Proliferation Processes Research Articles

Circadian fluctuations of endothelial nitric oxide synthase activity in females with rheumatoid arthritis: a pilot study.

Rheumatoid arthritis (RA) is a disease associated with circadian disorders of steroid hormones or cytokine secretion which induce inflammatory, destructive and proliferative processes in the synovial joints. Angiogenesis plays an important role in RA, but circadian rhythms of the angiogenic mediator production, especially endothelial nitric oxide synthase (NOS3), are still unclear. NOS3 takes part in regulation of endothelial functions, inflammation, and bone remodeling process. Studying circadian rhythms of NOS3 production in RA patients will make an improvement in understanding the angiogenic-inflammatory pathways relevant to rheumatic diseases. The aim of the study was to test the hypothesis of a diurnal variation in circulating levels of NOS3 in RA patients. A cross-sectional monocentric pilot study of circadian variability of endothelial nitric oxide synthase in a Ukrainian population was conducted between March and July 2017. We examined 36 RA patients (100% women) and 34 age-matched healthy women without joint diseases and autoimmune diseases (control). Blood samples were collected four times per day (at 08:00; 14:00; 20:00 and 02:00) for two consecutive days. Serum NOS3 concentration was measured by ELISA (Cloud-Clone Corp kit). The study was conducted in compliance with bioethical standards. The SPSS22 software package was used for statistical processing of the results. A diurnal variation in circulating levels of NOS3 in healthy women was established, with peak values appearing in the evening and acrophase at 20:00, and low values in the morning, with batiphase at 08:00. In patients with RA serum, NOS3 levels were substantially decreased throughout the day compared to the control. In RA patients, a diurnal variation in circulating levels of NOS3 was also established. However, the variability of NOS3 production was higher in RA patients than in the control group. For example, in RA patients the difference between morning/evening values of NOS3 was 1.3 times higher (p < 0.05) than in the control. Negative correlations were found between the morning NOS3 levels and RA activity markers such as DAS28 and the number of tender and swollen joints. The diurnal variation in circulating levels of NOS3 in women with RA as well as in healthy women was found. However, in RA patients, a decrease in NOS3 production was observed, especially in the morning, which was associated with an increase in the disease activity. Thus, the circadian rhythm of circulating NOS3 can be opposite to the circadian rhythm of secretion of main inflammatory regulators in RA.

Feasibility of MRI in diagnosis and characterization of intra-articular synovial masses and mass-like lesions

BackgroundClassifications of intra-articular masses are infectious granulomatous diseases, non-infectious synovial proliferative processes (synovial chondromatosis, lipoma arborescens, rheumatoid arthritis, pigmented villonodular synovitis [PVNS]), vascular malformations, deposition disorders, neoplastic, and miscellaneous conditions. The aim of this study is to correlate the results of MRI with arthroscopy in characterization of different varieties of intra-articular synovial masses and mass-like lesions. This observational prospective study was conducted between February 2018 and August 2019. We screened 1000 routine musculoskeletal MRI examination during this period, 32 of which showed intra-articular synovial masses/mass-like lesions. The selected 32 patients (20 males and 12 females) have a mean age of 49.20 ± 2.0 years; all presented with joint swelling, pain, or difficulty of movement according to the joint affected. All patients underwent arthroscopy for histopathological correlation.ResultsThe final diagnosis was synovial chondromatosis in 14 patients (43.8%), PVNS in ten patients (31.3%), and lipoma arborescens in five patients (15.6%). Synovial chondrosarcoma, synovial hematoma, and synovial ganglion cyst each in one patient (3.1%). The concordance of MRI to arthroscopy was 96.6% accuracy, 91.7% sensitivity, 99% specificity, 52.3% PPV, and 99.9% NPV.ConclusionGood correlation was observed between MRI and arthroscopy in diagnosis of intra-articular synovial masses/mass-like lesions.

Імуногістохімічна оцінка проліферативно-апоптотичних процесів в ембріональному раку яєчка

Імуногістохімічна оцінка проліферативно-апоптотичних процесів в ембріональному раку яєчка

Signs of proliferative process after laser treatment of advanced glaucoma

To evaluate the condition of SFOT in dynamics with Visante OCT after one-step combined laser technique consisting of modified selective laser activation of the trabecula (MSLAT) and DGP in advanced POAG patients with normalized IOP who have pronounced pigmentation of the trabecular meshwork and stage II pseudoexfoliation syndrome (PES). OCT scans of 117 patients (117 eyes) were analyzed before laser treatments and after 1, 3, 6, 12 and 24 months. The study included 62 patients (62 eyes) comprising the main group who underwent MSLAT + DGP, and the control group consisting of 55 patients (55 eyes) who only underwent DGP. Visante OCT scans revealed that parameters of the filtration bleb (FB) and intrascleral cavity (ISC) in the main study group were more stable than in the control group during the whole follow-up. In the main study group there were less incorporations in the ISC and they had lower optical density, compared with the control group where there were denser incorporations in the ISC which gradually increased in count. According to Visante OCT, the growing count and the increase in density of incorporations in the ISC can be defined as adverse signs of an active proliferative process in SFOT. A one-step MSLAT with DGP help achieve both a long-lasting hypotensive effect, and decrease of active proliferative process signs in SFOT.

Differential microRNA-21 and microRNA-221 Upregulation in the Biventricular Failing Heart Reveals Distinct Stress Responses of Right Versus Left Ventricular Fibroblasts.

The failing right ventricle (RV) does not respond like the left ventricle (LV) to guideline-directed medical therapy of heart failure, perhaps due to interventricular differences in their molecular pathophysiology. Using the canine tachypacing-induced biventricular heart failure (HF) model, we tested the hypothesis that interventricular differences in microRNAs (miRs) expression distinguish failing RV from failing LV. Severe RV dysfunction was indicated by elevated end-diastolic pressure (11.3±2.5 versus 5.7±2.0 mm Hg; P<0.0001) and diminished fractional area change (24.9±7.1 versus 48.0±3.6%; P<0.0001) relative to prepacing baselines. Microarray analysis of ventricular tissue revealed that miR-21 and miR-221, 2 activators of profibrotic and proliferative processes, increased the most, at 4- and 2-fold, respectively, in RV-HF versus RV-Control. Neither miR-21 or miR-221 was statistically significantly different in LV-HF versus LV-Control. These changes were accompanied by more extensive fibrosis in RV-HF than LV-HF. To test whether miR-21 and miR-221 upregulation is specific to RV cellular response to mechanical and hormonal stimuli associated with HF, we subjected fibroblasts and cardiomyocytes isolated from normal canine RV and LV to cyclic overstretch and aldosterone. These 2 stressors markedly upregulated miR-21 and miR-221 in RV fibroblasts but not in LV fibroblasts nor cardiomyocytes of either ventricle. Furthermore, miR-21/221 knockdown significantly attenuated RV but not LV fibroblast proliferation. We identified a novel, biological difference between RV and LV fibroblasts that might underlie distinctions in pathological remodeling of the RV in biventricular HF.

The effect of red light (660 nm) on proliferative activity and growth reactions in seedlings of plants with contrast photoperiodic reaction

The results of a study of the effect of red light irradiation (660 nm) on the proliferative activity of root meristems and growth reactions of plant seedlings with contrast photoperiodic reactions are presented in this paper. Plants of the family Fabaceae contrasting in the photoperiodic reaction were used as plant material: long-day plants (LDP) of peas (Pisum sativum L.) of the Metsenat variety and short-day plants (SDP) of soybean (Glycine max (L.) Merr.) of the Korsak variety. Phytochromes were activated by irradiating the aerial part of the experimental seedlings with monochromatic red light (RL) of 660 nm using an LED matrix for 30 minutes for 5 days. The proliferative activity of meristem cells was determined by analysis of the mitotic index (MI). The growth reaction was studied by linear growth indicators: the total length of the seedling, the length of the aerial part and roots, and the integral indicator of growth and biosynthetic processes – the accumulation of biomass. According to the results of the experiments, it was shown that the mitotic activity of root meristems under the influence of red light on the aerial part in seedlings of the LDP of pea Metsenat decreased slightly – by 8 %, and in the seedlings of the SDP of soybean Korsak increased significantly – by 47 %. The linear growth and accumulation of biomass in the aerial part under the action of RL irradiation in seedlings of pea of the Metsenat variety and soybean of the Korsak variety decreased, and this effect was more pronounced in soybean than in pea. During irradiation of RL the linear root growth and their biomass accumulation in seedlings of LDP pea decreased slightly, while at the same time, these processes in the roots of soybean SDP seedlings were significantly stimulated. Under the influence of RL in pea seedlings, the growth rate did not change in the length of the aerial part, but in the roots increased, while the rate of biomass accumulation by them decreased. In soybean seedlings during RL irradiation, the growth rate of both the aerial part and the roots decreased, the biomass accumulation rate by the aerial part increased, and by the roots – decreased. LDP of pea Metsenat and SDP of soybean Korsak variety differ in the nature of the reaction of growth processes in response to irradiation of RL. The activation of the phytochrome system in the aerial part causes changes in the proliferative activity and growth processes of the roots, which indicate a systemic response of the plant organism to the action of this factor. The relationship of the photoperiodic reaction of plants with the realization of phytochrome signal in the plant by activating or inhibiting the proliferative activity of root meristems and growth reactions is discussed.

ВОЗРАСТНЫЕ ОСОБЕННОСТИ МОРФОГЕНЕТИЧЕСКИХ СВОЙСТВ ЛИМФОИДНЫХ КЛЕТОК СЕЛЕЗЕНКИ

Aim. The aim of the study is to determine the features of the morphogenetic properties of the spleen lymphoid cells in animals of different age groups. Materials and research methods. In the experiments, a model of adoptive transfer of lymphoid cells of the spleen of nephrectomized animals from different age groups was used. The studies were carried out on male Wistar rats of mature (8-10 months, weighing 200-250 g) and old (19-22 months, weighing 400-500 g) age. Study groups: control group — model of adoptive transfer of splenocytes from mature animals to mature ones; second — experimental group: model of adaptive transfer of lymphoid cells from old — old animals; the third group — transplantation of lymphoid cells from old animals — to mature ones; the fourth group — transplantation of lymphoid cells from mature animals — to old ones. The morphogenetic properties of the spleen cells of nephrectomized animals from different age groups were studied 19 hours after unilateral nephrectomy (donor interval). The resulting suspension was injected intravenously into recipients at 400×10³ cells per 0.2 kg of animal weight. 8 hours before slaughter, the animals received a single intraperitoneal dose of 2 mg/kg of vinblastine. Recipients were sacrificed 40, 48 and 56 hours after splenocyte transfer. Research results. Transplantation of splenocytes obtained from old donors to old recipients did not reveal any stimulation of proliferative processes in the epithelium of the kidney tubules of the latter. The transfer of the same splenocytes to mature donors is accompanied by the manifestation of their morphogenetic function. At the same time, the activity of proliferative processes in the kidneys of the recipients was not less pronounced than in the control group.

THE EFFECT OF PHOTODYNAMIC THERAPY AND PLATELET-ENRICHED PLASMA ON THE HEALING OF SKIN RADIATION ULCERS INFECTED BY STAPHYLOCOCCUS AUREUS.

To determine in experiment the quality of healing of skin radiation ulcers infected with Staphylococcusaureus (S. aureus) under the photodynamic therapy (PDT) administration and the use of platelet-rich plasma (PRP). The experiment was performed on 95 male WAG rats of 6 months of age, which were divided into three groups. Group 1 included animals in whom a skin radiation ulcers in the thigh area was simulated, followed by application of a 0.2 ml suspension of reference strain of S. aureus to its surface on the 7th day after irradiation. Group 2 included animals with S. aureus-infected skin radiation ulcers, in whom the PET was administered aday after infection contamination. Group 3 included animals with S. aureus-infected skin radiation ulcers, in whomthe PDT was administered a day after infection in the morning, and the PRP was manifold injected in periwound areain the afternoon. The skin with underlying soft tissues from the area of radiation damage were the material for morphological examination. The hematoxylin and eosin, picrofuxin according to van Gizon, Mallory staining wereapplied to micropreparations. A morphometric study was conducted. In animals with skin radiation ulcers, in whom the PDT was administered upon infection with S. aureus(group 2), compared with animals with simulated infected skin radiation ulcers without treatment (group 1), Theactivation (i.e. accelerating) of the healing occurred for the period from the 14th to the 52nd day of experiment dueto the active processes of wound cleansing from necrotized tissues, less pronounced inflammatory changes in thelesion, and active of appearance and maturation of granulation tissue, less pronounced hemodynamic, ischemic andalternative disorders in the dermis, hypodermis, muscle tissue surrounding the wound cavity, activation of proliferative processes in epithelial layer localized in the marginal parts of the wound. Formation of pathological (hypertrophic or keloid) scar of the skin was the result of healing of skin radiation ulcer infected with S. aureus. In animalswith radiation ulcers infected with S. aureus, in the case of PDT and PRP (group 3) the regenerative process wasdirected not only at accelerating the rate of healing, but also on restoration of original structure of the lost parts ofthe skin compared with only PDT administration (group 2). Acceleration of the healing of the infected skin radiation ulcer in animals of groups 2 and 3 was due to similar processes. Photodynamic therapy activates and accelerates the healing process of skin radiation ulcers infectedwith S. aureus and leads to formation of a pathological scar (hypertrophic or keloid). Healing of the infected S. aureusradiation ulcers occurs more actively upon the photodynamic therapy administration in combination with multipleperiwound injections of the platelet-enriched plasma, compared with only photodynamic therapy administration,and finishes with an organotypic regeneration and almost complete skin recovery.

Prevalência e caracterização das lesões orais na Clínica de Estomatologia da Policlínica Piquet Carneiro – Estudo Retrospectivo de 12 anos

Objetivo: avaliar a prevalência dos principais tipos de lesões submetidas à biópsia e identificar o perfil dos pacientes atendidos no ambulatório de Estomatologia da Policlínica Piquet Carneiro (PPC/UERJ, Rio de Janeiro) no período compreendido entre 2000 e 2012. Material e Métodos: estudo transversal e retrospectivo em que prontuários de 2078 pacientes foram avaliados e dados referentes às doenças, idade, gênero, cor da pele e localização anatômica das lesões foram coletados e analisados de forma descritiva. Resultados: 69% dos pacientes (1441 casos) obtiveram o diagnóstico conclusivo através de exame histopatológico, ao passo que 31% (637 casos) obtiveram um laudo histopatológico descritivo. Dos casos com diagnóstico histopatológico conclusivo, 58% eram mulheres, 31% homens e em 11% o sexo não foi informado. A média de idade da população estudada foi de 50,63 anos e em 58% dos casos os pacientes eram leucodermas. O maior número de lesões foram as do grupo dos processos proliferativos não-neoplásicos, sendo a hiperplasia fibrosa inflamatória (30,1%) a mais prevalente. Conclusão: o perfil epidemiológico do paciente atendido no período estudado foi composto predominantemente por mulheres com mais de 50 anos de idade e a lesão oral mais prevalente foi a hiperplasia fibrosa inflamatória. Este estudo reforça a importância do papel da análise histopatológica como método auxiliar de diagnóstico e que possibilita a elaboração de estratégias específicas para prevenção e detecção precoce das doenças orais mais frequentes na população.

DERMAL NODULAR FASCIITIS AFFECTING THE FACE: DIFFERENTIAL DIAGNOSIS AND IMMUNOHISTOCHEMISTRY ANALYSIS

Nodular fasciitis (NF) is a benign/reactive myofibroblastic proliferative process with unknown etiology, which presents as a solitary, painless, fast-growth nodule, commonly located on the limbs and trunk; the head and neck region is affected between 10% and 20% of cases. Noteworthy, uncommon NF variants such as intravascular, intramuscular, cranial, ossifying, proliferative, and intradermal have been reported. A 64-year-old man was referred complaining of a painful swelling in the right side of the face for 3 months, which appeared after trauma. Extraoral examination revealed a nodular lesion measuring 4.5 × 4.0 × 3.0 cm. Radigraphic examination was unremarkable. Incisional biopsy results evidenced a benign spindle cell proliferation arranged in bundles, focally exhibiting storiform pattern, surrounded by myxoid stroma. Scattered lymphocytes and extravasated red blood cells were also present. Immunohistochemistry results showed vimentin and α–smooth muscle actin were strongly positive. We present a dermal NF, which should be differentiated from dermatofibroma, dermatofibrosarcoma protuberans, and atypical fibroxanthoma.

STUDY OF ORAL LESIONS BIOPSED AND DIAGNOSED IN STOMATOLOGY CLINIC OF THE UNIVERSITY DURING THE PERIOD FROM 2002 TO 2017

Our objective was to report the principal biopsied and diagnosed oral lesions in a stomatology clinic in a private university between 2002 and 2017. We have conducted a descriptive study in which the data from the histopathologic reports were analyzed on ExcelT and were compared to each other so as to analyze age, sex, type, and prevalence of lesions. Data from this study has been compared with data from other studies published between 2015 and 2017 dealing with the prevalence of oral lesions. We have also compared the relation between the diagnostic hypothesis (when informed by the dentist) and the definitive diagnosis (informed by the pathologist). We observed that a larger percentage coincided to each other, but 42.5% were observed to be contrary. The most incident lesion found on our results was fibrous hyperplasia, followed by the reaction lesion and nonneoplastic lesions. Gercica (2015), in her study, has also found that fibrous hyperplasia also appeared as the most recurrent lesion. Other studies have yielded fewer specific results, however, reporting the occurrence of nonneoplastic proliferative processes or soft-tissue reactive lesions. We have concluded from our analysis that fibrous hyperplasia was the main oral lesion diagnosed in patients of our clinic.

Immune profile of oil production enterprise employees

Introduction. The assessment of the immune profile of employees of the oil-producing enterprise, the formation of the immunological status of which is determined by the conditions of harmful production factors affecting their health.The aim of the study was to assess the state of cellular immunity in oil-producing enterprise employees (on the example of the Perm region).Materials and methods. 60 men working at the oil-producing enterprise of the Perm region were examined. In the observation group (n=30) were included surveyed male workers-operators of oil production, in the comparison group — surveyed male workers — representatives of the administrative apparatus. The state of cellular immunity was assessed by indicators of cellular regulation and apoptosis. Cell differentiation marker T-reg-CD4+CD127 -, expression level of Bcl–2, Bax, p53 proteins, TNFR receptors and AnnexinV-FITC+7AAD negative cells were determined by flow cytometry.Results. The comparative analysis with physiological norm indicators allowed to reveal reliable hyperproduction of membrane and intracellular factors of cellular immunity in oil production operators. Expression of regulatory marker CD127-, proteins Bax, Bcl–2 and p53, TNFR receptor content and AnnexinV-FITC+7AAD negative cells responsible for natural cell death (p&lt;0.05) was established. The indicators of the observation group differed significantly from those of the comparison group. There was a significant inhibition of expression of CD-marker CD127-and apoptic protein Bcl–2 by more than 10%, an increase in TNFR, AnnexinV-FITC+7AAD negative cells, protein Bax and p53 by 1.3, 1.6 and 1.2 times, respectively.Conclusions. The results of immunological screening allowed to establish an imbalance of cellular immunity in oil-producing enterprise workers — a deficiency of regulatory cells and a protein-controller of cell death with simultaneous excessive activation of cell reception, which later forms the phenomenon of cellular immunodeficiency. The high sensitivity of the membrane and cytoplasmic components of the immune profile allows them to be used as indicators of the health status of oil production operators, timely identify the development of regulatory imbalance of the immune system, early violations of cell-associated pathological processes (cellular immunodeficiency, autoimmune and proliferative processes), as well as timely and effective implementation of measures to prevent the development of production-related diseases working at oil production facilities.

Anti-Influenza Virus Activity of Adlay Tea Components.

Our previous study showed anti-influenza virus activity in adlay tea prepared from adlay seeds, naked barley seeds, soybean, and cassia seeds. In this study, we evaluated the anti-influenza virus activity of each component of this tea and analyzed their active ingredients. Each component was roasted and extracted in hot water; the extracts were tested for antiviral activity and their mechanisms of action were studied. All the tea components showed antiviral activity against the H1N1 and H3N2 influenza subtypes and against influenza B. The viral stages inhibited by the components were virus adsorption and replication in proliferative process, suggesting that the action mechanisms of the components might differ from those of oseltamivir acid. Of the tea components, soybean showed the strongest activity. Therefore, we analyzed its active ingredients by liquid chromatography quadruple time-of-flight mass spectrometry (LC/qTOF-MS) and daidzein and glycitein were detected as active ingredients. Here, anti-influenza virus action of glycitein was the first report.

Specifics of Hormonal Status in Combined Dishormonal Pathology of the Uterus and Mammary Glands in Reproductive Age

The combined dyshormonal pathology of the uterus and mammary glands represents a great danger to the health of a woman, as well as impairs the quality of life, reduces the reproductive capacity of a woman and leads to premature loss of reproductive function. Steroid hormones play a large role in the regulation of proliferative changes in the uterus and mammary glands. Regulation of target organs, uterus and mammary glands, due to the presence of common mechanisms associated with the presence of the receptor apparatus in the tissues of these organs to sex hormones. The general links of pathogenesis and the high frequency of combined pathology of the uterus and mammary glands are of interest to study not only isolated forms of proliferation, but also the development of a unified systematic approach to the study of this pathology. In recent times, there are opposing views on the role of hormonal dysfunction as a factor in proliferative processes. The management tactics of patients with pathological changes in the mammary gland in various gynecological diseases is an assessment of endocrine status, normalization of hormonal and metabolic disorders, especially when progesterone and cortisol are excreted, testosterone levels are increased, and hyperprolactinemia is affected. Special attention should be paid to patients with menstrual disorders, reproductive health disorders. We believe that the problem of the hyperproliferative processes of the uterus and mammary glands should not be considered only from the perspective of gynecological or mammological practice. This pathology is polymorphic and should have broad interdisciplinary connections with such disciplines as oncology, endocrinology, gastroenterology, psychiatry, therapy, pathomorphology, histology, obstetrics and gynecology. Only by studying all possible links of etiopathogenesis, by combining interdisciplinary communication, it is possible to effectively fight for the quality of patients with a combined pathology of the uterus and mammary glands. Family planning, prevention of unplanned pregnancy, timely implementation of maternity, prevention of miscarriage, the use of modern contraceptives, support for breastfeeding is also of high importance for the prevention of disorders and the preservation, extension of reproductive capabilities, and the prevention of combined dyshormonal pathology of the uterus and breast.

Large Granular Lymphocytic Leukemia Coexists with Clonal Hematopoiesis of Indeterminate Potential

Large granular lymphocytic leukemia (LGL) is a lymphoproliferative cytotoxic T cell (CTL) that typically presents in elderly population. The spectrum of the disease ranges from semi-reactive oligoclonal to clonal CTL expansion, and from silent to a chronic leukemia with para-neoplastic manifestation. However the description of the disease still preceded the new genetic landscape mapping techniques. In lieu of this, we analyzed the genetic landscape of LGL using a set of 33 genes. Interestingly, not only did the deeper analysis help with a better understanding of the complex CTL proliferative processes but indicated a suspected association with conditions such as clonal hematopoiesis of indeterminate potential (CHIP). Association of LGL with age related CH has been described in the past by us and others. Our results indicate that LGL is often associated with the presence of myeloid mutations, generally consistent with the most common typical CHIP mutations (DNMT3A, TET2, ASXL1). We then analyzed a set of 13 patients with coexistent MDS/LGL. This observation raises the question that LGL is, at least in some cases, a tumor surveillance response. All LGL patients were diagnosed using a stringent single center diagnostic criteria and at the time of diagnosis, were also checked for other conditions including MDS to prevent any risks of overlooked diagnoses. A previously well described diagnostic standard of &gt;3/5 positive criteria was used; (i) presence of large granular lymphocytes (&gt;500/μL, by differential counts from complete blood count) for &gt;6 months; (ii) abnormal cytotoxic T lymphocytes expressing CD2, CD56 and CD57 and lacking CD28; (iii) preferential usage of a TCR Vβ family by flow cytometry; and (iv) TCR gene rearrangement by PCR; (v) bone marrow infiltration with LGL is another diagnostic criterion but a designated marrow biopsy is often not performed in clear LGL which are otherwise asymptomatic. Coexistent presence of MDS and LGL was confirmed in 13/240 (5%) of the patients. These patients displayed typical features of MDS including abnormal cytogenetics (8/13), dysmorphia of myeloid cells in the bone marrow (13/13), ringed sideroblasts (1/13) and the presence of highly clonal somatic myeloid mutations (8/13) with an average VAF of 28+3%. When compared to LGL only, the MDS/LGL series had 15% vs. 39% (P=0.014) STAT3/5b mutations. We detected the presence of mutant myeloid clones in 25% (41/161) of the patients with pure LGL with an average VAF of 35+ 2%. Suspecting that these mutations may be present early in MDS and CHIP, we compared the mutational spectrum of LGL against MDS (n=835) and CHIP. Indeed, an overlap between the typical CHIP mutations was noted with LGL; in addition the clonal burden in CHIP was observed to be lower, 13% vs. 33% in LGL indicating a more advanced myeloid disease in LGL. This could be due to overlapping demographics or through a common pathophysiologic link. Spliceosomal mutations, cohesion complex, PRC2 and RAS mutations were overrepresented in MDS and CHIP in comparison to LGL. Our results indicate that LGL is often associated with myeloid mutations that are also typical in CHIP. Though, age-related changes or other mutagenic stressors, including inflammatory changes could be contributing factors to both LGL and CHIP outgrowth, conversely LGL may evolve as a consequence of a tumor surveillance response to myeloid neoplasms or CHIP. While the coexistence of MDS and LGL has been described in the past, and our analysis corroborates this, we observed that LGL may also coexist with CHIP in some patients. The implication of this would be beneficial to our understanding of, not only, the individual diseases but could also impact care in CHIP survivorship. Disclosures Nazha: MEI: Other: Data monitoring Committee; Novartis: Speakers Bureau; Jazz Pharmacutical: Research Funding; Incyte: Speakers Bureau; Tolero, Karyopharma: Honoraria; Daiichi Sankyo: Consultancy; Abbvie: Consultancy. Saunthararajah:EpiDestiny: Consultancy, Equity Ownership, Patents &amp; Royalties; Novo Nordisk: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Novartis: Consultancy; Alexion: Consultancy.

Parameters of chronic toxicity of the solution for intrauterine use “Yodozol”

The study of the chronic toxicity of the solution for intrauterine use in the form of aerosol – “Yodosol”, is a mandatory stage of preclinical study of the drug, which is a new development of PE «Biopharm» and the Experimental Station of epizootology of the Institute of Infectious Diseases of NAAN. In a scientific experiment on laboratory animals, it is possible to evaluate the safety of the drug at different times of use, to determine the area of toxic action and doses that do not cause adverse health effects. Therefore, the purpose of the study was to study the chronic toxicity of the drug “Yodosol”, in particular the determination of tolerant and toxic doses for rodents. The experiments were carried out in accordance with the requirements for biomedical research, the selection of analogues for testing and control, ensuring the same conditions of feeding and retention, as well as accounting for results. “Yodosol” is a light yellow foamy liquid with 1 ml containing 5 mg iodine and 10 mg potassium iodide. The drug is used for the prevention and treatment of postpartum intrauterine infections in cows, pigs, sheep and goats (endometritis, pyrometers, cervicitis, vaginitis, delayed litter caused by iodine-sensitive microorganisms), after delivery of rhododerma, caesarean delivery and caesarean delivery. The drug has antimicrobial, anti-inflammatory and analgesic effects, improves proliferative processes in the tissues of the genital organs, helps to reduce the time of recovery of animals. The drug is used according to the guideline, after its livestock products are used without restrictions. No significant deviations in the behavior of the experimental animals were observed in the studies of chronic toxicity of the drug “Yodosol”. Visually noted only a slight inhibition of the rats of the experimental group, which received a 10-fold overdose. According to biochemical studies, in the group, compared with the control animals, there was a slight deviation of the indicators of protein metabolism and activity of hepatospecific enzymes: growth of total protein, alkaline phosphatase and aspartateaminotransferase. However, such changes in the blood parameters of the experimental animals were short-lived and restorative, characterizing the study drug as low-toxic. All studies conducted to determine the parameters of chronic toxicity of the solution for intrauterine use of “Yodosol” included in the registration materials of the medicinal product.

MicroRNA-186 improves fracture healing through activating the bone morphogenetic protein signalling pathway by inhibiting SMAD6 in a mouse model of femoral fracture: An animal study.

ObjectivesMicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture.MethodsMicroarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined.ResultsMicroRNA-186 was predicted to regulate SMAD6. Furthermore, SMAD6 was verified as a target gene of miR-186. Overexpressed miR-186 and SMAD6 silencing resulted in increased callus formation, BMD and BV/TV, as well as maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. In addition, the mRNA and protein levels of SMAD6 were decreased, while BMP-2 and BMP-7 levels were elevated in response to upregulated miR-186 and SMAD6 silencing.ConclusionIn conclusion, the study indicated that miR-186 could activate the BMP signalling pathway to promote fracture healing by inhibiting SMAD6 in a mouse model of femoral fracture.Cite this article: Bone Joint Res 2019;8:550–562.

A NOVEL FINDING OF HYPERREFLECTIVE MATERIAL IN THE SILICONE-RETINA INTERFACE: An Optical Coherence Tomographic and Histopathological Study.

To describe novel findings of hyperreflective material in the silicone-retina interphase on spectral domain optical coherence tomography (SD-OCT) imaging in eyes with silicone oil tamponade. Retrospective observational clinical study of consecutive patients who underwent primary pars plana vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment. Repeat clinical examination and spectral domain optical coherence tomography macular imaging performed 3 months after surgery were evaluated to identify any macular pathologies, including formation of epiretinal membranes, intraretinal changes, subretinal fluid, and edema before scheduled secondary vitrectomy for silicone oil removal. Eighty-two patients (mean age 54 years, range 22-89) were included. Twelve eyes (14%) showed discrete preretinal hyperreflective organized coarse material in the silicone-retina interphase on spectral domain optical coherence tomography. The material was scattered in the posterior pole, with several foci showing additional hyperreflectivity of the inner retinal layers beneath. These findings did not resemble silicone oil emulsification in size, shape, or reflectivity. This is the first report on hyperreflective material detected by spectral domain optical coherence tomography in the silicone-retina interphase in eyes with silicone oil tamponade. These findings may represent an inflammatory response to silicone oil exposure that may be the initial manifestation of a future proliferative process, warranting a rigorous follow-up protocol for affected patients.

Microscopic changes in the digestive organs of domestic canaries poisoned with canthaxanthin

Intoxication of canaries with canthaxanthin has been recorded more and more often since the late 1990s. This problem is related to active use of this substance for changing or increasing the colouration of this species of bird. For determining morphological changes during canthaxanthin toxicosis, we formed one control and three experimental groups of domestic canaries, which were given canthaxanthin in different doses. The material for microscopic surveys was isolated from the digestive organs of the examined birds; from this material, histological sections were prepared and stained with hematoxylin and eosin. According to the results of microscopic analysis, we determined that the intoxication of the organism of canaries with canthaxanthin causes a certain complex of changes at the tissue level. We found that canthaxanthin intoxication leads to chronic pathological processes in the digestive organs, both the digestive canal and digestive glands (pancreas, liver). In the organs of the digestive tract (glandular stomach or proventriculus, muscular stomach or gizzard, and the intestine) we found chronic catarrhal inflammation, and also proliferative processes – cellular infiltration of the stroma, overgrowth of the connective tissue. In some cases we also found distrophic processes such as keratinization of the epithelium of the mucous membrane of the glandular stomach. In the pancreas, except for edema of the stroma, no pathological processes were observed. In the liver, we found different types of dystrophy – protein (granular, hydropic) and fatty (infiltrational). With introduction of the highest doses of canthaxanthin used in the experiment, we determined a tendency towards exacerbation of pathological processes, because, apart from the already mentioned changes, we recorded manifestations of alteration (necrotic processes, disorders in blood circulation). Therefore, we proved that irrational use of canthaxanthin in canary-keeping is a factor that can negatively influence the health of these animals. Using the data we obtained, use of canthaxanthin in the diet of canaries can be correlated with their diet, thus avoiding risk of bird diseases. There is scope for further studies on the impact of canthaxanthin on other organs and the systems of the organs at microscopic level, as well as conducting biochemical and morphological analyses of blood, which would allow the creation of a new complete clinical-anatomical description of this pathology.

Cytogenetic status of the residents of the Gydansky Peninsula (Gydan)

The relevance of the study on the Gydansky Peninsula lies in poor knowledge and inaccessibility of the territory, planned intensive industrial development of the Gydansky Peninsula, in 2011 there were received licenses for the exploration of license areas at the peninsula up to 2031. Industrial development will inevitably lead to certain environmental shifts, emission of the harmful substances into biosphere, the accumulation of anthropogenic pollutants in soil and water sources. The proposed development of the territory of the Peninsula Gydan sets the task of assessment of the impact of gas and oil production in conditions of the far North on health, as well indigenous persons as employees recruited to this of the region. One of the informative approaches to the assessment of population health is the assessment of the cytogenetic status with the use of noninvasive analysis of buccal epithelium. The aim of the study is to determine the cytogenetic status of the inhabitants of the village of Antipayuta of the Yamal-Nenets Autonomous Okrug for the assessment of the impact of environmental factors on the health of the population at the present stage of the industrial development of the territory. Samples of buccal epithelium of 81 alien and indigenous people of the Yamal-Nenets Autonomous district were the object of the investigation. There was performed the analysis of indices of cells of buccal epithelium of the residents living in the village in comparison with the control group. The analysis of samples was performed on a Nikon Eclipse E100 microscope. For the assessment of the cytogenetic status of the individual there was used the proposed by Sycheva L. P. (2012-Index of accumulation of cytogenetic damages (Iac). It is shown that the frequency of occurrence of micronucleus and nuclear protrusions does not exceed the performance of the control group. The index of accumulation of cytogenetic damage for the population of the village is 0.78±0.07% and corresponds to a low level. The analysis of indices of buccal epithelial cells of residents living in rural areas was performed in the comparison with the control group The prevalence rate of cells with micronuclei and protrusions were shown to account of 14.6% andfail to exceed indices in the control group. Accumulation index of cytogenetic damages for the village population is 0.78 ± 0.07 % and corresponds to the low level. The amount of cells with micronuclei and protrusions in the current study is by 14.6% lower than the average of the control group. The intensity of proliferative processes and apoptosis in the comparison groups occurs evenly.