Biomedical subjects

Egidijus Kevelaitis

Publications and source records attributed to Egidijus Kevelaitis.

10 recordsLinked to original sources

PubMed2006

Enhanced contractility of small blood vessels in JNK knockout mice.

The c-Jun N-terminal kinases (JNKs) form a subfamily of the mitogen-activated protein kinases (MAPK). These signalling pathways regulate various processes such as mitosis, cellular differentiation, stress response or apoptosis in multicellular organisms. There is rising evidence about the role of JNKs activities in neurodegenerative and metabolic diseases as well as in immunological disorders. The physiological functions of JNKs, however, remain to be elucidated. Recent data have demonstrated an essential role of JNKs in the cardiovascular system and the regulation of carbon hydrate and glucose metabolism. Therefore, we have investigated the contractility of blood vessels in mice with genetically deleted JNK1, JNK2, JNK3 and JNK2+3 isoforms and their respective wildtypes. The contractility of the isolated segments from A. carotis communis was measured by small blood vessel wire myograph. Contraction induced by 80 mM KCl was significantly increased in arteries from JNK2+3 double knockout compared to controls and single knockouts. The maximal contraction generated by the alpha-agonists phenylephrine or noradrenaline (10 microM) was significantly enhanced in JNK2+3 knockout arteries compared with arteries from the remaining strains. Inhibition of NOS by Nw-nitro-l-arginine did not change the pattern of vasoconstriction, but vasoconstriction by noradrenaline following NOS inhibition was significantly enhanced in the arteries from JNK2+3 double knockout mice. In conclusion, genetic deletion of JNK2+3 in mice results in altered contractility of carotid arteries and this might depend on the function of the smooth muscles rather than on the endothelium. These findings have implications for the long-term treatment with pharmacological JNK inhibitors for neurodegenerative or metabolic diseases such as stroke or diabetes.

Animals↗

PubMed2006

[Diabetes mellitus and cellular immunity].

Interaction between diabetes mellitus and cellular immunity is reviewed in several aspects. Importance of cellular immunity in the development of type 1 diabetes mellitus is discussed. Experimental mice models of this disease are presented which after the evaluation of similarities of immunologic parameters provide clues to potential mechanisms of the pathogenesis of type 1 diabetes mellitus. In an animal model of spontaneous type 1 diabetes mellitus, the non-obese diabetic mouse develops a spontaneous T cell-mediated insulitis, which is followed by overt diabetes. Disease can be transferred to young non-obese diabetic mice with diabetogenic T cells from older, affected animals. T cells can recognize various islet antigens, including insulin and islet cell enzyme called glutamic acid decarboxylase. Induction of T cell tolerance to these antigens retards the onset of diabetes in mice. Transgenic mouse models of type 1 diabetes mellitus confirm above-mentioned facts. Later alterations of cellular immunity are under the investigation. Disorders of mobilization and chemotaxis, phagocytosis and adherence of polymorphonuclear leukocytes, monocyte function, defects of acquired cellular immunity are thoroughly discussed. Diabetes mellitus, particularly poorly controlled diabetes, impairs different functions and links of cellular immunity. Infections, which are found relatively more frequently in diabetic patients and against which primarily cellular immunity protects, are also reviewed.

Animals↗

PubMed2006

Inotropic and lusitropic effects of Perilla frutescens (L.) Britton extract on the rabbit myocardium.

BACKGROUND: Common perilla (Perilla frutescens (L.) Britton) is a plant cultivated in many countries around the world. Although its immunomodulating and antioxidative properties are well known, there is a lack of data about the cardiotropic activity of the plant. The objective of this study was to determine the influence of Perilla frutescens extract on the myocardial contractility in vitro and as a food supplement in vivo. MATERIAL AND METHODS: Rabbits of the experimental group were fed with a supplement of 100 mg/kg of Perilla frutescens extract for 14 days. Rabbits of control group were fed with ordinary food. The maximal mechanical activity of isolated myocardial preparations, obtained from the rabbits of both groups, was tested during the perfusion with Ringer's solution containing 5 microM of adrenaline and 4.5 mM of CaCl2. For the assessment of the direct influence of Perilla frutescens extract on the myocardial contractility in vitro isolated heart preparations were perfused with 0.01, 0.1, and 1.0 mg/ml of Perilla frutescens extract. RESULTS: The maximum force of isometric contraction, maximum velocity of force development, and maximum velocity of relaxation were higher among the atrial and ventricular preparations from the experimental group, as compared with the control group. Perfusion of the myocardial preparations with different concentrations of Perilla frutescens extract revealed slight dose-dependent increase in the parameters of contraction and relaxation. CONCLUSIONS: The consumption of Perilla frutescens extract as a food supplement leads to an increase in the contractility of the rabbit myocardium. Perilla frutescens extract in vitro had a dose-dependent positive inotropic and lusitropic effect on the rabbit myocardium.

Animals↗

PubMed2005

Na+/H+ exchange inhibition in hypertrophied myocardium subjected to cardioplegic arrest: an effective cardioprotective approach.

OBJECTIVE: This study was designed to assess whether the protective effects of Na+/H+ exchange (NHE) inhibition, which have been largely demonstrated in normal hearts, are also manifest in a more surgically relevant model of hypertrophied myocardium subjected to cardioplegic arrest. METHODS: Left ventricular hypertrophy was created in 3-week-old rats by coarctation of the ascending thoracic aorta with a hemoclip. Eight weeks later, hearts were excised, isovolumetrically perfused and subjected to 1 h of potassium cardioplegic arrest followed by 2 h of reperfusion. Hearts were allocated to one of the following four groups: sham-operated and aortic banding hearts without any treatment or treated with the NHE inhibitor cariporide (1 micromol/L) given as an additive to cardioplegia and over the first 15 min of reperfusion. RESULTS: The major effect of cariporide was to reduce ischemic peak contacture and to improve post-ischemic diastolic function in both sham-operated and hypertrophied hearts. Total creatine kinase release over the first 45 min of reperfusion was significantly reduced in hypertrophied hearts treated with cariporide. The endothelium-dependent coronary vasodilation to 5-hydroxytryptamine was observed in all sham-operated hearts before cardiac arrest, however, it was significantly impaired following cardioplegic ischemia and reperfusion. Hypertrophied hearts demonstrated markedly impaired endothelium-dependent and -independent coronary vasodilations during both pre- and post-ischemic period that were not affected by the treatment with cariporide. CONCLUSIONS: The cardioprotective effects of the NHE inhibitor cariporide are also manifest in hypertrophied myocardium, which supports the potential usefulness of NHE inhibition in the setting of cardiac surgery.

Animals↗

PubMed2005

[The influence of common perilla (Perilla frutescens (L.) Britton) on non-specific cell-mediated immunity--phagocytosis activity].

OBJECTIVE: To examine the effect of plant preparations, obtained from Perilla frutescens (L.) Britton introduced in Lithuania, on non-specific cell-mediated immunity. MATERIALS AND METHODS: Non-specific cellular immunity was estimated by phagocytosis activity. The study of phagocytosis activity in peripheral rabbits blood (ability of leukocytes to phagocyte polystyrene latex parts of 0.8 microm diameter) was performed before (control) and after the experiments (injecting or administering per os perilla leaves extracts for one week and four weeks, respectively). The extracts were prepared from the leaves of perilla using repercolation method. For the studies in vitro the extract containing 1 mg/ml of perilla was used. In the studies in vitro two preparations of Perilla frutescens were used: 1) 32% sterile aqueous solution derivable from extract of perilla leaves and 2) 38% ethanol extract of perilla leaves. RESULTS. The phagocytosis activity studies in vitro showed that after 30 minutes of incubation with Perilla frutescens (L.) Britton extract phagocytosis activity was stimulated from 39+/-1.2 to 61+/-2.2% (p<0.001). Phagocytosis index increased from 1.26 to 1.79. The experiments in vivo showed that injected perilla leaves preparation to rabbits (1.2 mg/kg) increased phagocytic activity compared to the control (32.17+/-2.13%). The largest increase of phagocytosis activity was detected after seven days - 40.67+/-4.68%. Phagocytic activity of neutrophils in peripheral blood of rabbits increased after oral administration of perilla leaves extracts already after one week, but the largest increase of phagocytic activity was detected after four weeks (62.00+/-2.76%). CONCLUSIONS: Perilla frutescens (L.) Britton contains natural substances that increase the activity of phagocytes in vivo and in vitro and stimulate phagocytosis.

Administration, Oral↗

PubMed2004

[Etiology and pathogenesis of acute respiratory failure].

The aim of this study was to determine factors influencing acute respiratory failure and pathogenesis according to literature and clinical findings in critically ill patients. The term "respiratory failure" implies the inability to maintain either the normal delivery of oxygen to tissues and release or the normal removal of carbon dioxide from the tissues. There are many patients suffering from acute respiratory failure caused by nosocomial pneumonia, septic syndrome, aspiration, interstitial or alveolar lung edema, thromboembolism of a. pulmonalis, polytrauma and lung contusion, acute respiratory distress syndrome, long-term mechanical ventilation of the lungs, acute lung injury, status asthmaticus, rather massive transfusions of blood products, and lipid embolism in the intensive care unit. There are actually three processes involved: the transfer of oxygen across the alveolus, the transport to the tissues (by cardiac output), and the removal of carbon dioxide from blood into the alveolus with subsequent exhalation into the environment. Failure of any step in this process can lead to respiratory failure. Long-term hypoxia causes ischemic changes and dysfunction of brain, heart, kidney, lungs and can worsen the course of disease or cause higher mortality. It is important to determine the pathogenetic mechanisms of acute respiratory failure, estimate the main parameters and their interrelations and prescribe proper treatment.

Acute Disease↗

PubMed2004

[Compensatory reactions of immune system and action of Purple Coneflower (Echinacea purpurea (L.) Moench) preparations].

UNLABELLED: The objective of the study was to investigate the mechanisms of action of Purple Coneflower (Echinacea purpurea (L.) Moench) preparations on the immune system and to define which part of the plant is the most effective as an immunostimulator. MATERIAL AND METHODS: The extracts from overground parts and roots of Purple Coneflower were injected into rabbits at the dose of 1 ml/kg. The stimulation of T lymphocytes in vitro was tested by incubation of rabbit blood with the different concentrations of the Purple Coneflower preparation (10, 50, 100 microg/ml) and assessed by the method of spontaneous rosettes. The number of lymphocytes, which bind to heterogenic erythrocytes, was counted. In order to determine the local effect, 30 ml of Purple Coneflower preparation (95 mg of dry material/1 ml) was used for the rinsing of mouth cavity in humans. The reaction of phagocytosis was assessed by using latex particles and calculating phagocytosis activity and phagocytosis index. RESULTS: Purple Coneflower extracts from roots were more effective phytoimmunostimulators than those from overground parts. They significantly increased in vivo the number of leucocytes and lymphocytes, especially T lymphocytes, in peripheral blood of rabbits as compared with the control group (p<0.001). The stimulation of T lymphocytes by Purple Coneflower preparation in vitro was the most pronounced at the concentration of 50 microg/ml (20.8+/-1.01% of spontaneous rosettes, p<0.001 with control). An increase in concentration till 100 microg/ml was followed by non-specific inhibition (9.16+/-1.6% of spontaneous rosettes, p>0.05 with control). Purple Coneflower preparations activated phagocytosis of neutrophils in vitro and in vivo. After rinsing mouth cavity with 30 ml of Purple Coneflower root preparation for 15 minutes, phagocytosis activity was significantly increased till 36% (p<0.05 as compared with the control (27%), where physiological solution was used for the rinsing). This local application of Purple Coneflower root preparation has significantly increased phagocytosis index up to 1.03 (p<0.02 as compared with the control index (0.65) after rinsing of the mouth cavity with physiological solution). CONCLUSIONS: Purple Coneflower preparations from roots activate the cellular immunity and stimulate phagocytosis of neutrophils in vitro, in vivo and after rinsing of mouth cavity.

Adjuvants, Immunologic↗

PubMed2004

[Effect of hypodynamic stress on the adrenaline-induced contraction of the smooth muscles of the thoracic aorta].

UNLABELLED: Aim of the study was to investigate the influence of hypodynamic stress on the contractile responses of the smooth muscles to adrenaline. MATERIAL AND METHODS: Hypodynamic stress was induced by fixation of Chinchilla rabbits (n=8) in the metal hutches for 48 days (B. M. Fiodorov method). Rabbits in the control group (n=8) were kept in ordinary conditions of vivarium for the same period of time. Isolated preparations of the thoracic aorta were obtained from both groups of the rabbits. The contractile responses of the thoracic aorta preparations to 10(-7)mol/l and 10(-6)mol/l of adrenaline were registered in vitro by micromechanographic device under isometric conditions. RESULTS: The contractile responses of the thoracic aorta preparations under the influence of adrenaline at concentration 10(-7)mol/l were not significantly higher (p>0.05) and at concentration 10(-6)mol/l they were significantly higher (p=0.021) in rabbits after hypodynamic stress than in control ones. CONCLUSION: Long-term hypodynamic stress in rabbits leads to the significantly increased adrenaline-induced contraction of the smooth muscles of the thoracic aorta.

Animals↗

PubMed2003

[Role of nitric oxide and other endothelium-derived factors].

The endothelial cell layer displays the features of a distributed organ and has a variety of biological functions such as keeping the balance between coagulation and fibrinolysis, expression of adhesion molecules for cells in the immune system, metabolism of noradrenaline and 5-hydroxytryptamine, and conversion of angiotensin I and bradykinin. The endothelium also regulates the underlying smooth muscle layer and vascular tone by release of endothelium-derived relaxing factors such as nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF) as well as vasoconstricting factors such as endothelin, superoxide (O(2)(-)), and thromboxane. We have reviewed the nature, mechanisms of action, and role of these factors in regulation of vascular tone, with special emphasis on NO. By a process catalyzed by NO synthase, NO and citrulline is formed from the substrates molecular O(2) and L-arginine. The main receptor for NO is guanylyl cyclase leading to formation of smooth muscle cyclic guanosinmonophosphate and relaxation. EDHF is an endothelium-derived factor causing vasorelaxation of the underlying smooth muscle layer by hyperpolarization. The nature of EDHF is still unknown, but several candidates for EDHF have been proposed such as potassium ions, hydrogen peroxide, and epoxyeicosatrienoic acids. Prostaglandins such as prostacyclin and prostaglandin E2 binds to specific receptors followed by increases in cyclic adenosinmonophosphate and vasorelaxation, while contractile prostaglandins constrict vessels by activation of thromboxane and endoperoxidase receptors. Superoxide anions induce contraction of vascular smooth muscles cells by scavenging NO. Endothelin is a potent endothelium-derived contractile factor. The synthesis of endothelin-1 is induced by hypoxia, thrombin, interleukin-1, transforming growth factor-beta1, vasopressin, and catecholamines. Cardiovascular risk factors like age, hypertension, and hyperlipidemia are associated with impaired endothelium-dependent vasodilation either as a consequence of increased inactivation of endothelium-derived vasodilators or increased formation of endothelium-derived contracting factors. This imbalance of endothelium-derived factors plays a role for development of atheroslerosis and ischemic vascular diseases.

Age Factors↗

PubMed2003

[Mechanisms of nitric oxide synthesis and action in cells].

Nitric oxide (NO) is a free radical gas, which is a product of reaction between molecular oxygen and L-arginine. Great diffusibility of nitric oxide determines its quick three-dimensional distribution around the cell which is a source of nitric oxide. Single electron makes it into very reactive radical, interacting with metals incorporated in enzyme structure, heme, superoxids, oxygen, etc. The synthesis of nitric oxide is catalyzed by enzyme nitric oxide synthase (NOS) which has three isoforms: endothelial nitric oxide synthase, neuronal nitric oxide synthase, macrophagal nitric oxide synthase. Due to mechanisms of action NOS enzymes are also classified as constitutive nitric oxide synthase and inducible nitric oxide synthase. Constitutive forms are found in cytosol and membranes, they are dependent on Ca(2+)/calmodulin concentration and are extremely important in the regulation of physiological processes. Inducible forms are synthesized in cells after induction by bacterial endotoxins or cytokines, do not depend on Ca(2+)/calmodulin concentration and are being considered as pathological isoforms. It is thought that nitric oxide synthase catalyses transport of electrons for reactions between molecular oxygen and L-arginine. This consideration based on fact that flavine co-enzymes and hem are found as structural units in nitric oxide synthase. Although all isoforms catalyze the same reactions, every one of them has its own unique structure and localization. These features determine differences of activation pathways as well as specificity of inhibitors. The characteristic features of nitric oxide and functional differences among the nitric oxide synthase isoforms determine its different role in regulation of many physiological and pathophysiological processes.

Cytoplasm↗