Moskalenko R. Pathomorphological features of soft tissue biomineralization

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0518U000062

Applicant for

Specialization

  • 14.03.02 - Патологічна анатомія

07-02-2018

Specialized Academic Board

Д 64.600.03

Essay

The dissertation eludicates the study of morphological, immunohistochemical, molecular genetic and chemical features of soft tissue biomineralization during various general pathological processes such as benign and malignant tumor growth, chronic inflammation, dystrophy and atherosclerosis. The studies were conducted on a material from 270 patients with diseases associated with biomineralization. Research methods such as macroscopic examination, histology, histochemistry, optical and fluorescent immunohistochemical research, Western blot analysis, immune-dot, transmission and scanning electron microscopy with chemical analysis, atomic force microscopy, X-ray diffraction, infrared spectroscopy, mathematical and statistical data analisis. The dissertation presents a theoretical synthesis and a new solution to the scientific problem, which concerns the improvement of the diagnosis quality of diseases associated with biomineralization by the identifying the morphogenesis features of soft tissues pathological biomineralization in the human body on the background of atherosclerosis, proliferative processes and chronic inflammation provided different organ localization. In this work the structure of diseases related to biomineralization in the Sumy region was investigated, orientation and biological behavior of pathological biomineralization processes under the conditions of different pathologies were determined. It has been established that in the mineralized tissue of the aorta and aortic valves the main phase of pathological biomineralization was carbonate-containing, defective, weakly crystallized apatite. With the help of methods of applied material science, a wide spectrum of biomineral crystals morphology was revealed, which testify to the various mechanisms of their origin and growth in the cardiovascular system tissues. The main type of the thyroid gland pathological biomineralization is vascular-dependent calcification, including psammoma bodies and vascular calcification, which are more common in malignant thyroid tumors. The stromal calcification is characteristic for all thyroid diseases (defeat of the capsule, intercellular and interpholucular connective tissue), the parenchymal calcification is characteristic for benign thyroid processes (calcification of colloid and follicular epithelium). All cases of thyroid vascular calcification with its most common malignant tumors corresponded to the calcium-phosphate type of biomineralization, the main phase of biomineral deposits in the thyroid malignant tumors was structurated hydroxyapatite with в-TCMF impurities. For the first time, by X-ray spectroscopy, the presence of organic material in psammoma bodies (20%, and 80% of hydroxyapatite) was conducted, which confirms the assumption about the role of the protein component in the formation of psammoma bodies lamellar structure. The mineral base of the prostate concretions is a carbonate bioapatite with a minor inclusion of foreign chemical elements. Based on the results of the pathomorphological study and the methods of physical material science, man can conclude that the dominant mechanism of the concretions formation is the direct precipitation from the prostate secretion, and not the dystrophic calcification of corpora amylacea. Different topologies and formation conditions lead to the formation of various crystalline phases and/or different structural organization of gallbladder biominerals. The presence of S100A8 and S100A9 proteins, also as calprotectin, is confirmed by their co-localization in the pathological processes during the study of mineralized tissues of different localization. The high concentration of S100A9, the active component of calprotectin, in the cardiovascular system and in prostatoliths is confirmed by dot-blot and western blot. Under conditions of inflammation such effect of S100A8 / S100A9 triggers apoptosis processes, which is reflected by the high Casp 3 expression in the group of mineralized tissues samples compared to the control groups. Calprotectin-dependent damage of soft tissues can be a critical element in the pathological biomineralization morphogenesis in the case of different nosologies. In the mineralized tissues the high OPN protein expression may indicate its protective and formative role in biomineralogenesis. The main mechanisms of ectopic biomineralization are mineralization on the organic matrix ("tissue biomineralization": cardiovascular calcification, porcelain gallbladder) and direct precipitation from a supersaturated solution ("cavity biomineralization": prostatoliths, gallstones, sialoliths). Separately, the secondary mineralization of dead tissues in the areas of necrosis (comedo-calcifications, malignant tumors, chronic inflammation), which develops under influence of mixed mechanism, should be highlighted.

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