Search

The aim: To investigate the distribution of proteolytic activity and cytokine profile in the heart of rats with hyperhomocysteinemia. Materials and methods: A total of 60 albino non-linear male rats was used in the study. Hyperhomocysteinemia was induced by intragastric administration of DL-homocysteine thiolactone. Total proteolytic activity was measured using casein as a substrate. To determine the activity of metal-dependent and serine proteases, ethylenediaminetetraacetic acid, and phenylmethylsulfonyl fluoride were used. The level of matrix metalloproteinases, tissue inhibitor of metalloproteinases-1, and cytokines was studied by enzyme-linked immunosorbent assay. Results: It was found an increase in the total proteolytic activity in the heart of young, adult, and old animals. In addition, the redistribution of proteolytic activity was revealed – the portion of metal-dependent enzymes increased in all groups while the percentage of serine proteases decreased in the old animals with hyperhomocysteinemia. The state of mild inflammation, evidenced by the increased level of some pro-inflammatory cytokines, was found in the heart of young and old animals with hyperhomocysteinemia. Conclusions: The pathogenesis of hyperhomocysteinemia is accompanied by a change in the proteolytic activity in the heart as well as a change in the cytokine profile.

One of the most commoncharacteristics of obesity is the development of a systemic low-grade proinflammatory state in the entire body, including the immune organs. Spleen enlargement during diet-induced obesity contributes to the development of chronic inflammation. Melatonin due to immunomodulatory, antioxidant, and systemic metabolic rolesis proposed to be an effective candidate for anti-obesity therapy. As immune systems demonstrate pronounced circadian rhythmicity and immune cells have different types of melatonin receptors, a chronotherapeutic approach might be used to choose the most effective regimes of melatonin administration for the correction of obesity-provoked damage to the spleen. Thus, the main goal of our research was the analysis of the rats' spleen histophysiology during the development of high-calorie diet-inducedobesity (HCD) after administering melatonin daily at different times (morning or evening). Melatonin was administered by gavage for 7 weeks in the dose of 30 mg/kg 1 h before lights-off (HCD ZT11, M ZT11, evening), or 1 h after lights-on (HCD ZT01, M ZT01, morning). For assessment of the morpho-functional state of the spleen,the histopathological evaluation of red and white pulp in different zones of lymphoid follicles was implemented. It was observed that obesity development wasaccompaniedbyhyperemia and vessel dilatation in the red pulp; while in the white pulp notable deformation of germinal centers and destroyed borders between zones of lymphoid follicles were noticed.The HCD group demonstrated a decrease inthe relative amount of the white pulp, the crosssectional area of germinal centers, and the cross-sectional area of the marginal zone; whilethe increased relative amount of red pulp and marginal zone/germinal centers ratiowere detected compared with control. Melatonin administration to obese rats increases the relative amount of the white pulp (HCD ZT11 group), the cross-sectional area of germinal centers (HCD ZT01 and HCD ZT11 groups), and the cross-sectional area of the marginal zone (HCD ZT11 group), and decreasesmarginal zone/germinal centers ratio (HCD ZT01 group) in comparison with the HCD group.Also,it was demonstrated that a choice between the morning or evening regimes of the melatonin treatment did not affect the histophysiology of the spleen in rats receivingthe standard diet (M ZT01 and M ZT11 groups). These results indicate that melatonin can be considered to be a powerful potential therapeutic agent for the amelioration of obesity-induced changes in the spleen.

Ulcers and slow wound healing are common in diabetic polyneuropathy (DP), as well as shooting or burning pain, sensitivity to touch or lack of sensitivity, low oxygenation of nerve tissue, conductivity disorders and various vascular disorders. The mechanisms of DP development are complex and have not been completely studied. To take into account the role of B group vitamins, we investigated histological structure of nerve tissue, the level of different growth factors and the qualitative composition of active proteolytic enzymes in rats with DP and after the use of the metabolic drug Cocarnit for 9 days. This drug composition include nicotinamide, cocarboxylase, cyanocobalamin, adenosine triphosphate disodium trihydrate. We used an histological study of sciatic nerve; enzyme-linked immunosorbent assay and enzyme electrophoresis methods. In rats with DP, fragmentation of nerve tissue and their necrosis was established. Moreover, degraded forms of plasmin that has a fully functional serine proteinase domain are evident, and, therefore, it exhibits proteolytic properties. DP led to a decrease of neuron growth factor (NGF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). After treatment, the histological structure of nerve tissue was significantly improved, and the expression of growth factors NGF and bFGF was increased. Our study demonstrated that administration of Corcarnit brought about the complete restoration of the activation potential of plasmin and the almost disappearance of all degraded forms which were evident in the group with DP.

C60 fullerenes have proved their therapeutic effects and efficacy by the results of countless experiments. For further usage of these nanoparticles, the systematic toxicological investigations are required. Blood compatibility should be studied for C60 fullerenes due to the potential blood contact. Currently, available data is not systematic and has not provided insights into possible side effects of C60 fullerenes on blood components. In this study, water-soluble pristine C60 fullerenes were tested in vitro to assess their biocompatibility in rabbit. The blood compatibility has been evaluated looking at the impact of C60 fullerenes on erythrocyte integrity, platelet aggregation, and some blood factors involved in coagulation. Our results revealed that C60 fullerenes cannot elicit hemolysis at studied concentrations and did not show any effect on coagulation process. C60 fullerenes in concentration-dependent manner increased ADP-dependent platelet aggregation and changed the key kinetic parameters of these processes. C60 fullerenes inhibited thrombin amidolytic activity but did not affect the activities of other studied coagulation factors. The prothrombotic property of C60 fullerenes could be the potential risk factor that leads to enhancement of vascular thrombosis. The ability of fullerene to inhibit thrombin activity is important for the pharmacological use of these carbon nanoparticles as anticoagulant agents.

Bladder cancer (BC) is a worldwide common disease with a high mortality rate. Recognizing the dynamic changes in plasma that proteases and their inhibitors undergo might be valuable in understanding the carcinogenesis of invasive bladder cancer and in identifying BC patients with poor prognosis. This study aims to determine the activity of the proteolytic enzyme system and their inhibitors in patients with BC. In this paper, the total proteolytic activity, the activity of matrix metalloproteases (MMPs) and serine proteases was analyzed by the method of caseinolytic activity. For detection of activity of some inhibitors of proteolysis, we used the unified method for determining the activity of alpha-1-antitrypsin (α1A) and alpha-2-Macroglobulin (α2M) in human plasma. The level of medium-mass molecules (MMM) was assessed spectrophotometrically by applying the Nikolaichik method. The activity of MMPs was elevated in all groups of patients. Moreover, the activity of serine proteases was found to be enhanced in patients with Stage I, III and IV BC, while the activity of α1A was up by 1.4 and 1.3 times in patients with Stage I and Stage IV. The most significant increase was observed with regard to the activity of α2M in patients with I and III stages of BC. In addition, the level of MMM correlated with cancer stage. Indeed, the highest increase in the activity of protease inhibitors was observed in Stage I bladder cancer patients, which might signify their protective role at the onset of the bladder carcinogenesis. In contrast, significant growth in activity of α2M in patients with III stage of BC may point at a compensatory mechanism that inhibits tumor growth.

Glomerular damage and proteinuria are important pathophysiological signs of chronic kidney disease. This study provides data obtained using a model developed based on the use of the anti-cancer drug sorafenib. Sorafenib is a tyrosine kinase inhibitor that acts through the signaling pathway associated with vascular endothelial growth factor and is widely used to treat various types of cancer. Sorafenib, on the other hand, causes serious side effects in patients, including the development of chronic kidney disease. This study was aimed at using the nephrotoxic properties of sorafenib to model chronic kidney disease in rats. We showed that rats treated with sorafenib for 8 weeks along with a diet high in salt (8% NaCl) develop hypertension with high systolic blood pressure of 80 mmHg, proteinuria with an increase in protein content of 75% higher , and a 4-fold increase in glomerular damage compared to the control group. In case of damage to the renal glomeruli caused by sorafenib, the level of transcripts that are involved in the synthesis of key glomerular proteins such as nephrine, podocin, synaptopodin and subplanin is significantly reduced. Also, when studying this model, activation of the endothelial-mesenchymal transition is observed. In the group of rats treated with sorafenib, the mRNA level for the WT-1 endothelial cell marker was reduced by 20%, while the concentration of the Col III, FSP-1, α-SMA and vimentin mesenchymal cell markers increased by 2–3 times. Thus, we developed a preclinical model of chronic kidney disease, expressed in damage to the renal glomeruli. We also demonstrated that glomerular damage in this model is associated with decreased expression of key structural glomerular proteins and activation of the endothelial-mesenchymal transition of the kidneys.

Bladder cancer (BC) continues to be a disease with a high mortality rate. Bladder cancer is the sixth for men and seventeenth for women in the incidence of malignancy worldwide. The invasion and metastasis of malignant tumors are caused by a sequence of processes, including loss of cell-cell and / or cell-matrix adhesion, proteolysis, and induction of angiogenesis. Different protease systems are involved in these processes, especially during the invasion and development of metastases. One such protease system is a plasminogen activation system or fibrinolysis system. Changes in the balance of plasminogen activation systems have been investigated in many types of malignancies, and these changes may not only indicate the functioning of this system but may also have prognostic significance. In malignancies, the components of this system are involved in the growth, invasion, and metastasis of tumors, affecting cell migration and angiogenesis. The main, but a well-studied component of the plasminogen activation system is serine proteinase – urokinase-type plasminogen activator (uPA). In contrast to uPA, tissue-type plasminogen activator (tPA) is characterized by a high affinity for fibrin and is involved in thrombolysis. Both types of plasminogen activators are synthesized in tumor tissues: tPA and uPA. The largest player among the inhibitors of fibrinolysis is the plasminogen activator inhibitor type 1 (PAI-1), involved in the pathogenesis of many cardiovascular diseases, as well as in cancer. The purpose of this study was to detect changes in the content of plasminogen activator tissue type tPA and PAI-1 in the blood plasma of patients with BC at different stages of the disease. The study involved 40 men who were verified with a diagnosis of BC. The content of tPA and PAI-1 in preoperative blood plasma was determined by enzyme immunoassay in ELISA modification. In our study, changes in the tPA and PAI-1 content of the blood plasma at different stages were identified, which can characterize tumor growth and invasion and can supplement existing disease information.

Introduction: As a result of alkaline substances entering the esophagus wall, necrosis occurs, as well as destruction of the mucous, submucosal and muscular layers of the esophagus. The cellular immune system plays an important role in regulating the various phases of the wound healing process, during which, depending on the time and through specific adhesion interactions, polymorphonuclear leukocytes, macrophages, and lymphocytes penetrate the site of the trauma and lead to an intensive proliferation of fibroblasts, endothelial cells, and keratinocytes. The substances of natural origins based on polyphenolic compounds are possible as a remedy for the normalization of physiological and biochemical parameters in a condition of various pathologies. Phaseolus vulgaris pods extract (PVPE) are an example of a rich source of bioactive compounds with proven human health benefits. Our results revealed imbalance of pro-inflammatory and anti-inflammatory cytokines in esophageal homogenates in rats with alkali burn of esophagus II degree, which can indicate a prolonged inflammation in the burned area. In the groups of animals with the alkaline burn of the esophagus, that were injected extract there can be traced a change of the indicators in the direction of normalization, indicating about the therapeutic effect of aqueous extract of pods of Phaseolus vulgaris. Objective: The cellular immune system plays an important role in regulating the various phases of the wound healing process, and can be used as a marker of pathological post-burn wound healing, Phaseolus vulgaris pods extract (PVPE) are an example of a rich source of bioactive compounds with proven human health benefits. The aim of the study was to investigate changes in cytokines levels in rat esophageal supernatants in the condition of alkali burn esophagus second degree (AEB 2) and treatment with Phaseolus vulgaris pods extract. Material and Methods: The animals were experimentally simulated with the alkali esophageal burn with 20% (grade II) solvent of NaOH. Levels of cytokines in esophageal tissue homogenates were done by ELISA. Results: In the present study, we investigate the imbalance of pro-inflammatory and anti-inflammatory cytokines in esophageal homogenates in rats with AEB 2, which can indicate a prolonged inflammation in the burned area. In the groups of animals with the AEB 2, that were injected extract there can be traced a change of the indicators in the direction of normalization. Conclusion: The administration of the extract, in conditions of alkaline burn of the esophagus, contributes change of the indicators in the direction of normalization indicating the therapeutic effect of aqueous extract of pods of Phaseolus vulgaris.

Kidney fibrosis is a key event in the development of chronic kidney disease, leading to end-stage renal failure. Unfortunately, there are now few drugs capable of preventing fibrosis in the kidneys, which is accompanied by the progression of chronic kidney disease in the terminal stage of renal failure. The results show the effectiveness of the use of a new dual-acting agent DM509 in the prevention of renal fibrosis using a model of unilateral obstruction of the ureter in mice. DM509 is both a farnesoid X-receptor agonist and a soluble epoxyhydrolase inhibitor. In this study, there were 8-12 week old C57BL/6J males undergoing surgery, which led to the development of unilateral ureteral obstruction and a control group. Mice received DM509 (10 mg/kg/day) or DM509-free solution together with drinking water for 10 days the day before surgery. Samples of kidney and blood tissues were collected at the end of the experiment. In the unilateral ureteral obstruction group, kidney dysfunction was detected, which was accompanied by increased urea nitrogen content in the blood compared to the control group (63 ± 7 vs. 34 ± 6 mg/d). The reduction of urea nitrogen in the blood by 36 % in mice with unilateral ureteral obstruction treated with DM509 is shown compared to mice with this pathology without treatment, which in turn proved the effectiveness of DM509 in preventing renal dysfunction. In mice with unilateral ureteral obstruction, which did not receive DM509, the development of kidney fibrosis with a high content of hydroxyproline in the kidneys and also increased collagen content in histological sections of the kidneys were detected. In the DM509 group, the renal and collagen hydroxyproline content was 34-66 % lower, indicating the effectiveness of this agent in the treatment of renal fibrosis. Thus, we have shown that the new DM509 is effective in preventing renal dysfunction and renal fibrosis using a murine model of unilateral ureteral obstruction.

Bladder Cancer (BC) is a common disease worldwide. Chronic inflammation is one of the key mechanisms for the development of BC. This study enrolled 40 patients. Preoperative plasma levels of IL-1β, IL-4, IL-6, IL-10, IL-12β, TNF-α and IFN-γ were determined by ELISA. In our study, we observed diverse changes in the levels of cytokines in patients with BC Stage I, II, III and IV. The levels of IL-1β was increased for stage I, stage II, and stage III. The level of TNF-α was increased for stage II, stage III, stage IV. The levels of IL-4, IL-6, IL-10 and IL-12β were increased in patients with stage III and IV only. The levels of IFN- γ declined for stage II, stage III and stage IV with the lowest levels in patients with Stage IV. In our study, we investigated alteration in levels of Th-1 and Th-2-like cytokine profile, but some deficiency in Th1- status discovered in patients with BC.

Background: The pathogenesis of hepatic encephalopathy (HE) is only partially understood. Beside ammonia accumulation in brain, a proinflammatory component has been suggested as precipitating event. Objectives: To evaluate the role of cytokines in cirrhosis for development of HE. Methods: Pro- and anti-inflammatory cytokine profiles were determined in rats with CCL4-induced cirrhosis and HE as well as in patients with cirrhosis either due to metabolic disorders or chronic hepatitis C virus (HCV) with various grades of concomitant HE and depression. Results: In the rat model and human cirrhosis a proinflammatory cytokine pattern (elevation of interferon gamma, interleukin [IL]-1β, IL-6) was registered which in humans correlated to the degree of HE and depression. The most prominent elevation of proinflammatory cytokines was observed in chronic HCV as an additional inflammatory stimulus. In all cases of cirrhosis a comparable background activation of anti-inflammatory cytokines (e.g., IL-4) was detected which was interpreted as a physiologic counterbalance mechanism. Conclusions: The degree of HE and depression correlated with a proinflammatory cytokine pattern. It suggests that beside ammonia elevation, inflammatory cytokines determine occurrence and severity of hepatic encephalopathies. Thus, it can be defined a preferential therapeutic target.

Bladder cancer (BC) is the 9th most commonly diagnosed cancer worldwide, with the highest rates in developed countries. About ¾ of the patients are men. The risk of developing of malignancies increases with chronic inflammation. Chronic inflammation can be caused by infections, autoimmune diseases and other factors. In conditions of chronic inflammation, cytokines are involved in leukocyte recruitment due to enhanced expression of cell adhesion molecules and chemoattraction. Cytokines are involved in the inflammatory response, for example, they are the main determinants of cellular infiltration, cellular activation and systemic response to inflammation. It is now well established that the role of cytokines is to participate in many aspects of biology, including malignancies. Cytokines can be secreted not only by proinflammatory cells but also by stromal cells and malignant cells, thus establishing a network with various factors that may be involved in the development of BC. The progression of BC causes an imbalance between local and general immunity. The relationship between neoplastic cells and their microenvironment is essential in the proliferation and invasion of malignant cells. The purpose of this work was to determine the content of cytokines IL-1b, IL-4, IL-6, IL-10, TNF-α and IFNγ in tumor tissues, depending on the grade of cell differentiation. In our study the content of IL-1b, IL-4, IL-6, IL-10 was higher in the wall samples of bladder cancer tissues in patients with G3-4 grade BC, which may be an important characteristic of malignant cells in BC, and explain the high invasiveness of BC. The content of TNF-α, IFNγ did not significantly change depending on grade. The data of our study are consistent with the data of previous studies conducted in the study of other neoplasms, which indicate the relationship of the studied indicators with the development of cancer.

Background: Urinary bladder cancer (UBC) is the ninth most frequently diagnosed cancer worldwide. Early diagnosis and treatment can improve survival of patients. In order to improve the diagnostic accuracy of non-invasive urinary bladder cancer, a large number of tumor markers have been identified and strictly assessed. Some of the best candidates as predictive markers in oncologic diseases belong to the family of matrix metalloproteinases (MMPs). The main focus of investigation in this study was on MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) as plasma biomarkers in patients with urinary bladder cancer (depending on tumor stage). Methods: Plasma levels of MMP-9 were significantly higher in all patients with UBC compared to control subjects. The plasma level of MMP-8 in Stage III UBC patients was 1.2 times higher than in control group. The plasma level of MMP-3 was higher in patients with bladder cancer of Stage I, II or III (compared to control subjects). Moreover, high plasma levels of TIMP-1 were observed in patients with UBC stages III and IV. Results: Overall, the measurements of circulating blood levels of MMP-1 and MMP-2 are progressively dissimilar among the various groups (UBC versus control subjects). Thus, changes in MMP levels may be used for monitoring and/or predicting progression of UBC.

Background and purpose: Shifts of the balance between coagulation and fibrinolysis play a crucial role in pathogenesis of cerebral ischemia. However, its relevance to post-acute disease period requires further elucidation. This study aimed to characterize whether hypercoagulation markers differ for patients in acute and the same patients in the post acute phase of ischemic stroke. Materials and methods: Systemic generation of hemostasis markers was monitored and fraction composition was described during one year of disease development and treatment. Results: Increased concentration of the markers of hypercoagulation in blood plasma of patients in acute as well as one year past acute phase ischemic stroke were shown. Thus, not all markers of hypercoagulation become relevant to norm one year past ischemic stroke. It's the first time characterization of the coagulation markers in acute and post acute period of the absolutely same group of patients was done. Our study demonstrates the difference in quantity and quality of the fractions of proteins with prothrombin origin and soluble fibrin monomer complexes which could be used as a potential target for the prevention of the stroke repetition. Conclusions: We assume that prothrombin plays the most important role in the development of pathology tested, hence it may provide future targets for therapeutic strategies.

The aim of this study was to investigate the effect of probiotic strains of Lactobacillus casei IMV B-7280, Bifidobacterium animalis VKL, B. animalis VKB on the pro- and anti-inflammatory cytokines production in Wistar male rats with monosodium glutamate (MSG)-induced obesity. It was established that neonatal administration of MSG to rats leads to increasing levels of the interleukin (IL)-1β and IL-12, and to decreasing ofthe IL-4, IL-10 and tumor growthfactor (TGF)-β levels in the bloodserum. After administration of the B. animalis VKL - B. animalis VKB - L. casei IMV B-7280 composition to obese rats the level of the IL-lP in blood serum wasn't differ from that in the obese rats, that didn't receive of the probiotic bacteria. But there was no statistically signifcant difference comparing with intact rats. The level of the IL-12B p4O in blood serum was decreased under influence of the B. animalis VKL - B. animalis VKB - L. casei IMV B-7280 composition (18.9%, p < 0.05) and B. animalis VKL (10.5%, p < 0.05) compared with obese rats, not receiving probiotic bacteria, but remained higher than in intact animals. After administration to obese rats ofthe B. animalis VKL - B. animalis VKB - L. casei IMV B-7280 composition the levels ofthe IL-4, IL- 10 and TGF-β increased in blood serum comparing with obese rats, not receiving probiotic bacteria. The level of the IL-10 also increased under influence of the B. animalis VKB, and IL-4 - under influence of the L. casei IMVB-7280. Our results suggest that these probiotic bacteria and probiotic composition are able to down-regulation the inflammation in rats with MSG-induced obesity but the strongest anti-inflammatory effects have probiotic composition. The ability of lactobacilli and bifdobacteria to alter the pro- and anti-inflammatory cytokines production, opens perspectives to create new treatments for obesity and metabolic syndrome based on probiotics.

Recently, in a large scale screening test, we have found that S-((1,4-dimethoxy-9,10-dioxo-9,10-dihydroanthracen-2-yl)methyl)4-aminobenzenesulfonothioate, a chemically synthesized thiosulfonate derivative of quinone, possessed an antiplatelet activity. To elucidate the mechanism of its antiplatelet action, a series of experiments were performed. The compound was found to inhibit the ADP-induced platelet aggregation. The inhibitory effect was dose-dependent on concentration and preincubation time. The derivative also disaggregated the preformed platelet aggregates induced by ADP.

We had characterized low-, medium- and high-molecular protein fractions of hepatocytes under development of glutamate-induced obesity and correction of nanocrystalline cerium dioxide and pioglitazone. Protein fractions were separated by electrophoresis using a 10 % Laemmli SDS-PAGE sodium dodecyl sulfate. Protein hepatocytes change under glutamate-induced obesity: high-protein reduced, and low-protein increased. Changes in hepatocyte proteins are consistent with previously established changes in protein content of hepatocytes under the influence HCD rich in fats and carbohydrates. We had noticed similar changes in protein of hepatocytes under correction cerium dioxide, but compared with glutamate-induced obesity, low proteins were lower. Pioglitazone didn't show a positive effect on hepatocyte proteins that may be associated with short-term administration.

Renal fibrosis is a contributor to chronic kidney disease and an important predictor of long-term prognosis. We developed a dual soluble epoxide hydrolase inhibitor-PPAR-γ agonist (sEHi/PPAR-γ), RB394, and investigated its ability to attenuate renal fibrosis in a mouse unilateral ureteral obstruction (UUO) model. RB394 efficacy was compared to an sEH inhibitor (sEHi), a PPAR-γ agonist rosiglitazone (Rosi), or their combination (sEHi + Rosi). All interventional treatments were administrated in drinking water 3 days after UUO induction surgery and continued for 7 days. UUO mice developed renal fibrosis with higher collagen formation and RB394 significantly attenuated fibrosis (P < 0.05). Renal expression of α-smooth muscle actin (α-SMA) was elevated in UUO mice and all treatments except sEHi significantly attenuated renal α-SMA expression. Renal mRNA expression fibrotic and fibrosis regulators were higher in UUO mice and RB394 and sEHi + Rosi treatments attenuated their expression. Renal inflammation was evident in UUO mice with increased infiltration of CD45 and F4/80 positive cells. RB394 and sEHi + Rosi treatments attenuated renal inflammation in UUO mice. UUO mice had renal tubular and vascular injury. Renal tubular and vascular injuries were attenuated to a greater extent by RB394 and sEHi + Rosi than sEHi or Rosi treatment alone. Renal mRNA expression of oxidative stress markers were significantly higher in UUO mice (P < 0.05). RB394 and sEHi + Rosi attenuated expression of oxidative stress markers to a greater extent than other interventional treatments (P < 0.05). These findings demonstrate that RB394 can attenuate renal fibrosis by reducing renal inflammation, oxidative stress, tubular injury, and vascular injury. In conclusion, RB394 demonstrates exciting potential as a therapeutic for renal fibrosis and chronic kidney disease.

Background: Oxidative stress is the main cause of mortality in chemical burn-induced esophageal injury. Melanin, a natural antioxidant compound from yeast-like fungus Nadsoniella nigra strain X- 1, has been shown to decrease the content of lipid peroxidation products after burn. The aim of this study was to investigate the protective effect of melanin in the treatment of esophageal injury after a chemical burn. Methods: A alkali burn model was used to induce injury to the esophagus in immature rats. Changes in the levels of malondialdehyde, secondary products of lipid peroxidation (thiobarbituric acid reactive substances), superoxidase dismutase, and catalase in the blood, as well as changes in the esophagus tissue, were examined. Results: Melanin decreased the content of lipid peroxidation products following burn injury. Melanin increased the activity of superoxidase dismutase and reduced the activity of catalase, as well as reduced esophagus oxidative injury in our chemical burn model. Conclusion: Melanin treatment may protect against chemical burninduced esophageal injury, possibly by inhibiting burn-induced oxidative stress.

The influence of the aqueous pods extract of kidney bean (Phaseolus vulgaris) on indicators of carbohydrate metabolism under the condition of experimental type 1 diabetes in rats was studied. It was shown that long-term oral administration of the extract at a dose of 200 mg/kg to rats leads to the decreasing of blood glucose and glycosylated hemoglobin in the background of chronic hypoinsulinemia conditions. The use of studied extract led to an increase of glycogen synthase activity in rat muscle cells and hexokinase activity in rat liver cells under the conditions of type 1 diabetes. It was estimated that administration of the aqueous extract to control rats and animals with studied model of diabetes increases GLUT-4 protein content in muscle tissue. Thus, the mechanisms of P. vulgaris hypoglycemic action can be related with the ability of the particular phytoconstituents directly effect on key intracellular elements of insulin target tissues carbohydrate metabolism under the conditions of type 1 diabetes.

According to the current understanding, the hyperactivation of platelets may lead to increased intravascular coagulation and thrombosis. Today a relevant issue is the search for new anti-thrombotic agents that are able to modulate the activity of platelet receptors, thus, influence the processes of activation and aggregation of platelets. The aim of this study was to investigate the effects of newly synthesized thiosulfonate derivatives on platelet aggregation. The activity of the compounds was tested in vitro using platelet-rich plasma. As a result of the screening test, structural formulas of four agents with high antiaggregative activity were established. These compounds inhibited ADP- and collagen-induced platelet aggregation in a dose-dependent manner. Two of these compounds were shown to be more effective inhibitors of aggregation induced by ADP (IC50 ~ 8-10 µM), as well as collagen (IC50 ~ 1.5-2.0 µM).

Insulin resistance is the characteristic feature of type 2 diabetes mellitus. This condition is manifested in decreased sensitivity of peripheral tissues to the biological action of insulin and is expressed in the inhibition of cell glucose uptake and metabolism in response to the hormonal stimulation. At the cellular level, impairments realized both at the receptor and the postreceptor levels and associated with changes in the content or dysfunction of the main molecules of the signal cascade can serve a molecular prerequisite to the formation of insulin resistance. Thus, the insulin receptor, as well as the other related signaling molecules can be considered as ideal therapeutic targets for the correction of insulin resistance and low molecular weight effectors, which act on the individual links of the insulin signaling cascade, may be positioned as a new generation of anti-diabetic agents. This review summarizes current knowledge on regulators of the insulin receptor cascade, main advantages and disadvantages of their effects on biological targets and prospects for their therapeutic use as anti-diabetic agents.

Despite the important role of Metalloproteinase (MMP) in β-cellular matrix remodeling there is clearly not enough data concerning the MMP proteolytic activity during first three weeks (early scar changes) of postoperative gastric ulcers. Thus the main aim of our work was the MMP, TIMP-1 and bFGF overall activity determination as well as their role in post-burn wound healing in case of the 2nd degree esophagus acid burn infliction. The greatest increase in the metalloproteinase activity and bFGF level was observed at 21st d of our experiment. In addition, the greatest increase in the TIMP-1 level in the esophageal mucosal was observed at 7th d after burn. These changes may be an evidence of chronic inflammatory processes and scar changes in rat esophagus after the EAB infliction.

Objective: We determined the plasma protein C and coagulation factor X activities, prothrombin, fibrinogen and soluble fibrin monomer complex (SFMC) content and performed the haemostatic screening coagulation time tests under acute ischemic stroke patients with or without type 2 diabetes mellitus, as well as evaluated the significance of biochemical haemostatic markers as predictors of mortality in stroke regardless of diabetes presence. Methods: The baseline data were collected from 87 patients during the admission. Neurological disturbances were assessed using the NIH stroke scale. The functional outcome was estimated using Barthel index. All patients underwent fibrinogen and SFMC (gravimetric methods), prothrombin level (ELISA), plasma protein C and coagulation factor X activity assessment, haemostatic screening coagulation time tests with coagulation analyzer, glucose and glycosylated hemoglobin content and BMI (body mass index) measurements. Results: The conducted research had established the changes of fibrinogen and SFMC levels in both investigated patient groups comparing to the control. The protein C activity was found to be significantly decreased in blood of patients with ischemic stroke with and without diabetes. There were differences in factor X activity change in patients with stroke only comparing with patients with diabetes and stroke and high level of this parameter as well as the increase in SFMC can be regarded as death predictors of stroke independently of diabetes mellitus presence. Conclusion: Among ischemic stroke patients with type 2 diabetes mellitus the differences were more significant for all Time tests of the coagulation cascade, but deviations of haemostatic biochemical markers were more pronounced in ischemic stroke patients without diabetes mellitus.

The study of molecular and biological aspects of the platelets functioning with the use of biochemical methods, new technologies of cell and molecular biology became the basis for understanding signaling cascades regulating the activation, adhesion and aggregation of these cells. In this review, the general modern information of the role of platelet membrane receptors in physiological and pathological processes of thrombus formation was performed. The possible role of platelet receptors as target of antiagregatory agents was analyzed. Also, new promising areas of searching for effective and specific antithrombotic agents were identified.

The influence of new derivatives of 9,10-anthraquinone with benzoylthiourea, thiazole, triazole and amino acid fragments on the activity of membrane-associated tyrosine kinases was investigated. Inhibitors of protein tyrosine kinase activity of the membrane fraction, as promising agents to search for new potential anticancer agents among the studied compounds, were discovered.

Nowadays the problem of insulin resistance, which has close cause-effect relations with obesity, diabetes mellitus type 2, metabolic syndrome, etc., is of urgent importance in medicine. We have revealed bidirectional changes of the IR content in crude membrane and cytosol of the adipose tissue cells in rats under conditions of the long-term high-energy diet. It is possible that reduction of the IR content in the adipose tissue cells has been predetermined by the disruption of lipid bilayer of adipocytes as a result of peroxidation processes activation. Increase in the IR content in the cytosol of cells of this tissue may indicate the activation of synthesis of this protein; however, it is possible that the IR translocation process disorder occurs due to the damage of plasma membrane, preventing the transfer of newly synthesized molecules of the receptor to the membrane and causing their accumulation in cytosol. The obtained results show that the tissues react to the long-term consumption of high-energy food in different ways. Thus, the content of insulin receptors in the plasma membrane of the muscle tissue cells increases, and, on the contrary, it decreases in adipose tissue cells. Such results may indicate that IR development at the late period of the experiment is likely the result of the adipose tissue cells disfunction. The obtained data may be of high significance in understanding the mechanism of the IR development under conditions of the long-term consumption of the high-energy food.

Today, cardiovascular diseases are one of the main causes of disability of the population. Most of the illnesses, including stroke, are accompanied by the appearance immunoglobulin G (IgG) in the blood circulation. According to the literature sources and previous experiments, it is known that IgG made influence on the hemostasis system. Objectives of the investigation are pure enzymes: thrombin, factor X, proenzyme of protein C and prothrombin under the influence of IgG fraction that were separated from the plasma of patients with atherothrombotic and cardioembolic ischemic stroke and patients with other neurological diseases. IgG was separated by affinity chromatography. Disc electrophoresis was used to control antibodies' purity. The main goal of the experiment is to test the potential influence of all fractions of separated IgG on the process of hydrolysis of specific chromogenic substrates by the key factors of the hemostasis system such as thrombin, factor X and protein C. The appearance of IgG in the blood stream during the atherothrombotic and cardioembolic ischemic stroke and other neurological diseases was proved. Concentration of the IgG in plasma of patients with cardioembolic ischemic stroke was significantly higher compared with healthy donors, whereas the IgG in plasma of patients with atherothrombotic ischemic stroke and other neurological disorders was not significantly different. Their potential ability to influence the enzymes such as thrombin, factor X, proenzyme of protein C and prothrombin was shown. It was proved that the antibody fractions of all experimental groups significantly accelerate the process of splitting chromogenic substrate by thrombin but inhibited cleavage of a specific chromogenic substrate by protein C.

Exogenous poisoning with alkalis takes the leading position among causes of acute poisoning. Esophageal burns as a result of accidental swallowing of caustic material are seen frequently in children ages 1 to 8 years. A burn wound is perhaps the most intense stress that a human body can suffer. In the place of chemical trauma localization the processes of synthesis and degradation of proteins increase. As a result the structure and functions of vital organs and immune system suffer. The inflammation process after burn injury is determines the changes in protein expression. In our research we have shown that chemical burn of the esophagus is characterized by decreased level of total proteolytic activity, total protein and development of endogenous intoxication of the body as indicated by elevated MMM level. Obtained results suggest that the development of chemical burns of the esophagus grade 2 is characterized by more substantial changes in the protein composition of blood compared with grade 1. An in-depth study of this disease has a crucial scientific and practical importance for development of pathogenically oriented methods of wound process healing after the chemical esophageal burns depending on the stage and extent of the burn process.