Roles of Thyroid Hormones, Mast Cells, and Inflammatory Mediators in the Initiation and Progression of Autoimmune Thyroid Diseases.

BACKGROUND: Interrelation between thyrocytes and immunocytes has been established. However, the roles of mast cells and thyroid hormones in the triggering mechanism of thyroid autoimmune processes have been insufficiently investigated. This study evaluated the role of thyroid hormones and mast cells in the mechanisms of losing tolerance to thyroid autoantigens. MATERIALS AND METHODS: Two groups of patients were studied: patients with Graves' disease and patients with nodular euthyroid goiter. Wistar rats with induced exogenous hypothyroidism, thyrotoxicosis, and thyrotoxicosis in parallel with administration of interleukin-2 were used. The levels of hormones, autoantibodies, and cytokines in the serum and thyroid tissue were analyzed through the enzyme-linked immunosorbent assay. Morphological verification was performed through the immune-histochemical method with antibodies against tryptase and CD86. Transmission electron microscopy and laser confocal microscopy were used. RESULTS: In both Graves' disease and induced thyrotoxicosis, we detected a significant increase in the levels of interferon-γ, active interfollicular infiltration and degranulation of mast cells, and the intrathyroid overexpression of CD86. Complex analysis of the rat's thyroid morphofunctional state and systemic and local levels of cytokines in induced thyrotoxicosis and hypothyroidism demonstrated an increase of intrathyroid degranulation of mast cells and a drastic disruption of IFNγ/IL10 balance. CONCLUSIONS: When exposed to excessive amounts of thyroid hormones, an inflammatory response is triggered in the thyroid gland, and mast cells overexpress costimulating CD86 in the thyroid. This finding confirms their possible involvement in auto-antigen presentation. Significant increase in the levels of interferon-γ shows a determining influence of cytokine on the progression of the pathological process.

Paragonimus heterotremus Chen et Hsia, 1964 (Digenea: Paragonimidae): species identification based on the biological and genetic criteria, and pathology of infection.

As a result of the experimental infection of rats with metacercariae of Paragonimus heterotremus Chen et Hsia, 1964 from crabs (Potamiscus tannanti) caught in Yen Bai province, Vietnam, it was found that worms migrated into the lungs, to the liver and less frequently to the tissue that lines body cavities of the hosts, where they reached the adult stage, but in the muscles, worms stayed at the larval stage. Studies have shown that for P. heterotremus, rats can simultaneously play the role of the final and paratenic host; herewith, an infection with the trematode of this species can lead to the development of three forms of paragonimiasis: pulmonary, hepatic and muscular. Eggs from the adult worms localised in the liver, unlike eggs from the adult worms localised in the lungs, were not excreted into the external environment, but accumulated inside the organ. Histology and description of changes, which take place on the external surface of organs affected with P. heterotremus, are given in this study. Based on the behavioural characteristics of worms during rat infection and molecular genetic data, we established that worms from Vietnam and India should be assigned to different species of Paragonimus. P. heterotremus distribution is limited to the territory of the Southeast China, Northern Vietnam, Laos and Thailand.

Development of Novel Tetrapyrrole Structure Photosensitizers for Cancer Photodynamic Therapy.

The effectiveness of photodynamic therapy (PDT) is based on the triad effects of photosensitizer (PS), molecular oxygen and visible light on malignant tumors. Such complex induces a multifactorial manner including reactive-oxygen-species-mediated damage and the killing of cells, vasculature damage of the tumor, and activation of the organism immunity. The effectiveness of PDT depends on the properties of photosensitizing drugs, their selectivity, enhanced photoproduction of reactive particles, absorption in the near infrared spectrum, and drug delivery strategies. Photosensitizers of the tetrapyrrole structure (porphyrins) are widely used in PDT because of their unique diagnostic and therapeutic functions. Nevertheless, the clinical use of the first-generation PS (sodium porfimer and hematoporphyrins) revealed difficulties, such as long-term skin photosensitivity, insufficient penetration into deep-seated tumors and incorrect localization to it. The second generation is based on different approaches of the synthesis and conjugation of porphyrin PS with biomolecules, which made it possible to approach the targeted PDT of tumors. Despite the fact that the development of the second-generation PS started about 30 years ago, these technologies are still in demand and are in intensive development, especially in the direction of improving the process of optimization split linkers responsive to input. Bioconjugation and encapsulation by targeting molecules are among the main strategies for developing of the PS synthesis. A targeted drug delivery system with the effect of increased permeability and retention by tumor cells is one of the ultimate goals of the synthesis of second-generation PS. This review presents porphyrin PS of various generations, discusses factors affecting cellular biodistribution and uptake, and indicates their role as diagnostic and therapeutic (theranostic) agents. New complexes based on porphyrin PS for photoimmunotherapy are presented, where specific antibodies are used that are chemically bound to PS, absorbing light from the near infrared part of the spectrum. Additionally, a two-photon photodynamic approach using third-generation photosensitizers for the treatment of tumors is discussed, which indicates the prospects for the further development of a promising method antitumor PDT.