Histological Variants of Papillary Thyroid Cancer in Relation to Clinical and Morphological Parameters and Prognosis.

The correlation of histological features of papillary thyroid cancer with clinical and morphological prognostic factors and cause-specific mortality was analyzed in a case-control study within a cohort of patients from the Altai Regional Oncology Center (25 cases with lethal outcome and 64 follow-up controls). Significant variability was revealed in the histological structure of papillary thyroid cancer with the prevalence of classic (62%) and less frequent follicular (19%), tall cell (8%), and solid (7%) variants. In comparison with the classic variant, the solid variant was more often associated with male sex and large tumor size; follicular and tall cell variant was associated with more frequent metastases to regional lymph nodes; follicular and solid variants were associated with an increased proportion of cases with disease stages III-IV. The main differences reflecting the effect of histological factor on the disease outcome were associated with the solid variant of papillary thyroid cancer that was detected in 21% of lethal cases and only in 2% of control subjects. The detection of this variant can be of importance as an additional prognostic factor of the postoperative survival in papillary thyroid cancer.

Features of Cell Reactions during Implantation of Biodegradable Polymer and Polypropylene in the Experiment.

Quantitative and qualitative characteristics of cell infiltrates in male Wistar rats were studied from 14 days to 12 months after implantation of polypropylene and a biodegradable polymer obtained by electrospinning and consisting of 65% polycaprolactone and 35% polytrimethylene carbonate. It was found that a predominantly macrophage-giant cell reaction developed around the biodegradable polymer; it spread into the matrix and the number of cells in the infiltrate decreased, as the degradation progressed. Around polypropylene, mainly lymphocytic and leukocytic reaction was seen; it also decreased with time, but was characterized by a reverse increase in the number of lymphocytes. Immunohistochemical analysis showed that the proportion of CD38+ cells 12 months after implantation increased around polypropylene to a greater extent than around the biodegradable polymer, while the proportion of CD68+ cells decreased. These findings suggest that implantation of a biodegradable polymer caused no prolonged lymphocytic and plasma cell reaction in animals as in the case of polypropylene, which indicates that biodegradable polymer is a promising material for tissue engineering.

Modeling of Benign Prostatic Hyperplasia in Rats with a High Dose of Testosterone.

In order to optimize the testosterone model of benign prostatic hyperplasia, we studied the effect of castration and different doses of testosterone on the induction of the proliferative process in the prostate of Wistar rats. It was shown that 4-week subcutaneous administration of testosterone propionate in a dose of 20 mg/kg causes pronounced proliferative and hemodynamic disorders in the dorsolateral gland morphologically similar in castrated and non-castrated males. Administration of testosterone in a dose of 3 mg/kg had no significant effect on the dynamics of the pathological process in non-operated rats and normalized the structure of the gland in castrated animals. Morphological study showed that castration of males provides no visible advantages in reproducing the testosterone model of benign prostatic hyperplasia. The proposed non-traumatic modification of the model with a high dose of testosterone has good reproducibility and sensitivity to therapeutic agents, as shown by the example of finasteride.

Experimental Study of Antitumor Activity of Pefagtal Addressed to αvß3 Integrins.

We studied the effect of a new targeted drug Pefagtal that represents a conjugate in which the MS2 phage filled with a substance toxic to cells (thallium salts) is covalently linked to peptides containing the RGD motif. The antitumor and pronounced antimetastatic effects of Pefagtal were demonstrated on transplanted mouse tumors differing in histological type and status of metastasis: Krebs-2 ascites adenocarcinoma of the mammary gland, Lewis lung adenocarcinoma, hepatoma-29, and lung adenocarcinoma. It is assumed that the RGD motif mediates primary binding of the construct to αvß3 and αvß5 integrins that are predominantly overexpressed in the endothelial cells of tumor blood vessels and in tumor and metastatic cells.

Comparative Analysis of Connective Tissue Responses to Implantation of Biodegradable Material and Polypropylene in Experimental Animals.

We compared qualitative characteristics of the connective tissue at the site of implantation of polypropylene or a biodegradable polymer synthesized by electrospinning and consisting of 65% polycaprolactone and 35% polytrimethylene carbonate. Synthetic materials were implanted into the interfascial space of the muscles on the back of Wistar rats. The parameters of cellular and non-cellular structures of the forming connective tissue were studied in 1, 2, 3, 6, 9, and 12 months after implantation. It was found that the number of fibrocytes and fibroblasts around biopolymer and polypropylene increased during the period from 1 to 9 months, with a significant lag in case of biopolymer implantation; by 12 months, the number of fibrocytic cells did not significantly differ. The fibroplastic and angioplastic processes developed in the thickness of both materials, but with a one-month lag in case of biopolymer implantation due to degradation properties and nonporous structure of this polymer. Collagen fibers were actively synthesized around both materials, but in case of polypropylene, this process was more pronounced. In 6 months after implantation of polypropylene, dense regular connective tissue was formed; in 12 months after implantation of the biopolymer, the formation of dense irregular connective tissue was observed at the site of implantation. The biopolymer can be used to strengthen the core muscles.

Features of Remodeling of Prostate Stroma in Chronic Abacterial Prostatitis.

We performed a complex morphological study of biopsy samples of prostate gland from 30 men (mean age 46±11 years) with chronic abacterial prostatitis who were exposed unfavorable anthropogenic factors. The ultrastructural heterogeneity of smooth muscle cells was shown, among which cells with destructive changes in organelles predominated, solitary cells with signs of secretory function were revealed. Most endothelial cells in microvessels were characterized by low pinocytotic activity, destruction of organelles; focal hyperplastic ultrastructural changes were noted in some endotheliocytes. Along with fibroblasts, the stroma contained single mast cells; no inflammatory infiltration was revealed. The results of the study attested to complex mechanisms of remodeling of the prostate gland stroma in chronic abacterial prostatitis involving microvessels, smooth muscle cells, and probably mast cells, which determines the development of degenerative, destructive, and fibrotic processes.

Prostatotropic Action of Glycyrrhizic Acid Disodium Salt in Benign Prostatic Hyperplasia Models.

The prostatotropic activity of glycyrrhizic acid disodium salt (Na2GA) was studied in the models of benign prostatic hyperplasia (BPH) induced by chronic injection of sulpiride (40 mg/kg intraperitoneally for 8 weeks) or testosterone propionate (20 mg/kg subcutaneously for 4 weeks) in the Wistar rats. The oral administration of Na2GA in a dose of 100 mg/kg produced a moderate antiproliferative effect in both BPH models resulting in reduced volume density of prostatic epithelium (in the testosterone model) and increased volume density of the glandular lumen (in both models). The observed prostatotropic effects of Na2GA were similar to those of Permixon and finasteride, but they were less pronounced as confirmed by smaller drops in epithelial volume density and epithelial-to-stromal ratio compared to the effects of both reference drugs.

Ultrastructural Analysis of Urethral Polyps against the Background of Urogenital Infection.

We performed an electron microscopic study of samples of urethral polyps obtained from 90 women (mean age 52.5±4.9 years). According to PCR and culture studies, the most common infectious agent in patients with urethral polyps is U. urealyticum (100% cases). In 70% cases, this infectious agent was present as monoinfection, of these, clinically significant concentration (>106 CFU/ml) were found in 53.3% cases. In 30% cases, associations with C. trachomatis, T. vaginalis, and M. genitalium were found. We observed significant ultrastructural heterogeneity of the epithelial cells in urethral polyps, which manifested in a combination of hyperplastic and metaplastic changes and signs of cytodestruction. Detection of mycoplasma-like bodies in connective tissue mononuclear cells and viral particles in epithelial cells during ultrastructural study, including cases with negative PCR results, indicates the pathogenetic role of latent infection in the formation of urethral polyps.

Relationship between Cooling Medium and Hepatocyte Ploidometric Parameters in Albino Rats.

Relationship between the method of hypothermic exposure and ploidometric characteristics of hepatocyte nuclei of rats were studied immediately after hypothermic exposure and during the posthypothermic period. The following cooling modes were used: single submersion into 5°C water (until rectal temperature drop to 20-25°C; deep hypothermia) and single exposure at air temperature of -25°C (until rectal temperature drop to 30°C; moderate hypothermia). A manifest destructive effect of deep hypothermia on rat liver was detected: the exposure caused manifest alteration of hepatocytes (alteration index increased 81-fold immediately after the exposure and remained 16-fold higher than normally after 14 days) and an increase of DNA accumulation index with predominance of hepatocytes with 5c-8c nuclei (60% of the population) during the entire period of observation, which indicated intensification of the compensatory and adaptive processes in the liver with predominating high-ploid population of hepatocytes. Hepatocyte alteration processes in response to moderate hypothermia were less intense (hepatocyte alteration index increased 19-fold immediately after the exposure and remained 3-fold higher than normally after 14 days). The DNA accumulation index increased moderately immediately after the exposure and returned to normal after 14 days, with emergence of 2c hepatocytes and an increase in the level of 4c hepatocytes (51% of the population), which indicated realization of a different strategy of liver regeneration - recovery of the cell population intrinsic to intact animals.

Status of the Microcirculatory Network as a Factor of Prognosis and Evaluation of Therapeutic Efficiency in Prostate Cancer Treated by High-Intensity Focused Ultrasound in Combination with Androgen Deprivation.

Immunohistochemical and morphometric analysis of the microcirculatory bed in the tumor and non-tumor parenchyma of the prostate was carried out with the use of endothelial cell marker CD34 in patients treated by high-intensity focused ultrasound (HIFU). The numerical density of microvessels in the adenocarcinoma focus did not correlate with the degree of its differentiation, while high values of this parameter were associated with lower incidence of local progression after HIFU. Effective HIFU ablation led to progressive fibrosis and significant reduction of the microcirculatory bed in zones of intact non-tumor glands in control samples; an inverse relationship between the degree of reduction of the microcirculatory bed and the probability of relapse was revealed. The use of HIFU in combination with androgen deprivation was associated with a decrease in numerical density of microvessels in zones of tumor and non-tumor parenchyma in patients with relapses.

[Morphological changes in tumor and nontumor tissue in the treatment of prostate adenocarcinoma with high-intensity focused ultrasound in combination with androgen deprivation]. / Morfologicheskie izmeneniia opukholevoi i neopukholevoi tkani pri lechenii adenokartsinomy predstatel'noi zhelezy vysokointensivnym fokusirovannym ul'trazvukom v sochetanii s androgennoi deprivatsiei.

OBJECTIVE: To investigate structural changes in the tumor and nontumor tissues of the prostate in patients with its cancer (PC) after treatment with high-intensity focused ultrasound (HIFU) in combination with androgen deprivation to clarify criteria for evaluating the efficiency of treatment. SUBJECT AND METHODS: Comparative morphological, immunohistochemical, and morphometric analyses were carried out to examine 253 pre- and postoperative biopsy specimens, as well as transurethral resection specimens from 32 patients with localized PC and with or without a local recurrence within 3 years after a HIFU session. RESULTS: HIFU ablation was accompanied by coagulation necrosis and progressive pancreatic fibrosis with complete tumor regression or by a reduction in the number of positive columns (by an average of 58%) in cases with recurrence. An inverse relationship was found between the degree of a reduction in the nontumor parenchyma in the control specimens and the probability of a recurrence - a less than 20% reduction in the non-tumor glands corresponded to a 3.4-fold increased risk of tumor progression. The development of recurrence was associated with less differentiated PC (GS ≥4+3) and the presence of cribriform structures in the pretreatment samples. Combined androgen deprivation as the maximum blockade was associated with the most pronounced signs of therapeutic pathomorphism, with a reduction of the microcirculatory bed in the focus of residual tumor, and a decrease in the frequency of local progression. CONCLUSION: Neoadjuvant hormone therapy contributes to the enhanced efficiency of HIFU treatment for PC. A less than 20% reduction in nontumor parenchyma volumes in the control biopsy specimens may indicate insufficient ablation in pancreatic tissue and serve as a marker for increased risk of local progression.

Immunohistochemical Study of the Expression of Vascular Endothelial Growth Factor Receptor-2 (KDR/Flk-1) during Myocardial Infarction.

Immunohistochemical study showed that vascular endothelial growth factor receptor-2 (KDR/Flk-1) is expressed in the cytoplasm of viable cardiomyocytes, mononuclear cells of the granulation tissue, and smooth muscle cells of intramural arteries at all terms of postinfarction reparative regeneration. Cardiomyocytes were highly heterogeneous by the intensity of staining. This feature was typical of cardiomyocytes in the ischemic area (no staining), as well as within various muscle bundles and one muscle bundle. KDR/Flk-1 expression was revealed in mononuclear cells of the necrotic area (macrophages and fibroblast cells). The distribution of KDR/Flk-1 remained practically unchanged with lengthening of the postinfarction period (more than 7 days). The increase in the heterogeneity of cardiomyocyte staining under these conditions illustrates variations in the intensity of cytoprotective processes during ischemia. KDR/Flk-1 expression in smooth muscle cells of intramural arteries was shown to increase in a later period of observations.

Involvement of the Coronary Bed in Patients with Coronary Heart Disease against the Background of Primarily Coronary and Generalized Atherosclerosis.

Significant associations between clinical history factors, lipid metabolism parameters, and type of atherosclerotic process (area of vascular lesions and severity of clinical manifestations) were detected. The predominance of generalized atherosclerosis in chronic coronary heart disease group was associated with patients' age, more incident excessive body weight and type 2 diabetes mellitus, and more severe course of arterial hypertension. Increased lipid spectrum atherogenicity was significantly more often observed in generalized atherosclerosis in the myocardial infarction group. Angiography and postmortem examination of coronary arteries detected two trends of atherogenic remodeling of the coronary vessels: more pronounced stenosis of the main vessels in autopsy specimens from myocardial infarction patients with mainly coronary atherosclerosis and more extensive coronary bed involvement in chronic coronary heart disease patients with generalized atherosclerosis.

Structural Characteristics of Gastric Cell Populations in Chronic Gastritis and Chronic Hepatitis under Conditions of Helicobacter pylori Persistence.

Helicobacter pylori persistence in patients with chronic gastritis is associated with a complex of nonspecific structural reactions, the type of these reactions correlates with the severity of infection: catarrhal fibrotic changes in the gastric mucosa predominate in cases with manifest colonization, while the absence of H. pylori is associated with predominance of fibrotic process. Analysis of the incidence of some pathomorphological phenomena (degeneration, atrophy, metaplasia, and dysplasia of the surface epithelium) shows no relationship between the presence of H. pylori and colonization intensity. In all patients with chronic hepatitis, the gastric mucosa is involved in the pathological process; fibrosis (gastropathy) was the most common process. No appreciable correlations between the structural changes and hepatitis activity and the presence of H. pylori were detected.

Pathomorphological Analysis and Evaluation of Microcirculation in Polyps of the External Urethral Meatus in Women.

Combinations of various factors of polypogenesis determine the formation of a mixed structural phenotype of urethral polyps consisting of heterogeneous changes of the epithelium (hyperplasia, metaplasia, and erosions), inflammatory cell infiltration of the stroma, and dilatation of the venous plexus vessels. Urogenital infections are associated with the predominance of symptoms of inflammation, high serum levels of IL-1ß and TNF-α, more extensive areas of inflammatory infiltration and subepithelial microvascular bed, predominance of hyperemic form of microcirculatory disorders. The combination of hyperplastic reactions of the epithelial layer with neoangiogenesis and myofibroblast proliferation in the subepithelial zone confirms the key role of dysregeneratory hyperplasia in the mechanisms of polypogenesis.

Immunohistochemical Analysis of MMP-2 Expression in the Myocardium During the Postinfarction Period.

Immunohistochemical analysis revealed 2.5-fold increased of expression MMP-2 in myocardium samples during the early period (up to 3 days) of postinfarction reparative regeneration. During this period, MMP-2 was detected mainly in monocytes/macrophages circulating in the blood and migrating to the necrotic zone, while expression in the intermuscular and perivascular connective tissue was lower. At later terms, with development of large focal and diffuse cardiosclerosis, MMP-2 expression significantly decreased (to the initial level) and was detected mainly in the foci of intermuscular and perivascular fibrosis, its area in the sections increased by 1.8 times. Evaluation of MMP-2 expression in the blood vessels showed that the immunohistochemical reaction was the most pronounced in the walls of new sinusoidal vessels and the minimum in the intramural arteries of medium diameter. These results attest to an important role of MMP in connective tissue remodeling (proteolytic degradation) during the early period of postinfarction reparative regeneration. The decrease in MMP-2 expression observed at later terms correlated with myocardial fibrosis progression.

Ultrastructure of hepatorenal cell populations in patients with HCV and HBV infection markers. Hepatorenal associations.

Hepatorenal cell populations were studied in patients with HCV and HBV infection markers and renal dysfunction. Pronounced mosaicism of ultrastructural changes in hepatocytes was associated with polymorphic cytopathic effects caused by RNA-genome hepatitis C virus and DNA-genome hepatitis B virus. The destructive component of the tubular compartment predominated in renal biopsy specimens from patients, with subsequent degeneration of the tubular epithelium associated with progressive interstitial fi brosis. Immunohistochemical studies detected HCV NS3Ag and HBcAg structural marker in the tubular epitheliocytes. An appreciable part of the structural and functional changes in the liver in patients with HCV and HBV infections was caused by the therapeutic complex, including programmed hemoperfusion.

Microcirculation and structural reorganization of the bladder mucosa in chronic cystitis under conditions of ozone therapy.

Structural reorganization of the bladder mucosa in chronic cystitis and its correction by ozone therapy were studied. A relationship between the epithelial layer restructuring of different kinds (dystrophy, metaplasia, and degeneration), level of cell proliferation, and ultrastructural organization of urotheliocytes was detected. This complex of structural reactions was combined with dysregulation of tissue bloodflow in the bladder mucosa, shown by laser Doppler flowmetry. Positive structural changes were most marked in intravesical and less so in parenteral ozone therapy added to the therapeutic complex and manifested in reduction of inflammation and alteration in parallel with more intense reparative reactions. A special feature of parenteral ozone therapy was a significant improvement of microcirculation in the bladder mucosa.

Role of lipid infiltration of hepatocytes in the morphogenesis of chronic hepatitis C.

Immunohistochemical and PCR analysis of the structure of lipid-containing hepatocytes and replication of chronic hepatitis C viral particles revealed no positive correlation between the presence of HCV RNA in blood specimens, number of infected hepatocytes (by expression of HCV NS3Ag) with clinical biochemical parameters and intensity of structural changes in biopsy specimens. Small-vesicular subcytolemmal lipid infiltration of hepatocytes was detected, presumably associated with hepatitis C virus replication phase. Characteristic subcytolemmal location of the lipid droplets can reflect their involvement in virus transport from the cell and indicate a virus-induced nature of lipid metabolism disorders.

Pathomorphological analysis of the pancreaticoduodenal organs in experimental pancreonecrosis induced by trypsin injection.

Acute experimental pancreatitis induced by injection of trypsin into the pancreatic tissue exhibited characteristics of fulminant hemorrhagic pancreonecrosis (intense exudation of interlobular stroma, massive plasmo- and hemorrhages, foci of acinar cell autolysis involving by the end of day 1 an appreciable portion of the organ with formation of fields of necrosis and hemorrhagic imbibition of the glandular parenchyma, virtually completely without demarcation cellular reaction). Marked microcirculatory disorders and degenerative and necrobiotic changes in the duodenal mucosa and liver reflected the polyorgan nature of the pathological process. This model of hemorrhagic pancreonecrosis corresponded to the most severe forms of this conditions observed clinically.