[Secretory phenotype of the human endothelial cells associated with replicative and induced aging.]

The aging-associated secretory phenotype (SASP) is a heterogeneous phenotype of cells secreting pro-inflammatory cytokines, growth factors, apoptosis' regulatory molecules, and proteases. SASP is one of the three main hallmarks of senescent cells. Dysregulation of the synthesis of SASP-forming molecules leads to the development of age-associated diseases, including cardiovascular pathology. The aim of this study is to characterize the SASP of human endotheliocytes during replicative and induced aging. Isolated human umbilical vein endothelial cells HUVEC were used to model replicative and inflammation-induced aging. It has been established that the molecules that form SASP during replicative and inflammation-induced aging of HUVEC are molecules that control apoptosis (p16, p21, p53), adhesion (E-selectin, VCAM-1) and some cytokines (IL-1ß, IL-6). With replicative aging of endotheliocytes, the synthesis of apoptosis' regulatory molecules increases to a greater extent. Inflammation-induced aging of HUVEC is characterized by a multiple increase in the synthesis of adhesion molecules and pro-inflammatory cytokines.

[Surgical treatment of internal carotid artery kinking following fibromuscular dysplasia]. / Rezul'taty khirurgicheskogo lecheniya patologicheskoi izvitosti vnutrennei sonnoi arterii na fone fibrozno-myshechnoi displazii.

OBJECTIVE: To evaluate the results of surgical treatment of internal carotid artery kinking following fibromuscular dysplasia. MATERIAL AND METHODS: There were 32 patients who underwent surgical treatment of internal carotid artery kinking following fibromuscular dysplasia. Structural changes of carotid artery wall were analyzed using immunohistochemical survey. Considering destructive changes revealed, we divided all patients into 2 groups in order to assess long-term postoperative outcomes: 1 - ICA resection followed by anastomosis in end-to-end fashion; 2 - ICA replacement. Postoperative analysis included incidence of stroke, thrombosis and deformities of anastomosis zone, regression of cerebrovascular insufficiency. RESULTS: The main «phenotype¼ of arterial wall in patients with ICA kinking following fibromuscular dysplasia is a large number of smooth muscle cells releasing matrix matelloproteinases-2 and -9 and low level of their tissue inhibitor type 1. Postoperative deformities are more common within a year after surgery. Maximum incidence is observed after 12 months. Both ICA resection and replacement are followed by similar incidence of deformity later. No severe deformities were diagnosed. Resection of ICA kinking on the background of fibromuscular dysplasia is followed by comparable results with ICA replacement regarding the incidence stroke, thrombosis and regression of cerebrovascular insufficiency. CONCLUSION: Despite degradation of extracellular matrix, destruction of elastic fibers and their fragmentation, no significant deformities are observed in long-term postoperative period in patients with ICA kinking and fibromuscular dysplasia.

[The morphological and molecular genetic characteristics of nephroblastomas in immature ovarian teratoma in adult patients]. / Morfologicheskaia i molekuliarno-geneticheskaia kharakteristika nefroblastomy v nezreloi teratome iaichnikov u vzroslykh bol'nykh.

The paper describes 2 cases of immature ovarian teratoma with elements of nephroblastoma (ICD-0 code 9080/3) in patients aged 61 and 70 years. Microscopic examination revealed that both cases had blastemal cells with scant cytoplasm and basophil nuclei sticking together. Epidermal, glandular, rhabdomyoblastic, chondroid, bone, neuroectodermal, and histiocytic components were determined. Papillary and glomeruloid structures and primitive tubules were immured in the sarcomatous stroma. Immunohistochemical studies showed a strong reaction with Wilms tumor 1 (WT1), paired box gene (PAX-2), cytokeratin 7, desmin, smooth muscle actin, and α-1 antitrypsin. The recurrent tumors displayed a 1.8- to 6.1-fold increase in the level of p53. At the same time, the molecular genetic study revealed p53 gene mutation. In both cases, serous ovarian cystadenocarcinoma was misdiagnosed, ineffective chemotherapy was performed, and a recurrence occurred. The literature review revealed only 8 such cases.

[The morphological and molecular genetic characteristics of sarcomatoid chromophobe renal cell carcinoma]. / Morfologicheskaia i molekuliarno-geneticheskaia kharakteristika sarkomatoidnoi khromofobnoi pochechno-kletochnoi kartsinomy.

The paper describes a case of chromophobe renal cell carcinoma growing into the muscular layer of the descending colon and with metastases in 4 lymph nodes of paranephral tissue in a 66-year-old woman. The tumor had a zonal structure with an alternation of epithelioid and sarcomatoid structural sites and with the signs of grades I, II and III according to the grading system by Paner and et al. (2010). The sarcomatoid renal component occupied about 70.0% of the tumor. There was a pronounced immunohistochemical reaction with VEGF-A (5 scores), a high Ki-67 proliferation index (70%), and a large number of tumor cells with nuclear p53 expression (85%) in the areas with minimal differentiation and sarcomatoid elements (Grade III). These signs can serve as criteria for the aggressive behavior of the tumor. A large volume of the sarcomatoid carcinoma component and a strong reaction with VEGF-A are indications for targeted therapy with anti-VEGF drugs.

[Solitary epithelioid hemangioendothelioma concurrent with nodular parenchymal amyloidosis of the lung and Rosai-Dorfman disease]. / Solitarnaia épitelioidnaia gemangioéndotelioma v sochetanii s noduliarnym parenkhimatoznym amiloidozom legkogo i bolezn'iu Rozai-Dorfmana.

The paper describes a case of solitary epithelioid hemangioendothelioma concurrent with nodular parenchymal AL amyloidosis of the lung and Rosai-Dorfman disease in a 70-year-old woman. The core of the tumor was represented by bone tissue with dendriform ossification, as well as by amyloid that showed green apple birefringence at polarized light microscopy. The peripheral portions of the tumor and the myxohyaline stroma exhibited slit-like structures, epithelioid and fusiform cells with small cytoplasmic vacuoles. These cells expressed CD31, CD34, factor VIII, and cytokeratins 7 and 18. The Ki-67 proliferation index was 10%. S100- and CD68-positive histiocytes with the phenomenon of emperipolesis were revealed in the tumor and in the lymph nodes of the mediastinum and lung hilum. There was a positive reaction to immunoglobulin lambda light chains in the lymphocytic infiltration around amyloid clumps. The frequency of epithelioid hemangioendothelioma was less than 1 case per million people annually. We found only one case of its concurrence with pulmonary amyloidosis in the English-language literature. No relationship could be revealed between this tumor and Rosai-Dorfman disease.

[Prospects of buccal epithelium application for noninvasive diagnosis of coronary heart disease in people of different age.]

Cardiovascular diseases caused by atherosclerosis, in many countries of the world are one of the most important social and economic problems due to the high morbidity and mortality rate of the working population. Recently, the immunological theory of atherosclerosis and coronary heart disease (CHD) has been actively developed, and the search for markers of inflammation characterizing immuno- and atherogenesis has been conducted. Buccal epithelium (BE) can be used as biological material for in vivo molecular-cellular studies, allowing to diagnose CHD by inflammation markers. The purpose of the work was a comparative study of the expression of IL-1ß, IL-6, IL-10, MCP-1 and GDF-15 in BE in patients of different ages with CHD and without cardiovascular disease. The material of BE in healthy donors and patients with 2nd stage CHD was divided into groups according to age classification of the WHO: the 1st - middle-aged people (45-59 years) and the 2nd - elderly people (60-74 years). Control material was obtained from people of middle and old age without cardiovascular disease. According to the immunocytochemical study, the area of IL-1ß expression in BE is 3 times higher in middle-aged people with CHD, and in 4,4 times higher in elderly people compared to healthy individuals of the same age group. The area of IL-6 expression in middle-aged and elderly people with CHD was in 7,9 and 7,4 times higher, respectively, than in the control group. In middle-aged and elderly patients with CHD, IL-10 expression was in 1,6 and 2,8 times higher, respectively, compared to healthy donors of the same age group. The expression of MCP-1 in BE of middle-aged and elderly people in normal and ischemic heart disease did not differ. GDF-15 expression is in 6,8 and 6,6 times higher in middle-aged and elderly people with CHD than in healthy people of the same age. The findings showed that the expression of the cytokines IL-1ß, IL-6, IL-10 and GDF-15 increase in BE in patients with CHD of middle-aged and elderly people compared with persons of the same age group without cardiovascular disease. Thus, BE can serve as an informative material for noninvasive molecular diagnosis of CHD in people of different ages.

[Eosinophilic granuloma of the parietal bone of an adult patient with BRAF mutation]. / Éozinofil'naia granulema temennoi kosti s mutatsiei gena BRAF u vzroslogo patsienta.

The paper describes a case of eosinophilic granuloma of the parietal bone in a 32-year-old man. Histological examination revealed a large number of bean-shaped Langerhans cell histiocytes with lobed nuclei and nuclear grooves. The histiocytes alternated with the foci of obvious eosinophilic infiltration and with eosinophilic microabscesses. There were osteoclast-like multinucleated giant cells, bone resorption, and numerous bone rods covered with osteoblast chains. The histiocytes expressed CD1α, langerin, CD68, S100, and p53 (in 90.0% of the tumor cells). The Ki-67 proliferation index was 18.0%. A molecular genetic study identified BRAFV600E mutation (nucleotide substitution s.1799 T>A (p.V600E) in the heterozygous state). Clinical and morphological data and the results of molecular genetic studies led to the conclusion that there was eosinophilic granuloma of the right parietal bone (the unifocal form of Langerhans cell histiocytosis (LCH), type I, group A1, with the monoossal nature of lesion and with BRAFV600E mutation). In adults, this disease is extremely rare (2-5 cases of LCH per million people, bone loss in the fourth decade of life in 2.5% of the patients).

[BRAF-positive paucicellular variant of anaplastic carcinoma in the presence of tall cell variant papillary thyroid cancer]. / BRAF-pozitivnyi malokletochnyi variant anaplasticheskoi kartsinomy na fone papilliarnogo raka shchitovidnoi zhelezy iz vysokikh kletok.

To paper describes a case of paucicellular anaplastic cancer in the presence of tall cell variant papillary thyroid carcinoma. Microscopic examination showed that the differentiated component of the tumor was composed of papillary structures with tall cells, the height of which exceeded 3-4 times the width. Its anaplastic component consisted of fibrous tissue with occasional spindle-shaped cells and focal lymphocytic infiltration to the extent of 70%. The spindle-shaped cells expressed cytokeratins, ß-catenin, p53, and vimentin. The tumor cells and lymphocytes showed an association with Epstein-Barr virus. Molecular genetic study of the tumor revealed the following mutations: BRAF p.Val600Glu (p.V600e was), HRAS p.His27His (p.H27H), PIK3CA p.Glu545Lys (p.E545K), TP53 p.Arg248Gln (p.R248Q).

[Aging of the myocardium and dilated cardiomyopathy: morphological and molecular aspects].

The review considers various aspects of myocardium aging in normal and dilated cardiomyopathy (DC). There is a partial fibrosis of the heart tissue due to accumulation of collagen type 1, and accumulation of amyloid during normal aging. Men myocardial aging is accompanied by loss of cardiomyocytes and increased volume of the remaining cells, whereas in women this effect is absent. There is an expression of nuclear proteins decrease (lamin A and C), the accumulation of lipofuscin, increased content of reactive oxygen species, reduction of protein synthesis Sirt1 in cardiomyocytes with aging. Sirt1 has a cardioprotective effect, supports the balance of lipid metabolism, inhibits the development of inflammation and the formation of atherosclerotic plaques. Reduction of its expression not only indicates the accelerated pace of myocardial aging, but can be a predictor of the development of DC. In DC occurs stretching of the heart cavities and systolic dysfunction, predominantly in the left ventricle. DC is characterized by the development of inflammation in the myocardium. Its markers is increased expression of ICAM-1 adhesion molecule, MMP-2, MMP-9 matrix metalloproteinases, TIMP-1 tissue inhibitor of matrix metalloproteinases and decreased expression of MMP-1 matrix metalloproteinase.

[Clinical and morphological signs of viral damage to a kidney transplant]. / Kliniko-morfologicheskie priznaki virusnogo porazheniia pochechnogo transplantata.

AIM: Тo compare morphological changes and results of immunohistochemical (IHC) identification of viruses (polyomaviruses, adenoviruses, and herpesviruses) in the biopsy specimens with their clinical manifestations in recipients of renal transplants. MATERIAL AND METHODS: Morphological and IHC studies were conducted using 71 needle renal transplant biopsy specimens from patients in the study group and 10 renal biopsy specimens from those in the control group. A number of clinical indicators were estimated. RESULTS: IHC examination revealed the expression of adenoviral antigens more commonly in patients with posttransplant nephritis than in recipients without nephritis or in control individuals (p<0.05). The association of patient age and time after kidney transplantation with the severity of viral damage was confirmed: graft loss in children occurred within the first months of surgery (p<0.05). Polyomavirus was detected by PCR in patients with the morphological patterns of polyomavirus nephropathy. Determination of HSV-1 and HSV-2 in the biopsy specimens showed no significant associations with morphological changes. CONCLUSION: By taking into account a variety of factors that influence the development of viral nephritis, morphological and IHC examinations should be combined with evaluation of clinical findings.

[Parosteal osseous lipoma of the temporal bone concurrent with involvement of the parotid salivary gland]. / Parosteal'naya ossifitsiruyushchaya lipoma visochnoi kosti v sochetanii s porazheniem okoloushnoi slyunnoi zhelezy.

The paper describes a case of parosteal lipoma of the temporal bone, by simultaneously involving the parotid salivary gland. Computed tomography performed in a 48-year-old man showed that in the area of the posterior edge of the glenoid fossa of the right temporal bone there was a massive (1.5×1.7×0.9-cm) exostosis extending down from the skull base. The exostosis was surrounded by a 3.5×3.6×5.3 soft tissue mass that was located in the projection of the right parotid salivary gland with a capsule and minor calcifications. Morphological examination determined a sessile exostosis-like mass in the area of the periosteum of the temporal bone. Foci of desmal and enchondral ossification (types III and IV according to the classification of Miller et al.) could be seen in the adjacent fatty tissue. The tumor underwent necrotic and dystrophic changes (Milgram's Stage 3). Temporal bone involvement was accompanied by osseous sialolipoma of the right parotid salivary gland. In this case, the fatty component accounted for 60-80% of salivary gland volume. Terminal secretory segments, ducts, and bone trabeculae with calcification foci and hematopoietic elements were uniformly distributed among the fatty tissue. None similar case has been found in the literature.

[Aortic aneurysm in Erdheim's idiopathic cystic medial necrosis in autopsy and forensic medical practice]. / Anevrizma aorty pri idiopaticheskom kistoznom medionekroze Erdgeima v patologo-anatomicheskoi i sudebno-meditsinskoi praktike.

UNLABELLED: To date, the modern Russian literature has not covered morphological studies of aortic aneurysm in Erdheim's idiopathic cystic medial necrosis on autopsy and surgical materials, by using immunohistochemical studies, and it has not estimated the magnitude of pathohistochemical changes in the aortic media either. AIM: to conduct a morphological examination of aortic aneurysm in Erdheim's idiopathic cystic medial necrosis, by using the material of pathology and forensic medical departments. MATERIAL AND METHODS: 41 surgical samples from patients with idiopathic cystic medial necrosis of the ascending aorta and autopsy samples from 17 sudden deaths from aortic rupture were examined. The aortic wall was histologically and histochemically studied. Immunohistochemical examination was done using antibodies to smooth muscle actin, collagens types I and III, elastin, CD3 (T lymphocytes), CD20 (B lymphocytes), CD45 (leukocyte common antigen), CD68 (macrophages), apoptotic marker p53, tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1). RESULTS: Morphological examination showed lamellar unit destruction, fibrosis, medial necrosis, and elastic fiber fragmentation. These signs were assessed by their degree. The immunohistochemical examination of collagens types I and III determined fascicles of randomly positioned fibers. The multidirectional orientation of smooth muscle cells was confirmed by the expression of smooth muscle actin. There was an obvious expression of the apoptotic marker p53 in the smooth muscle cells of the aortic media and in the aortic adventitia. The expression of TNF-α was revealed in the cells of an inflammatory infiltrate in the aneurysm wall and that of ICAM-1 was found in the aortic endothelium, vasa vasorum, and in the cells of an inflammatory infiltrate in the media and adventitia. The paper proposes a design of postmortem and forensic medical diagnosis, which reflects the components of pathogenesis and tanatogenesis in Erdheim's idiopathic cystic medial necrosis and which allows ICD-10 diagnosis coding. CONCLUSION: The main histopathological signs of aortic aneurysm in Erdheim's idiopathic cystic medial necrosis were presented; structural changes in the primary components of the aortic wall were characterized; the cells of an inflammatory infiltrate were investigated; and the formulation of autopsy and forensic medical diagnoses was proposed.

[Expression of matrix metalloproteinases and their inhibitors in the internal carotid artery wall in pathological tortuosity]. / Ekspressiya matriksnykh metalloproteinaz i ikh ingibitorov v stenke vnutrennei sonnoi arterii pri patologicheskoi izvitosti.

UNLABELLED: The principal morphological sign of fibromuscular dysplasia in pathological tortuosity (PT) of the internal carotid artery (ICA) is the fragmentation of elastic fibers that are degraded by matrix metalloproteinases 2 and 9 (MMP-2, MMP-9). Nevertheless, the role of MMPs and their inhibitors in the pathogenesis of ICA PT remains completely unexplored. AIM: to investigate the expression of elastin-degrading MMPs and their inhibitors in the wall of the ICA in PT by immunohistochemistry and confocal laser scanning microscopy. METHODS: Immunohistochemical examination was made using antibodies to MMP-2, MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2. MMP-9 and TIMP-1 levels were determined by confocal laser scanning microscopy. RESULTS: Immunohistochemical examination revealed a statistically significant predominance of high concentrations of MMP-2 and MMP-9 and a low level of their inhibitor TIMP-1 in ICA PT, while simultaneous obvious accumulation of both markers was most often identified in the control group (p<0.05). Analysis of MMP-2/TIMP-2 and MMP-9/TIMP-2 ratios showed the prevalence of the simultaneously high expression of both proteins in ICA PT and in the control group too. The similar data were also obtained by confocal microscopy: the control group showed elevated MMP-9 and TIMP-1 expressions and the ICA PT control displayed a high proteinase and low inhibitor levels (p<0.05). CONCLUSION: Elastic fiber fragmentation in ICA PT is due to imbalance between MMPs and their inhibitors; namely, the prevalence of MMP-2 and MMP-9 over their inhibitor TIMP-1, which leads to the degradation of extracellular matrix components, primarily elastin.

[Von Hippel-Lindau disease type 2-related pancreatic neuroendocrine tumor and adrenal myelolipoma].

The paper describes a case of von Hippel--Lindau-related pancreatic neuroendocrine tumor and adrenal myelolipoma in a 44-year-old woman. The pancreatic tumor and a left retroperitoneal mass were removed in the women in July 2014 and May 2015. Histological examination of the pancreatic tumor revealed that the latter consisted of clear cells forming tubular and tubercular structures showing the expression of chromogranin A, synaptophysin, and cytokeratins 18 and 19 and a negative response to CD10 and RCC. The adrenal medullary mass presented as clear-cell alveolar structures with inclusions of adipose tissue mixed with erythroid, myeloid, and lymphoid cells. The clear-cell component of the adrenal gland expressed neuroendocrine markers with a negative response to cytokeratins, CD10, and RCC. Molecular genetic examination yielded a signal corresponding to two copies of the VHL gene. No deletions or amplifications of the gene were detected. Cases of von Hippel--Lindau disease concurrent with adrenal pheochromocytoma and myelolipoma and simultaneous pancreatic involvement were not found in the literature.

[Impact of preoperative drug therapy on the expression of apoptosis markers in colorectal liver metastases].

AIM: to estimate the expression of p53 protein, effector caspases-3 and -7, and the antiapoptotic protein survivin in colorectal adenocarcinoma metastases to the liver in patients who have received preoperative cytotoxic and combined cytotoxic and target anti-VEGF therapies. SUBJECTS AND METHODS: Intraoperative samples from 122 patients with colorectal carcinoma metastases to the liver were immunohistologically examined. The investigation included patients who had received preoperative treatment with cytotoxic drugs, combined cytotoxic and targeted anti-VEGF therapy. A control group consisted of patients who had not received preoperative anti-tumor drug treatment. RESULTS: Expression of Caspase 3, including that of survivin, was significantly more frequently detected in the patients who had received combined cytotoxic and anti-VEGF therapy as compared to both those treated with only cytotoxic agents (p=0.00004) and the control group (p=0.0008) As compared to the latter, the women who had received cytotoxic therapy were found to have no survivin expression (p=0.015). Investigation of the expression of caspase-7 and p53 revealed no statistically significant differences between the three groups. CONCLUSION: Addition of bevacizumab to preoperative standard therapy regimens for colorectal adenocarcinoma metastases to the liver leads to activated apoptosis in tumor cells, by enhancing the expression of effector caspase 3. At the same time, standard cytotoxic chemotherapy regimens in women results in activated apoptosis, by decreasing the expression of the antiapoptotic protein survivin.

[Morphological diagnosis of viral damage to a kidney transplant]. / Morfologicheskaia diagnostika virusnogo porazheniia pochechnogo transplantata.

Due to the development of organ transplantation and its accompanying immunosuppression, recent years have been marked by the higher incidence of opportunistic viral infections that are of considerable importance among posttransplantation complications. A variety of viral infections, the possibility of their concomitant or subtle course, and the ability to cause life-threatening complications in recipients make relevant the description of existing diagnostic methods. The article summarizes the data available in the literature on the etiology, clinical symptoms, and morphological manifestations of viral infections, such as polyomaviruses, adenoviruses, herpesviruses, including HSV-1, HSV-2, cytomegalovirus (CMV), and Epstein-Barr virus. It describes the principles of differential diagnosis of kidney transplant damage caused by these viruses and that with acute cellular and humoral rejection, which plays an important role due to opposite approaches to treating these diseases.

[Impact of preoperative drug therapy on adhesion molecule expression in colorectal cancer liver metastases].

OBJECTIVE: To study E-cadherin and ß-catenin expression in colorectal cancer (CRC) liver metastases in order to assess the impact of different drug therapy regimens on the adhesive properties of tumor cells. MATERIAL AND METHODS: Intraoperative metastatic CRC samples from patients who had received preoperative cytotoxic chemotherapy or combined cytotoxic and targeted anti-VEGF (vascular endothelial growth factor) therapy were immunohistochemically examined using antibodies to E-cadherin and ß-catenin. A comparison group consisted of patients who had not received drug therapy. RESULTS: Combined therapy with cytotoxic and anti-VEGF agents was shown to result in a significant increase in the number of cases of normal membrane localization of E-cadherin as compared with control (p = 0.00043) and cytotoxic therapy-alone (p = 0.01) groups. A comparison of ß-catenin levels in three patient groups revealed no significant differences, but addition of an anti-VEGF agent caused some decrease in the number of cases of abnormal nuclear localization of the protein as compared to both the control group and the cytotoxic therapy groups. The comparison of E-cadherin and ß-catenin localization in tumor cells showed that a combination of normal E-cadherin membrane localization and ß-catenin membrane-cytoplasmic expression prevailed in the combined therapy group compared to the control (p = 0.009) and cytotoxic therapy (p = 0.04) groups. CONCLUSION: The addition of a targeted anti-VEGF agent to the drug therapy of metastatic CRC has a positive impact on the cadherin-catenin complex, leading to increased intercellular contacts and suppressed ß-catenin functioning as a transcription factor that enhances tumor cell proliferation.

[Expression of plasminogen activator system components in the gastric mucosa in portal hypertensive gastropathy].

OBJECTIVE: to study the expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the gastric mucosal (GM) vascular endothelium and epithelial cells of patients with portal hypertensive gastropathy (PHG) and those with portal hypertension (PH) without signs of PHG as compared to a control group. MATERIAL AND METHODS: GM biopsy specimens from patients with PHG, those with PH without signs of PHG, and controls with the normal gastric mucosa were immunohistochemically examined. RESULTS: Comparison of the expression of uPA in the GM vascular endothelium and epithelial vessels revealed no significant differences in the patient groups. The level of PAI-1 in the GM vessels was statistically significantly higher in the control group than in the groups of patients with PHG and PH without PHG. PAI-1 expression in the GM epithelial cells was significantly more commonly absent in the PHG group than in the control group. An analysis of an uPA and PAI-1 expression ratio showed a statistically significant predominance of the expression of uPA over its inhibitor in the GM vascular endothelium of the patients with PHG and those with PH without PHG as compared to the controls. CONCLUSION: The predominance of uPA over PAI-1 in the GM vessels and epithelial cells can play a role in the development of GM bleeding.

[Signal molecules of endometrium: gerontological and general pathhological aspects].

The review describes neuro-immuno-endocrine signal molecules expression in human endometrial cells in the normal conditions, in the pathology and during aging. Human endometrial cells synthesizes estrogen, progesterone, estradiol, progestin, cell adhesion molecules (integrines α1ß1, α4ß1, αVß3, L-selectin, Е-catgerin, MUC1), grow factors (TGF, EGF, HB-EGF, IGF), cytokines (IL-1, IL-2, INF-α, IL-12, СХСL10, CXCL11, CXCR3), various immune cells markers (CD68, CD105, CD163, CD16, CD56, CD4, CD8), heat shock proteins (HSP60, HSP70, HSP90, VEGF, MMP). Changes of this molecules expression level are the base of the social significant diseases as endometriosis, endometrial cancer and infertility. Thus, the investigation of neuro-immuno-endocrine interactions in endometrial cells can be used for new drugs creating, in differential diagnostics of endometrial cancer and increasing of extracorporal fertilization success.

[The structure of the internal carotid artery wall in pathological tortuosity].

OBJECTIVE: to study a change in the content of main components of the internal carotid artery (ICA) wall in pathological tortuosity (PT) resulting from fibromuscular dysplasia, using immunohistochemistry and confocal laser scanning microscopy. MATERIAL AND METHODS: Immunohistochemical (IHC) analysis using antibodies to elastin, collagen types I and III, and smooth muscle actin was made. The levels of elastin and matrix metalloproteinase 9 (MMP-9) were determined by confocal laser scanning microscopy. The relative area of expression and the area of co-location of these markers were measured. RESULTS: IHC examination of the expression of elastin revealed that the patients with PT of ICA had its higher content than the controls, but they were observed to have fiber fragmentation. Comparison of collagen types I and III expressions showed no significant differences between the groups. The found significantly lower smooth muscle actin expression in the patients with PT of ICA than in the controls was suggestive of the decreased levels of smooth muscle cells. Confocal microscopy analysis showed high elastin and low MMP-9 expressions in the control group and, on the contrary, low elastin and high proteinase levels in the PT group (р<0.05). CONCLUSION: One of the causes of PT is impairment in vascular elastic properties due to the destruction of elastic fibers and to their fragmentation, as well as to the decreased count of smooth muscle cells, which in turn causes enhanced MMP-9 activity and tissue matrix degradation.