In Vivo Safety of New Coating for Biodegradable Magnesium Implants.

Biodegradable Magnesium (Mg) implants are promising alternatives to permanent metallic prosthesis. To improve the biocompatibility and with the aim of degradation control, we provided Plasma Electrolytic Oxidation (PEO) of pure Mg implant in silicate-based solution with NaOH (S1 250 V) and Ca(OH)2 (S2 300 V). Despite the well-structured surface, S1 250 V implants induced enormous innate immunity reaction with the prevalence of neutrophils (MPO+) and M1-macrophages (CD68+), causing secondary alteration and massive necrosis in the peri-implant area in a week. This reaction was also accompanied by systemic changes in visceral organs affecting animals' survival after seven days of the experiment. In contrast, S2 300 V implantation was associated with focal lymphohistiocytic infiltration and granulation tissue formation, defining a more favorable outcome. This reaction was associated with the prevalence of M2-macrophages (CD163+) and high density of αSMA+ myofibroblasts, implying a resolution of inflammation and effective tissue repair at the site of the implantation. At 30 days, no remnants of S2 300 V implants were found, suggesting complete resorption with minor histological changes in peri-implant tissues. In conclusion, Ca(OH)2-contained silicate-based solution allows generating biocompatible coating reducing toxicity and immunogenicity with appropriate degradation properties that make it a promising candidate for medical applications.

ER and COX2 expression in endometrial hyperplasia processes.

Endometrial hyperplastic processes (EHPs) encompass various morphological changes, characterized by an increased ratio of endometrial glands to stroma. These changes manifest as endometrial hyperplasia (EH) and endometrial polyps. The objective of this study was to investigate the expressions of ER and Cyclooxygenase-2 (COX2) in EH and endometrial polyps, and determine their correlation with histological and anthropometric parameters. Tissue samples were obtained during hysteroresectoscopy and divided into 3 groups: non-atypical EH, glandular EP, and glandular-fibrous EP. We examined the immunoprofile of epithelial and stromal cells using rabbit polyclonal anti-COX2 antibodies and rabbit monoclonal anti-ER antibodies (clone SP1). Our results indicate that there is no association between the expressions of ER and COX2 and the type of EHP. Furthermore, the expression levels of ER and COX2 are not influenced by the patients anthropometric parameters. However, tissues with EHPs exhibited significantly higher COX2 expression compared to intact tissues. We also observed a direct correlation between ER and COX2 expression in the endometrial epithelium. The variability in ER and COX2 expressions observed in hyperplastic processes of the endometrium potentially suggests their synergistic involvement in the initiation and progression of EHPs, as well as their potential role in subsequent tumor transformation.

Relationship of microvascular density on histological and immunohistochemical features in endometrioid adenocarcinomas of the uterus: experimental study.

The most common malignant tumors of the uterus are endometrioid adenocarcinomas (EA). Their prognosis depends on the qualitative characteristics of the neoplastic cells and their stroma. The neovascularization of EA tissues and level of microvascular density (MVD) influence tumor progression. Our study aims to establish the relationship between MVD in EA tissue and the histological and immunohistochemical features of tumors. Materials and methods: The authors studied 30 cases of endometrial ЕА and compared their histological and immunohistochemical characteristics with the MVD of tumor tissues. Results: Our study indicated that MVD in EA tissue depends on the grade of the tumors and their FIGO stage. Increased MVD was correlated with a depression of E-cadherin and PR expression and enhanced expression of VEGF and Ki-67. MVD enhancement during VEGF overexpression is a manifestation of the functional activity of these proteins. The increase in MVD was accompanied by more frequent metastasis of the EA to the lymph nodes. Conclusion: EA progression is accompanied by qualitative and quantitative variations of parenchymal and stromal patterns of tumors. Dedifferentiation of EA leads to overexpression of VEGF, which becomes diffuse in tumors cells, resulting in an increase of adenocarcinomas' MVD and their metastatic potential. Correlations between histological and immunohistochemical features of EAs indicate the synchronicity of the occurrence and progression of morphological and immunological anaplasia, which can be used in predicting the course of the disease.

Case report: Metastasis of Merkel cell carcinoma in the small intestine.

Merkel cell carcinoma is a rare primary neuroendocrine malignant neoplasm of the skin, which recurs in about 40 % of cases. The main factors are Merkel cell polyomavirus (MCPyV) and mutations caused by ultraviolet radiation [Paulson, 2018]. In this study, we report a case of Merkel cell carcinoma with metastasis to the small intestine. In a 52-year-old woman, a subcutaneous formation of a nodule up to 2.0 cm in diameter was detected during the examination. This neoplasm was removed and sent for histological analysis. Dot-like expression of CK pan, CK 20, chromogranin A, and Synaptophysin was observed in tumor cells, and Ki-67 in 40 % of tumor cells. There is no reaction in tumor cells to CD 45, CK 7, TTF 1, and S100. The morphological picture corresponded to Merkel cell carcinoma. A year later, the patient underwent surgery for intestinal obstruction. The pathohistological changes and immunophenotype of the small bowel tumor were consistent with Merkel cell carcinoma metastasis.

Lung Metastases to the Heart with Atypical Clinical Manifestations of Cardiac Failure.

The heart is a rare site of cancer metastases, even from the most common malignancies, such as lung cancer. Cardiac metastases may lead to myocardial dysfunction. This report presents a case of lung cancer metastases to the left ventricular myocardium that clinically manifested as atypical symptoms of cardiac dysfunction. The metastases were not revealed until after the patient died. Posthumously, the anamnesis, autopsy results, and morphological examination were evaluated. We demonstrated that the atypical symptoms of cardiac dysfunction were caused by occult (undiagnosed) metastases of lung cancer cells to the heart. The doctors did not consider this variant as possible metastatic lung cancer, because the patient had been treated radically one year earlier.

Decision-making support system for diagnosis of oncopathologies by histological images.

The aim of the study is to increase the functional efficiency of machine learning decision support system (DSS) for the diagnosis of oncopathology on the basis of tissue morphology. The method of hierarchical information-extreme machine learning of diagnostic DSS is offered. The method is developed within the framework of the functional approach to modeling of natural intelligence cognitive processes at formation and acceptance of classification decisions. This approach, in contrast to neuronal structures, allows diagnostic DSS to adapt to arbitrary conditions of histological imaging and flexibility in retraining the system by expanding the recognition classes alphabet that characterize different structures of tissue morphology. In addition, the decisive rules built within the geometric approach are practically invariant to the multidimensionality of the diagnostic features space. The developed method allows to create information, algorithmic, and software of the automated workplace of the histologist for diagnosing oncopathologies of different genesis. The machine learning method is implemented on the example of diagnosing breast cancer.

Neuroendocrine Tumor of the Fallopian Tube and Serous Adenocarcinoma of the Ovary: Multicentric Primary Tumors.

Neuroendocrine tumors (NETs) comprise a large group of tumors that are most often localized in the gastrointestinal tract and lungs. They are rarely found in the organs of the female reproductive tract; such NETs are primarily localized in the ovaries. We present a case of multicentric primary low-grade NET of the fallopian tube and high-grade ovarian serous adenocarcinoma. In both tumor regions, the histotypes of neoplasms were determined by morphological and immunohistochemical investigations. The NET of the fallopian tube was diffusely positive for chromogranin A and CD56, but wild type for p53 and negative for CK7, CK20, and ER; Ki-67 expression was observed in 3% of the neoplastic cells. The ovarian serous adenocarcinoma was positive for CK7 and ER, mutant for p53, but negative for chromogranin A, CK20, and CD56; Ki-67 expression was observed in 45% of the tumor cells. These results support the possibility that NET can occur in the female reproductive tract and coexist with other malignant tumors.

Detection of melanin in the rat skin.

Melanogenesis disorder is called dyschromia, is involved in various conditions including vitiligo, solar lentigo, and melanoma, the last of which is the most malignant type of skin cancer. AIM: The aim of study was focused on histological visualization of melanogenic system. MATERIALS AND METHODS: To investigate the roles of melanocytes and melanin, we used a rat skin as an experimental animal. Samples were stained using hematoxylin-eosin, the Schmorl's technique, the Fontana-Masson technique, the Warthin-Starry technique, and the S100 immunohistochemistry marker technique. Microscopy images were analyzed using the ImageJ free software protocol. RESULTS: We found Fontana-Masson staining to be the most suitable for obtaining reliable results compared with the other methods, which had more disadvantages. We also found the S100 marker staining to be an effective tool for measuring the melanocyte count. CONCLUSIONS: We consider the ImageJ processing protocol and staining procedures to be useful tools to estimate melanin and melanocyte pathology.

Invasive Breast Carcinoma of No Special Type with Medullary Pattern: Morphological and Immunohistochemical Features.

OBJECTIVE: Our study investigated the morphological and immunohistochemical characteristics of invasive breast carcinoma of no special type (IBC-NST) with medullary pattern to explore the inconsistencies between the structural and clinical traits of this category of tumor. MATERIAL AND METHOD: The breast carcinoma samples (n = 26) with medullary pattern (defined according to established criteria) were subjected to immunohistochemical assays of the following receptors: ER, PR, HER2/neu, Ki-67, p53, Bcl-2, VEGF, MMP1, E-cadherin, EGFR, Hsp70, Hsp90, CD20, CD3, CD4, CD8, CD68, CD163, CD56, CD138, MPO, S100, IgG, IgM, and PD-L1. RESULTS: IBC-NST with medullary pattern was found to have negative expression of ER, PR, and HER2/neu; strong positive expression of Kі-67, mutant р53, Bcl-2, E-cadherin, EGFR, and PD-L1; moderate positive expression of Hsp70 and Hsp90; and low or negative expression of VEGF and MMP1. Furthermore, there was pronounced variability in the qualitative composition of tumor immune infiltrates with regards to T-lymphocytes, B-lymphocytes, macrophages, plasmocytes, and granulocytes. CONCLUSION: IBC-NST with medullary pattern has many unfavourable morphological and immunohistochemical prognostic characteristics, which are balanced against the pronounced protective properties of the tumor cells and the qualitative characteristics of the tumor microenvironment. These can lead to a favourable disease course despite the relatively adverse features of the carcinoma cells.

Morphological features of the rat uterus.

The rat uterus is an important female reproductive organ that has essential for the organism's reproduction. That is why it is necessary to understand all the rat uterus' morphological features as a perfect biomodel for studying the molecular peculiarities of the female reproductive system and pathologies development in experimental studies. AIM: The aim of research was to perform the comprehensive morphological analysis of the uterine in intact female rats. MATERIALS AND METHODS: The uterine of reproductive-aged intact female rats were used in this research. The cytological study of vaginal smears, histological (H and E), and immunohistochemical (estrogen, progesterone, and Ki-67 receptors) analysis of uterus tissues were used for light microscopic examination. RESULTS: The rat's vaginal smears' cytological features showed a specific qualitative cellular composition (variation of leukocytes, nucleated and anucleated cornified epithelial cells) in different estrous cycle phases (proestrus, estrus, metestrus, and diestrus). Uterine histology showed the structural regularities of parenchymal and stromal components with clear differentiation on the endometrium, myometrium and perimetrium. It was presented uterus sensitivity to the influence of the sex hormones (positive to estrogen and progesterone receptors) and the variable cellular proliferation activity (Ki-67 expression) in the organ wall. CONCLUSIONS: Our research demonstrated that the rats« uterus has a unique structural organization, sex hormones sensitivity, and variable proliferation in the parenchymal and stromal components. The rat estrous cycle should be considered while studying the morphological features of the uterus. The rat's uterus may serve as an acceptable object for modeling various pathological processes with the following results' extrapolation.

The Expression of Prolactin Receptors in Benign Breast Tumors Is Not Associated with Serum Prolactin Level.

The role of prolactin (PRL) and its receptors in the initiation and development of benign breast tumors (BBT) has not been sufficiently studied. An imbalance in the system of hormone homeostasis is crucial in the development of BBT. In particular, an association between elevated prolactin levels and the development of BBT has been reported. Our study showed no significant differences between PRL receptor (PRL-R) expression in BBT tissue under normal and elevated serum PRL levels. There was also no significant correlation between age, PRL-R expression in BBT tissue, intact tissue, and PRL level in the serum. There was a strong significant correlation (p < 0.01; r = 0.92) between PRL-R expression in BBT samples and intact breast tissue, which did not depend on the serum PRL level. There was also no significant difference in the expression of the proliferative marker Ki-67 in BBT tissues from women with normal and elevated levels of serum PRL (p > 0.05). No signs of PRL and its receptors were detected in the BBT cystic fluid women with elevated serum PRL levels. In summary, our prospective study showed that the expression of PRL-R in the tissue of BBT and physiological breast tissue does not depend on the level of serum PRL.

REPARATIVE PROCESSES FEATURES IN TROPHIC ULCERS CAUSED BY DIABETES MELLITUS WITH THE USE OF PLATELET-RICH PLASMA.

OBJECTIVE: The aim: Was following: the improvement of the treatment results of the lower limbs ulcers, caused by the diabetes mellitus by using our technique of the platelet-rich plasma application; the study of the features of the morphological and immunohistochemical changes, and the effect of the growth factors of the platelet-rich plasma on the regeneration and healing of the ulcers. PATIENTS AND METHODS: Materials and methods: 38 patients with the trophic ulcers of the lower limbs, caused by diabetes mellitus were involved in the study. To assess the morphological features of the reparative processes before and after the treatment with PRP, the histological and immunohystochemical studies of the biopsy specimen of ulcers were carried out. RESULTS: Results: The total epithelialization of the ulcers in the patients from the main group was achieved on 46.5 day, and in the comparison group - 81.7 day. The light and optical study of the specimen of the main group, using the autologous platelet-rich plasma revealed the elimination of the destructive changes and reduction of the mixed-cellular infiltration compared to the patients from the comparison group. The immunohystochemical study revealed the increase of the growth factors receptors. CONCLUSION: Conclusions: The usage of the autologous platelet-rich plasma in the treatment of the trophic ulcers results in the rapid regeneration by the decrease of the destructive and inflammatory changes as well as the improvement of the vascularization.

Features of the morphological state of bone tissue of the lower wall of the maxillary sinus with the use of fixed orthodontic appliances.

AIM: The aim of the study was to identify the consequences of the use of fixed otrhodontic appliances (FOAs) on the morphological state of the tissues of the lower wall of the maxillary sinus, depending on the duration of their use. MATERIALS AND METHODS: The study involved 115 male and female patients aged 18 to 25 years. All patients were divided into 2 research groups depending on the period of wearing brace systems. The control group consisted of patients who did not require orthodontic treatment orthodontic appliances. The density and thickness of the lower wall of the maxillary sinus were calculated in all groups. RESULTS: In the control group, the average minimum thickness of the lower wall of the maxillary sinus was 4.6±1.5 mm, the minimum density was 13.46±132.6 Hu, in prolonged wearing of FOAs (from 2 to 3 years) these indicators were: 4.96±1.22 mm and -160±187.4 Hu, respectively. In less severe malocclusion in people with a period of FOAs wearing from 1 to 1.5 years, these indicators were 5.03±1.06 mm and - 80.98±167.7 Hu. When measuring the density after one year, it increased and amounted to 25.6±184.4 Hu in wearing FOAs up to 1.5 years and 105.47±173.84 Hu in prolonged wearing of brace systems. CONCLUSIONS: It can be assumed that wearing of braces affects the morphological state of not only the enamel of the teeth, but also of the surrounding tissues, and this effect is more intense in prolonged wearing of FOAs.

Prostate Cancer with Intraluminal Inclusions: the Association of the Immunophenotype with Grade Score.

BACKGROUND & OBJECTIVE: To study the immunophenotype of prostate cancer (PC) with the presence and absence of intraluminal inclusions (IIn), depending on the grade score. METHODS: A total of 30 PC samples with IIn (group E) and 30 PC samples without them (group C) were studied. These groups were divided into 2 subgroups, depending on the grade of malignancy, which was determined according to the Gleason score as moderate and high-grade tumors. Macroscopic analysis, hematoxylin-eosin staining, immunohistochemistry (androgen receptors, p53 and Bax proteins, Hsp70 and Hsp90, CD68, VEGF, OSN, MMP-1) were used. RESULTS: The expression level of VEGF was higher in the more differentiated tumors of the control group (P<0.01). Increased expression of prognostic-adverse markers p53 (in the presence of IIn, P<0.01) and MMP-1 (P<0.05) was observed. Also, a higher level of OSN expression was found in PC tissue with IIn (P<0.01) due to its participation in the processes of biomineralization. The expression level of CD68 and Bax protein was higher in the PC group with IIn (both P<0.01). Furthermore, Hsp90 had a significantly lower expression level in the PC of group E (P<0.05). CONCLUSION: the presence of IIn in the PC samples of group E promotes tissue remodeling with mechanical trauma, chronic inflammation, and fibrosis development. The presence of IIn in PC leads to the increase of OSN, CD68 and Bax expression and decrease of Hsp90 and VEGF expression. High expression of p53 and MMP-1 and low expression of OSN and VEGF was identified as a characteristic of high-grade tumors.

Serous Adenocarcinoma of Fallopian Tubes: Histological and Immunohistochemical Aspects.

BACKGROUND: Although primary cancer of the fallopian tubes is a relatively rare type of tumor in female reproductive organs, its mortality is quite high. It is important to identify molecular and biological markers of this malignancy that determine its specific phenotype. METHODS: The study was carried out on samples received from 71 female patients with primary cancer of the fallopian tubes. The main molecular and biological properties, including hormone status (estrogen receptor [ER], progesterone receptor [PR]), human epidermal growth factor receptor (HER2)/neu expression, proliferative potential (Ki-67), apoptosis (p53, Bcl-2), and pro-angiogenic (vascular endothelial growth factor) quality of serous tumors were studied in comparison with clinical and morphological characteristics. RESULTS: ER and PR expression is accompanied by low grade neoplasia, early clinical disease stage, and absence of lymphogenic metastasis (p < .001). HER2/neu expression is not typical for primary cancer of the fallopian tubes. Ki-67 expression is characterized by an inverse correlation with ER and PR (p < .05) and is associated with lymphogenic metastasis (p < .01). p53+ status correlates with high grade malignancy, tumor progression, metastasis, negative ER/PR (p < .001), and negative Bcl-2 status (p < .05). Positive Bcl-2 status is positively correlated with ER and PR expression and low grade malignancy. CONCLUSIONS: Complex morphologic (histological and immunohistochemical) study of postoperative material allows estimation of the degree of malignancy and tumor spread to enable appropriate treatment for each case.

Morphofunctional features of articular cartilage structure.

BACKGROUND: Articular cartilage is highly-organized nonvascularized tissue which is responsible in humans for pressure absorption under load, as well as for the smoothness of the opposite tangential bone surfaces. The purpose of our research is to study structural and functional features of articular cartilage at light- optical level by using state-of-the-art research methods of bone-cartilage tissue. MATERIAL AND METHODS: the study was conducted on samples of femoral heads. Hyper fine sections were subject to hematoxylin and eosin, Van Gieson's and PAS staining. In order to identify the receptor profile of chondrocytes and the features of protein arrangement in extracellular matrix we undertook an immunohistochemical study. RESULTS: An articular cartilage is quite organized tissue. As any other organ, it has parenchyma and stroma. Parenchyma is represented by one type of cells - chondrocytes, which, depending on how deep they are located in cartilage, have a different shape, size and functional features. The chondrocytes and extracellular matrix have different degrees of receptors expression. CONCLUSIONS: the cartilage is being constantly self-renewed, what is manifested by means of a rather slow division of the surface-located chondrocytes and programmed death of dystrophic-modi ed cells. The features of extracellular matrix structure determine the originality of cell location in different areas of cartilage tissue. Due to synthesis of specific proteins, chondrocytes self-regulate properties of cartilage tissue.

Morphological and crystal chemical characteristic of panсreatic lithiasis.

OBJECTIVE: Introduction: Information on chemical and phase composition of pancreoliths is limited and discrepant. There are reports, that pancreoliths are composed by calcium, phosphate, calcium carbonate or combination of calcium with fatty acids The aim of the work is studying of structural characteristics of pancreatoliths in 5 clinical cases. PATIENTS AND METHODS: Materials and methods: Morphological and crystal-chemical study of five cases of pathological biomineralization in the pancreas were conducted in the work. RESULTS: Results: Two stones were located in the pancreatic duct, in other cases - in the ductal system of pancreas. Concretion sizes ranged from 0.5 to 1.5 cm in diameter. Pancreatic lithiasis' form depended on the location: in the duct of Wirsung single concretions were found (they were relatively large, oval stones with smooth, regular edges); multiple, small concretions with irregular edges, coral-like stones dominated in the ductal system of pancreas. Histological study of pancreas showed the signs of chronic pancreatitis, tissue fibrosis, atrophy and edema of glandular component, system distension of ducts, nidal mix-cell inflammatory infiltrates, vessels' plethora. Structural phase and chemical analysis of pathological biominerals responded calcite in all studied cases. CONCLUSION: Conclusion: The presence of pancreatic lithiasis was found to be accompanied by significant morphological changes of the pancreas. The pancreatolith crystal phase was established to be calcium carbonate in the form of calcite.

The case of undiagnosed immunodeficiency in child from mother with leukemia anamnesis.

Acute lymphoblastic leukemia (ALL) in pregnant women is rare experience, but it can complicate the gestation by increasing the risk of miscarriage and premature birth. However, the adequate carrying of the pregnancy is possible for women who suffered from leukemia in childhood and achieved the remission during the treatment. Furthermore, there are some facts about the possibility of immunosuppression in children whose parents suffer from various immunodeficiency disorders, including ALL. This clinical case demonstrates the importance of correct diagnostics in order to reveal the congenital pathologies of the immune system in children, whose parents suffered from lymphocytic leukemia, even in case of full clinical and laboratory remission for a significant period of time. In the hospital, the thread metric approach was used for sepsis diagnostics. Conducted treatment was ineffective due to the inadequate immune response in the child and lack of the targeted adjusted measures to immunodeficiency disorder. The present case demonstrates the congenital T-cells immunodeficiency in a child who was complicated by the development of acute ulceronecrotic enterocolitis after vaccination. The treatment that was targeted mainly at the agent eradication did not give the desired results due to non-responsiveness of the immune system of the child.

Changes in the Hematopoietic System and Blood Under the Influence of Heavy Metal Salts Can Be Reduced with Vitamin E.

OBJECTIVE: The aim of our work was to study the blood parameters and bone marrow morphological changes in rats exposed to increased amounts of heavy metal salts and the effect of vitamin E. MATERIAL AND METHOD: Investigation of bone marrow structural features and blood parameters was performed in sexually mature Wistar male rats (n=84). RESULTS: Exposure to increased amounts of heavy metal salts led to the inhibition of erythropoiesis and leukopoiesis, as well as a synchronized increase in the number of megakaryocytes which was clearly reflected in the blood: the number of erythrocytes, leukocytes and Hb decreased, and the number of platelets increased. These changes in the blood and bone marrow were less pronounced when vitamin E was used as an adjuster. CONCLUSION: When increased amounts of HMS enter the rats` bodies, suppression of erythropoiesis and leukocytopoiesis occurs while thrombocytopoiesis increases. These changes depend on the period of intake of heavy metal salts. The adjustment of vitamin E reduces the severity of the cytotoxic effect of heavy metals and improves readaptation in the recovery period.

The features of morphological changes in the urinary bladder under combined effect of heavy metal salts.

PURPOSE: This study is aimed to the investigation of the features of morphological changes in the urinary bladder of mature rats. RESULTS: Received results shown that the experimental group of rats that had the intake of heavy metal salts (HMS) mixture during 30 and 90 days were observed histological and immunohistochemical changes in all structures of the urinary bladder. Depending on the period of influence of heavy metal ions on the wall of the organ, the pathological changes developed in cellular layers of the wall can lead to degenerative and later to atrophic and sclerotic changes. CONCLUSIONS: This study demonstrates that high concentrations of HMS can significantly influence the body. The histological and immunohistochemical studies showed that the influence of the HMS combination leads to deep morphological changes in all structures of the urinary bladder. These changes depend on the period of intake of HMS. Analysis of the obtained results demonstrates the dependence of expression of morphological changes in the urinary bladder on the experiment duration. The final result of these changes may lead to the disorders of bladder's functions.