RÉSUMÉ
AIM: to determine the efficiency of different doses of erythropoietin and carbamylated darbepoetin, to prove experimentally the possibility of increasing the efficiency of carbamylated darbepoetin when using the levorotatory stereoisomer of ethoxidol. MATERIALS AND METHODS: On the model of ischemia-reperfusion injury in male CD-1 mice that were undergone to contralateral nephrectomy, the nephroprotective effect of different doses of erythropoietin alfa, carbamylated darbepoetin, L-ethoxidol (the levorotatory enantiomer of ethylmethylhydroxypyridine malate), and the combined use of L-ethapylated carboxypyridine malate and L-etapoietin alfa was studied. The parameters of microcirculation and glomerular filtration rate were studied one day after 30-minute ischemia. RESULTS: It has been established that the prophylactic use of erythropoietin alfa and carbamylated darbepoetin in the model of ischemia-reperfusion injury of a single kidney reduces the severity of microcirculatory impairment and ensures the preservation of the glomerular filtration rate in dose-dependent manner. The synergistic effect of L-ethoxidol and carbamylated darbepoetin was found when these substances were used together. CONCLUSION: Prevention of ischemia-reperfusion kidney injury by analogs of human erythropoietin and their combination with ethylmethylhydroxypyridine derivatives is experimentally-proved.
Sujet(s)
Érythropoïétine , Maladies du rein , Défaillance rénale chronique , Animaux , Darbépoétine alfa , Ischémie , Rein , Souris , MicrocirculationRÉSUMÉ
The antiarrhythmic activity and acute toxicity of a series of 2-(2'-hydroxy-2')-substituted ethyloctahydropyrrolo[1,2-a]pyrazines were studied. Two most promising compound (PV-238) is characterized by high antiarrhythmic activity, broad spectrum of action, and low toxicity.
Sujet(s)
Antiarythmiques/pharmacologie , Coeur/effets des médicaments et des substances chimiques , Pyrazines/pharmacologie , Animaux , Antiarythmiques/usage thérapeutique , Antiarythmiques/toxicité , Troubles du rythme cardiaque/traitement médicamenteux , Femelle , Rythme cardiaque/effets des médicaments et des substances chimiques , Techniques in vitro , Dose létale 50 , Mâle , Pyrazines/usage thérapeutique , Pyrazines/toxicité , RatsRÉSUMÉ
The antiarrhythmic activity and acute toxicity of a series of 2-(2'-hydroxy-2'-substituted) ethyl-1,2,3,4-tetrahydropyrrolo[1,2- a]pyrazines were studied. Two most promising compounds (PV-168 PV-174) are characterized by a high antiarrhythmic activity, a broad spectrum of action, and low toxicity.
Sujet(s)
Antiarythmiques/synthèse chimique , Pyrroles/synthèse chimique , Animaux , Antiarythmiques/composition chimique , Antiarythmiques/pharmacologie , Troubles du rythme cardiaque/induit chimiquement , Troubles du rythme cardiaque/mortalité , Femelle , Cochons d'Inde , Dose létale 50 , Mâle , Souris , Pyrroles/composition chimique , Pyrroles/pharmacologie , Rats , Relation structure-activité , Tests de toxicité aigüeRÉSUMÉ
The authors have carried out experimental studies of thymogen action on the course of acute pancreatitis and acute peritonitis in white albino rat males. The preparation was introduced into the abdominal cavity early after the modeling and every 24 hours for 5 days. The results of the trial demonstrate that the degree of autoenzyme aggression (the data of blood serum alpha-amylolytic activity control) and the content of lipid peroxidation products (assessment of malonic dialdehyde quantity in tissue homogenate) were low in the experimental group as compared to the untreated animals. In the experimental group less pronounced depression of antiradical activity (superoxide dismutase and catalase activity control) was found, leukocytosis and leukocyte intoxication index were diminished. Thus, the efficiency of thymogen in acute inflammatory and destructive abdominal diseases has been proved.
Sujet(s)
Dipeptides , Pancréatite/traitement médicamenteux , Peptides/usage thérapeutique , Péritonite/traitement médicamenteux , Maladie aigüe , Animaux , Modèles animaux de maladie humaine , Mâle , RatsRÉSUMÉ
The anti-ischemic properties of thymogen were studied on an isolated heart model. Its cardioprotective effect was higher than that of dalargin and verapamil. The mechanism of the thymogen anti-ischemic action is realized without the participation of the opiate receptors and blockade of calcium entrance into the cardiomyocytes.
Sujet(s)
Antiarythmiques/pharmacologie , Dipeptides , Coeur/effets des médicaments et des substances chimiques , Ischémie myocardique/traitement médicamenteux , Lésion de reperfusion myocardique/traitement médicamenteux , Peptides/pharmacologie , Animaux , Antiarythmiques/usage thérapeutique , Calcium/métabolisme , 2-Alanine-leucine-enképhaline/analogues et dérivés , 2-Alanine-leucine-enképhaline/métabolisme , 2-Alanine-leucine-enképhaline/pharmacologie , Techniques in vitro , Magnésium/métabolisme , Contraction myocardique/effets des médicaments et des substances chimiques , Myocarde/cytologie , Myocarde/anatomopathologie , Myoglobine/métabolisme , Naloxone/métabolisme , Naloxone/pharmacologie , Antagonistes narcotiques/métabolisme , Antagonistes narcotiques/pharmacologie , Peptides/métabolisme , Peptides/usage thérapeutique , Rats , Vérapamil/métabolisme , Vérapamil/pharmacologieSujet(s)
Circulation cérébrovasculaire , Vertèbres cervicales , Traitement par les exercices physiques , Massage/méthodes , Ostéochondrite/rééducation et réadaptation , Spondylite/rééducation et réadaptation , Vertèbres thoraciques , Adulte , Association thérapeutique , Hémodynamique , Humains , Adulte d'âge moyen , Ostéochondrite/physiopathologie , Spondylite/physiopathologieRÉSUMÉ
The antiarrhythmic and antifibrillary effects of thymogen were determined by using 6 models of arrhythmias induced by aconitine, calcium chloride, strophanthin, low-sodium, reperfusion, and epinephrine. The dose-response curve was examined. The mechanism of thymogen's action was also studied.
Sujet(s)
Adjuvants immunologiques/usage thérapeutique , Antiarythmiques/usage thérapeutique , Dipeptides , Peptides/usage thérapeutique , Aconitine , Animaux , Troubles du rythme cardiaque/induit chimiquement , Troubles du rythme cardiaque/traitement médicamenteux , Chlorure de calcium , Modèles animaux de maladie humaine , Relation dose-effet des médicaments , Évaluation préclinique de médicament , Femelle , Cochons d'Inde , Mâle , Rats , Rat Wistar , Strophantines , Relation structure-activitéRÉSUMÉ
The influence of the local anesthetics hydrocortisone hemisuccinate and peptide drugs (thymogen and dalargin) on Na-H exchange activity and passive proton permeability of the sarcolemma was studied in experiments on isolated rat hearts. It was established that neither local anesthetics or hydrocortisone hemisuccinate, nor peptide drugs affected Na-H exchange activity. Lidocaine (5 mM), procaine (5 mM), hydrocortisone hemisuccinate (500-750 mg/l) inhibited sarcolemmal passive proton permeability by 40-70%. Aetaphone in the micromolar range attenuated the role of these effects in the antiarrhythmic action of local anesthetics and aetaphone.
Sujet(s)
Perméabilité des membranes cellulaires/effets des médicaments et des substances chimiques , Coeur/effets des médicaments et des substances chimiques , Hydrogène/métabolisme , Myocarde/métabolisme , Protons , Sarcolemme/effets des médicaments et des substances chimiques , Sodium/métabolisme , Animaux , Concentration en ions d'hydrogène , Techniques in vitro , Perfusion/méthodes , Rats , Sarcolemme/métabolisme , Facteurs tempsRÉSUMÉ
Five models of arrhythmias (aconitine-, calcium chloride- and low-sodium-induced models on rats, coronary artery ligation and reperfusion in dogs) were used to study the antiarrhythmic and antifibrillatory effects. The latters were not inferior to those shown by the well-known antiarrhythmics. The mechanisms of the action of dalargin are discussed in the paper.
Sujet(s)
Antiarythmiques/usage thérapeutique , Troubles du rythme cardiaque/traitement médicamenteux , 2-Alanine-leucine-enképhaline/analogues et dérivés , Aconitine , Animaux , Troubles du rythme cardiaque/induit chimiquement , Troubles du rythme cardiaque/physiopathologie , Chlorure de calcium , Modèles animaux de maladie humaine , Chiens , Évaluation préclinique de médicament , 2-Alanine-leucine-enképhaline/usage thérapeutique , Hémodynamique/effets des médicaments et des substances chimiques , Techniques in vitro , Lidocaïne/usage thérapeutique , Morphine/usage thérapeutique , Rats , Rat Wistar , Fibrillation ventriculaire/traitement médicamenteux , Fibrillation ventriculaire/étiologie , Fibrillation ventriculaire/physiopathologieRÉSUMÉ
Aethaphonium (dialicor) in 5-20 microM concentrations causes the dose dependent Ca decreasing in resting smooth muscle cells of rabbit aorta. In dose of 0.5-2.0 microM dialicor decreases the extent of transient in cytosolic-free calcium induced by application acetylcholine (10 microM) and high extracellular K (119 microM). This effect of dialicor is most expressed in attitude to the myocytes, containing the hyper K medium.
Sujet(s)
Calcium/métabolisme , Muscles lisses vasculaires/métabolisme , Propafénone/analogues et dérivés , Acétylcholine/pharmacologie , Animaux , Aorte , Cytoplasme/métabolisme , Techniques in vitro , Muscles lisses vasculaires/effets des médicaments et des substances chimiques , Potassium/pharmacologie , Propafénone/pharmacologie , LapinsRÉSUMÉ
In experiments on 126 rabbits and 156 guinea pigs, a study was made of specific activity, subacute and chronic toxicity of a new hemostatic feracryl-based plaster. The data obtained indicate a pronounced and stable hemostatic activity of the plaster in different types of wounds demonstrated in two species of animals, including hypocoagulation state. The plaster exerts no local irritative, resorptive toxic effect on tissues and possesses no allergenic properties.
Sujet(s)
Résines acryliques/usage thérapeutique , Bandages , Techniques d'hémostase , Résines acryliques/effets indésirables , Animaux , Cochons d'Inde , LapinsRÉSUMÉ
During experiments (128 rabbits) it was shown that under ischemia and hyperoxia the pharmacodynamics of lidocaine, anaprilin and ethacizine changed in centrogenic and peripheral arrhythmias induced by aconitine. Hyperoxia significantly potentiated the antiarrhythmic effect of the drugs except lidocaine action in centrogenic arrhythmias.
Sujet(s)
Antiarythmiques/usage thérapeutique , Maladie coronarienne/traitement médicamenteux , Oxygène/administration et posologie , Aconitine , Animaux , Troubles du rythme cardiaque/induit chimiquement , Troubles du rythme cardiaque/traitement médicamenteux , Maladie coronarienne/induit chimiquement , Évaluation préclinique de médicament , Association de médicaments , Femelle , Lidocaïne/usage thérapeutique , Mâle , Phénothiazines/usage thérapeutique , Propranolol/usage thérapeutique , LapinsRÉSUMÉ
Five variants of myocardial lesions of different degree were simulated in experiments on 8 dogs, 61 rabbits and 30 rats, namely micronecrosis, diffuse myocarditis, focal dystrophy, small- and large-focal myocardial infarction. The experimental models of heart lesions can be used for studying the pathophysiological mechanisms in cardiac pathology and evaluation of the therapeutic efficacy of new drugs in experimental pharmacology.
Sujet(s)
Cardiomyopathies/induit chimiquement , Modèles animaux de maladie humaine , Animaux , Cardiomyopathies/traitement médicamenteux , Chiens , Évaluation préclinique de médicament , Électrocardiographie , Femelle , Mâle , Infarctus du myocarde/induit chimiquement , Infarctus du myocarde/traitement médicamenteux , Myocardite/induit chimiquement , Myocardite/traitement médicamenteux , Myocarde/anatomopathologie , Nécrose , Lapins , RatsRÉSUMÉ
Experiments in 104 white mice subjected to hyperoxia at different regimens of oxygenation, carried out by means of mathematical modelling of three hyperoxic effects (bradypnea, convulsions, lethality) revealed the dependence of biological (physiological, toxic) effects of hyperoxia upon both components of the oxygenation regimen (oxygen pressure, time of exposure). The proposed concept of integral dose allows to determine pressure-exposure correlations corresponding to a given biological phenomenon and to prognosticate the effects of hyperoxia.
Sujet(s)
Oxygène/toxicité , Animaux , Chambres d'exposition à l'atmosphère , Relation dose-effet des médicaments , Oxygénation hyperbare , Dose létale 50 , Mâle , Souris , Modèles biologiques , Pronostic , Facteurs tempsSujet(s)
Modèles animaux de maladie humaine , Infarctus du myocarde , Animaux , Chiens , Femelle , MâleRÉSUMÉ
In dogs, pituitrin increases, and isadrin reduces, the tonicity of coronary arteries. Successive administration of the two agents to rabbits causes functional and metabolic unbalance of the heart, with resultant myocardial necrotic foci in the presence of blood hypercoagulation and heart muscle contractility disordered. The disorder of cardiomyocyte stereo architectonics is an essential element of the pathophysiologic mechanism of small-focal myocardial infarction.
Sujet(s)
Contraction myocardique , Infarctus du myocarde/physiopathologie , Myocarde/métabolisme , Nucléotides adényliques/métabolisme , Animaux , Coagulation sanguine , ADN/métabolisme , Chiens , Femelle , Mâle , Mitochondries du myocarde/métabolisme , Infarctus du myocarde/métabolisme , Infarctus du myocarde/anatomopathologie , Myocarde/ultrastructure , Phosphorylation oxydative , ARN/métabolisme , LapinsRÉSUMÉ
Oxygen, under conditions of elevated pressure 303.975 kPi, was shown to alter oxidative phosphorylation in mitochondria of rabbit heart. Inhibition of oxidative phosphorylation in intact animals and stimulation--in rabbits with myocardial ischemia were observed under conditions of high oxygen pressure. With an increase in frequency of the hyperbaric oxygenation treatments the inhibitory effect if high pressure oxygen was strengthened.