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Background: In recent years, the study of acne pathogenesis has continued, and genetic regulation, innate and adaptive immune responses, and the contribution of several endocrinologic mechanisms have been reported. A sebaceous-hair follicle (SHF) is known to be regulated by sex hormones, including androgens, estrogens, and progesterone. At present, there is evidence of the involvement of sex hormones in the pathogenesis of acne. Still, there is no data on immunohistochemical (IHC) analysis of sex hormone receptor expression in the skin of severe acne (SA) in the available literature. There is also no IHC analysis of predictors of acne development. The present study aimed to determine and analyze the immunohistochemical expression of androgen, estrogen, and progesterone receptors in the skin of SA patients and to evaluate their predictive potential using artificial intelligence methods. Methods and Results: This prospective, open, non-randomized, single-center comparative study was conducted between 2019 and 2023. The study included 53 patients (the main group [MG]) with SA and 21 apparently healthy individuals (the comparison group [CG]). Participants were between 15 and 46 years old (the median age was 22.0 years). An IHC study was performed in the Pathomorphological Department at the NMRC PHOI, named after Dmitry Rogachev (Moscow, Russia). Skin samples from patients were collected by punch biopsy. To perform the IHC study, we used the mouse monoclonal anti-androgen receptor (AR) antibody (Clone AR441, diluted 1:50; DAKO, Denmark), mouse monoclonal anti-estrogen receptor (ER) antibody (Clone 1D5, RTU; DAKO, Denmark), and mouse monoclonal anti-progesterone receptor (PR) antibody (Clone PgR636, RTU; DAKO, Denmark). For each marker under study, positivity was determined in three compartments: epidermal keratinocytes, dermal fibroblasts, and sebocytes of sebaceous glands. Quantitative AR, ER, and PR expression assessment was performed using QuPath image analysis software according to the manufacturer's protocol. Statistical analysis was performed using Python 3.11. The predictive potential of the studied IHC markers was assessed using mathematical modeling methods and artificial intelligence. Our study revealed for the first time a significant increase in the AR expression in epidermal keratinocytes and dermal fibroblasts in SA patients compared to healthy individuals, with no significant difference in the AR expression in sebocytes of sebaceous glands and overall positivity. A significant ER overexpression in dermal fibroblasts of SA patients with no significant differences for other studied compartments and overall positivity was also found. Moreover, the studied compartments had no statistically significant differences in progesterone receptor expression. Conclusion: Mathematical modeling methods using artificial intelligence have made it possible to establish for the first time that the AR expression in dermal fibroblasts is a significant predictor of severe acne.

Aim. To assess the incidence of chronic myocarditis in patients with atrial fibrillation.Material and methods. The study included 145 patients. The majority of patients were male — 118 (81.4%). The median age was 45 (38; 50) years. Most had paroxysmal AF — 60 (41.4%), slightly fewer had persistent AF — 55 (37.9%), 30 (20.7%) patients had long-term persistent AF. All patients underwent radiofrequency ablation of AF and endomyocardial biopsy (EMB) with subsequent histological and immunohistochemical studies (IHC). Morphological verification of myocarditis was performed in accordance with the Dallas criteria modified by the World Heart Federation.Results. Signs of chronic myocarditis were identified in 64 patients (44.1%). The median age of patients with myocarditis was 44 (36.5;49) years, without myocarditis — 46 (38;51) years. In men, myocarditis was detected in 50 cases (42%), in women — in 14 (51.9%). In paroxysmal AF, myocarditis was detected in 25 patients (41.7%), in persistent AF — in 23 (41.8%), and in long-term persistent AF — in 16 (53.3%). The groups with and without chronic myocarditis were comparable when compared based on the main echocardiographic parameters. Regression analysis did not show a significant influence of these factors on the probability of detecting chronic myocarditis in patients with AF. In patients under 30 years of age, there were no signs of inflammation without the presence of myocardial fibrosis, while the maximum stage of fibrosis occurred in patients from 31 to 40 years of age. The stage of fibrosis did not depend on gender. More often than others, a combination of enterovirus and herpes virus type 6 was detected in biopsy specimens. In patients over 51 years of age, biopsies generally did not express any virus on immunohistochemical studies.Conclusion. Chronic myocarditis in patients with AF was significantly more often detected in younger patients (up to 50 years inclusive), and was more common in women, as well as in the presence of a long-term persistent form of AF, regardless of gender. Detection of myocardial fibrosis signs is more typical for young patients with the maximum stage at the age of 31 to 40 years.

Background. According to literature data, errors in the diagnosis of gastrointestinal tumors (GIST) are uncommon, accounting for approximately 6% of cases that results in treatment failure. Case report. Here, we describe a rare case of a 58-year-old female patient with extragastrointestinal stromal tumor (EGIST) in the evidence of testicular feminisation syndrome (TFS) – Morris syndrome. This hereditary pathology is associated with complete insensitivity of target organs to androgens and was described in 1953 by the American gynaecologist John Morris. The patient was referred to the cancer clinic, where she was wrongly diagnosed with uterine leiomyoma. Interdisciplinary approach, cancer alarm, active surgical tactics, additional immunohistochemical (IHC) and molecular genetic studies (MGI) allowed verifcation of the true diagnosis. There are reported cases of EGIST of the bladder, prostate, retroperitoneum, mesentery, omentum, and posterior mediastinum. However, we were not able to fnd publications regarding the cases of EGIST originating from the vaginal wall. Combination of TFS and EGIST is a unique case in our clinical practice. Conclusion. The study of rare cases expands the understanding of the molecular pathogenesis of malignancies. Patients with rare types of malignant tumors should be obligatorily examined and treated in specialized cancer clinics with involvement of certifed oncologists, surgeons, chemotherapists, geneticists.

Background. Classical Hodgkin’s lymphoma is a B-cell lymphoproliferative disease, the tumor substrate of which is Berezovsky–Reed–Sternberg cells, characterized by CD30, PAX-5, CD15 expression and the absence of CD3, CD45. In some cases, tumor cells express CD20. modern anticancer therapy has increased the survival probability for most patients, not only with early but also with advanced stages of classical Hodgkin’s lymphoma. Such successes are mainly due to the distribution of patients into prognostic groups and the choice of an appropriate treatment regimen. tumor infiltration of the bone marrow suggests assigning patients to the advanced stages group, followed by the choice of an intensive therapy program. Aim. To determine the bone marrow involvement frequency according to positron emission tomography combined with computed tomography (PET/CT), with 18F-fluorodeoxyglucose (FDG) and bone marrow trephine biopsy (bmtb), to compare the results obtained with primary tumor immunophenotype and bone marrow cellular composition, and to identify of prognostic risk factors. Materials and methods. The study included 107 patients with newly diagnosed classical Hodgkin’s lymphoma, who underwent a diagnostic examination at the moscow research institute of oncology named after P. A. Herzen – a branch of the National Medical Research Center for Radiology and the “Lapino” clinical Hospital from 2015 to 2022, followed by anticancer therapy and further follow-up. Morphology of the primary tumor biopsy specimen in all patients and immunohistochemical (IHC) study using a wide panel of monoclonal antibodies (CD15, CD30, CD3, CD45, CD20, PAX-5 anti-gens; in some cases epstein–barr virus proteins expression) in most cases were performed. All patients underwent a morphological and / or IHC study of BMTB and the majority underwent aspiration biopsy and PET/CT with 18F-FDG. Results. The most common histological variant of classical Hodgkin’s lymphoma was nodular sclerosis (86.9 %). The majority of patients (51.4 %) were assigned to the advanced stage prognostic group. bone marrow tumor infiltration was statistically significantly more frequently diagnosed during PET/CT with 18F-FDG compared with the results of the BMTB – in 27.1 % and 12.1 % of cases, respectively (p < 0.05). when comparing the results of both diagnostic methods, it was found that in 17.1 % of cases, bone marrow infiltration, detected during PET/CT, was not confirmed by IHC examination of the trephine biopsy. In addition, it was found that the majority of cases with CD20+/± and CD15+/± expression in the primary tumor were observed in the group of patients without bone marrow involvement. when assessing the cellular composition of bone marrow aspirates, it was revealed that in patients with bone marrow tumor infiltration, an increase in cellularity and megakaryocytes number along with a decrease in the plasma cells number is observed. Conclusion. The results suggest further study of bone marrow immunomorphological features in order to identify prognostic factors and search for new therapeutic targets. a more extended analysis of bone marrow aspirate immunomor-phological characteristics using new modern diagnostic methods, minimal residual disease status as a surrogate marker seems to be relevant and necessary to confirm the depth of the antitumor response achieved. Detection of CD20+/±- and cd15+/±-Berezovsky–Reed–Sternberg cells according to primary tumor IHC analysis indicates a low probability of bone marrow tumor infiltration, but further analysis is required on a large clinical and laboratory material.

The authors conducted a literature review of the current state of immunohistochemical diagnostics in determining the durability and time of occurrence of mechanical damage in forensic medical practice. Problems in the selection of immunohistochemical markers and the need to create immunohistochemical panels for qualitative research and definitive results were revealed. The authors recommend further scientific and practical research to improve knowledge and methods that should be implemented for routine research in forensic medical practice. [ABSTRACT FROM AUTHOR]

Research objectives: to study age-related changes in the structure of vaginal tissues in women with pelvic prolapse (PP). Materials and methods. The structure of the vaginal wall was studied in 29 women with PP, who were divided into three groups: the first group – 11 women aged of 45 in the reproductive period with regular menstrual function; the second group – 8 women aged 45–55 in perimenopause with irregular menstrual function; the third group – 10 women aged 55–65 who have been postmenopausal for more than three years. All women underwent immunohistochemical detection of the CD34 marker and vascular endothelial growth factor (VEGF), podoplanin, the number of estrogen receptors, type 1 matrix metalloproteinase (type 1 collagenase) and type 1 collagen were determined. Results. The reproductive age was characterized by an active metabolism, which was reflected in the fullness of all vaginal layers, their thickening, heterochromia of the nuclei, increased metabolism in the connective tissue and synthesis of vasculogenesis stimulators. The expression of estrogen receptors was not increased due to a sufficient concentration of estrogens in the body. Atrophic changes in the perimenopausal age were determined as the thinning of the vaginal layers, sclerotic changes, and a decrease in protein synthesis in the form of nuclear hyperchromia. The number of estrogen receptors was compensatory increased due to their deficiency. A feature of this age is vascular imbalance, which was subjectively expressed in climacteric symptoms. Atrophic and sclerotic changes were observed in the postmenopausal period in the form of thinning of the vaginal wall, hyperchromia of the nuclei, an increase in the collagen level relative to an unchanged collagenase level, a decrease in lymphatic drainage, and an increase in the number of estrogen receptors. Conclusions. This study shows that all groups of women with PP have characteristic signs associated with age changes, features of the mestral cycle and hormonal saturation of the body. Factors affecting the PP development include: in reproductive age – increased collagenase activity, in perimenopause and postmenopause – atrophic dyshormonal and dyscirculatory processes in tissues.

We investigated the impacts of photobiomodulation (PBM) and human allogeneic adipose-derived stem cells (ha-ADS) together and or alone applications on the stereological parameters, immunohistochemical characterizing of M1 and M2 macrophages, and mRNA levels of hypoxia-inducible factor (HIF-1α), basic fibroblast growth factor (bFGF), vascular endothelial growth factor-A (VEGF-A) and stromal cell-derived factor-1α (SDF-1α) on inflammation (day 4) and proliferation phases (day 8) of repairing tissues in an infected delayed healing and ischemic wound model (IDHIWM) in type 1 diabetic (DM1) rats. DM1 was created in 48 rats and an IDHIWM was made in all of them, and they were distributed into 4 groups. Group1 = control rats with no treatment. Group2 = rats received (10 × 100000 ha-ADS). Group3 = rats exposed to PBM (890 nm, 80 Hz, 3.46 J/cm2). Group4 = rats received both PBM and ha-ADS. On day 8, there were significantly higher neutrophils in the control group than in other groups (p < 0.01). There were substantially higher macrophages in the PBM + ha-ADS group than in other groups on days 4 and 8 (p < 0.001). Granulation tissue volume, on both days 4 and 8, was meaningfully greater in all treatment groups than in the control group (all, p = 0.000). Results of M1 and M2 macrophage counts of repairing tissue in the entire treatment groups were considered preferable to those in the control group (p < 0.05). Regarding stereological and macrophage phenotyping, the results of the PBM + ha-ADS group were better than the ha-ADS and PBM groups. Results of the tested gene expression of repairing tissue on inflammation and proliferation steps in PBM and PBM + ha-ADS groups were meaningfully better than the control and ha-ADS groups (p < 0.05). We showed that PBM, ha-ADS, and PBM plus ha-ADS, hastened the proliferation step of healing in an IDHIWM in rats with DM1 by regulation of the inflammatory reaction, macrophage phenotyping, and augmented granulation tissue formation. In addition PBM and PBM plus ha-ADS protocols hastened and increased mRNA levels of HIF-1α, bFGF, SDF-1α, and VEGF-A. Totally, in terms of stereological and immuno-histological tests, and also gene expression HIF-1α and VEGF-A, the results of PBM + ha-ADS were superior (additive) to PBM, and ha-ADS alone treatments. [ABSTRACT FROM AUTHOR]

A complex clinical case of acute myelomonocytic leukemia with extramedullary lesion of the testis is presented. patient yu., born in 1968, applied to the National Medical Research Centre for Oncology (Rostov-on-don) after an injury to the inguinal region. ultrasound was performed: in the right testicle in the middle third, a mass of 30 × 23 × 16 mm was revealed. A biopsy was performed: the morphological picture is characteristic of a typical seminoma. Orchofuniculectomy was performed on the right. Histopathological conclusion: the morphological picture is more characteristic of a typical seminoma, but does not allow excluding lymphoma. In order to differentiate between a germ cell tumor and a lymphoproliferative disease, an immunohistochemical study of the tumor tissue, a morphological and immunophenotypic study of the bone marrow were performed. According to the immunohistochemical data, the morphological picture and immunophenotype of tumor cells are characteristic of extranodal NK/T-cell lymphoma of the testis with Cd4 co-expression. However, according to the myelogram data, 20 % of morphologically heterogeneous blast cells were found: with round or bean-shaped nuclei, delicate mesh structure of chromatin, 1–2 nucleoli and a monocytoid form of nuclei with indistinct nucleoli. The cytoplasm of varying basophilia degrees, vacuolized, with delicate azurophilic granularity. The content of the monocytoid population was increased (19 %), represented mainly by promonocytes, which corresponds to acute myelomonocytic leukemia. According to flow cytometry, the immunophenotype of blast cells corresponds to acute myeloid leukemia with Cd56 co-expression. In connection with the new data obtained, the histological preparation was revised again with the expansion of the immunohistochemical study. Result: morphological picture and immunophenotype of tumor cells are characteristic of acute myelomonocytic leukemia with extramedullary lesions of the right testicular tissue. final diagnosis: acute myelomonocytic leukemia with extramedullary lesion of the right testicle, with Cd56 co-expression. The presented clinical case showed the need to use a wide range of diagnostic techniques to determine the nature of the disease. The results of morphological and cytometric studies of the bone marrow were decisive in establishing the diagnosis of M4 acute myeloid leukemia with extramedullary lesions of the right testicle in this patient.

Introduction. Uveal melanoma pathogenesis is determined by a number of factors, including the tumor molecular genetics, the organism’s immune response, and other ones. One of the approaches to studying the peculiarities of pathogenesis of this cancer is to determine the local subpopulations of lymphocytes and macrophages in combination with the study of the proliferative activity of tumor cells.Objective – to study the immunohistochemical features of uveal melanoma and its cellular microenvironment.Materials and methods. 24 enucleated eyes with uveal melanoma (144 histological and 216 immunohistochemicalpreparations) without previous treatment were analyzed. Cells of the immune microenvironment were analyzed: lymphocyte subpopulations and CD 68+ and CD 163+ antigens expressed by macrophages in the melanoma stroma and 2–3 mm from it. The tumor cell proliferation index Ki-67 was diagnosed.Results. All tissue samples of uveal melanoma revealed the presence of lymphocytes in the microenvironment of tumor cells. A large proportion of the studied subpopulations of lymphocytes were T-cytotoxic CD28+ lymphocytes (absolute content: 607.3 ± 431.2, relative: 18.84 % ± 12.12 %) (p = 0.018). A smaller proportion, but in equal proportions, were T-helpers CD4+, T-cytotoxic CD8+ and CD25+ lymphocytes (p = 0.6). The absolute number of natural killer cells subpopulation CD16+ was lower compared to CD56+ (p = 0.05). However, an almost equal relative content of the studied subpopulations was noted (p = 0.9). Histological examination revealed the presence of uveal melanoma macrophages in the microenvironment of the tissue. The immunohistochemical study of CD68+ and CD163+ antigens expressed by anti-inflammatory and pro-tumor macrophages showed that their absolute and relative content in the uveal melanoma tissue is almost the same with a slight predominance of CD163+ (p = 0.7). Immunohistochemical analysis showed that the nuclei of melanoma cells contain, on average, 575.2 ± 388.5 significant cells of the Ki-67 proliferation protein. This protein was found in 16.69 ± 10.88 % of tumor cells.Conclusion. Immunohistochemical study allows to identify subpopulations of lymphocytes infiltrating the tumor, to determine the subtypes of macrophages and to estimate the Ki-67 index of tumor cell proliferation. The data obtained will make it possible to further evaluate the significance of individual immune cells (in particular, T-cytotoxic CD28+ lymphocytes) in the pathogenesis of uveal melanoma in order to develop targeted effects, substantiate new immunotherapeutic approaches to the treatment of primary tumors and reprogramming altered immune cells.

Lymphatic malformations are benign neoplasms that form as a result of impaired formation of embryonic lymphatic sacs during embryogenesis. Lymphangiomas and lymphgemangiomas (visceral forms) rarely develop in the intra-abdomen, such localization does not exceed 8–15% of all observed lymphangiomas in children. Among the visceral forms are more common the forms that involve intestines, mesentery, spleen, omentum, liver in the pathological process, less often - the lymphatic vessels and lymph nodes of the mediastinum, and retroperitoneal tissue. The clinical presentation of lymphatic malformations is multivaried and depends on their localization, the patient age, and the development of complications. In case of complications, the clinic manifestation of “acute abdomen” requires emergency surgical intervention, during which the diagnosis and scope of surgical treatment are specified. a 14-year-old boy was admitted to the department of infectious diseases with complaints of fever, weakness, abdominal pain, sore throat and loose stools. Previously, the patient had complaints of abdominal pain for a year; ultrasound examination of the abdominal cavity was performed repeatedly, in which no pathological changes were detected. The patient underwent laparoscopic appendectomy; During the revision of the abdominal cavity, a space-occupying lesion emerging from the mesentery of the ascending colon and twisted around the vascular pedicle by 3 turns was revealed. Education removed. Histological and immunohistochemical examination confirmed the diagnosis of lymphatic-venous malformation. No signs of malignancy of lymphatic malformations are described in the literature. However, though lymphatic malformations are benign in nature, they tend to have an infiltrative growth pattern, often relapse, and sometimes become infected. The available literature doesn’t provide a proper description and analysis of the results of treatment of intra-abdominal lymphatic malformations using endovideo technologies. Transabdominal access provides the best exposure of the complete surgical field, freedom of movement and clarity of anatomical landmarks. The main advantages over open abdominal surgery are minimal trauma to the anterior abdominal wall and rapid rehabilitation of patients.

Malignant soft tissue tumors localized in the skin, particularly leiomyosarcoma, are rare. Cutaneous leiomyosarcomas could have superficial and deep forms, while subcutaneous leiomyosarcomas are usually nodular. The tumor can spread to the underlying muscle fascia. The immunophenotype of leiomyosarcoma is determined by the following antibodies: ASMA, desmin, and N-caldeston; expression of PanCK is also possible. Researchers do not have any common opinion on the clinical course and biological behavior of cutaneous leiomyosarcomas. This is probably due to the tumor heterogeneity and the carcinogenesis specificity associated with molecular genetic changes. We detected these tumors at the histological examination which resulted in an analysis of the literature and our own material. We analyzed cutaneous tumors diagnosed in 2522 patients during 5 years (2016–2020). Squamous cell and basal cell histotypes were the most common ones. We did not diagnosed cutaneous leiomyosarcoma in our material during this period. This article presents two cases of cutaneous leiomyosarcoma localized in the scalp and calf skin. Morphological and immunohistochemical profiles of the tumors are described. The immunohistochemical analysis confirmed the morphological diagnosis and established the tumor immunophenotypes. The morphological diagnosis in one case was complicated due to the rarity of this pathology and the ambiguity of the interpretation of histological changes. Analysis of histological preparations and immunohistochemical study allowed verification of the tumor as leiomyosarcoma with its characteristic immunophenotype. All of the above demonstrate the need to perform morphological and immunohistochemical tests in specialized research cancer centers.

Solitary fibrous tumors (SFT) are rare spindle cell mesenchymal neoplasms of presumably fibroblastic origin with undefined malignancy potential and rare metastasis. Their most frequent localization is in the pleura, where they have been first described. The incidence of solitary fibrous tumors localized in liver is extremely low. The clinical picture of SFT is nonspecific and is not due to the anatomical location of the tumor and it's size.In the majority of cases these tumors are benign. However, a number of them still may have signs of malignancy: an aggressive course with possible local recurrence and distant metastasis. The main method of treatment of hepatic solitary fibrous tumor (as well as SFT of other localization) with it's resectability is surgery. Radical removal of the tumor in the majority of cases leads to recovery. Subsequently, the operated patients should be subjected to strict dynamic observation with regularity as in malignant neoplasms (MN).The importance for chemotherapy and radiation therapy in the treatment of hepatic solitary fibrous tumor has not been determined in clinical guidelines to date.There are isolated reports of the use of chemotherapy or radiation therapy for the treatment of cases when tumor resection is not radical or there are signs of malignant neoplasm.In literature, there are numerous reports of a combination of a solitary fibrous tumor of any localization with malignant neoplasms of other organs in the same patients.In this report, we represent a clinical case of a 64-year-old woman, who had a solitary fibrous tumor of the liver and highly differentiated rectal adenocarcinoma. The patient underwent resection of the first segment of the left lobe of the liver. After a month and a half, transanal excision of the villous tumor of the rectum. The pathologic and immunohistochemical examination of the liver tumor revealed a malignant solitary fibrous tumor. After researching villous tumor of the rectum - a highly differentiated adenocarcinoma with a depth of invasion of the submucous layer of the intestinal wall up to 1/3 (T1sm1 according to Kikuchi). During dynamic observation for twenty-five months after the operation, the patient has no signs of tumor recurrence and metastasis.

BackgroundOnychopapilloma is generally recognized as a benign tumor of the nail bed and distal matrix. However, the origin of onychopapilloma has not been explained yet.ObjectiveTo clarify the origin of onychopapilloma, we detected the expression patterns of hair-related keratins and epithelial keratins, which are expressed specifically in the nail unit.Materials and methodsThe clinical and histopathologic features of 11 patients with onychopapilloma were analyzed, and the expression patterns of hair-related and epithelial keratins were detected.ResultsHistologically, all subjects showed acanthosis, papillomatosis and matrix metaplasia within the nail bed. Immunohistochemically, the expression pattern of keratins in our standard nail unit was consistent with previous reports. “Nail matrix-related keratins” HK31, HK34, HK85, and HK86 were only expressed in the nail matrix, and “Nail bed-related keratins” HK75 and K6/K16 were only expressed in the nail bed. However, in onychopapilloma, whether adjacent to the matrix or in the distal nail bed, all cases were positive for nail bed-related keratins and HK31 but negative for other nail matrix-related keratins.ConclusionOur study suggests that onychopapilloma may originate from the nail bed rather than the nail matrix. Furthermore, the expression of nail bed-related keratins and HK31 could be used as diagnostic markers of onychopapilloma.

Introduction Despite being a rare daily histopathologic diagnosis, malignant salivary gland (SG) tumors show significant morphologic diversity that could obscure their diagnosis. Recognizing specific microscopic patterns together with the aid of ancillary techniques, such as immunohistochemistry, represent the clues to precise diagnosis. Mammaglobin (MMg) is a member of secretoglobin protein family that is widely associated with breast cancer and strongly expressed by secretory carcinoma of SGs. Its expression in other malignant SG neoplasms should be investigated. Objectives Investigating the immunohistochemical expression of MMg in some malignant SG tumors to detect its potential diagnostic value. Material and Methods Nineteen paraffin-embedded, archival specimens of malignant SG tumors were divided into two groups according to presence or absence of ductal differentiation. Specimens were immunohistochemically stained using anti-MMg protein. Results MMg expression was more upregulated in the ductal differentiation group as compared to the other group of neoplasms. Conclusion MMg would represent a promising diagnostic tool in discriminating SG tumors with ductal and/or secretory activity. [ABSTRACT FROM AUTHOR]

Extensive use of abamectin (ABM) as an anthelmintic in veterinary systems adversely affects the health and welfare of animals and humans. Zinc nanoparticles (ZnNPs) have therapeutic benefits and ameliorate the effect of environmental pollutants. In this study, we assessed the ameliorative effect of ZnNPs against the sub-lethal toxicity of ABM in rats. Forty healthy rats were randomly selected into four groups (n = 10); the control received normal saline and test rats were treated orally twice weekly with ABM (1 mg/kg bwt), ZnNPs (10 mg/kg bwt) and ABM + ZnNPs for 28 days. Upon completion of the study period, blood and tissue samples were collected and prepared for hematological, biochemical, pathological, and immunohistochemical analysis. Our results showed that ABM treatment significantly decreased body weight gain (BWG), red blood cells (RBCs), hemoglobin (Hb), hematocrit (HC), and platelet (PLT); while it significantly increased white blood cells (WBCs) and lymphocytes. ABM also significantly decreased antioxidant enzyme activities: superoxide dismuthase (SOD), glutathione peroxidase (GPx), and catalase (CAT) and increased hydrogen peroxide and malondialdehyde levels compared with other groups. ABM significantly raised alanine aminotransferase (ALT), aspartate amino transaminase (AST), and alkaline phosphatase (ALP) levels, which was restored by co-administration of ZnNPs. Moreover, ZnNPs ameliorated ABM-mediated negative histopathological changes in the liver and kidney tissues, exhibiting a significant protective effect. Cyclooxygenase 2 (COX-2) + immunoexpression were reduced after pretreatment with ZnNPs. These findings suggested that co-administration of ZnNPs with ABM mitigated its toxicity by combating oxidative stress and boosting antioxidant capacity, indicating the efficacy of ZnNPs in attenuating ABM toxicity. [ABSTRACT FROM AUTHOR]

Extensive use of abamectin (ABM) as an anthelmintic in veterinary systems adversely affects the health and welfare of animals and humans. Zinc nanoparticles (ZnNPs) have therapeutic benefits and ameliorate the effect of environmental pollutants. In this study, we assessed the ameliorative effect of ZnNPs against the sub-lethal toxicity of ABM in rats. Forty healthy rats were randomly selected into four groups (n = 10); the control received normal saline and test rats were treated orally twice weekly with ABM (1 mg/kg bwt), ZnNPs (10 mg/kg bwt) and ABM + ZnNPs for 28 days. Upon completion of the study period, blood and tissue samples were collected and prepared for hematological, biochemical, pathological, and immunohistochemical analysis. Our results showed that ABM treatment significantly decreased body weight gain (BWG), red blood cells (RBCs), hemoglobin (Hb), hematocrit (HC), and platelet (PLT); while it significantly increased white blood cells (WBCs) and lymphocytes. ABM also significantly decreased antioxidant enzyme activities: superoxide dismuthase (SOD), glutathione peroxidase (GPx), and catalase (CAT) and increased hydrogen peroxide and malondialdehyde levels compared with other groups. ABM significantly raised alanine aminotransferase (ALT), aspartate amino transaminase (AST), and alkaline phosphatase (ALP) levels, which was restored by co-administration of ZnNPs. Moreover, ZnNPs ameliorated ABM-mediated negative histopathological changes in the liver and kidney tissues, exhibiting a significant protective effect. Cyclooxygenase 2 (COX-2) + immuno-expression were reduced after pretreatment with ZnNPs. These findings suggested that co-administration of ZnNPs with ABM mitigated its toxicity by combating oxidative stress and boosting antioxidant capacity, indicating the efficacy of ZnNPs in attenuating ABM toxicity.

Purpose of the study. Evaluation of expression of the epithelial-mesenchymal transition markers E-cadherin and ZEB1 in patients with stage II-IV colorectal cancer (CRC).Materials and methods. The study included operational material obtained from 299 patients aged 42–86 years (mean age 64.2±1.7 years) with stage II-IV CRC treated at National Medical Research Centre for Oncology in 2013-2017. Stage II CRC (T3-4 N0 M0 ) was diagnosed in 110 patients, stage III (T1-4 N1-2 M0 ) – in 88 patients, stage IV (T1-4 N0-2 M1 ) – in 101 patients. Polyclonal rabbit antibodies to ZEB1 (Biorbyt Ltd., UK) and mouse monoclonal antibodies to E-cadherin (Diagnostic BioSystems, USA) were used for an IHC analysis. The intensity and degree of tumor cell staining, percentage of stained tumor cells in the sample and the number of patients with positive and negative marker expression were determined. Groups were compared using the Mann–Whitney U test and the Pearson's chi-square test.Results. Positive expression of E-cadherin was found in 64.5 % (193 of 299 patients), ZEB1 – in 80.6 % (241 of 299 patients). The number of patients with E-cadherin-positive tumors statistically significantly decreased (χ2 =15.888 at p

Study objective: to optimize diagnostic measures in patients with adenomyosis and/or hyperplastic endometrial processes (HEP). Material and methods. The study included 128 patients aged from 27 to 53 years. The first group included 38 (29.6%) patients with a grade I–II adenomyosis, the second group included 41 (32.1%) patients with a combination of grade I–II adenomyosis and HEP and/or uterine leiomyoma, the third group included 39 (30.5%) women with only HEP, the fourth (control) group included 10 (7,8%) women without endometrial pathology. Patients underwent hysteroscopy with targeted biopsy, elucidated the pathomorphological features of connective tissue component of the endometrium and uterus transitional zone, studied specific markers of adenomyosis progression, namely vascular endothelial growth factor and Ki-67 proliferation index, and also determined the parameters of shear wave ultrasound elastography. Results. Routine histological examination of adenomyosis was confirmed only in 11 (30.6%) cases out of 36 suspected, while HEP (polyps, glandular hyperplasia) and hyperplastic pathology of endocervix (polyps) – in 34 (97.1%) cases out of 35 suspected. Ki-67 antigen expression was positive in the nuclei of epithelial cells in the adenomyosis glands and in the cytogenic stroma cells. A greater value of expression was in the epithelium of glands in superficially located heterotopies – with grade I–II adenomyosis compared with other studied groups. Shear wave elastography showed significant differences in the myometrium color between the first, third and control groups. The unchanged myometrium in all patients of the control group was characterized by staining in shades of blue, while in 9 (90%) patients the color was uniform. Conclusion. It is recommended to use a shear wave ultrasound elastography in laboratory and instrumental examination with determination of Ki-67 proliferation protein expression and intensification of the neovascularization process in endometrial biopsy specimens to improve the diagnosis of adenomyosis.

Introduction: HER2 overexpression in mammary carcinoma is associated to a higher biological activity of the tumor and to an unfavorable prognosis. Objective: to determine the incidence of pure overexpression of HER2/neu oncogene in mammary carcinomas in "Celestino Hernández" Hospital from Villa Clara Province and its relationship with other variables of prognostic value. Methods: descriptive, retrospective study was carried out at the "Celestino Hernández" Hospital between January 2017 and June 2019. It was included 293 women with diagnosis of infiltrating breast carcinoma, the biopsies were subjected to immunohistochemical study to determine the incidence of HER2 oncogene overexpression and its relationship with other variables of prognostic value. Results: 22 cases (7.5%) with exclusive overexpression of the HER2/neu oncogene were found in the series. Of the patients with carcinomas with HER2 overexpression, 17 (77.3%) were older than 50 years, 20 (90.9%) had tumor size greater than 2 centimeters and 21 (95.45%) were associated with the non-special histological type (ductal carcinoma) of mammary carcinoma. The relationship between HER2/neu oncogene overexpression and moderately and poorly differentiated histological forms of mammary carcinoma stands out. The proliferation index determined by Ki67 was greater than 30% in 17 patients (77.27%). Conclusion: postmenopausal age, non-special histological type, high histological grade, high Ki67 indices and tumor size greater than two centimeters are frequently associated with HER2 overexpression in mammary carcinomas. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Acyl-CoA-binding protein (ACBP), also known as diazepam binding inhibitor (DBI), is a small phylogenetically conserved protein. This ancestral peptide is multifunctional, performing intracellular activities as ACBP protein or extracellular roles as DBI. Several studies showed its endless facets, including a relevant activity as appetite stimulator and as anabolic factor. High levels of ACBP have been described in erythrocytes, liver, kidney, and gut cells. The aim of this study was to analyze, at immunohistochemical level, the expression of ACBP in fetal human tissues during development, focusing on the developing kidney. MATERIALS AND METHODS: Immunohistochemistry for ACBP was performed on 30 human fetal kidneys, from 15 fetuses of gestational age ranging from 13 to 19 weeks. At autopsy, all kidney samples were 10% formalin-fixed, routinely processed and paraffin-embedded. Five micron-thick paraffin sections were stained with Hematoxylin and Eosin and PAS stain for a morphological examination. RESULTS: ACBP was detected in all 30 kidneys analyzed in this study. No significant changes in ACBP expression were observed at different gestational ages. Immunostaining for ACBP was restricted to the epithelium covering the renal pelvis, the papillae, the collecting tubules, and the proximal and distal tubules. On the other hand, medullary regions and in the metanephric mesenchymal stem/progenitor cells did not show any reactivity for ACBP. CONCLUSIONS: According to our findings, ACBP should be considered as a new player in the complex field of human nephrogenesis, given that it was detected in all fetal kidneys immunostained. Its preferential localization in the renal structures derived from the Wolf duct, such as pelvis epithelium and collecting ducts, suggests a major role for ACBP in the induction of the metanephric mesenchymal cells toward the differentiation into glomerular structures. ACBP expression in proximal and distal tubules, two structures originating from the metanephric mesenchyme, indicates a further role of this protein in nephron development. In conclusion, ACBP should be added to the multiple molecules involved in human nephrogenesis. [ABSTRACT FROM AUTHOR]

Aims: The present study investigates the effectiveness of platelet-rich plasma (PRP) gel without adjunct to induce cartilage regeneration in large osteochondral defects in a rabbit model. Methods: A bilateral osteochondral defect was created in the femoral trochlear groove of 14 New Zealand white rabbits. The right knees were filled with PRP gel and the contralateral knees remained untreated and served as control sides. Some animals were killed at week 3 and others at week 12 postoperatively. The joints were harvested and assessed by Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) MRI scoring system, and examined using the International Cartilage Repair Society (ICRS) macroscopic and ICRS histological scoring systems. Additionally, the collagen type II content was evaluated by the immunohistochemical staining. Results: After 12 weeks post-surgery, the defects of the PRP group were repaired by hyaline cartilage-like tissue. However, incomplete cartilage regeneration was observed in the PRP group for three weeks. The control groups showed fibrocartilaginous or fibrous tissue, respectively, at each timepoint. Conclusion: Our study proved that the use of PRP gel without any adjuncts could successfully produce a good healing response and resurface the osteochondral defect with a better quality of cartilage in a rabbit model. Cite this article: Bone Joint Res 2021;10(3):192–202.

Introduction. According to different authors, 4 to 40% of the child and adult population suffer from chronic tonsillitis (СT), with many authors noting an increase in the number of cases and no tendency to decrease the frequency of this pathology.Objective. To optimize diagnostics and treatment tactic of taking patients with chronic tonsillitis (CT) using our own clinical and laboratory data and morphological data as well as literature data.Materials and methods. Аt the first stage of work, 166 patients were examined. They were divided into 4 categories (experimental groups) depending on clinical CT classification according to B.S. Preobrazhensky and V.T. Palchun. We also formed a group of patients who did not have CT symptoms. All patients underwent tonsillectomy or tonsillotomy. All tissue samples of palatine tonsils we got were investigated using immunohistochemical markers and default histological colorings. At the second stage, the dynamics of complaints, clinical symptoms and laboratory parameters were assessed in 247 patients diagnosed with CT Toxic-Allergic Form I (CT TAF I) before conservative treatment and 3 months after conservative treatment. Patients were divided into 3 groups depending on the conservative treatment regimen: a course of flushing the lacunae of the tonsils; antibiotic therapy with a retard form of clarithromycin; complex treatment combining the first two options.Results. Тhe chronic inflammatory process in the palatine tonsils changes their cytoarchitectonics. At the same time, there is a direct correlation between the presence and severity of changes with the clinical classification of chemotherapy according to B.S. Preobrazhensky and V.T. Palchun.Conclusion. With CT TAF II, the palatine tonsil not only loses its importance as an organ of the immune system, but also becomes a hotbed of infection in the body, which can cause severe complications. Only tonsillectomy can effectively protect the patient from these complications. At the stage of CT TAF I, the formation of metatansillar complications occurs. Patients with this form of CT require special attention, and correctly conducted conservative therapy can protect patients from local and general complications of CT. A variant of such conservative therapy that gives a lasting effect is complex therapy with washing the lacunae of the palatine tonsils with an antiseptic solution and simultaneous antibiotic therapy with 14-membered macrolides that can accumulate in the lymphadenoid tissue.

The aim of the study: to estimate the impact of different cellular phenotype of gastric tumors on the survival of patients treated according to standard protocols. Object and methods of research.The work presents the results of a study conducted on the basis of two medical institutions - the National Cancer Institute and the abdominal oncology and surgery department of the Odessa Regional Oncology Center. 221 patients underwent surgery for gastric cancer (GC) in the period 2007-2013. The average age of patients was 60.88 ± 10.5 years, men - 180, women - 41. Of the total number of operated, 143 patients underwent surgery in the amount of gastrectomy, 78 - subtotal distal resection. Results. All patients included in the study underwent radical surgery. Tumors removed during surgery were examined using histological, cytological, immunohistochemical methods and genetic tests. The obtained results are monitored for the presence/absence of clinical parallels and mathematical correlations. It was concluded that some combinations of immunohistochemical (IHC) markers were effective in separating groups of patients with different biology of gastric cancer. Conclusions. Performing more advanced operations (including the use of D2 lymph dissections) is the most effective option for surgical treatment of microsatellite-unstable and Epstein-Barr virus-associated gastric cancer.

Mesonephric‐like adenocarcinoma (MLA) is a rare tumor that occurs in the uterine endometrium and ovary. It morphologically and immunohistochemically resembles cervical mesonephric adenocarcinoma (MA). Here, we present a case of MLA of the ovary along with a literature review. An asymptomatic 84‐year‐old woman presented with a pelvic mass, detected by computerized tomography. Magnetic resonance imaging demonstrated a polycystic mass with a solid component in the left adnexal region. The solid component showed low signal intensity on T2‐weighted imaging and high signal intensity on diffusion‐weighted imaging. We strongly suspected an ovarian malignant tumor; therefore, surgical resection of the uterus and adnexa was performed. Macroscopically, the tumor was predominantly solid with yellowish‐tan cut surface. Microscopically, it showed a tubular pattern with intraluminal colloid‐like material resembling MA. The tumor cells were negative for estrogen receptor, calretinin, and CD10 and positive for PAX8 and TTF‐1. These findings are consistent with those of MLA. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is considered themostcommonmalignant disease in the female population. It isknownasanemerging epidemy with a great burden on women's health, which can be associated with poor outcomes. Some factors including histological type, immunohistochemistry (IHC), tumor grade, and tumor size can have effects on breast cancer. Objectives: This study aimed at assessing the effects of mentioned factors on IHC type of breast cancer. Methods: This retrospective cross-sectional study was conducted on 142 patients, who were referred to one of the referral centers for breast cancer in Mashhad. Information including age, histological type, familial history, menopause status, tumor grade, tumor size, and IHC properties was collected from the patient's medical records. Allred score was used for reporting hormonal status. The data were analyzed by version 26 of SPSS software. Results: The mean age of patient was 50.2 - 12.7. The frequency of luminal A and luminal B type was calculated as 29.7 and 18.9%, respectively. In addition, triple-negative IHC type has a prevalence of 24.3% and HER2 had a prevalence of 27%. There were no signifi- cant differences between age (P = 0.34), familial history (P = 0.42), menopause (P = 0.36), histological type (invasive: P = 0.11, in situ: P = 0.45), and IHC properties. However, tumor diameter (P = 0.0001) and tumor grading (P = 0.002) had significant association with IHC properties. Conclusions: Factors including tumor size and pathological grade can have effects on the gene expression properties of breast cancers. Luminal IHC type A is more common in breast cancer and is associated with better outcomes. However, age, histological type, familial history, and menopause status had no effects on the IHC properties of breast cancer. [ABSTRACT FROM AUTHOR]

Endomyocardial biopsy (EMB) is the method of choice for diagnosing a wide range of myocardial diseases.Aim. To assess the rationale for diagnostic EMB in children and adults.Material and methods. Morphological and statistical analysis of 2803 diagnostic EMBs in adults (n=811) and children (n=83), including those in heart transplantation (n=1909), was carried out.Results. In 231 (28%) cases, adults were diagnosed with myocarditis, of which in 6 patients — granulomatous, in 5 — eosinophilic and in 6 — lymphocytic-macrophage myocarditis after coronavirus infection. In children, myocarditis was found in 22 cases (27%). Arrhythmogenic right ventricular dysplasia took the second place in detection rate in children and adults. Immunohistochemical study revealed viral envelope protein 1 (VP1) antigen of enteroviruses in one third of myocarditis cases, and in half — other cardiotropic viruses. Dotted dystrophin expression was observed in myocarditis. A correlation was established between the perforin expression and myocarditis presence (Pearson χ2=27,8; Fisher's exact test=27,3; p=0,01).Conclusion. Analysis of diagnostic EMB results confirmed its rationale in adults and children not only for heart transplantation, but also for identifying cardiac pathology, including for myocarditis diagnosis. It has been shown that immunohistochemical study with antiviral antibodies can be considered as an alternative method for detecting viral infection. An immunohistochemical analysis for perforin and dystrophin can be recommended as additional morphological markers of myocarditis.

The purpose of systemic treatment in patients with breast cancer is based largely on the molecular characteristics of the primary tumor, but many clinical recommendations suggest also the study of metastatic nodes with an assessment of their receptor status (estrogen receptor ER, progesterone receptor RP, human epidermal growth factor receptor 2 Her2/neu). This is due to the fact that according to numerous studies, the discrepancy between the status of the primary tumor and the secondary nodes can reach high rates: 3–54 % for ER, 5–78 % for RP, and 0–34 % for Her2/neu. At the same time, more and more data actively demonstrate the imperfection of immunohistochemical analysis and the need to study additional parameters to improve the quality of diagnosis of patients with breast cancer. Material and methods. A morphological and immunohistochemical study of the tumor tissue of the primary node and axillary lymph nodes was performed in 199 patients with breast cancer (T1-3N0-3M0) using standard methods, and RT-PCR was also studied with the expression of 24 genes. Results. The incidence of differences between the molecular phenotypes of the main tumor and metastatic axillary lymph nodes was 26 (26 %) of 99 cases. Most often, differences were noted in cases of breast cancer with luminal A type – 13 cases (50 %). According to the results of a comparative PCR analysis of tissue samples from the primary tumor and metastatic regional lymph nodes, only the expression of the CD68, ERSR1, GRB7 and MMD11 receptors was statistically significant. Conclusion. The results indicate the need for an integrated approach and additional methods for the diagnosis of breast cancer, which will undoubtedly improve the quality of planning and the effectiveness of systemic treatment in patients with breast cancer.

Objective: To provide histopathological subtypes of medulloblastomas (according to 2007 WHO Classification of tumors of the central nervous system) that were previously diagnosed during 1998 to 2005 in Siriraj Hospital, and to characterize the immunophenotypic patterns of medulloblastomas in correlation with these subtypes. Methods: All diagnosed medulloblastomas collected during 1998 to 2005 in the Department of Pathology, Siriraj Hospital were reviewed and classified according to WHO classification (2007) by H&E staining. Furthermore, we performed immunohistochemical studies, including synaptophysin, glial fibrillary acidic protein (GFAP), neurofilament, and Ki-67 to characterize the immunophenotypical patterns of medulloblastoma correlated with morphological variants. Statistic analyses were Tukey HSD, Mann-Whitney test, and Fisher’s exact test. Results: Of 41 medulloblastomas, 32 cases were classic type (78.05%), 6 cases were large cell/anaplastic variant (14.63%), and 3 cases were desmoplastic variant (7.32%). This study showed significantly increased Ki-67 indices in the large cell/ anaplastic variant compared to either classic medulloblastoma or desmoplastic/nodular variant (p

Abstract Background In vitro studies showed that the aryl hydrocarbon receptor (AHR) contributed to the development of cutaneous squamous cell carcinomas, but supporting clinical data are lacking. Methods Immunohistochemical analysis was used to detect the expression of AHR, CYP1A1, EGFR, and Ki-67 in 10 actinic keratosis (AK) cases, 10 Bowen disease (BD) cases, 20 cutaneous squamous cell carcinoma (cSCC) cases and 20 normal skin samples. H-scores were used to assess the immunoreactivity. Results Weak positive AHR immunoreactivity was found in all normal skin samples, while strong positive AHR immunoreactivity was found in atypical squamous proliferation (AK, BD and cSCC) cases. H-scores and the rate of strong immunostaining of the atypical squamous proliferation cases were higher than those of normal controls (p 0.05). The H-score of AHR was positively correlated with EGFR expression (r = 0.54, p

Hypertensive heart disease with biventricular cardiac failure is not common in clinical practice. This diagnosis requires an extensive diagnostic search. We present the clinical case of the male patient of 38 aged. He was admitted to the clinic with heart failure 3-4 NYHA class. EchoCG revealed symmetric hypertrophy of the left ventricle up to 18 mm without its dilatation, a decrease in ejection fraction up to 42%, restrictive hemodynamics, overload of the right chambers, severe pulmonary hypertension (60 mm Hg). The clinical status included persistent arterial hypertension (180-220 and 120-150 mm Hg), effusion in both pleural cavities and pericardium, ascites, renal failure. During examination (multispiral computed tomography, magnetic resonance imaging, scintigraphy with 131I-MIBG), bladder paraganglioma was diagnosed (normatenafrin 1468 μg/day). The resection of the tumor was performed, according to immunohistochemical research – neuroendocrine carcinoma, G1. After 3 months a partial regression of hypertension and cardiac failure was observed with the preservation of a high level of creatinine. The criteria and differential diagnosis of the hypertensive heart disease and the syndrome of primary myocardial hypertrophy, diagnostics of the urinary bladder paraganglioma, complex mechanisms of myocardial damage within the pheochromocytoma and its prognosis are discussed.

Ductus deferens plays an important role in sperm transport and participates in the preservation of structure, maturation, and viability of sperm. In this study, we have immunohistochemically examined the ductus deferens in the goat. For immunohistochemical study the following monoclonal antibodies were used: cytokeratin 18, α-smooth muscle actin (α-SMA), vimentin and elastin. Morphologically, three distinct layers were identified in the goat ductus deferens — tunica mucosa, tunica muscularis and tunica adventitia. The epithelium of the mucosa was intensely stained with cytokeratin 18 (CK 18). The fibroblasts in the lamina propria and blood capillaries in the muscle layer showed positive reaction for vimentin. A positive reaction for α-SMA was observed in the smooth muscle cells of the tunica muscularis in the internal, middle and outer sublayers. An intense positive reaction for α-SMA was observed in the wall of the blood vessels. Elastic fibers in the form of a loose meshwork were present in all three layers. The high density of elastic fibers were found in the tunica adventitia.

Objectives: immunohistochemical study of the expression of molecular and biological markers (p53, bcl-2 and ki-67) in esophageal tumors of various stages and grades, and evaluation of the markers in the disease prognosis. Material and methods: the study included 30 patients of a retrospective group with stage II-III squamous cell carcinoma of the esophagus. Immunohistochemical study of paraffi n sections was performed using primary mouse monoclonal antibodies against p53, bcl-2 and ki67, and Reveal Polyvalent HRP-DAB Detection System. Results: diff erences in the rates and expression of molecular and biological markers (p53, bcl-2 and ki-67), controlling apoptosis and proliferation, depended on the tumor stage and grade. Conclusions: fdvanced cancer of the esophagus demonstrated an increase in rates and expression of p53+ and ki-67, as well as in the proliferative activity of tumor cells. Bcl-2 expression was more frequent and intensive in stage II tumors, compared to stage III. Esophageal tumors of higher grades were characterized with higher rates and expression of p53 and ki-67, and conversely for the bcl-2 expression. Th e revealed diff erences can be used in the disease prognosis.

Aim/Background: Ovarian I/R is a popular gynecological emergency, complicating ovarian torsion. TTS, reported to have many therapeutic effects along with being an antioxidant, anti- inflammatory and anti-apoptotic agent. The aim of this study was to estimate the probable protective role of Tribulus terrestris Saponin (TTS) in recovering the damaging effects of ischemia-reperfusion (I/R) in the female rats' ovarian tissue. Materials and Methods: TTS was treated to female rats in presence or absence of ovarian I/R. Results: I/R caused ovarian damage, represented by deformity in normal ovarian histological structure, with a significant oxidative and nitrosative stress along with obvious inflammatory damage. Pretreatment with TTS significantly reversed the I/R induced ovarian toxic effects. TTS may have valuable ovarian protective effects against ovarian I/R injury. Conclusion: TTS protection is given via antioxidant, anti-nitrosative, anti-inflammatory and anti-apoptotic mechanisms with advancement of vascular angiogenesis and pituitary-gonadal axis up regulation. [ABSTRACT FROM AUTHOR]

The forensic examination of a gunshot wound is considered to be one of the most complex kinds of forensic examinations. Currently, the gunshot injuries are often caused by grave crimes associated with the use of hand and often non-typical fire arms for military actions and criminal purposes. The forensic examination results of the gunshot injuries make it possible to answer the questions concerning determination of distance and sequence of shots, formation of wound, time limitation, lifetime nature, character and severity of bodily injuries, as well as identification of causes of death. To expand diagnostic opportunities of the histologic study, the immunohistochemical and semi-quantitative methods are used as they allow for identifying in the tissues the substances that cannot be identified by standard study methods, as well as objectifying the results obtained. This article provides the clinical and anatomical characteristics of the gunshot injuries. [ABSTRACT FROM AUTHOR]

Background: Mechanoreceptor is a subtype of somatosensory receptor. It conveys extracellular stimuli through intracellular signal conduction via mechanically gated ion channel. It conveys not only kinetic stimuli but also pressure, stretching, touch, and even sound wave. Few studies have determined whether mechanoreceptors are present in Achilles tendon allografts used during remnant-preserving posterior cruciate ligament (PCL) reconstruction (PCLR). Purpose/Hypothesis: The purpose was to investigate whether mechanoreceptors are present in remnant tissues of the PCL and allograft tissues after PCLR. It was hypothesized that mechanoreceptors may be present in the remnant PCL tissue of the patients who underwent remnant PCLR technique. Study Design: Controlled laboratory study. Methods: Tissue samples were obtained from 14 participants who had undergone PCLR by means of Achilles tendon allografts (PCLR group) and from 4 healthy controls (control group). Among the PCLR group, 12 patients had undergone a remnant PCLR technique and the remaining 2 patients had undergone a nonremnant PCLR technique. In the PCLR group, we obtained samples during second-look arthroscopy or total knee arthroplasty after PCLR. In the control group, 4 biopsy specimens of normal PCL tissues were obtained from patients who had undergone other arthroscopic procedures. To check the presence of mechanoreceptors, immunohistochemical studies were performed on all biopsy specimens to identify neuronal and neurocytic markers by using monoclonal antibodies against glial fibrillary acidic protein, neuron-specific enolase, neurofilament, and S-100 protein. Only 1 of these markers needed to be positive to prove the presence of mechanoreceptors. Results: Neural tissue analogs, confirmed to be mechanoreceptors with monoclonal antibodies by the Ultraview DAB detection kit, were found in all specimens obtained from the control group. Mechanoreceptors were not found in the allograft specimens. However, remnant PCL tissues were found to have mechanoreceptors in 11 of 12 samples (91.7%). Conclusion: The results demonstrate that Achilles tendon allografts lack mechanoreceptors. This study can be used as histological evidence to support the advantage of remnant-preserving techniques for PCLR because they preserve proprioception. Clinical Relevance: To preserve proprioception, which leads to better functional outcome, using the remnant technique is a better procedure for PCL reconstruction. [ABSTRACT FROM AUTHOR]

Background: The results of immunohistochemical (IHC) assessment in breast cancer may determine not only the outcome, but also the main directions of antitumor treatment.Aim: To study the results of IHC diagnosis of breast cancer in the Grodno region in 2010 to 2015, to determine the frequency of the BRCA1 gene mutations in triple-negative breast cancer.Materials and methods: 2008 cases of estrogen receptor and/or progesterone receptor positive and 2445 cases of HER2/neu expressing breast cancer were extracted from the database and IHC laboratory journals of the Grodno Regional Clinical Bureau for Pathological Anatomy. Standard DAKO kits (Denmark) were used for IHC. Molecular genetic studies of DNA samples for the presence of the BRCA genes mutations were done by polymerase chain reaction in 449 women with breast cancer. BRCA1 mutation was assessed in 39 cases of triple-negative breast cancer.Results: HER2/neu overexpression (3+) was found in 25.5% (622/2445) of all breast cancer cases, whereas of estrogen receptor and progesterone receptor positive tumors in 50.05% (1105/2008) of cases. Triple negative breast cancer was diagnosed in 19.8% (398/2008) of cases, and the mean age of the patients at the diagnosis was 56.2 years. The BRCA1 gene mutations were identified in 5 of 39 (12.8%) cases of triple negative breast cancer, which is significantly more often than in women with breast cancer without consideration of their hereditary predisposition (17/449, or 3.8%; χ2 = 4.87, p = 0.0274). Histological examination showed that among the tumors with the BRCA1 mutations, there were 3 cases with invasive ductal cancer (one G2 and two G3), one with medullary and one with undifferentiated G3 cancer. One patient had a metachronous bilateral lesion.Conclusion: In the region of Grodno, 50% of breast cancer patients would need hormonal therapy, 25% would need treatment with trastuzumab, and 20% with cytostatic agents. The prevalence of the BRCA1 mutation in triple negative breast cancer is higher compared to that in breast cancer patients without consideration of their hereditary predisposition.

The purpose of the study was to systematize the data available in the modern literature on the diagnosis and treatment of metastatic melanoma without clinically evident primary tumor. Materials and methods. The results of laboratory-instrumental diagnostics, surgical and drug treatment presented in randomized clinical trials, published over the past 10 years in Medline, Embase and the Cochrane Library were analyzed. Results. Despite continuous improvement in imaging techniques, melanoma accounts for up to 12.6 % of all cases of metastatic cancer with an unknown primary site. Metastatic melanoma without clinical evidence of primary tumor accounts for approximately 1% to 8% of all melanoma cases. Conclusion. Metastatic melanoma without clinically evident primary tumor has not been extensively studied. Until now, only a few reports on metastatic melanoma without clinically evident primary tumor have been available. Therefore, further prospective studies of clinical course and optimization of diagnosis and treatment of patients with metastatic melanoma without clinically evident primary tumor are needed.

Abstract Background CUL4A has been known for its oncogenic properties in various human cancers. However, its role in intrahepatic cholangiocarcinoma (iCCA) has not been explored. Methods We retrospectively investigated 105 iCCA cases from a single medical institution. Tissue microarrays were used for immunohistochemical analysis of CUL4A expression. CUL4A expression vectors were introduced in cell lines. Cell migration and invasion assays were used to compare the mobility potential of iCCA cells under basal conditions and after manipulation. Then we evaluated the effects of CUL4A on the cell growth by proliferation assay, and further checked the susceptibility to cisplatin in iCCA cells with or without CUL4A overexpression. Results CUL4A overexpression was detected in 34 cases (32.4%). Patients with CUL4A-overexpressing tumors exhibited shortened disease-free survival (mean, 27.7 versus 90.4 months; P = 0.011). In the multivariate analysis model, CUL4A overexpression was shown to be an independent unfavorable predictor for disease-free survival (P = 0.045). Moreover, stably transfected CUL4A-overexpressing iCCA cell lines displayed an increased mobility potential and enhanced cell growth without impact on susceptibility to cisplatin. Conclusions Our data demonstrate that overexpression of CUL4A plays an oncogenic role in iCCA and adversely affects disease-free survival. Thus, it may prove to be a powerful prognostic factor and a potential therapeutic target.

Soliterfibröz tümörler SFT , genellikle plevra yerleşimli, nadir görülen spindle hücreli neoplazmlardır. Fakat bu tümörler ekstraplevral bölgelerde de nadir olarak görülebilirler. Ürogenital lokalizasyon ise oldukça nadirdir. Biz, ürogenital yerleşimli 2 olgu sunacağız. İlk olgumuz, 33yaşında erkek hastada ürogenital sistemde mesane yerleşimli, ikinci olgumuz ise 49 yaşında bayan hastada böbrekte perirenal yağ doku yerleşimlidir. Her iki olguda da tümör iyi sınırlı olup, spindle hücrelerden oluşmakta idi. Bu tümörler immünhistokimyasal olarak CD-34, BCL-2 ve CD-99 ile pozitif, sitokeratin, CD-117, S-100 ve kas markerları ile negatif ekspresyon göstermekte idi. %90 olgu benign seyirli olup, immünhistokimyasal çalışmalar tanıda anahtar rol oynamaktadır

Topicality: Today, laryngeal cancer occupies an important place in the structure of tumors of the head and neck. The survival rate of patients with laryngeal cancer remains unchanged for a longtime. One of the main mechanisms of tumor growth and metastasis is invasion into the surrounding tissues, followed by the expansion of tumor cells. This process is regulated by a system of enzymes - matrix metalloproteinases (MMP) and their inhibitors - tissue inhibitors of matrix metalloproteinases (TIMP). Aim: To study the in formativeness of immunohistochemical study and determining of the expression of molecular markers MMP-1; MMP-9; TIMR-1 and TIMR-2 in patients with laryngeal cancer, to determine the possibility of predicting regional metastases and recurrences. Materials and methods: 70 patients with laryngeal cancer of III-IV stages (T3-4N0-3M0) and II clinical group were understudy. Of these, 39 patients from the main group had regional metastases of laryngeal cancer, in 31 patients of the comparison group regional metastases were not detected. The age of patients ranged from 33 to 74 years. The average age of patients was 61.9 years. Male patients made up an absolute majority of 99% (No=69). All patients were histologically diagnosed with squamous cell carcinoma. Monoclonal antibodies to MMP-1 were used as primary molecular markers; MMP-9 as well as TIMP-1 and TIMP-2 (Termo Scientific, USA). In evaluating IHC reactions with the marker, the expression was calculated as the percentage of cells with a cytoplasmic reaction at increased (× 400) in 4 gradations: (1+) - <10%, (2+) - from 10% to 50%, (3+) - from 51% to 100%. The expression of TIMP1 and TIMP2 was assessed as negative with a percentage of stained cells <30%, "-" - 0, and > 30% as "+" - 1. Results: Statistically significant difference in the expression of MMP-1 and MMP-9 between the groups in the presence of metastases (p <0.01) was revealed: patients with metastases were more likely to have moderate (++) and high (+++) expression of biomarkers, and rarely - low expression (+). Positive TIMP-2 was significantly more common among patients with metastases (p = 0.05). MMP-1 and TIMP-2 were significant predictors of metastasis (Table 2). Increase in the expression of MMP-1 by one category increased the chances of metastasis almost by 5 times (OR = 4.75 (95% CI 1.77 - 14.75)). In positive TIMP-2, the chances of tumor metastasis were by 2.7 times higher (95% CI 1.01 - 7.89) than with negative TIMP-2. The difference between the ROC curves for MMP-1 and TIMP-2 was not statistically significant (p = 0.30). Expression of any of the indicators did not allow predicting the recurrence of the disease. The inclusion of age in the regression model did not have a positive effect on the prognostic ability of predictors. Conclusion: Expression rates of molecular markers MMP-1, MMP-9, TIMP-1 and TIMP-2 were statistically associated with the degree of tumor differentiation (p <0.05). According to the results of statistical data processing, MMP-1 and TIMP-2 were significant predictors of metastasis (p <0.01). Increase in the expression of MMP-1 to a positive or high level increased the chances of metastasis by 5 times (OR = 4 .75 (95% CI 1 .77 - 14.75). In positive TIMP-2 the chances of tumor metastasis were by 2.7 times higher) (95% CI 1.01 -7.89) than in the negative. [ABSTRACT FROM AUTHOR]

Background: Laryngeal cancer is a common localization of squamous cell carcinoma of the head and neck. The main factor influencing the survival of patients is the presence of regional metastases. The malignant degeneration of a cell is always accompanied by disruption of the cell cycle, in particular a sharp increase in proliferative activity. The molecular marker Ki-67 is used to investigate the proliferative activity of tumor cells. Aim of the study: To study the informative content of immunohistochemical investigation and to determine the expression of the molecular marker Ki-67 in patients with laryngeal cancer, prior to the prediction of regional metastasis and relapse. Materials and methods: 70 patients with cancer, stage III-IV (T3-4N0-3M0) clinical group II were under observation. Of these, 39 patients from the main group were with regional laryngeal cancer metastases, and 31 patients in the comparison group - without revealed regional metastases. Patients' age ranged from 33 to 74 years. The average age was 61.9 years. Male patients made up the absolute majority of 99% No = 69. All patients were histologically diagnosed with squamous cell carcinoma. Monoclonal antibodies to Ki67 (TermoScientific, USA) were used as the primary molecular markers. The proliferation index (PI) was rated as low in the range of 0-30% and as high in more than 30% of positive cells with an intranuclear label. Results: The study of molecular markers Ki-67 showed its expression at 69 [60.2; 77.5]% (Me [25%; 75%]) for the squamous cell laryngeal cancer group, without metastases - 60 [29; 70.5]%, for the group with metastases - 72 [67; 80]% (P <0.001). In statistical data processing, the AUC value (0.777) was set for Ki-67 for metastasis and showed an increased degree of expression for laryngeal cancer metastasis. Ki-67 has a good diagnostic value and can be used as an additional method for predicting regional laryngeal cancer metastases. However the practical use of this marker as a prognostic one for determining the volume of surgery on the lymphatic structures of the neck requires further investigation. It should be noted that this study did not reveal the link of Ki-67 AUC (0.588) with the degree of differentiation of laryngeal cancer and its recurrence, but more in-depth study of molecular markers in the future may reveal other patterns of tumor growth and be used in the prognosis and personalization of treatment. Conclusion: Expression of Ki-67 allowed to accurately predict tumor metastasis. A 1% increase in Ki-67 expression resulted in an 8.3% increase in the chance of tumor metastasis (95% CI - 1.043-1.142), and the age dependence on metastasis is not reliable. Determination of expression of Ki-67 does not accurately predict the possibility of recurrence of laryngeal cancer (p=0.27; AUC (95% CI) - 0.588 (0.414-0.763)) herewith age dependence of chance of a recurrence was not revealed. [ABSTRACT FROM AUTHOR]

Purpose: Uterine angioleiomyoma is a rare type of leiomyoma variant and there are few cases reported in the literature. The definitive diagnosis is usually obtained only after the histopathologic examination because there are no specific imaging criteria for this disease. The objective of this article is to review published cases about this clinical condition.Methods: We report a case of giant angioleiomyoma superinfected by S. agalactiae with the development of latero-cervical distant metastasis in a premenopausal woman. Firstly, the case herein reported was orientated as an endometrial stroma sarcoma in the peri-operative histologic examination by frozen sections. It was treated with laparotomic total hysterectomy, bilateral salpingo-oophorectomy, inframesocolic omentectomy and pelvic and paraaortic lymph node dissection. Postoperative definitive anatomopathological analyses using a proper immunohistochemical panel revealed a case of uterine angioleiomyoma. We also review other case reports published about this clinical condition.Results: We present the first case reported in the literature, in our knowledge, of a giant angioleiomyoma superinfected by S. agalactiae with the development of distant septic metastases. Immunohistochemistry permitted the definitive diagnosis of angioleiomyoma. Treatments previously reported are hysterectomy or tumor resection and any patient recurred.Conclusions: The definitive diagnosis is usually obtained after the definitive histopathologic examination since the use of immunohistochemical study has an important role in this regard. Complete surgical removal of the lesion is the treatment of choice, with no recurrent cases reported to date. [ABSTRACT FROM AUTHOR]

Background: Fatty acid synthase (FAS) is a valuable lipid enzyme involved in lipid biosynthesis and suggested to contribute in tumor carcinogenesis. Vascular endothelial growth factor (VEGF) is considered a serious angiogenic growth factor in the angiogenic pathway which is a very important in tumor growth and metastasis. Thus, inhibition of lipid biosynthesis and tumor angiogenesis can be new goals for colorectal cancer (CRC) treatment. Aim of the Work: The assessment of the expression of FAS and VEGF protein and the relationship between them in CRC with the clinicopathological parameters. Methods: The present retrospective study included 63 paraffin blocks previously diagnosed as primary cases of CRC. The slides were subjected to FAS and VEGF immunohistochemical staining using a streptavidin-biotin-peroxidase. The relationships among FAS and VEGF expression and clinicopathological parameters were statistically analyzed. Results: The expression rate of FAS was 81% and VEGF was 84.1% in the studied cases. FAS expression was significantly associated with histopathological type (p = 0.02) and grade (p = 0.04), and highly associated with lymph node metastasis and stage (p < 0.001).VEGF was significantly associated with histopathological type (p = 0.01) and tumor depth (p = 0.02); highly associated with grade, lymph node metastasis, and stage (p < 0.001). There was a positive association between FAS and VEGF expression in CRC (p < 0.001). Conclusion: FAS and VEGF showed a highly significant expression in the studied primary CRC cases. A significant association was observed between their expressions, suggesting the involvement of FAS in tumor angiogenesis. So they constitute potential targets in cancer prevention and treatment and make FAS an attractive antiangiogenic target. [ABSTRACT FROM AUTHOR]

Pesticides are responsible for many occupational health hazards among farmers in developing countries. Chlorpyrifos (CPF) is one of the broad-spectrum organophosphorus (OP) insecticides used for agricultural, domestic and industrial purposes. The present study was designed to examine the effects of CPF on cardiac muscles and to evaluate the possible protective role of crocin using biochemical and histological methods with the intention to recognize the molecular tools of its probable cardioprotective effects. Thirty-six adult male albino rats were used in this study and were divided into 4 equal groups (9 rats each): negative control group, positive control group, CPF treated group and CPF & crocin treated group. The heart was removed for histological and immunohistochemical studies. Stained sections of cardiac muscle fibers of group III with H&E revealed remarkable histological changes in the form of disorganization of the fibers with increase in the interstitial spaces between these fibers. Congested dilated blood capillaries could be observed with extravasation of the red blood cells leading to interstitial hemorrhage. Focal areas of mononuclear cellular infiltration could be seen in the interstitial tissue. A number of cardiac fibers achieved pale acidophilic vacuolated sarcoplasm while others achieved dark homogenous acidophilic sarcoplasm. Some nuclei were peripherally situated and pyknotic while others were centrally situated and encircled with halos. Apparently increased masses of collagen fibers among the cardiac muscle fibers and around the congested dilated blood vessels with the presence of focal parts of extensive collagen fiber deposition were noticed in Mallory-stained sections of group III. Strong positive immunoreactions in the endomysium and perimysium of the cardiac fibers, along with the walls of blood capillaries and in interstitial cells, could be detected in immunohistochemical staining sections of group III with vimentin antibody. Immunoreactivity to caspase 3 was higher in the sarcoplasm of the cardiac fibers of group III compared to that of control group. A highly significant decrease in the cardiac level of SOD and CAT; however, a highly significant increase in MDA level was noted between the control groups and CPF treated group. Additionally, there was a significant improvement of the chemical and histological representations of group IV, and these improvement pictures were toward the normal. The study concludes that crocin can alleviate the toxic effect of chlorpyrifos caused by oxidative stress on cardiac muscle. [ABSTRACT FROM AUTHOR]

Loading of the upper eyelid with palpebral implants made of noble metals is the modern standard of surgical treatment for paralytic lagophthalmos, and is aimed at increasing the mobility of the upper eyelid and normalizing involuntary blinking movements. This review presents the results of morphological studies, including immunohistochemical studies, reflecting the features of biointegration of palpebral implants in uncomplicated and complicated course of the postoperative period, and describes the modern understanding of the causes and immunopathological processes underlying the development of nonspecific inflammatory response, which is one of the most serious complications that often becomes an indication for implant removal.

Objective: Aim: To evaluate the state of the gingival stromal elements in the portion of the third molars requiring extraction of these teeth due to orthodontic indications considering the stage of tooth germ formation., Patients and Methods: Materials and Methods: The surgery to extract third molars due to orthodontic indications was performed on 95 children aged 11 to 18 years. The three groups of observation were isolated according to clinical-radiological signs: І (n=30) - children aged 11-13 years; ІІ (n=35) - children aged 13-16 years, and ІІІ (n=30) - children aged 16-18 years. During surgery, the samples of gums were taken from the adjacent areas for examination. The samples were fixed, dehydrated, paraffinized for further histological processing. Immunohistochemical methods were used according to the protocols supplied by a producer. In particular, by means of immunohistochemical method, Ki-67, CD-34 antigens and vimentin with primary antibodies against them were determined. The primary antibodies were visualized by the polymeric visualization system with diaminobenzidine giving a brown color to the places of location of the antigens examined. The data obtained were statistically processed., Results: Results: The results of the study showed that specific gravity of the vascular bed in the gingival papillary layer of children was the most variable. It ranges from (12,7±0,09) % at the stage of "D" root formation to (54,8±0,17) % at the "H" stage. Lower concentrations of CD-34 antigens and vimentin are found in the endotheliocytes of children aged 13-16 and 16-18 years, compared to the children aged 11-13 years (p<0,05). No changes were found in the specific volume of the blood vessels, CD-34 antigens and vimentin in the reticular gingival layer of children from the groups of observation., Conclusion: Conclusions: Therefore, the conducted histological and immunohistochemical study of the connective gingival tissues in the portion of the third molars in children enables to draw a conclusion that in the process of formation of the root of this tooth a number of changes occur in the gingival stroma. They include an increase of the blood flow volume in the papillary gingival layer on the background of a decreased concentration of CD-34 genes and vimentin, a longer stage of development of the third molar root. The specific volume of the islets of neoangiogenesis of the papillary gingival layer is the largest in children aged 13-16 years.