RESUMEN
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)-1ß and IL-12, and to decreasing ofthe IL-4, IL-10 and tumor growthfactor (TGF)-ß 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-ß 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.
Asunto(s)
Antiinflamatorios/administración & dosificación , Bifidobacterium/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Lacticaseibacillus casei/fisiología , Obesidad/terapia , Probióticos/administración & dosificación , Animales , Animales Recién Nacidos , Regulación de la Expresión Génica/inmunología , Inflamación , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Obesidad/inducido químicamente , Obesidad/inmunología , Obesidad/patología , Ratas , Ratas Wistar , Glutamato de Sodio/administración & dosificación , Glutamato de Sodio/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/inmunologíaRESUMEN
Connection of the cytokins profile with experimental hepatic encephalopathy (HE) in rats was studied. Investigation was conducted on 20 laboratory rats, in which HE was simulated, using СCl4 injection. The Ñnterleukins (ÐL) level, including, ÐL1ß, ÐL4, ÐL10 and interferonγ(IFNγ), was determined using immunoassay method with the help of polyclonal antibodies. Enhancement of the proinflammatory ÐL1ß and ÐÐФγ content in the rats blood serum while induced HE by 57.9 and 39.5% accordingly (p <0.05), comparing with such in a control and the compensation enhancement of the anti'inflammatory IL4 and IL10 level by 34.6 and 75.9% (p < 0.05) was established. The results obtained confirms the cytokins role in pathogenesis of HE, determination of their level constitutes significant criterion for the posttransplantation complications prog' nostication. Inflammation and profile of cytokins constitute the main target in therapy of HE in patients, suffering liver cirrhosis
Asunto(s)
Encefalopatía Hepática/inmunología , Interleucina-10/inmunología , Interleucina-1beta/inmunología , Interleucina-4/inmunología , Animales , Tetracloruro de Carbono , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Expresión Génica , Encefalopatía Hepática/inducido químicamente , Encefalopatía Hepática/genética , Encefalopatía Hepática/patología , Humanos , Inflamación , Interleucina-10/sangre , Interleucina-10/genética , Interleucina-1beta/sangre , Interleucina-1beta/genética , Interleucina-4/sangre , Interleucina-4/genética , RatasRESUMEN
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.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Phaseolus/química , Extractos Vegetales/farmacología , Administración Oral , Animales , Animales no Consanguíneos , Glucemia/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Femenino , Regulación de la Expresión Génica , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Hemoglobina Glucada/metabolismo , Glucógeno Sintasa/genética , Glucógeno Sintasa/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/enzimología , Hexoquinasa/genética , Hexoquinasa/metabolismo , Hipoglucemiantes/química , Masculino , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/enzimología , Extractos Vegetales/química , Ratas , Semillas/química , Estreptozocina , Residuos/análisis , Agua/químicaRESUMEN
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).
Asunto(s)
Plaquetas/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/síntesis química , Agregación Plaquetaria/efectos de los fármacos , Ácidos Tiosulfónicos/síntesis química , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Ésteres , Estructura Molecular , Inhibidores de Agregación Plaquetaria/química , Inhibidores de Agregación Plaquetaria/farmacología , Plasma Rico en Plaquetas/citología , Conejos , Relación Estructura-Actividad , Ácidos Tiosulfónicos/química , Ácidos Tiosulfónicos/farmacologíaRESUMEN
The main result of esophagus burn is the formation of scars, that caused by excessive synthesis of collagen and changes the balance of metalloproteinases and their tissue inhibitors. It was studied the activity of proteolytic enzymes, participation of MMP (metalloproteinase) and their tissue inhibitors (TIMP) in alkali burns of the esophagus 1st and 2nd degrees. We have shown a significant increase of TIMP level in homogenate after alkali burns of the esophagus (an average of 31-56% depend on of burn degree). We observed a reduced activity of serine proteinase after 1st degree burns on 15th, 21st day 35 and 18% respectively, after burns 2nd degree on 15th, 21st day 54 and 50%. The decrease of activity MMP after 1st degree burns on 15th and 21st day 30, 19%, respectively, in conditions of chemical burns 2nd degree on 15th and 21st day 30, 37%. These data may indicate the development of scarring after burn simulation of 2nd degree. Further investigation of the MMP and TIMP in the process of wound healing can be useful in creating effective approaches to prevent formation of post scarring of the esophagus.
Asunto(s)
Quemaduras Químicas/enzimología , Cicatriz/enzimología , Esófago/enzimología , Metaloproteinasas de la Matriz Secretadas/metabolismo , Membrana Mucosa/enzimología , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Factores de Edad , Animales , Animales no Consanguíneos , Quemaduras Químicas/patología , Cicatriz/patología , Esófago/lesiones , Esófago/patología , Membrana Mucosa/lesiones , Membrana Mucosa/patología , Ratas , Repitelización/fisiología , Hidróxido de Sodio , Índices de Gravedad del TraumaRESUMEN
We investigated the changes in key parameters of carbohydrate and lipid metabolism, which correspond to the clinical picture that accompanies the development of prediabetic condition on the background of chronic alcohol intoxication. From the analysis of glycemic curves obtained during the insulin-glucose test, a speed of glucose uptake by peripheral tissues increased at the 1st day (1.5 fold) and the third day (1.3 fold) of administration of alcohol solution. At the later periods, at 7 and 11 days of ethanol administration, a decreased rate of glucose uptake in animals with chronic alcohol intoxication was detected. We also detected an increased content of serotonin in the blood serum and a decreased (1.2 fold) serotonin content in rat brain during the whole period of development of chronic alcohol intoxication.
Asunto(s)
Alcoholismo/metabolismo , Glucemia/metabolismo , Etanol/administración & dosificación , Estado Prediabético/metabolismo , Alcoholismo/complicaciones , Alcoholismo/fisiopatología , Animales , Animales no Consanguíneos , Transporte Biológico , Encéfalo/metabolismo , Femenino , Insulina/metabolismo , Resistencia a la Insulina , Masculino , Estado Prediabético/complicaciones , Estado Prediabético/fisiopatología , Ratas , Serotonina/sangreRESUMEN
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.
Asunto(s)
Tejido Adiposo/metabolismo , Ingestión de Energía , Resistencia a la Insulina , Músculos/metabolismo , Receptor de Insulina/biosíntesis , Fracciones Subcelulares/metabolismo , Animales , Glucemia/análisis , Membrana Celular/metabolismo , Citosol/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Insulina/sangre , Transporte de Proteínas , Ratas , Ratas WistarRESUMEN
This study concerns the influence of streptokinase and antistreptokinase antibodies on rabbits platelets in blood plasma depleted of plasminogen. The immune complex streptokinase-antibody causes platelets activation, whereas other investigated immune complexes didnot express such activity. Platelets aggregation wasnot detected in any case. It was determined that streptokinase induces platelets activation in the rabbit plasma with high titre of antistreptokinase antibodies in absence of plasminogen.
Asunto(s)
Activación Plaquetaria/efectos de los fármacos , Estreptoquinasa/farmacología , Animales , Anticuerpos Monoclonales/farmacología , Complejo Antígeno-Anticuerpo/inmunología , Células Cultivadas , Plasminógeno/metabolismo , Activación Plaquetaria/inmunología , Agregación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/inmunología , Conejos , Estreptoquinasa/inmunologíaRESUMEN
Influence of proteins from the Agkistrodon blomhoffii ussuriensis snake venom on platelet activation and aggregation was developed on different model systems in vitro. It was shown that novel disintegrin (Blomus-B) and phospholipase A2 (Blopholipase) from the venom, activated platelets and inhibited their aggregation. Fibrino(geno)lityc enzyme (Blomulyse) does not activate platelets and has no effect on their aggregation stimulated by collagen, but inhibit ADP and adrenalin-stimulated platelet aggregation. Thrombin-like enzyme (Ancistron-Bu) activates platelets but has no effect on their aggregation. Obtained proteins can be used under development of new antiplatelet agents and as instruments for detailed elaboration and deep investigation of processes which proceed with participation of platelets.
Asunto(s)
Agkistrodon , Venenos de Crotálidos/química , Inhibidores de Agregación Plaquetaria , Agregación Plaquetaria/efectos de los fármacos , Proteínas , Animales , Hemostasis/efectos de los fármacos , Humanos , Técnicas In Vitro , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , Inhibidores de Agregación Plaquetaria/farmacología , Proteínas/aislamiento & purificación , Proteínas/farmacologíaRESUMEN
The study is devoted to research of the blood coagulation key proenzyme complexation process. It is prothrombin, and the E-fragment of fibrin can be a component in blood circulation. It is shown, that non-enzyme activation of prothrombin by the E-fragment proceeds as a result of formation of stable non-covalent prothrombin-E fragment complex. The cringle structures of prothrombin and the N-terminal site of beta-chain of E-fragment of fibrin are important for formation of the given complex. It has been defined, that other fragments of fibrin (D and DD) are not capable to induce amydolytic activity of prothrombin.
Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno/química , Protrombina/química , Coagulación Sanguínea/fisiología , Western Blotting , Cromatografía en Gel , Productos de Degradación de Fibrina-Fibrinógeno/fisiología , Humanos , Técnicas In Vitro , Protrombina/fisiologíaRESUMEN
The influence of streptokinase on plasminogen activators inhibitor of type I (PAI-1) was investigated with the use of model systems in vitro and in vivo. It was defined, that intravenous streptokinase injection causes an increase in PAI-1 content in mammals' blood plasma. Experiments in vitro have shown that the increase in PAI-1 concentration takes place as a result of streptokinase action. It occurs due to platelets activation with subsequent PAI-1 secretion from their a-granules. It is established, that PAI-1 is secreted by platelets both in free and in complex forms. The data obtained in the work, allow to assume, that the simultaneous substantial increase in PAI-1 content with platelets activation, as a result of streptokinase influence, can lead to new thrombotic complications risk.
Asunto(s)
Inhibidor 1 de Activador Plasminogénico/sangre , Estreptoquinasa/farmacología , Animales , Plaquetas/efectos de los fármacos , Western Blotting , Hemostasis/efectos de los fármacos , Activación Plaquetaria/efectos de los fármacos , Conejos , PorcinosRESUMEN
Platelet aggregation inhibitor--"Blomus-B" from Agkistrodon blomhoffii ussuriensis venom has been isolated by affinity and ion-exchange chromatography. The purified inhibitor is a novel non-enzymatic single-chain protein with molecular weigth of 13 kDa. "Blomus-B" causes a change of platelets shape and takes effect on ADP- and adrenalin-induced platelet aggregation.
Asunto(s)
Agkistrodon , Venenos de Crotálidos/química , Inhibidores de Agregación Plaquetaria , Agregación Plaquetaria/efectos de los fármacos , Animales , Cromatografía en Gel , Técnicas In Vitro , Peso Molecular , Inhibidores de Agregación Plaquetaria/aislamiento & purificación , Inhibidores de Agregación Plaquetaria/farmacología , Conejos , Factores de TiempoRESUMEN
Plasminogen activator "Ahh-32" from Agkistrodon halys halys venom has been isolated and purified using affinity and ion-exchange chromatography. The purified enzyme consists of the single peptide-chain with molecular weigth of 32 kDa. It can convert free plasminogen into active form--plasmin. "Ahh-32" was inhibited by DFP and benzamidine. Besides, the enzyme influences significantly the activation of plasminogen by streptokinase without having effect on analogical process in case of usage of tissue tipe plasminogen activator. The obtained protein can be used as an instrument under investigation of protein-protein interactions in haemostasis system.
Asunto(s)
Agkistrodon , Venenos de Crotálidos/química , Activadores Plasminogénicos/aislamiento & purificación , Animales , Benzamidinas/farmacología , Cromatografía de Afinidad , Cromatografía por Intercambio Iónico , Isoflurofato/farmacología , Peso Molecular , Activadores Plasminogénicos/antagonistas & inhibidores , Inhibidores de Proteasas/farmacologíaRESUMEN
It has been shown that rat pheochromocytoma PC-12 cells degraded fibrin clots in vitro. SDS-PAGE performed in the gels of different density and Western blotting using monoclonal antibodies against DD- and D-fibrin fragments demonstrated that both high and low molecular weight degradation products similar to those of fibrin hydrolysis by plasmin had been formed. Enzyme electrophoresis, chromogenic assay and enzyme-linked immunosorbent assay using tPA-specific antibodies demonstrated that PC-12 cells constitutively secreted both plasminogen and tPA. The results obtained allow using PC-12 cells as a model to examine the interaction of nerve cells with the fibrin clot.
Asunto(s)
Fibrina/metabolismo , Fibrinólisis , Plasminógeno/metabolismo , Activador de Tejido Plasminógeno/metabolismo , Animales , Anticuerpos Monoclonales , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Hidrólisis , Células PC12 , RatasRESUMEN
The paper is dedicated to the study of structure and physiological functions of tissue type plasminogen activator and its inhibitor PAI-1, changes of these parametres in normal and pathology conditions. The interrelation of the coagulation and the fibrinolytic system during the range of pathologies was studied. It was demonstrated that simultaneous analysis of the coagulation and fibrinolytic systems analysis allow to diagnose the thrombotic complications.
Asunto(s)
Enfermedades Cardiovasculares/metabolismo , Hemostasis , Inhibidor 1 de Activador Plasminogénico/fisiología , Activador de Tejido Plasminógeno/fisiología , Enfermedades Cardiovasculares/sangre , Humanos , Inhibidor 1 de Activador Plasminogénico/sangre , Inhibidor 1 de Activador Plasminogénico/metabolismo , Activador de Tejido Plasminógeno/sangre , Activador de Tejido Plasminógeno/metabolismoRESUMEN
The changes of the haemostasis system parameters were studied under treatment by streptokinase (Sk, thrombolytic agent of bacterial origin) with the use of model systems in vivo. We were especially interested in the study of the changing fibrinolytic system parameters such as tissue type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), plasminogen, alpha2-antiplasmin activities. After treatment by Sk the activity and quantity of t-PA were significantly increased while the activity of PAI-1 was decreased. The parameters of haemostasis system evidenced for a disbalance which occurred under treatment by Sk: decrease of fibrinogen levels and appearance of soluble fibrin and accumulation of fibrin degradation products. Thus analysis of the data has displayed besides the well-known Sk function the influence of Sk on the change of fibrinolytic system potential probably due to its effect on the endothelial cells.
Asunto(s)
Hemostasis/efectos de los fármacos , Estreptoquinasa/farmacología , Animales , Western Blotting , Electroforesis , Plasminógeno/biosíntesis , Inhibidor 1 de Activador Plasminogénico/sangre , Conejos , Porcinos , Activador de Tejido Plasminógeno/sangre , alfa 2-Antiplasmina/biosíntesisRESUMEN
It was shown that heterogeneous surfaces of two phases influence on fibrin films structures. The clot formed between two phases have the surface layer which is different from fibrin clot surface structure. Transmission electron microscopy revealed to determine the thickness of the surface layer for desAA- and desAABB-fibrin. The surface layer thickness is 25,8 and 29 nm for desAA- and desAABB-fibrin respectively.
Asunto(s)
Fibrina/metabolismo , Fibrina/ultraestructura , Fibrinógeno/metabolismo , Fibrinógeno/ultraestructura , Serina Endopeptidasas/química , Trombina/química , Biopolímeros/química , Electroforesis en Gel de Poliacrilamida , Humanos , Microscopía Electrónica de Transmisión , Serina Endopeptidasas/metabolismo , Trombina/metabolismoRESUMEN
Complex analysis of pregnant women haemostasis system before and after caesarian section allowed find the coagulation system activation. It was shown the thrombotic markers accumulation, AT III and protein C levels decrease. Also change of ratio fibrinolytic system components was exposed. Definition of t-PA and PAI-1 activities can be used as prognostic markers of the fibrinolytic chain haemostasis system disfunction.
Asunto(s)
Biomarcadores/sangre , Cesárea , Fibrinólisis/fisiología , Hemostasis/fisiología , Antitrombina III/metabolismo , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/fisiopatología , Femenino , Humanos , Plasminógeno/metabolismo , Inhibidor 1 de Activador Plasminogénico/metabolismo , Cuidados Posoperatorios , Embarazo , Cuidados Preoperatorios , Pronóstico , Proteína C/metabolismo , Activador de Tejido Plasminógeno/metabolismo , alfa-Macroglobulinas/metabolismoRESUMEN
Activators of fibrinogen, prothrombin and protein C isolated from venoms of Agkistrodon halys halys and Echis multisquamatus may be used as a tool both for thrombosis investigations in the model systems and for diagnostic in the clinical practice. The complex of diagnostic tests developed on the base of these activators allows to characterize the haemostatic system at different pathologies and as well as to determine the unbalance between separate components of haemostasis. The tests are approved on plasma of patients with heart diseases, ulcers, nephrites, hestoses etc. The tests are sensitive, informative, easy to use and do not require an additional equipment. They have no analogues in Ukraine.