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.

The Relationship of Immunoexpression of Ki-67 and Hsp70 with Clinical and Morphological Parameters and Prognosis of Papillary Thyroid Cancer.

We studied the correlations of the expression of Ki-67 proliferation marker and localization of heat shock protein Hsp70 in tumor cells of papillary thyroid cancer with some clinical and morphological parameters and a 10-year survival prognosis. High variability of the proliferative activity (by Ki-67 index) of tumor cells was revealed. It was found that Hsp70 protein has different localization in tumor cells: cytoplasmic, nuclear, nucleolar, and mixed. Nuclear translocation of the Hsp70 protein correlated with the stage of the process and the prognosis of the disease, but did not correlate with sex, tumor size, capsule invasion, and lymph node metastasis. Ki-67 index of tumor cells correlated with sex, stage of the process, size of tumor formation and prognosis, but did not correlated with age, invasion into the capsule and metastasis to the lymph nodes. Depending on the variants of Hsp70 and Ki-67 co-expression, three molecular types of papillary thyroid cancer can be distinguished: favorable, intermediate, and poor prognosis.

Ultrastructure of the Liver in Response to Cyclophosphamide and Triterpenoids.

Ultrastructural reorganization of liver cells after isolated injections of cyclophosphamide, betulonic acid or its ß-alanylamide, and combined treatment with the cytostatic and each of the triterpenoids is studied. Cyclophosphamide causes significant ultrastructural changes in all intracellular compartments of hepatocytes. Both triterpenoids cause moderate cytotoxic and stimulatory effects on the liver cell populations (hepatocytes, sinusoidal endotheliocytes, and Kupffer cells), when used alone. The cytotoxic effect of betulonic acid manifests in modification of the fine structure of hepatocyte mitochondria, sequestration of glycogen, intensification of autophagic processes, emergence of necrobiotic changes in hepatocytes and endotheliocytes; betulonic acid amide actively modifies the mitochondrial fine structure (hypertrophic organelles, matrix rarefaction, uneven dilatation of cristae). The effects of combinations of cyclophosphamide with betulonic acid or its amide on liver are polytarget: the cytotoxic activity of the cytostatic is potentiated towards some cells, while in other cells the regeneratory reactions are stimulated. The common cytological cytoprotective effects of betulonic acid and its amide used alone and in combination with cytostatics include stimulation of the endocytotic (pinocytotic) activities of the cells and stimulation of intracellular regeneration processes in them.

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.

Structural Analysis of the Myocardium in Experimental Anthracycline-Induced Cardiomyopathy Combined with Adrenergic Stimulation.

We studied dynamic changes in the total number of cardiomyocytes and the character of structural lesions in the myocardium in rats with modeled anthracycline-induced cardiomyopathy provoked by a single injection of doxorubicin in a dose of 10 mg/kg alone or in combination with subsequent adrenergic stimulation. The injections of epinephrine during the development of anthracycline-induced cardiomyopathy resulted in more pronounced loss of body weight, stronger decrement of the heart weight, and more severe decrease of the cardiomyocyte count in comparison with the corresponding changes induced by doxorubicin alone. The basic lesions of cardiomyocytes in anthracycline-induced cardiomyopathy are the lytic alterations and subsegmental contractures; in contrast, combined use of doxorubicin and epinephrine provoked degree II and III contractures. The revealed necrobiotic changes of cardiomyocytes resulted in their death and pronounced decrease of their number at the initial terms of the study. Hypertrophy observed at later terms of the experiments in parallel with partial recovery of cardiomyocyte number reflected the development of regenerative and adaptivecompensatory processes induced by massive death and elimination of the parenchymatous cells (up to 36-37% of population).

Mast Cells in Renal Cancer: Clinical Morphological Correlations and Prognosis.

Morphofunctional activity of mast cells in renal cancer is studied on specimens from the center of the tumor, peritumorous zone (with an obligatory fragment of the pseudocapsule), and from renal tissues maximally distant from the tumor. The counts and areas of tumor cells were maximum in the peritumorous zone in comparison with intact kidney tissue and central zone of the tumor. Analysis of correlations revealed a direct correlation between the tumor cell count in the peritumorous zone and some clinical morphological parameters of the tumor (anaplasia degree, size, presence of invasion and metastases, and angiogenesis). The count of mast cells in the renal peritumorous zone inversely correlated with 5-year survival: 100% cumulative 5-year survival in patients with mast cell count <6.7±1.6 per field of view.

Depression of Macrophages Modifies Serum Lipid Profile in Hyperlipidemia.

Suppression of functional activity of macrophages by gadolinium chloride, suppressing the macrophage population and the endocytosis velocity, was studied in vivo. Injection of GdCl3 led to an increase in serum cholesterol concentration. Preliminary injection of GdCl3 to mice with lipidemia 24 h before poloxamer 407 reduced the concentrations of triglycerides and LDL during marked depression of macrophages (in 24 h). Macrophage repopulation (days 5, 7) was associated with development of a trend to an increase of triglyceride and LDL levels. lectron microscopic study of Kupffer cells after injection of poloxamer 407 and its combination with gadoliniun chloride detected the intralysosomal accumulation syndrome in these cells (formation of auto- and heterophagolysosomes). Activity of cathepsin B, characteristic of macrophages, reduced 24 h after injections of GdCl3 and poloxamer 407 alone and restored in response to their combination.

Ultrastructural Analysis of the Prostate Gland under the Effect of Factors of Chemical Industry.

We analyzed ultrastruciture of the cell populations in the prostate gland in chronic nonbacterial prostatitis in a chemical industry worker. It was shown that ultrastructural reorganization of the epithelium consisted in reduction of the secretory compartment of the cytoplasm and dystrophic-degenerative changes in cell organelles. Endothelial cells of the capillaries showed signs of significant degeneration and low intensity of micropinocytosis. Most of the smooth muscle cells underwent dystrophic-degenerative modifications of ultrastructural elements. The dominance of degenerative cell changes in the epithelial and stromal cell populations along with intensification of collagen formation in the absence of inflammatory elements allows us to interpret this pathological condition of the prostate gland as prostate pathology of occupational or mixed genesis.

Bioimpedancemetry in the diagnostics of inflammatory process in the mammary gland.

The changes in mammary gland bioimpedance were examined in the dynamics of the inflammatory process. Bioimpedance of affected gland was 2-3-fold lower than that of the contralateral one; normally, this difference did not exceed 10%. The phases of inflammation development were paralleled by changes in bioimpedance. During wound epithelization, impedance increased and approximated the normal level. Further increase of bioimpedance by more than 30% and its stabilization at this level attested to recurrence of inflammation, while its irreversible drop indicated devitalization the tissues. The diagnostic criterion attesting to the development of local inflammatory reaction is deviation of bioimpedance in the impaired area by more than 15% from that of the adjacent intact site.

Proliferative activity of cadriomyocytes in chronic hypercholesterolemia.

We studied proliferative activity of cardiomyocytes (using proliferation marker Ki-67) and compared it with their total number in the heart under conditions of experimental chronic hypercholesterolemia and its combination with hypothyroidism. It was found that Ki-67-positive cells are primarily located in the subepicardial layer near the heart base in both intact and experimental animals. Replicative cardiomyocyte pool in intact rats constituted 1.67 ± 0.33‰ of the total cardiomyocyte population; after 68-day atherogenic diet with exogenous cholesterol alone, the replicative cardiomyocyte pool decreased by 16 % (to 1.40 ± 0.24‰). Treatment with mercazolil against the background of exogenous cholesterol increased this parameter by 40 % (to 2.33 ± 0.88‰). Changes in replicative activity of cardiomyocytes correlated with their total number in the heart and organ weight. We conclude that replicative cardiomyocyte pool primarily includes non-terminally differentiated cardiomyocytes (small mononuclear cardiomyocytes) and their proliferation maintains the total number of cardiomyocytes in the heart under conditions of cytopathic influences and provides the basis for physiological and reparative regeneration of the myocardium.

Structural changes in the myocardium and serum lipid spectrum in experimental hypercholesterolemia and hypothyroidism.

We studied the peculiarities of lipid spectrum of the blood and structural reorganization of the myocardium in experimental hypercholesterolemia with and without hypothyroidism. It was found that alimentary hypercholesterolemia accompanied by elevated total cholesterol, LDL, HDL, and triglyceride concentrations led to a decrease in body weight, heart weight, number of cardiomyocytes in the heart and induced pronounced lytic changes in cardiomyocytes, circulation disorders (sludge syndrome, echinocytosis of erythrocytes, lymphostasis), diffuse fibrosis of the stroma, and appearance of foam cells among diffuse mononuclear infiltrate cells. The combination of hypercholesterolemia with hypothyroid status caused more pronounced changes in the lipid spectrum and atherogenic index and more pronounced lytic and necrobiotic changes in cardiomyocytes. These findings suggest that elevated cholesterol concentrations in the blood, especially against the background of suppressed thyroid function, can directly induce considerable damage to cardiomyocytes, intramural vessels, and erythrocytes without the development of myocardial ischemia and in the absence of atherosclerotic plaques.

Immunocytochemical analysis of proliferative activity of endometrial and myometrial cell populations in focal and stromal adenomyosis.

Immunocytochemical study has shown that Ki-67 antigen is detected in adenomyosis in both endometrial and myometrial cell populations (in the eutopic and ectopic endometrial glandular epithelium, stromal cells, smooth muscle cells, and vascular endotheliocytes of the endometrium and myometrium), the label index differing significantly in different cell populations. The highest labeled cell index is found in the endometrial gland epitheliocytes in focal adenomyosis (23.2 ± 2.9%); in the stromal variant this index is by 2.8 times lower despite the fact that this variant is associated with endometrial glandular hyperplasia in the majority of cases. Proliferative activity of secretory epitheliocytes is significantly lower in both adenomyosis variants than in the normal eutopic endometrium. Stromal adenomyosis is characterized by 2-fold higher proliferative activity of the cytogenic stroma than that in focal adenomyosis.

Role of sexually-transmitted infections in the structural and functional reorganization of the prostate.

Intracellular reorganization of secretory epitheliocytes in the main, intermediate, and periurethral prostatic glands was studied in chronic prostatitis under conditions of sexually-transmitted infections. The destructive and autophagic processes in the secretory epitheliocytes were stimulated by persistence of microorganisms, Mycoplasmataceae (mainly mycoplasmas and ureaplasmas) and Chlamydia trachomatis, in the prostatic terminal compartments, epithelial layer, and epitheliocytes. Significant intracellular reorganization of smooth-muscle cells was found: focal destruction of ultrastructures (mainly in the perinuclear zone) and lythic changes in the myofilaments (focal and diffuse).

Ultrastructurural picture of cyclophosphamide-induced damage to the liver.

We studied the ultrastructural reorganization of hepatocytes and other populations of liver cells after cyclophosphamide treatment. Single administration of cyclophosphamide was followed by significant ultrastructural changes in two major populations of liver cells (hepatocytes and sinusoidal endothelial cells). This treatment was also accompanied by reactive changes in Kupffer cells, lymphocytes, and plasma cells migrating into the spaces of Disse. Cyclophosphamide-induced spatial reorganization of hepatocytes was associated with a progressive decrease in the structural density of mitochondria, significant reduction of the smooth endoplasmic reticulum, and increase in autophagocytosis (e.g., sequestration of glycogen). Intracellular reorganization of endothelial cells was related to the following two factors: damage (necrobiosis) of some cells; and increase in metabolic processes, phagocytosis, and regenerative reactions in other cells.

Ultrastructure and stereology of cardiomyocytes in the development of regenerative and plastic myocardial insufficiency during ontogeny.

The age-related features of ultrastructural reorganization of cardiomyocytes were studied in rats with anthracycline-induced injury. The development of regenerative and plastic insufficiency of cardiomyocytes in animals of various age groups was accompanied by stereotypic ultrastructural reorganization. The major changes concerned the nucleus, myofibrillar compartment, and rough sarcoplasmic reticulum. Intracellular reorganization of cardiomyocytes in young animals was observed in the same period, but included a greater decrease in the volume density of myofibrils as compared to that in old rats. The recovery of cardiomyocyte ultrastructure in young animals occurred in the earlier period. Cardiomyocytes of old rats were characterized by greater structural modification of mitochondria and considerable area of lytic changes in myofibrillar bundles. Cardiotoxicity of doxorubicin in young animals was manifested in severe destruction of the capillary endothelium, which occurred in the early period after treatment.

Ultrastructure of acinar cell injuries in experimental acute pancreatitis created by common bile duct ligation.

Morphogenesis of acute pancreatitis induced by ligation of the common bile duct and the ultrastructure of autolytic transformations of acinar cells were studied. Autolytic changes in acinar cells started from the basal zones and then involved the apical zones. Violation of the zymogen granules integrity, interactions of their contents with the adjacent ultrastructures, destruction (melting) of ultrastructures, and formation of huge autophagosomes play an important role in the development of autolysis. Disordered secretion of zymogen granules (foci of their accumulation in the apical zone), hyperplasia and hypertrophy of centroacinar cells and ductal epitheliocytes aimed at restoration of the pancreatic secretion discharge pathways were seen in the retained acini.

Morphogenesis and histostereological analysis of hepatopathy induced by cyclophosphamide.

Characteristics and regularities of structural reorganization of the liver in experimental cyclophosphamide hepatopathy were studied. Single injection of the drug caused pronounced morphofunctional changes in the liver (small focal hepatocyte necroses mainly in the periportal zone, mononuclear cell infiltration developing in the presence of circulatory disorders). The key event in the spatial reorganization of the liver after cyclophosphamide injection is reduction of hepatocyte volume density, increase of their surface density and surface/volume ratio. The percentage of binuclear hepatocytes increases in the liver early after cyclophosphamide injection; later the percentage of mononuclear cells increases. Other important changes in the spatial reorganization of the liver under the effect of cyclophosphamide are the increase in the volume and surface densities of sinusoids. These changes develop as a result of augmenting vascular plethora and blood cell stasis with the development of thrombosis during later periods.

Structural reorganization of the adrenal cortex in OXYS rats during ontogeny.

Study of the structural reorganization of the adrenal cortex in OXYS and Wistar rats during aging showed that age-associated reorganization of the adrenal cortex in these rats consisted in atrophy, particularly pronounced in OXYS rats. Age-specific changes in the architectonics of the organ were noted mainly in the zona glomeruloza and zona fasciculata. The vessel-parenchyma relationships play the key role in the spatial reorganization of the adrenal cortex in OXYS and Wistar rats. The volume density of the sinusoidal capillaries in the zona fasciculata and zona reticularis increases during the late ontogeny, particularly so in Wistar rats, causing, in turn, an increase of the stroma/parenchyma volume proportion.

Regenerative reactions of the myocardium in plastic insufficiency of cardiomyocytes during ontogeny.

Structural reorganization of the myocardium was studied in rats of various age groups (periods of progressive and regressive growth) with anthracycline-induced regenerative and plastic insufficiency. The specific features included the prevalence of cardiomyocyte lysis, diffuse and microfocal changes, and diffuse or microfocal cardiosclerosis. During the late ontogeny, myocardial damage was characterized by more pronounced cardiosclerosis (primarily microfocal cardiosclerosis). The development of regenerative and plastic insufficiency of cardiomyocytes determines dilatation remodeling of the heart in rats of various age groups. Comparative study of the morphogenesis of heart failure in rats of various age groups showed that cardiotoxic exposure during the early ontogeny induced more pronounced remodeling of the heart compared to that in late ontogeny. Differences in proliferative activity of cardiomyocytes and ability for hypertrophic growth are the main cellular mechanisms of age-related features of structural reorganization.