ABSTRACT
Thyroxine (T4) inhibits the development of lipid metabolism disorders and experimental atherosclerosis in rabbits (model N.N. Anichkov). The study of the hypothalamic-pituitary system, thyroid, and the microvascular bed also revealed a beneficial effect of thyroxine on their morpho-functional state. Thus, the role of neuroendocrine regulation and disorders of microcirculation in atherogenesis shown.
Subject(s)
Atherosclerosis/drug therapy , Hypothalamo-Hypophyseal System/metabolism , Lipid Metabolism/drug effects , Microcirculation/drug effects , Thyroxine/pharmacology , Animals , Atherosclerosis/metabolism , Disease Models, Animal , Male , RabbitsABSTRACT
The modern concept of development of autoimmune diabetes mellitus is considered. The authors discuss possibilities to correct immune disturbances and support?--cells regeneration by therapy with the use of donor pancreatic cells, bone marrow cells (hemopoietic and stromal) and umbilical cord blood cells.
Subject(s)
Autoimmunity , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/therapy , Insulin-Secreting Cells/immunology , Insulin-Secreting Cells/transplantation , Islets of Langerhans Transplantation , Bone Marrow Cells/classification , Bone Marrow Cells/immunology , Cells, Cultured , Fetal Blood/cytology , Fetal Blood/immunology , Humans , Immune Tolerance , Immunosuppression Therapy/methods , Insulin-Secreting Cells/physiology , Regeneration , Stem Cell Transplantation , Stem Cells/immunology , Stem Cells/physiologyABSTRACT
This review describes up-to-date concepts of the type I diabetes mellitus pathogenesis and its complications. The leading role of the immune system malfunction in pancreatic islet of Langerhans and in vessel wall regeneration impairment is emphasized. It is suggested, that cell therapy of the type I diabetes mellitus with pancreatic islet and bone marrow cell transplantation promote beta-cell regeneration due to normalization of intracellular interaction in these tissues and immune homeostasis in whole organism.
Subject(s)
Bone Marrow Transplantation/methods , Diabetes Complications/therapy , Diabetes Mellitus, Type 1/therapy , Insulin-Secreting Cells/transplantation , Diabetes Complications/prevention & controlABSTRACT
Diabetes mellitus type 1 (DM-1) was modeled by a single intraperitoneal injection of streptozotocine (STZ) in a dose 65 mg/kg in two groups of Wistar rats: control (n=6) and test (n=14). Clinical and pathomorphological examinations of different organs were conducted for 4.5 months. It was found that the above model represents clinical picture and vascular diabetic complications (microangiopathy with parenchymal lesions) accompanied with destruction and depression of spleen activity. It is shown that rats, more resistant to the toxic action of STZ restore the ability for regeneration of the pancreatic islets and regress of glycemia and angiopathy, for positive changes in splenic structure and function.
Subject(s)
Diabetes Complications/pathology , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Type 1/complications , Disease Models, Animal , Rats , Animals , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Type 1/chemically induced , Male , Rats, Wistar , Streptozocin/toxicityABSTRACT
The article is dedicated to the pathogenetic mechanisms of the development of immune inflammation in the vascular wall, as well as hepatic functional disregulation in dislipidemia and atherosclerosis. The authors emphasize that the decompensation of the process of cell regeneration in actively functioning organs (vascular endothelium, hepatocytes) and a concomitant immune disregulation become the main factors of the progression of dislipidemia and atherosclerosis. The authors consider the conditions for and factors of cell therapy, based on the use of allogenic fetal hepatic cells and autological bone marrow cells.
Subject(s)
Atherosclerosis/therapy , Bone Marrow Transplantation , Dyslipidemias/therapy , Hepatocytes/transplantation , Animals , Atherosclerosis/etiology , Atherosclerosis/immunology , Atherosclerosis/physiopathology , Bone Marrow , Bone Marrow Cells/physiology , Cells, Cultured , Diet, Atherogenic , Disease Models, Animal , Disease Progression , Dyslipidemias/etiology , Dyslipidemias/immunology , Dyslipidemias/physiopathology , Endothelium, Vascular/physiology , Endothelium, Vascular/physiopathology , Follow-Up Studies , Humans , Liver/embryology , Liver/physiopathology , Liver Regeneration , Rabbits , Regeneration , Time Factors , Transplantation, HomologousABSTRACT
A comparative analysis of the impact of cell therapy (allogenic fetal liver cells, stem cells of autologic bone marrow) on lipid homeostasis, microcirculatory disturbances and structural changes in some organs was made using the atherosclerosis model in guinea-pigs. A positive effect of cell therapy on these parameters was established. The effect was stronger and prolonged after transplantation of stem cells. Atherogenic diet weakens the effect of cell therapy. Thus, cell therapy is more effective in restriction of atherogenic risk factors.
Subject(s)
Bone Marrow Transplantation/methods , Cell Transplantation/methods , Dyslipidemias/therapy , Animals , Atherosclerosis/pathology , Atherosclerosis/therapy , Diet, Atherogenic , Dyslipidemias/pathology , Guinea Pigs , Liver/embryology , Liver/pathology , Male , MicrocirculationABSTRACT
Effects of perfluoran, a plasma substitute with a gas-transport function, were studied at the stage of dyslipidogenic microangiopathy in rabbits. Changes in microcirculation, hemorheology, morphology of the liver, phospholipid composition of hepatocytic membranes were examined histologically, histochemically, electron microscopically and biochemically. Perfluoran produced a positive effect on microcirculation, phospholipid composition of hepatocytic membranes. Individual features of these parameters' dynamics were determined for animals.
Subject(s)
Antioxidants/pharmacology , Arteriosclerosis , Fluorocarbons/pharmacology , Liver Circulation/drug effects , Liver/ultrastructure , Animals , Antioxidants/administration & dosage , Antioxidants/therapeutic use , Arteriosclerosis/drug therapy , Arteriosclerosis/pathology , Arteriosclerosis/physiopathology , Cell Membrane/drug effects , Cell Membrane/metabolism , Fluorocarbons/administration & dosage , Fluorocarbons/therapeutic use , Hemorheology , Injections, Intravenous , Liver/blood supply , Male , Microcirculation/drug effects , Phospholipids/metabolism , RabbitsABSTRACT
We studied the effect of dyslipidemia on lipid metabolism, state of microcirculatory system, and morphological alterations in the aorta and liver of guinea pigs at the early stages of experimental atherogenesis. The important role of microcirculatory disorders in the development of regional pathology and atherosclerosis is confirmed. The proposed alimentary model can be used in the development of novel methods for prevention and treatment of atherosclerosis.
Subject(s)
Arteriosclerosis/metabolism , Blood Vessels/metabolism , Guinea Pigs/physiology , Hyperlipidemias/metabolism , Microcirculation/metabolism , Animals , Aorta/anatomy & histology , Aorta/metabolism , Arteriosclerosis/pathology , Blood Vessels/pathology , Cholesterol, Dietary , Hyperlipidemias/pathology , Lipid Metabolism , Liver/anatomy & histology , Liver/metabolism , Male , Microcirculation/pathologyABSTRACT
We evaluated whether perftoran can be used for the correction of structural and metabolic changes in the liver during alimentary atherosclerosis. Perftoran in a dose of 0.3 g/kg normalized the contents of phosphatidylserine, phosphatidic acid, and phosphatidylcholine in the plasma membranes of liver cells in rabbits feeding an atherogenic diet for 2 months. Architectonics of hepatic trabeculae returned to normal, the degree of granular and vacuolar degeneration in hepatocytes decreased, and phagocytic activity of macrophages increased. Individual peculiarities of the effect of perftoran on structural and metabolic changes in the liver were revealed.
Subject(s)
Arteriosclerosis/etiology , Diet, Atherogenic , Fluorocarbons/therapeutic use , Liver/metabolism , Liver/pathology , Animals , Cell Membrane/chemistry , Drug Evaluation, Preclinical , Male , Phospholipids/analysis , RabbitsABSTRACT
Changes in lipid metabolism and morphofunctional state of neuroregulatory and circulatory systems during dyslipidemia were studied in rabbits with high and low resistance to this risk factor. It was found that impairment of neuroregulatory systems plays an important role in initiation and progression of microcirculatory disorders and atherosclerosis. Atherogenic index is the most informative parameter for evaluation of pathological changes in the vascular system during dyslipidemia.
Subject(s)
Arteriosclerosis/metabolism , Arteriosclerosis/pathology , Hyperlipidemias/pathology , Animals , Hypothalamus/metabolism , Lipid Metabolism , Male , Pituitary Gland/metabolism , Rabbits , Risk Factors , Time FactorsSubject(s)
Adrenergic Fibers/pathology , Arteriosclerosis/drug therapy , Blood Vessels/innervation , Calcium Channel Blockers/pharmacology , Hypothalamo-Hypophyseal System/drug effects , Verapamil/pharmacology , Animals , Aorta/pathology , Arteriosclerosis/pathology , Arteriosclerosis/physiopathology , Hypothalamo-Hypophyseal System/physiopathology , Lipoproteins/blood , Male , Microcirculation , Rabbits , Tunica Intima/pathologyABSTRACT
Thymalin and alpha-tocopherol were studied for their effects on the morphofunctional status of the hypothalamopituitary neurosecretory system, thyroid, and adrenals in early atherogenesis. Correction of abnormal changes in the neuroendocrine organs restored lipid hemostasis, lowered the rate of lipid peroxidation, and prevented the progression of atherosclerotic changes in the great arteries.
Subject(s)
Arteriosclerosis/drug therapy , Hyperlipoproteinemias/drug therapy , Neurosecretory Systems/drug effects , Adjuvants, Immunologic/therapeutic use , Animals , Antioxidants/therapeutic use , Arteriosclerosis/pathology , Diet, Atherogenic , Drug Evaluation, Preclinical , Hyperlipoproteinemias/pathology , Male , Microcirculation/drug effects , Microcirculation/pathology , Neurosecretory Systems/pathology , Rabbits , Thymus Hormones/therapeutic use , Time Factors , Vitamin E/therapeutic useSubject(s)
Arteriosclerosis/pathology , Neurosecretory Systems/drug effects , Thymus Hormones/pharmacology , Vitamin E/pharmacology , Adrenal Glands/drug effects , Adrenal Glands/pathology , Animals , Arteriosclerosis/blood , Diet, Atherogenic , Hypothalamo-Hypophyseal System/drug effects , Hypothalamo-Hypophyseal System/pathology , Lipid Peroxidation/drug effects , Lipoproteins/blood , Neurosecretory Systems/pathology , Organ Size/drug effects , Rabbits , Thyroid Gland/drug effects , Thyroid Gland/pathologySubject(s)
Arteriosclerosis/complications , Enkephalin, Leucine/therapeutic use , Hyperlipoproteinemias/complications , Thymus Hormones/therapeutic use , Vascular Diseases/drug therapy , Animals , Aorta/pathology , Arteriosclerosis/metabolism , Arteriosclerosis/pathology , Lipid Metabolism , Lipid Peroxidation , Liver/pathology , Male , Microcirculation , Myocardium/pathology , Rabbits , Vascular Diseases/etiology , Vascular Diseases/metabolism , Vascular Diseases/pathologyABSTRACT
The influence of synthetic antioxidants (AOs) on hypothalamo-hypophyseal neuro-secretory system (HHNS), sympatho-adrenal system and microcirculatory bad in early stages of atherogenesis in rabbits (Anichkov's model) was studied. Correction of lipid metabolism and lipid peroxidation (LP) activation by AOs was accompanied by disappearing of structural changes in regulatory and microcirculatory systems, regression of atheromatosis in great arteries. Stabilization effect of AOs on neurons and erythrocytes membrane structures was noticed. Some distinctions in mechanism of action between mexidol and fenbutol were found. Thus, regulatory and microcirculatory disturbances, which appear on early atherogenesis stages and is the basis of chronic noninfectious pathology in different target-organs is reversible, for example trough LP correction.
Subject(s)
Antioxidants/therapeutic use , Arteriosclerosis/drug therapy , Arteriosclerosis/physiopathology , Adrenal Glands/physiopathology , Animals , Arteriosclerosis/blood , Diet, Atherogenic , Hypothalamo-Hypophyseal System/physiopathology , Lipoproteins/blood , Male , Microcirculation/drug effects , Neurosecretory Systems/physiopathology , Picolines/therapeutic use , Probucol/analogs & derivatives , Probucol/therapeutic use , Rabbits , Sympathetic Nervous System/physiopathology , Time FactorsABSTRACT
The dynamics of structural changes in the liver in experimental dyslipoproteinemia (DLP) and its correction was studied. Vessel-tissue changes found in the liver of rabbits in a short-term and stable DLP (4, 8 weeks) can be estimated as different stages of chronic active hepatitis. The microcirculation disorders and structural changes in the liver appeared at the early stages of DLP in the absence of atheromatosis in large arteries. The pathological changes in the liver existed 36 weeks after the rejection of atherogenic diet and correlated with DLP. Thus, DLP can be the risk factor as cardiovascular diseases as chronic nonspecific changes in the target organs.
Subject(s)
Hepatitis, Animal/etiology , Hyperlipoproteinemias/complications , Animals , Arteriosclerosis/complications , Arteriosclerosis/pathology , Cholesterol, Dietary/administration & dosage , Chronic Disease , Hepatitis, Animal/pathology , Hyperlipoproteinemias/pathology , Liver/ultrastructure , Male , Microscopy, Electron , Rabbits , Remission, Spontaneous , Time FactorsABSTRACT
The effect of antioxidant (AO) of the 3-hydroxypyridin class on microcirculatory system (MC) disorders of rabbits with dyslipoproteinemia (DLP) and its alimentary correction (the standard ration--9 months) was studied. Aorta, the intestinal mesentery microcirculatory bed, the microvessels adrenergic innervation, erythrocyte morphology were examined. The various lipoprotein fractions and lipid peroxidation (LP) products were studied in venous blood. After AO including into atherogenic diet (ATD) the lipid homeostasis disorders, the LP activation, MC disturbances, anomalous erythrocyte form appearance and atherosclerosis changes in aorta were less pronounced. Under the AO influence when DLP was corrected the initial level of lipid metabolism and LP restored, the MC disorders and the atherosclerosis changes in aorta regressed in a shorter period of time. The interrelation was observed between the DLP level, the structural and functional MC disorders and the extent of aorta atherosclerosis. Thus, DLP and LP correction at the early stages of pathological process can lead to the disappearance of MC disorders, what seems important for the prevention of atherosclerosis. The role of the LP activation in MC disorders in DLP and mexidol effect on them, especially in complex with DLP correction were evaluated.
Subject(s)
Antioxidants/therapeutic use , Hyperlipoproteinemias/therapy , Mesentery/blood supply , Pyridines/therapeutic use , Animals , Antioxidants/pharmacology , Arteriosclerosis/blood , Arteriosclerosis/physiopathology , Arteriosclerosis/therapy , Combined Modality Therapy , Diet, Atherogenic , Drug Evaluation, Preclinical , Hyperlipoproteinemias/blood , Hyperlipoproteinemias/physiopathology , Lipid Peroxidation/drug effects , Lipids/blood , Male , Microcirculation/drug effects , Microcirculation/physiopathology , Pyridines/pharmacology , Rabbits , Time FactorsABSTRACT
Lipid metabolism, intestinal mesentery microcirculatory bed (MCB) and erythrocyte (E) morphology in arterial and venous blood were studied in rabbits with experimental atherosclerosis (the model of N. N. Anichkov) and its spontaneous regression. The interrelation was determined between lipid metabolism (LM), MCB structural and functional disorders and anomalous E form appearance, and to a lesser extent the atheromatosis of the aorta. Microcirculatory (MC) disorders disappeared 12 months later in the regression of the early stages of atherogenesis (after 2 months of diet). The generalized character of MC disorders in LM suggests the existence of a trend towards MC reconstitution in prolonged regression in different organs and tissues. Thus, LM correction at the early stages of the pathological process can be accompanied by the disappearance of MC disorders, which seems important for the prevention of atherosclerosis.