Biomedical subjects
Publications and source records attributed to M Iu Iakovlev.
The role of endotoxin aggression in the development of hemostatic disorders was analyzed in 62 children who had undergone urgent and elective surgeries. It is demonstrated that indices of endotoxin-antiendotoxin system and hemostasis before surgery may be regarded as prognostic criteria for development of complications during and after surgery.
Endotoxin is a biologically active substance that has a lipopolysaccharide structure. It is found in the cell walls of microorganisms, principally gram-negative bacteria. By contacting with the cell, endotoxin enhances immunity. The findings suggest that acute myocardial infarction (AMI) occurs due to low immunity that remains the same at week 3 of the disease, thus the levels of antiendotoxin agents may be used in predicting AMI.
Bacterial endotoxins (BE) that are lipopolysaccharide complexes (LPS) are a structural component of the external membrane of gram-negative bacteria. In normalcy, BE interact with many types of cells in the mammals. In terms of the concentration, BE may cause cell damage or stimulate the production of many biological mediators, such as interleukins, prostaglandinds, alpha-TNF. Many gastrointestinal bacteria in humans are gram-negative and BE constantly enter the blood. In health, the absence of a toxic response to BE is explained by the presence of natural humoral and cellular antiendotoxic systems and the hepatic absorption of LPS. In patients with hepatitis A and B, the following indices of the blood antiendotoxic systems were determined: the level of antiendotoxic antibodies to Re-chemotype glycolipids was assessed by the passive hemagglutination reaction in the "Antiendotox-1-test"; the count of polymorphonuclear leukocyte (PMNL) fixating LPS on their own surface and endotoxin binding function of PMNL was in vitro measured by the strain ELISA and sandwich ELISA with Re-glycolipids, respectively (LPS-test); the endotoxin fixation function of serum high density lipoproteins (HDL) was also assessed. The humoral and cellular antiendotoxic systems in patients with mild advanced hepatitis A and B was studied when the disease was most clinically significant, at an early convalescence, and at convalescence itself. Finally, the findings indicate that there is a significant decrease in Re-antibody levels and there is a greater absorption ability of HDL than that in the control. Six different types of an antiendotoxic fixation reaction of PMNL were identified in patients with viral hepatitis in the different periods of the disease. The alterations observed may play an important role in the pathogenesis of toxemia in patients with viral hepatitis.
Alveolar macrophages (AM) represent a lung border system bringing about the protection of the organ from the environmental hazards, regulating cell and humoral response in the lungs, and eliminating endogenous toxic substances. However, in some situations AM are involved in the pathologic processes and even may serve as an initiating factor in the development of lung pathology. They realize their pathogenic effect in the bronchial asthma, acute respiratory distress-syndrome, pneumoconiosis releasing various biologically active compounds which take part in the formation of bronchial hyperreactivity, chemotaxis disturbances, haemostasis pathology. Particularly interesting is the possibility of lung tissue damage by AM when they interact with endotoxin-positive granulocytes.
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Due to its cell pool autoturnover, gram-negative intestinal microflora releasing the biologically active agent lipopolysaccharide may cause portal and systemic endotoxemias. Lipopolysaccharide may function in the activation of the polymorphonuclear leukocyte system and in complex antibacterial homeostatic processes, and, in some situations be the initiating factor in the development of various organ pathology, which is mediated by hyperactivated granulocytes.
With the help of immunofluorescent diagnostic system (specific immunoglobulins against glycolipid of S. minnesota Re-595) has been shown to permit the detection of endotoxin into eosinophil. Statistically significant differences in the occurrence of endotoxin in eosinophils of patients and healthy persons have been revealed. These data allow us to suppose that eosinophils are superaffined endotoxin-interaction cells of the human blood. Eosinopenia may be taken into account as an indirect marker of systemic LPS O-antigen mediated endotoxinemia.
An important role in the endotoxin immobilization and transport from the intestine into the portal circulation belongs to the granulocytes which are likely able to transfer lipopolysaccharide to Kupffer cells. If the endotoxin diffusion into the mesenterial microvessels increases and (or) the portal circulation speed decreases, the interaction of lipopolysaccharide with granulocytes may become irreversible and facilitate the development of the systemic endotoxemia and the leucocyte-mediated liver damage. Intestinal flora endotoxin takes part in the liver damage pathogenesis in various forms of hepatitis, cirrhosis in various forms of hepatitis, cirrhosis and conditions followed by the circulation deficiency.
The intestine being a natural depot of the gram-negative bacteria, may be the source of the systemic endotoxinemia in various pathologic processes followed by the increase of bacteria death, mucous membrane damage, pancreas endocrine function deficiency, liver barrier function depression, decrease of the portal circulation speed or its shunting. At the same time, the systemic endotoxinemia in itself may be one of the most important etiological factors of the various digestive organs injury. The authors observations and the literature suggest an important role of the endotoxin-positive granulocytes in the pathogenesis of the haemorrhagic infarct of the intestine, mesenteric vein thrombosis, destructive appendicitis and cholecystitis.
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Large amounts of lipopolysaccharides released in blood after death of Gram-negative bacteria are responsible for endotoxinemia and endotoxic shock. Endotoxin is eliminated from the body via different routes including the lungs. One of the mechanisms of lipopolysaccharides transport to the lungs, which respond with acute distress syndrome, is their transfer by polymorphonuclear leukocytes.
The proportion of misdiagnosis and errors in the treatment of urological diseases holds high, this being particularly true for iatrogenic pathology of the ureter and urinary bladder. The disturbances used to arise in response to traumatic gynecological and proctological surgical interventions and often remained undetected. The traumas are mainly induced by inaccurate use of the instruments and defects in surgical techniques. One of the serious iatrogenic complications is microcystic involvement of the urinary bladder as a result of radiotherapy for cancer. The method proposed by the authors for medical and social rehabilitation of such patients implies the replacement of the affected urinary bladder with isolated intestinal segment providing the recovery of natural uresis. Systemic endotoxinemia, another variant of urologic iatrogenesis, is associated with massive-dose antibiotics and extensive intracavitary operations. Early diagnosis and management of the conditions are supposed an effective protection against endotoxin shock.
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The myocardium of rabbits with endotoxin shock produced by two intravenous injections (0.1 and 0.3 mg/kg) of the typhoid fever bacillus antigen was studied histologically, histochemically, histoenzymatically and by polarization microscopy. Animals were killed by decapitation 0,5-1,5, 5-10, 24-30, 48-80, 120-194 hours after the 2nd injection; animals dying in the course of experiment were also examined. Morphological substrate of heart insufficiency, morphofunctional heterogeneity of cardiomyocytes of both inner and external myocardial layers were revealed. Hypoxia of a complex origin is the main cause of the above alterations.
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Literature data and the results of own research on the role played by lipopolysaccharide (endotoxin) of Gram negative bacteria in the initiation and progressing of atherosclerosis are summarized. Endotoxin promotes activation of all cells taking part in the formation of atherosclerotic plaques, induces the transformation of macrophages of arterial intima into foam cells as well as endothelial lesions and hyperlipidemia, reduces the ratio of cholesterol in lipoproteins of high specific density to total blood cholesterol. With chlamydiae and enterobacteria used as examples, the role of Gram negative bacteria and their endotoxin in the etiology and pathogenesis of atherosclerosis is discussed.
The functional state of cell-mediated and humoral antiendotoxin factors in patients with chronic viral hepatitides B and C has been studied. A decreased content of antibodies to glycolipid of chemotype Re and to Escherichia coli O14 with common enterobacterial antigen was shown to occur in these diseases. In addition, a decreased number of neutrophils, eosinophils and thrombocytes has been noted. The conclusion has been made that patients with chronic hepatitides are not protected from the pathogenic action of endotoxin penetrating from the intestines into the systemic blood stream.
Recent new data on the important role played by lipopolysaccharides (endotoxin) of Gram negative bacteria in physiology and pathogenesis of the most important human infectious and noninfectious diseases testify to the necessity of wide clinical trials of different methods for LPS detection in blood and other physiological fluids. Among presently available diagnostic methods for endotoxinemia detection, the highly sensitive LAL (Limulus Amebocyte Lysate) test in various modifications is most widely used. The LAL test is known to be non-specific, however many drawbacks of this test have been successfully overcome. The results of clinical studies on the determination of the LPS activity in the systemic blood stream and antibody titers to its most common determinants, as well as the reserves of endotoxin binding with granulocytes give grounds for optimistic evaluation of the future studies on the role of LPS in human physiology and pathology. In clinical practice both positive sides and drawbacks of the presently known methods for LPS detection, including the LAL test, must be borne in mind for the complex evaluation of endotoxinemia levels.