate logistic regression analysis, showed age, cardiac cause of death, cerebrovascular accident as cause of death or in medical history, and number of cardiovascular risk factors in a donor to be independent risk factors for morphological rejection of aortic valves. Age, sex, weight >100 kg and ruptured aortic aneurysm as cause of death were independent risk factors for morphological rejection of pulmonary valves. Being an organ donor was an independent predictor of morphological approval of aortic and pulmonary valves, while hypertension was an independent predictor for morphological approval of aortic valves. Thus, independent factors were identified that are associated with morphological rejection of aortic and pulmonary valves for transplantation, and that could be used to optimize donor selection by preventing unnecessary retrievals, limiting costs, while improving yield per donor with minimal compromise for availability.     

Comparative morphological analysis of peripheral endocrine glands of small mammals inhabiting areas with high levels of radioactivity and exposed to chronic irradiation in model experiments

Comparative study of cellular-tissue reactions in the endocrine organs (thyroid and adrenal glands and ovary) of rodents exposed to radiation under natural conditions (Radium station in the Komi Republic and 30-km zone of Chernobyl NPP) and under experimental conditions modeling chronic exposure is carried out. Evidence is found that low-dose chronic irradiation causes morphological disorders at different levels of structural organization (cellular-tissue, organism, and population levels). The experimental results show that the observed variations in the morphometric parameters of the thyroid and adrenal glands and ovary reflect natural changes in their functional activity (within the physiological limits). These changes are directed at the maintenance of homeostasis under altered conditions and have a compensatory and adaptive character. The effects of low-dose radiation in combination with other agents may be amplified at the level of cellular-tissue reactions. In comparison with the experimental results, natural conditions (high level of radioactivity due to α and β emitters, high natural radionuclides, toxic elements, and extreme climatic factors) induce more pronounced changes, including a significant increase in chromosomal and gene mutations in cells, destructive processes in the organs of the endocrine system, and disorders of reproductive functions.

     

Morphological changes in the human thyroid gland cultivated in continual flow system

In the present pilot study, the human thyroid gland tissue was cultivated under continuous culture conditions in the culture chambers of the ACUSYST-S system to determine morphological changes as well as the secretion of thyreoglobulin (Tgl) and thyroid hormones. After 24 hours of cultivation the follicular structure of the tissue was preserved in peripheral parts only, and there were regressive changes in the epithelium center. After 72 hours the regressive changes appeared in isolated follicles only; the size of the follicles increased, the height of the follicular epithelium decreased and there were macrophages present with phagocytized cell debris. After 144 hours disintegration of epithelia took place in the centre, while at the periphery the original follicles survived and very tiny new follicles formed, consisting of only 6 to 8 cells each and surrounding in section the homogeneous colloid. The parenchyma picture suggests a possibility of functional regeneration as an expression of adaptation to the conditions newly arisen during cultivation in a culture chamber. There was no significant influencing of the thyroid hormone secretion during cultivation. On the other hand, the Tgl secretion decreased throughout cultivation.     

Effect of lithium chloride on the thyroid gland of white rats]

The morphological and functional changes in the thyroid tissue of white rats injected lithium chloride at doses 0.5 mekv/kg and 1.0 mekv/kg (groups 1 and 2, respectively) during three weeks were studied by the radiometric, histological and biochemical methods. The radiometric, histological and biochemical methods. The inhibitory action of lithium chloride on hormonogenesis in the thyroid gland and secretion of thyroid hormones into the blood was proved to be directly related to the lithium dose and concentration in the blood. The data of intravital radiometric and morphological analysis of the organs of the 1st group animals suggest some activization of the gland function, with the secretion of the hormones into the blood being suppressed. Increased concentration of the drug inhibits hormonogenesis and secretion of thyroid hormones into the blood.     

Ultrasound study in the differential diagnosis of thyroid focal lesions of various origin

The present study deals with the ultrasound differential diagnosis of thyroid lesions. A hundred and ninety-two patients, including 130 patients with benign diseases (nodular colloidal goiter) (36.9%), chronic autoimmune thyroiditis (30.7%), and adenomas (32.3%) and 62 patients with malignant diseases (thyroid cancer (88%), lymphoproliferative diseases (6.4%), and recurrent thyroid cancer) (4.8%), were clinically examined. Ultrasound studies (USS) were performed in the B- and (see text symbols) modes. The diagnosis was verified from cytological and histological findings with mandatory morphological confirmation. Interdisease comparison has shown that USS is both a screening and diagnostic technique in revealing thyroid changes and determining their site, sizes, and structure. Ultrasound pathognomonic signs were detected in different morphological types of adenomas, thyroiditis, and nodular colloidal goiter, in the classical, pseudoadenomatous and pseudocystic types of thyroid cancer. At the same time there were characteristic ultrasound parameters at the stage of pronounced changes in undifferentiated thyroid cancer (pseudothyroiditis), lymphoproliferative diseases, and acute thyroiditis. The exception was the diffuse form of chronic autoimmune thyroiditis in which both thyroid lobes were always altered.     

The effect of one-time external low- and high-dose gamma-irradiation on rat thyroid structure at the acute and remote periods

A study of the morphological structure of the thyroid was made at the acute (1, 3, 6 hours) and remote periods (1, 4, 24, 48 weeks) following the external gamma-irradiation at doses of 0.25-5.0 Gy using histologic and electron microscopic methods. At the acute period, morphological changes prevailed, which reflect the functional alterations (changes of the nucleic and of the follicular diameters and of the colloid density). Frequently they hare a non-synchronous character. At more remote periods, destructive (colloidorrhage, desquamation, hemorrhage) and reparative changes reveal in thyroid, which and by the development of the sclerotic processes and of the morphological signs of decreased functional activity of the gland (increased follicular size and colloidal density, flatness of follicular epithelium and pronounced decreasing of the thyrocytes ultra structure number). The presence of such morphological changes after high and low-dose irradiation (<1.0 Gy) shows high sensitivity of the thyroid to single external radiation.     

Connexin-32 acts as a downregulator of growth of thyroid gland

Thyroid epithelial cells communicate through gap junctions formed from connexin (Cx)32, Cx43, and Cx26. We previously reported that reexpression of Cx32 in "gap junction-deficient" FRTL-5 and FRT thyroid cell lines induces a reduction of cell proliferation rate and an activation of expression of cell differentiation. The present study aimed at determining whether Cx32 could exert similar regulatory functions in vivo. We investigated morphological and functional characteristics of thyroid gland of Cx32-deficient mice (Cx32-KO), mice overexpressing Cx32 selectively in the thyroid (Cx32-T+), and Cx32-KO mice with a thyroid-selective Cx32 complementation obtained by crossing Cx32-KO and Cx32-T+ mice. In basal conditions, Cx32-KO mice did not present any detectable thyroid alteration, whereas Cx32-T+ mice showed a thyroid hypoplasia (20% reduction) associated with a slight increase in thyroid functional activity. Under thyrotropin stimulation (following sodium perchlorate treatment), Cx32-KO mice developed a larger goiter (< or =65% increase) than wild-type littermates, whereas Cx32-T+ mice exhibited the same thyroid hyperplasia as wild-type mice. Restoration of Cx32 expression in the thyroid of Cx32-KO mice abrogated the thyroid growth increase related to Cx32 deficiency. All together, these data show that Cx32 acts as a downregulator of growth of thyroid gland; an excess of Cx32 limits growth of thyroid cells in the basal state, whereas a lack of Cx32 confers an additional growth potential to TSH-stimulated thyroid cells.     

Thyroxine and triiodothyronine influence cultured throid cells: alterations of morphology and mucosubstances.

Further experimentation with the steer thyroid cell line indicates that the formation of "follicles" is enhanced by exposure to 8.9 X 10(-7) M thyroxine (T4) or triiodothyronine (T3) for 96 hr. The production of mucosubstances by the cultured thyroid cells is also increased by treating with T4 or T3, effects demonstrable after staining with PAS-alcian blue at pH 2.5. It is suggested that these in vitro effects bear on morphological organization and synthetic activity of the thyroid gland as well as on autoregulation and intraglandular homeostasis that may occur in situ.     

The role of oxidative stress in physiological and pathological processes in the thyroid gland; possible involvement in pineal-thyroid interactions

Reactive oxygen species (ROS) play an important role in physiological processes, but - when being in excess - ROS cause oxidative damage to molecules. Under physiological conditions, the production and detoxification of ROS are more-or-less balanced. Also in the thyroid, ROS and free radicals participate in physiological and pathological processes in the gland. For example, hydrogen peroxide (H2O2) is crucial for thyroid hormone biosynthesis, acting at different steps of the process. Additionally, H2O2 is believed to participate in the Wolff-Chaikoff's effect, undergoing in conditions of iodide excess in the thyroid. Much evidence has been accumulated indicating that oxidative stress is involved in pathomechanism of thyroid disease, e.g., Graves' disease, goiter formation or thyroid cancer. Melatonin (N-acetyl-5-methoxytryptamine) - the main secretory product of the pineal gland - is a well-known antioxidant and free radical scavenger, widely distributed in the organism. Mutual relationships between the pineal gland and the thyroid have - for a long time - been a subject of intensive research. The abundant to-date's evidence relates mostly to the inhibitory action of melatonin on the thyroid growth and function and - to a lesser extent - to the stimulatory effects of thyroid hormones on the pineal gland. It is highly probable that under physiological conditions melatonin and, possibly, other antioxidants regulate ROS generation for thyroid hormone synthesis. We believe that melatonin may protect against extensive oxidative damage in the course of certain thyroid disorders or in case of a harmful action of some external factors on the thyroid. Thus, oxidative damage and the protective action of antioxidants, melatonin included, may occur during both physiological and pathological processes in the thyroid, however, this assumption, requires further studies.     

Hormonal stimulation of the reparative process in the skin or fats with vitamin A deficiency]

The effect of thyroid hormone on the regeneration of skin of A-deficient rats was studied. It was established that the reparative process in such animals was considerably retarded due to disturbances of the intensity and the character of the reaction. Under these conditions the succession of main stages of the regenerative process was maintained but there occurred a number of important qualitative and quantitative morphological disorders which substantially changed the course of healing of skin wounds. An additional injection of the thyroid hormone against this background had a favourable effect upon the skin regeneration but failed to produce a typical stimulating effect, characteristic of the hormonal agent in normality.