Necrotic Process Research Articles

Оценка качества мясного птицеводческого сырья при использовании минерального адаптогена

Abstract. The article presents the results of a comprehensive study on the effect of feed mineral additives on meat products in poultry farming. The purpose of the work is to analyze the effects of mineral adaptogen on the quality of meat and poultry products. Research methods. Research and production experience was carried out using generally accepted zootechnical, pathomorphological, histological, veterinary-sanitary and statistical research methods. Results of the study. The causes of bird death and pathological changes in organs and tissues during autopsy in the experimental and control groups are described. Describes the results of studies of veterinary-sanitary expertise of meat quality when conducting organoleptic evaluation of carcasses and offal, this sub-microscopic features of striated skeletal and cardiac muscle, studied the microstructure of cartilage in the femoral head and the microarchitecture of the liver as the main organ of metabolism and by-product. During histological studies, the structure of cells and tissues, when using mineral adaptogen, was more morphologically mature and was in a functionally active state, and in the control group, dystrophic and necrotic processes and areas with immature muscle fibers were observed. When comparing the lifetime indicators for increasing the live weight of broilers when feeding mineral adaptogen, the average daily weight gain increases, which is associated with a decrease in the toxic load and due to the receipt of micro- and macronutrients necessary for the growth and development of poultry. The safety of broiler livestock and the slaughter yield of meat increases. Minerals contribute to the proper development of the musculoskeletal system and the formation of cartilage tissue, which affects the quality of fattening, the bird can move and consume food. during the veterinary and sanitary assessment of meat quality, the results confirming the high quality of meat products were also obtained. Scientific novelty. For the first time, the paper shows not only the effect on the clinical state of poultry during the fattening of Arbor Acres broilers, the safety of livestock, but also on the microstructure and maturity of meat and offal during the slaughter period.

Morphological Characterisation of Haemocytes in the Mealworm Beetle Tenebrio molitor (Coleoptera, Tenebrionidae).

Simple SummaryTenebrio molitor is a pest of stored grain, causing considerable damage. However, its easy maintenance makes this species also interesting as a food source and as a model for physiological, immunological, ecological and evolutionary studies. We used light and transmission electron microscopy to study the morphology of circulating haemocytes. Prohaemocytes, plasmatocytes, granular cells and oenocytoids were described based on their morphological features and staining affinity. Results are a baseline for further study aimed to clarify the structure and function of haemocytes in insects.The immunocompetence of the mealworm beetle Tenebrio molitor has been well investigated at molecular and physiological levels, but information on morphological and functional characteristics of its immune cells (haemocytes) is still scarce and fragmentary. This study provides an updated overview of the morphology of circulating immune cells from mealworm beetle adults, using light and transmission electron microscopy. Based on their affinities for May–Grünwald Giemsa stain, haemocytes were defined as either eosinophilic, basophilic or neutral. Ultrastructural descriptions allowed to detect four main cell types in the haemolymph: prohaemocytes, plasmatocytes, granular cells and oenocytoids. The morphological plasticity of haemocytes and the evidence of mitotic circulating cells, intermediate cell stages, as well as autophagic activities suggest haemocyte proliferation, turnover and transdifferentiation as constantly active processes in the haemolymph. Cytochemical tests revealed differences in the distribution of carbohydrates among cell types underling the great plasticity of the immune response and the direct involvement of circulating immune cells in the resource allocation. In addition, our results provide a detailed morphological description of vesicle trafficking, macro- and microautophagy, apoptotic and necrotic processes, confirming the suitability of T. molitor haemocytes as a model for studying evolutionarily conserved cellular mechanisms.

Intensity and duration of phases of wound healing after surgical intervention in сases of spontaneous periodontitis accompanied by various reactivity of the body

The usage of the principle of optimal management, namely such effects on complicated forms, when the course of the disease is close to that of uncomplicated course of the disease is very promising in drug therapy of patients with generalized periodontitis. The aim is to study the intensity and duration of the phases of wound healing of the mucosa after spontaneous periodontitis surgery accompanied by normo-, hyper- and hyporeactivity of the body by cytological examination of smear-imprints of wound exudate. Materials and methods: The experiments were performed on 24 adult mongrel dogs divided into three equal groups. In the first group, drugs that disrupt the reactivity of the organism were not used (normoreactivity of the organism). In the second group, the animals were simulated a сondition of hyperreactivity, in the third group – the hyporeactivity of the organism. All the animals with spontaneous periodontitis underwent a patchwork surgery. In the period after surgery, cytological examination was performed on the 1st, 4th, 6th and 9th day of the experiment. Results: It has been revealed that in cases of the normal reactivity of the organism the following periods of cellular reactions during the healing of the gums mucous membrane can be differentiated within the appropriate terms: the period of degenerative-inflammatory changes (1st day), active granulocyte-macrophage reaction (4th day), reparations (6th day) and the period of increase of reparative processes with a decrease in the overall cellular response (9th day). Examination of smear-imprints after surgical treatment in animals with spontaneous periodontitis with hyper- and hyporeactivity of the body allowed to identify the same periods of cellular reactions during the healing of the gingival mucosa, as in cases of normoreaction with hyperreation.Tthe intensity and duration of the wound healing phases differed from those which are typical for normoreactivity of the body: granulocyte-macrophage reaction was more pronounced and lasted longer until the 6th day, so later only on the 9th day there were cellular signs of regeneration. With hyporeaction, the intensity and duration of the wound healing phases differed from those which are typical for normoreactivity of the body: granulocyte reaction occurred later (only on the 6th day) and lasted longer, signs of active regeneration appeared later on the 9th day. Therefore, postoperative wound healing in animals with impaired body reactivity was delayed for 3-4 days. Conclusions: Thus, direct medical correction with transforming intensity and duration of the phases of the wound process which are characteristic for impaired reactivity of the body into the phases which are typical for normoreaction is essential. It provides synchronization of necrotic and reparative processes and creates conditions for normal uncomplicated healing of periodontal soft tissues

Выживаемость изолированных кожных эксплантатов при дистанционном взаимодействии со слоистыми периодическими структурами

Full-thickness skin grafts are used in reconstructive surgeries. Objectives Experimental study of the possibility of long-term preservation of viable skin grafts in severely impaired trophics at remote interaction with entities having stratiform periodic structure. Material and methods Full-thickness skin was excised from the rabbits' backside and dissected into explants sized 1.0 × 1.0 cm. The samples (n = 81) were divided into three groups and thermostated for 2 days at 37 °C at a various distance from the metal (aluminum) presented as a 20-layer package of smooth foil forming a stratiform periodic structure (SPS) (series I), chaotic layers of squeezed foil (series II) and a single-piece sheet (series III). Histological analysis was performed for the three series to evaluate the explants' viability after the thermostating. Results The highest survival estimates were seen in experimental explants of series I that interacted with the SPS of stratified foil layers. The wave nature of such remote interaction was suggested with delayed dystrophic and necrotic processes developing in the skin samples. Experimental samples of series III appeared to be less viable. The explant vitality in series II was sharply reduced due to rapidly spreading necrosis. Conclusion Skin explants were shown to retain viability for a longer time when interacting remotely with stratiform periodic structures in the absent trophics. These promising results can be practical for the development of wound dressings to improve survival of full-thickness skin transplantation in reconstruction of deep skin defects.

Dynamics of biochemical indicators in the process of mucous-bone wound healing in cases of spontaneous periodontitis on the background of different organism reactivity

The dynamics of biochemical parameters (lipid peroxidation, medium molecular peptides, prostaglandins) blood levels after periodontal tissues surgery of 24 dogs with spontaneous periodontitis has been studied. Animals were divided into groups with normal, hyper- and hyporeactivity of the body. It has been revealed that the changes of the studied biochemical parameters during normoreactivity of the organism are mutually correlated, which provides synchronization of necrotic and reparative processes in the healing of mucosal wounds after patch surgery in cases of spontaneous periodontitis. When hyperreactivity of organism is observed, the changes of indicators of lipid peroxidation, medium molecular peptides and prostaglandins promote strengthening of necrotic processes, and in cases of hyporeactivity they boost their slowing down that in both cases leads to delay of reparation in healing of an artificial mucous-bone wound. Keywords: spontaneous periodontitis, reactivity of the organism, wound healing, biochemical parameters.

TREATMENT OF DIABETIC OSTEOARTHROPATHY WITH THE ILIZAROV METHOD

We present the clinical observation of 55-year-old female patient with diabetic osteoarthropathy (Wagner 3; Brodsky 2; 3a) complicated with chronic osteomyelitis treated in the purulent osteology clinic. Long-term conservative treatment in the hospital at place of residence was not successful, so the patient was found requiring limb amputation. On admission to the purulent osteology clinic, the patient complained of vast purulent wound of the right foot, numbness of the fingers of both feet and disturbed support ability of the limb. The patient underwent complex restorative treatment with the Ilizarov method. Primary treatment outcomes were obvious healing of the osteomyelitis and restoration of the limb function persisting already for three years after treatment. The clinical case presented illustrates the possibility of the Ilizarov method in complex regenerative treatment of patients with diabetic osteoarthropathy, which allows to suppress the necrotic process, eliminate the existing deformation to fill the bone defect and thus restore function of the limb.

Extranodal NK/T cell lymphoma, nasal type: An updated overview.

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is an aggressive malignancy associated with Epstein-Barr virus infection, with a geographic and racial predilection for some Asian and Latin American countries. ENKTCL-NT manifests as a necrotic process affecting nasal or upper aerodigestive structures and, rarely, extranasal sites such as skin, and the gastrointestinal tract. ENKTCL-NT was characterized by its poor prognosis irrespective of clinical stage and therapy. However, during the last two decades, advances in its clinicopathologic, genetic and molecular characterization have been achieved, as have changes in the chemotherapy regimens that, in combination with radiotherapy, are significantly improving the survival of these patients, especially in initial stages. For these reasons, we present an overview of the historical background of ENKTCL-NT along with an updated review of its potential etiological factors, clinicopathologic and molecular features, as well as its prognostic models, current treatment protocols, and future directions on potential promising therapeutic approaches.

Pathogenetic rationale for usage of recombinant interleukins in the patients with mandibular fractures to prevent post-traumatic osteomyelitis

The paper presents the results on spontaneous and induced production of IFNγ, IL-4, IL-13 cytokines in blood cells of patients with mandibular fractures and post-traumatic osteomyelitis. Osteomyelitis of the jaw represents one of the urgent challenges in modern medicine. There are many reasons for development of purulent necrotic processes of the jaw bones, including disorders of innate and adaptive immune response. Currently, the immunological aspects of post-traumatic complications of maxillofacial region remain poorly understood. There are no unambiguous and systematic studies of immune mechanisms in pathogenesis of post-traumatic osteomyelitis of the lower jaw. The aim of our study was to theoretically confirm application of recombinant interleukins (IL-1β, IL-2, IFNγ) in the patients with jaw fractures, in order to prevent osteomyelitis, as based on the studies of spontaneous and induced cytokine production (IFNγ, IL-4, IL-13). Spontaneous and stimulated production of IFNγ, IL-4, and IL-13 cytokines by blood cells was determined using specific reagent kits from RD Diagnostic Inc. (USA). The results were recorded using an ELISA Multiscan analyzer (Finland). Statistical significance of intergroup differences was determined by the Mann–Whitney method. The level of statistical significance at which the null hypotheses were rejected was 0.05. To stratify the cases of post-traumatic osteomyelitis and uncomplicated mandibular fracture, the models were developed with a singlelayer neural network, using the nnet R-studio package. To assess quality of the models, the areas under the ROC curves (AUC), Akaike criterion (AIC), and the relative classification accuracy (OTC) were used, which was determined as the ratio of correctly established model diagnosis numbers to the total number of patients. The study results demonstrate that the patients with mandibular fractures exhibit a moderate impairment of LPS-induced IL-4 and IFNγ production by leukocytes with IL-13 activation. In presence of osteomyelitis, this imbalance is promoted, thus suggesting an impaired ability of the cells to produce IL-4 and IFNγ. An opportunity for usage immunomodulation when treating the patients with mandibular fractures is represented by P = 1/(1+e-z) where z is defined via IL-1β, IL-2 and IFNγ levels on the first day of observation. In vitro supplementation with recombinant IL-1β and IFNγ modulates cell function, improving the cytokine profile. The prognostic models, imitating binary logistic regression, were used to demonstrate that recombinant IL-1β could be used to prevent patients with mandibular fractures from developing post-traumatic osteomyelitis (AIC = 13.2, AUC = 0.96, р = 0.026).

Evaluation of the treatment of patients with diabetic foot syndrome complicated by necrotic process

Evaluation of the treatment of patients with diabetic foot syndrome complicated by necrotic process

Effect of Starvation as a Population Stress-Factor on the Activation of Covert Baculovirus Infection in the Gypsy Moth

The conditions of entomopathogen persistence in a host-insect organism and the mechanisms of their conversion to the acute form of infection is one of the most important questions for an understanding of epizootics functioning. Here, we estimate the dynamics of the physiological parameters of the gypsy moth (Lymantria dispar L.) responsible for insect protection from antivirals under stress (starvation) and their correlation with the activation of the latent form of L. dispar, multiple nucleopolyhedrosis. We find that starvation leads to an increase in the dopamine concentration in the larval hemolymph and a decrease in the total number of hemocytes, which is associated with the high necrotic cell death. The number of viral carriers in the studied population and their activation level with starvation are estimated to be more than 70%. Polymerase chain reaction analysis showed an increase in the number of virus-positive individuals starting from the first day of starvation. At the same time, the nonspecific mortality of insects began only after 7 days of starvation, whereas the mortality from an activated virus began after 2–3 days of starvation. Thus, we show that at high insect-population density, a lack of food resources plays the leading role in the activation of the covert form of baculovirus infection. When analyzing the dynamics of physiological parameters, we assume that the conversion of a covert baculovirus form into an acute infection can be triggered by necrotic processes induced by starvation.

TNF-α-dependent neuronal necroptosis regulated in Alzheimer's disease by coordination of RIPK1-p62 complex with autophagic UVRAG.

Background: Neuronal death is a major hallmark of Alzheimer's disease (AD). Necroptosis, as a programmed necrotic process, is activated in AD. However, what signals and factors initiate necroptosis in AD is largely unknown.Methods: We examined the expression levels of critical molecules in necroptotic signaling pathway by immunohistochemistry (IHC) staining and immunoblotting using brain tissues from AD patients and AD mouse models of APP/PS1 and 5×FAD. We performed brain stereotaxic injection with recombinant TNF-α, anti-TNFR1 neutralizing antibody or AAV-mediated gene expression and knockdown in APP/PS1 mice. For in vitro studies, we used TNF-α combined with zVAD-fmk and Smac mimetic to establish neuronal necroptosis models and utilized pharmacological or molecular biological approaches to study the signaling pathways.Results: We find that activated neuronal necroptosis is dependent on upstream TNF-α/TNFR1 signaling in both neuronal cell cultures and AD mouse models. Upon TNF-α stimulation, accumulated p62 recruits RIPK1 and induces its self-oligomerization, and activates downstream RIPK1/RIPK3/MLKL cascade, leading to neuronal necroptosis. Ectopic accumulation of p62 is caused by impaired autophagy flux, which is mediated by UVRAG downregulation during the TNF-α-promoted necroptosis. Notably, UVRAG overexpression inhibits neuronal necroptosis in cell and mouse models of AD.Conclusions: We identify a finely controlled regulation of neuronal necroptosis in AD by coordinated TNF-α signaling, RIPK1/3 activity and autophagy machinery. Strategies that could fine-tune necroptosis and autophagy may bring in promising therapeutics for AD.

Pathomorphological Changes in Organs of Rabbits with Experimental Colibacillosis

The aim of this research was to study pathomorphological alterations in the internal organs of rabbits through experimental reproduction of colibacillosis. The studies were conducted on 10 clinically healthy rabbits at the age of 3 months from a private farm. Animals were infected by intraperitoneal injection of a suspension of a pure culture of Escherichia coli isolated from a sand lizard. The disease of infected rabbits was accompanied by cachexia, dehydration and fever. The pathological process in the organism of infected animals was characterized by the violation of hemodynamics, the protein dystrophy of the parenchyma of liver, kidneys, myocardium and the formation of specific granulomas in the lungs and liver. The edema of reticular tissue and the hyperplasia of lymph nodes were observed in the organs of the immune system. The expressive edema of mucous membrane and submucosa, as well as alterative and necrotic processes were detected in the intestine.

Neuroprotective Effects of Methyl Caffeate against Hydrogen Peroxide-Induced Cell Damage: Involvement of Caspase 3 and Cathepsin D Inhibition.

Finding effective neuroprotective strategies to combat various neurodegenerative disorders still remain a clinically unmet need. Methyl caffeate (MC), a naturally occurring ester of caffeic acid, possesses antioxidant and anti-inflammatory activities; however, its role in neuroprotection is less investigated. In order to better characterize neuroprotective properties of MC, we tested its effectiveness in various models of neuronal cell injury in human neuroblastoma SH-SY5Y cells and in mouse primary neuronal cell cultures. MC at micromolar concentrations attenuated neuronal cell damage induced by hydrogen peroxide (H2O2) in undifferentiated and neuronal differentiated SH-SY5Y cells as well as in primary cortical neurons. This effect was associated with inhibition of both caspase-3 and cathepsin D but without involvement of the PI3-K/Akt pathway. MC was neuroprotective when given before and during but not after the induction of cell damage by H2O2. Moreover, MC was protective against 6-OHDA-evoked neurotoxicity in neuronal differentiated SH-SY5Y cells via inhibition of necrotic and apoptotic processes. On the other hand, MC was ineffective in models of excitotoxicity (induced by glutamate or oxygen–glucose deprivation) and even moderately augmented cytotoxic effects of the classical apoptotic inducer, staurosporine. Finally, in undifferentiated neuroblastoma cells MC at higher concentrations (above 50 microM) induced cell death and when combined with the chemotherapeutic agent, doxorubicin, it increased the cell damaging effects of the latter compound. Thus, neuroprotective properties of MC appear to be limited to certain models of neurotoxicity and depend on its concentrations and time of administration.

Enniatin B induces dosage-related apoptosis or necrosis in mouse blastocysts leading to deleterious effects on embryo development

The current study has focused on the effects of enniatin B (ENN B, a major mycotoxin produced by Fusarium fungi) on early embryonic development. In in vitro analysis, mouse blastocysts were incubated in medium with ENN B (0–40 μM) or 0.5% DMSO (control group) for 24 hours. In an animal study, blastocysts were collected from mice which were intravenously injected with ENN B (1, 3, 5, and 7mg/kg body weight/day) for 4 days in order to analyze apoptosis and necrosis via Annexin V/PI staining assay; and proliferation using dual differential staining. Exposure to low ENN B concentration (10 μM in vitro and 3 mg/kg/day in vivo) promoted Reactive Oxygen Species (ROS) generation and apoptosis in the Inner Cell Mass (ICM), the mass of cells inside the blastocyst, impairing post-implantation development alone. On the other hand, exposure to a higher ENN B concentration (40 μM in vitro and 7 mg/kg/day in vivo) induced ROS generation and decreased in intracellular ATP which encouraged necrotic processes in both trophectoderm (TE) and ICM of blastocysts leading to impaired implantation and post-implantation development. Moreover, 5 and 7 mg/kg/day ENN B intraperitoneal injection to female mice for 4 days has caused downregulation of CXCL1, IL-1β and IL-8 expressions and increased ROS generation in the liver of newborn mice. Over all, ENN B can induce apoptosis and/or necrosis depending on the treatment dosage in mouse blastocysts. ENN B-induced necrosis in blastocysts may exert long-term harmful effects on next-generation newborns.

Optical coherence tomography-based tissue dynamics imaging for longitudinal and drug response evaluation of tumor spheroids

We present optical coherence tomography (OCT)-based tissue dynamics imaging method to visualize and quantify tissue dynamics such as subcellular motion based on statistical analysis of rapid-time-sequence OCT signals at the same location. The analyses include logarithmic intensity variance (LIV) method and two types of OCT correlation decay speed analysis (OCDS). LIV is sensitive to the magnitude of the signal fluctuations, while OCDSs including early- and late-OCDS (OCDS e and OCDS l , respectively) are sensitive to the fast and slow tissue dynamics, respectively. These methods were able to visualize and quantify the longitudinal necrotic process of a human breast adenocarcinoma spheroid and its anti-cancer drug response. Additionally, the effects of the number of OCT signals and the total acquisition time on dynamics imaging are examined. Small number of OCT signals, e.g., five or nine suffice for dynamics imaging when the total acquisition time is suitably long.

Simulation of Acute Destructive Pancreatitis with Damage to the Adjacent Adipose Tissue in Pigs

The aim of the study was to develop a model of acute destructive pancreatitis with damage to the extra-organ adipose tissue. Materials and methods. Simulation of acute destructive pancreatitis with damage of the extra-organ adipose tissue was performed in 22 white breed boars aged 3 months. The animals were divided into groups in accordance with two series of studies, where the control (first) group included 15 animals with the pancreas and extra-organ adipose tissue remained intact. Acute destructive pancreatitis was simulated in 7 pigs of the experimental (second) group based on the proposed technique (patent for an invention No. 2668201). Ultrasound examination of the abdominal cavity and retroperitoneal region was applied to confirm the development of expected pathology in experimental animals. Intensity of blood supply was assessed using contrast radiography by injecting a contrast medium into the superior mesenteric artery. Complete blood count and biochemical assay were performed. In addition, during autopsy tissue samples were taken for histological and immunohistochemical investigations to assess changes in the internal organs. Results. Acute destructive pancreatitis with damage to the extra-organic adipose tissue was regarded as achieved when clinical manifestations of apathy, lethargy, feed refusal were registered in animals. Biochemical blood tests revealed a significant increase in the concentration of alkaline phosphatase and alpha-amylase enzymes. Nitrogenous toxins, in particular, creatinine, were accumulated in the body of the experimental animals. Complete blood count revealed leukocytosis, the fact supporting the onset of the expected inflammatory process in the pancreas and adjacent adipose tissue. The development of necrotic and inflammatory processes in the organ was evidenced by a sharp increase in the level of amylase, creatinine and alkaline phosphatase in the blood of animals. Ultrasound examination revealed a picture of the blurring of pancreatic contours, heterogeneity of the organ structure, increased echogenicity, and enlargement of the duct. Intensification of the vascular pattern and increase in pancreatic contours were detected during the contrast examination of the abdominal vascular system. At autopsy, there were signs of enzymatic peritonitis, namely, serous-hemorrhagic exudate in the abdominal cavity and the cavity of the omental bursa, increased pneumatization of the intestinal tube with a thinning of its wall and foci of small hemorrhages. The pancreatic tissue in all cases was edematous, full-blooded, with multiple foci of fatty necrosis and purulent inflammation. Similar changes were found in the adjacent adipose tissue. At the light-optical level, vascular congestion, small foci of steatonecrosis and micro-abscesses were determined in the pancreas. Immunohistochemical studies largely evidenced the onset of acute destructive pancreatitis with damage to the extra-organ adipose tissue.Conclusion. Thus, the proposed technique allows simulating acute destructive pancreatitis with damage to the extra-organ adipose tissue in pigs, the event frequently occurring in the clinical practice. In animals the disease is accompanied by clear clinical manifestations correlating with findings of instrumental and laboratory investigations, and autopsy results. Investigations of the pancreatic and extra-organ adipose tissue samples at the light-optical and molecular levels evidence the fact that the authors have simulated a model of acute destructive pancreatitis with involvement of the adipose tissue adjacent to the organ in the pathological process.

SECONDARY METABOLITES FROM RICE CULTURE OF ASPERGILLUS SP. ISOLATED FROM MELALEUCA SUBULATA (CHEEL) CRAVEN LEAVES AND THEIR ANTICANCER ACTIVITY

Objective: Aspergillus fungus is a rich source of natural products with broad biological activities. This study was conducted to identify secondary metabolites from the rice culture of Aspergillus species isolated from Melaleuca subulata leaves and evaluated their anticancer activity.
 Methods: Ethyl acetate extract was fractionated on silica gel and Sephadex columns. Structures of the compounds were established using physical and chemical methods. Cytotoxic activities of the extract and pure compounds against two human cancer cell lines (Mcf-7and Hep G2) were evaluated using microculture tetrazolium assay as well as the mode of the cytotoxicity was evaluated. Molecular docking studies have been performed using the Hsp 90 enzyme as an anticancer target.
 Results: Methyl linoleate (1), arugosin C (2), ergosterol (3), sterigmatocystin (4), diorcinol (5), alternariol-5-O-methyl ether (6), averufin (7), averufanin (8), and alternariol (9) were identified from ethyl acetate extract. All tested compounds exhibit week activity against MCF-7 and Hep G2 cell lines but a mixture of compounds 7 and 8 is considered to be more active towards both MCF-7 and Hep G 2 in comparison to other compounds. Compound 4 exhibits moderate activity against Hep G2 only as well as the ethyl acetate extract exerts moderate activity against MCF-7 cell line Moreover, compound 4 and a mixture of 7 and 8 caused a decrease in the number of Hep G2 cancer cells due to apoptotic and necrotic processes. Most active anticancer candidates 7 and 8 showed binding to the active site similar to geldanamycin reference ligand.
 Conclusion: Secondary metabolites identified from Aspergillus sp. and their anticancer activity were evaluated. Molecular docking suggested active candidates as Hsp 90 inhibitors.

Clinical Management of Nasal Skin Necrosis Caused by Hyaluronic Acid Filler.

Nose augmentation with Hyaluronic acid (HA) fillers has been considered the preferred technique for minimally invasive cosmetic procedures. Despite severe complications related to HA injection are rare, none of the existing treatment protocols has been established as standard. The aim of this report is to present an alternative approach to treat nasal skin necrosis related to HA injection. A high dose of hyaluronidase - 6000 IU was applied in the nose, for the purpose of reversing a necrotic process. The present findings suggest that a high dose of hyaluronidase could be a promising approach to treat severe nasal skin necrosis caused by HA filler.

STEM CELL CORRECTION OF TOXIC LIVER LESIONS

Assessment of the feasibility of fetal liver cells (FLC) for correction of a CCl4-induced acute toxic hepatitis was performed. Exposure to Cl4 in a dose of 3000 mg/kg caused well-defined centrilobular necrosis, hydropic, protein, carbohydrate, and adipose degeneration, as well as vascular disorders. The dynamics of morphological changes in the liver was studied, and the role of their intrinsic regenerative potential was assessed using pathomorphological, histochemical, and immunofluorescence methods. Phenotyping the cellular material was carried out to reveal expression of endodermal and mesodermal markers characteristic for the hepatic epithelium, hematopoietic stem cells, and mesenchymal cells. Three days after FLC transplantation, slowing down of necrotic and dystrophic processes in the liver parenchyma was observed. In some animals, the trabecular structure of the central hepatic zones was restored and, by 5th to 7th day of post-implantation, vascular disorders were eliminated. The resulting data can be considered as evidence for the use of fetal liver cells in the treatment of acute toxic hepatitis.

The condition of neuro-endocrine systems in acute experimental myocardial infarction against the background of various reactivity of the organism

The adequacy of recovery processes in myocardial infarction (MI) significantly depends on the state of reactivity of the organism, which, in turn, is determined by the adequacy of neuro-endocrine regulation, in particular, hypothalamic-pituitary-adrenocortical (HPA) and hypothalamic-pituitary-thyroid (HPT) system system.Purpose of the study. To investigate the condition of HPA and HPT in acute experimental MI against the background of different reactivity of the organism.Material and methods. The study was performed on 20 outbred adult dogs weighing 8-12 kg, in which MI was simulated by ligation of the anterior interventricular artery. Animals were divided into three groups (n =5 in each group). The condition of hyperreactivity was caused by the introduction of pyrogenal (group 2), the state of hyporeactivity - the introduction of azothioprine (group 3), in group 1 drugs were not used (state of normoreactivity). In the control group used 5 falsely operated dogs with thoracopericardiotomy. In animals before surgery, on 1, 4, 7, 11 and 15 days in the blood was determined by the content of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH) , cortisol (Cr), aldosterone (Ald), thyroxine and triiodothyronine. Statistical processing was performed using license packages Statistica 5.5 (Stat Soft Rus), Statistica Neural Networks (Statsoft Inc.).Results. Normoreactive course of myocardial infarction was characterized by primary activation of HPA, which was most pronounced for Cortisol, followed by restoration of ACTH and Aldosterone levels and duration of activation of the central link up to 4 days, peripheral - up to 7-11 days; reciprocal in relation to HPA inhibition of the functional activity of the HPT, most pronounced on the 4th day and lasting up to 15 days. Such changes caused the healing of myocardial infarction through the formation of a full-fledged post-infarction scar. The hyperreactive course of myocardial infarction was characterized by hypersecretion of ACTH with hypercorticism and hyperaldosteronism and less pronounced suppression of HPT with the restoration of its functional activity on the 7th day. The hyporeactive course of myocardial infarction was characterized by a minimally pronounced and delayed up to 4 days activation of HPA with Aldosterone hyposecretion on the 15th day; deep hypothyroidism of both central and peripheral genesis. Impaired reactivity was accompanied by an increase in the area of necrosis and a decrease in the thickness of the heart wall with the formation of postinfarction aneurysm.Conclusions. Desynchronization of necrotic and reparative processes with a change in reactivity leads to a disruption in the relationship between necrosis and repair with the formation of postinfarction aneurysm, which is accompanied by different activities of the HPA and HPT.