[The role of calcium sensitive and vitamin D receptors in the pathogenesis of sporadic multiple parathyroid gland disease].

BACKGROUND: Sporadic multiple parathyroid gland disease is » cases of primary hyperparathyroidism (PHPT). However, a single tactic for diagnosing and operating volume in patients with this variant of PHPT has not yet been developed. One of the possible directions in the search for pathogenetically substantiated methods of diagnosis and treatment is the study of the molecular genetic features of the disease and associated clinical and laboratory factors. AIM: To study the features of the expression of calcium sensitive (CaSR) and vitamin D (VDR) receptors on the surface of parathyroid cells in primary hyperparathyroidism with solitary and multiple lesions of the parathyroid glands, as well as its changes under the influence of a decrease in the filtration function of the kidneys. MATERIALS AND METHODS: In a single center observational prospective study with retrospective data collection, there were patients who during 2019-2021. operated on for PHPT, secondary hyperparathyroidism (SHPT) and all cases of tertiary hyperparathyroidism (THPT) operated during 2014-2021. The expression of CaSR, VDR and its relationship with the main laboratory parameters, the clinical variant of hyperparathyroidism, and the morphological substrate were studied. RESULTS: The study included 69 patients: 19 with multiple and 25 with solitary PTG near PHPT, 15 with SHPT, 10 with THPT. A statistically significant decrease in the frequency of detection of normal expression of CaSR and VDR receptors occurs in any morphological variant of hyperparathyroidism and is observed in 93-60% of drugs. A decrease in the normal expression of CaSR in hyperplasia is detected statistically significantly less frequently than in adenoma (p≤0.01). The median expression intensity in adenoma was 2.5 (2:3), in hyperplasia 3.5 (3-4) (p≤0.01). The difference in the molecular mechanisms of the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma (PHPT with solitary adenoma) or hyperplasia (SHPT and PHPT with multiple PTG lesions) is realized in the frequency of maintaining normal CaSR expression in the PTG tissue. These mechanisms are implemented at the local level, their variability does not change under the influence of RRT. A common molecular genetic mechanism for the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma or hyperplasia has been found to reduce the frequency of maintaining normal VDR expression in PTG (up to 7-13%), p<0.01. This mechanism is implemented at the local level, its variability changes under the influence of RRT, reaching statistically significant differences in patients with THPT. CONCLUSION: The study demonstrates the features of changes in the expression of CaSR and VDR in PHPT with multiple lesions of the parathyroid glands. The relationship between the expression of these receptors and the clinical variant of hyperparathyroidism, the morphological substrate, the main laboratory parameters, and renal function was shown.

Morphological Evaluation of Oxidative Phosphorylation System in Myocardial Infarction under Conditions of Modified Vascular Endothelial Growth Factor Concentration.

The relationship between vascular endothelium growth factor (VEGF) and cardiomyocyte oxidative phosphorylation level in experimental myocardial infarction, caused by diathermocoagulation of the periconical ventricular artery, was studied by immunofluorescent microscopy. Staining showed uneven distribution of cytochrome c in the mitochondria in the focus of myocardial infarction 2 h after the operation. After 24 h uneven staining of cardiomyocytes was found in the peri-infarction zone and no staining in the zone of myocardial infarction. This indicated a significant decrease in the level of redox enzymes. This picture persisted till day 14. Intraventricular injection of VEGF to animals led to a significant increase of the immunohistochemical reaction intensity, which reached the peak by day 7. The distribution of immunohistochemical reaction products under conditions of VEGF blocking was about the same as in spontaneous postinfarction reparative restitution. Our data indicated that increase of VEGF concentration in the myocardium maintained and stimulated oxidative phosphorylation in cardiomyocytes during the postinfarction period.

Endogenous progenitors as the source of cell material for ischemic damage repair in experimental myocardial infarction under conditions of changed concentration of vascular endothelial growth factor.

We studied the effect of VEGF-A in experimental myocardial infarction on attraction of progenitor cells into the regeneration zone. The appearance of CD34(+)CD45(+) cells known as low-differentiated progenitor cells was observed in the damaged myocardial tissue in the presence of a considerable excess of VEGF-A. These cells can act as precursors of mesenchymal tissues depending on the direction of differentiation.

[Influence of FGF2 level on the inflammation phase dynamics at the postinfarction cardiosclerosis].

We modeling myocardial infarction female Wistar rats (N=126). We used morphomethry for examination of infarction zone from 2 h to 30 days after operation. The study comprised three groups of animals: "Control", "FGF" with 100 Hz FCGF2 injection into left ventricle, "anti-FGF" with 2 microg monoclonal antiFCF2 antibodies injections at period 1.5 h, 6 h and 3 day after operation. We founded that FCF2 injections leaded to enlarged of infiltrative inflammatory stage and take effect on the early collagen synthesis in infarction regions (from 3 days in group with FGF2 injection vs. 7 days in control group). Opportunity,injection of anti-FCF2 antibodies leaded to decreasing collagen volume on 30 day after infarction (19.15 +/- 1.22% in "anti-FGF" group vs. 41.71 +/- 1.30% in "Control" group, p < 0.05).

Effect of endothelial growth factor on postinfarction remodeling of rat myocardium.

The reparative processes in the myocardium were studied during the postinfarction period after intracardiac injection of vascular endothelial growth factor. The cytoprotective and mitogenic effects of increased concentration of vascular endothelial growth factor on cardiomyocytes were revealed: viable muscle cells were present in the myocardial necrotic zone over 3 days, while cardiomyocytes in the periinfarction zone exhibited mitotic activity of within 7 days after infarction modeling. One of the main morphogenetic effects of high concentrations of vascular endothelial growth factor is stimulation of angiogenesis in all zones of the infarcted myocardium. On the other hand, injection of exogenous vascular endothelial growth factor stimulated collagen formation processes in the infarction zone (a 44% increase of the volume of collagen fibers) and formation of cardiosclerosis foci in neoangiogenesis zones in the intact myocardium, which is an unfavorable side effect of high concentrations of vascular endothelial growth factor.

[Impact of Yersinia pseudotuberculosis on the in vitro production of cytokines by whole blood cells of donors]. / Vliianie Yersinia pseudotuberculosis na produktsiiu tsitokinov kletkami tsel'noi krovi donorov in vitro.

The impact of two plasmid (47, 82 MD), single plasmid (47 MD) and non plasmid Y. pseudotuberculosis strains, Y. enterocolitica (47 MD) as well as Y. pseudotuberculosis superantigen (YPM) on the production of interleukin-1 (IL-1), interleukin-6 (IL-6), interferon-alpha (IFN = alpha) and tumor necrosis factor alpha (TNF-alpha) by whole blood cells obtained from donors was studied. All Y. pseudotuberculosis and Y. enterocolitica strains stimulated the production of IFN-alpha, IL-1, IL-6 and TNF-alpha by whole blood cells, but considerably less than Y. pseudotuberculosis lipopolysaccharide and YPM. These data are indicative of the pathogenetic role played by 82 MD plasmid in manifestation of Y. pseudotuberculosis immunosuppressive properties. The maximum stimulation of the production of cytokines was observed under the action of YPM, which confirmed an important role played by this superantigen in the pathogenesis of Y. pseudotuberculosis.

[An analysis of the antibodies to the outer cell membrane proteins in Yersinia in the varying course of human pseudotuberculosis]. / Analiz antitel k belkam naruzhnoi kletochnoi membrany iersinii pri razlichnom techenii psevdotuberkuleza u liudei.

Time course changes in the formation and spectrum of the antibodies to the proteins of Yersinia pseudotuberculosis external cellular membrane were studied by immunoblotting. A total of 154 samples of blood serum from 46 pseudotuberculosis (PT) patients were tested. 53 samples were obtained from PT patients with acute disease, 50 from PT patients with recurrences and 51 samples cam from PT subjects with protracted disease. Electrophoresis in polyacrylamide gel with sodium dodecyl sulfate disclosed a number of basic protein components with molecular characteristics: 22-26-33-37-45-59-67 kD. Irrespective of the disease clinical presentation, the antibodies were directed primarily to the protein component of 26 kD molecular mass this evidencing its immunodominant role. There appeared some specific features in formation rate and circulation time of the above antibodies. This finding may be utilized for diagnostic and prognostic purpose.