ABSTRACT
Metabolic disorders were evaluated in rats with alloxan diabetes mellitus after administration of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine (compound L-17). Administration of L-17 reduced the severity of metabolic disorders associated with diabetes mellitus. At the end of the experiment, the concentration of glucose, glycated hemoglobin, malonic dialdehyde, and catalase activity were significantly higher and peroxidase activity was significantly lower in the group of animals receiving L-17. The decrease of glycemia, glucose concentration, and glycated hemoglobin content was reached by the 3rd-4th week of the experiment. These data suggest that correction of biochemical parameters in rats with alloxan diabetes was reached after administration of L-17 for at least 3 weeks.
Subject(s)
Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Morpholines/pharmacology , Thiadiazines/pharmacology , Alloxan , Animals , Animals, Outbred Strains , Blood Glucose/metabolism , Catalase/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/physiopathology , Glycated Hemoglobin/metabolism , Injections, Intramuscular , Male , Malondialdehyde/blood , Peroxidase/blood , RatsABSTRACT
A significant role of the stress response to many different diseases prompted a search for new specialized and non-specialized anti-stress agents. This study examines the effect of the compound L17 from the group of 5-phenyl substituted-6H-1,3,4-thiadiazine-2-amines, on the manifestations of the stress response. The authors used a standard model of immobilization stress, in which an animal was immobilized on its back for 6h a day. Parameters of the morphological and functional states of the organs studied were measured and biochemical and enzyme-immunoassays were carried out on the first and second days. This study reveals that the main mechanism by which the L17 compound mediates of its anti-stress was by activation of macrophages on the second day of the experiments and the inhibition of apoptosis in the thymus. The results enable us to suggest that the compound L17 does not improve resistance to stress; however, it does lower the reaction to stress.
Subject(s)
Immunologic Factors/pharmacology , Stress, Physiological/immunology , Thiadiazines/pharmacology , Adrenal Glands/drug effects , Adrenal Glands/pathology , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Blood Glucose/analysis , Corticosterone/blood , Male , Pancreas/drug effects , Pancreas/pathology , Rats , Restraint, Physical , Spleen/drug effects , Spleen/pathology , Stress, Physiological/drug effects , Thymus Gland/drug effects , Thymus Gland/pathologyABSTRACT
It is reputed that the ideal therapeutic approaches to treatment of patients with acute coronary syndrome (ACS) and myocardium infarction (MI) should be aimed at the inflammation reaction triggers. This study investigated the effectiveness of the impact of L- 17 compound of the group of 5- phenyl substituted-6H-1,3,4-thiadiazine-2-amines upon the course of experimental MI as compared to the impact of a preparation, officially registered in Russia as an immunomodulator, Tamerit, belonging to phthalhydrazid derivative substance. Acute MI in rats was induced by left coronary artery coagulation. Histological study of the myocardium sections and biochemical analysis has been carried out at the 1st and 7th days of the experimental MI. The conducted investigations have shown that under the action of immunocorrectors the inflammation reaction character changes, exudative/destructive inflammation is replaced by a proliferative-cellular one. Animals' blood biochemical analysis at the background of L-17 and Tamerit introduction has shown a decrease of aminotransferases and lactatedehydrogenases activity in blood as compared to the reference group of animals' indicators, which is evidently caused by epicardial injury of myocardium and lesser amount of the alternative cardiomyocytes. At the same time, no noticeable difference in biochemical characteristics in groups, having been treated to immunomodulators of different chemical composition was identified, which is the sign of the essential similarity of their impact. Thus, immunocorrectors of different chemical groups (Tamerit and compound L17) diminish the volume of initial myocardial infarction and accelerate the granulation processes in course of MI, and represent a new category of treatment agents.
Subject(s)
Myocardial Infarction/immunology , Myocardial Infarction/pathology , Wound Healing/immunology , Animals , Hydrazines/therapeutic use , Inflammation/drug therapy , Inflammation/immunology , Inflammation/pathology , Male , Myocardial Infarction/drug therapy , Rats , Wound Healing/drug effectsABSTRACT
The influence of 2-morpholino-5-(thienyl-2)-6-H-1,3,4-thiadiazine (H-29) on the platelet aggregation has been studied in experiments on donor plasma in vitro. It is established that H-29 causes a decrease in the platelet interaction induced by ADP and arachidonic acid. The influence of H-29 on platelet aggregation was also studied in ex vivo experiments with intravenous and oral administration, and some parameters of plasmatic hemostasis were evaluated.
Subject(s)
Blood Coagulation/drug effects , Blood Platelets/drug effects , Morpholines/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Thiadiazines/pharmacology , Adenosine Diphosphate/pharmacology , Animals , Arachidonic Acid/pharmacology , Blood Coagulation Tests , Blood Platelets/cytology , Humans , Morpholines/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Count , Rabbits , Thiadiazines/chemical synthesisABSTRACT
The influence of new original 1,3,4-thiadiazines on the human platelet aggregation in vitro was studied. All substances inhibited the platelet aggregation induced by both ADP and arachidonic acid. 1,3,4-Thiadiazines L-19, H-30 and L-37 were the most effective inhibitors. Effect of the intravenous injection of L-19 in various doses on platelet aggregation and some parameters of plasmatic hemostasis were studied ex vivo.
Subject(s)
Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Thiadiazines/pharmacology , Adenosine Diphosphate/pharmacology , Animals , Arachidonic Acid/pharmacology , Drug Evaluation, Preclinical , Rabbits , Thiadiazines/chemistryABSTRACT
A series of new 1,3,4-thiadiazine derivatives have been synthesized and their effect on the human platelet aggregation in vitro has been studied. All the tested substances inhibit the human platelet aggregation induced by ADP and arachidonic acid in a broad concentration range. The most active 1,3,4-thiadiazines (L-19, L-28 and L-31) effectively inhibit platelet aggregation at concentrations within 0.01-1 mM.