[Elements of endotoxin theory in human physiology and pathology].
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Biomedical subjects
Publications and source records attributed to M Iu Iakovlev.
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The role of the kidneys in development of endotoxin aggression and participation of the latter in impaired regulation of hemostasis was demonstrated basing on examination of 30 children with congenital urological pathology. In progressive decline of accumulative-excretory function of the kidneys, compensated chronic endotoxin aggression in children with urological diseases transforms into a subcompensated or uncompensated one with definite clinical manifestation: fever, aggravation of chronic pyelonephritis, marked DIC syndrome, macrohematuria.
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It is shown that leukocytes binding endotoxin of gram-negative bacteria via Fe-receptor mediated mechanism can be detected in blood smears after the treatment with antibodies to Re chemotype glycolipid conjugated with horse-radish peroxydase. After pretreatment of blood smears by a solution of endotoxin and then by conjugated antibodies to Re glycolipid some leukocytes binding endotoxin in vitro can be detected. It means that some reserves of endotoxin binding by leukocytes can be estimated by this immunomorphological method. The presence of such reserves is characteristic for healthy people and animals. Such reserves were enhanced in animals immunized with heated vaccine from Re Salmonella mutant. The reserves of endotoxin binding by leukocytes are absent in patients with salmonellosis, dysentery, meningitis, viral hepatitis A and B, peritonitis.
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The treatment of thin blood smears with antibodies to glycolipid of chemotype Re, conjugated with horseradish peroxidase, revealed that under physiological conditions about 3.5% of leukocytes bound endotoxin of gram-negative bacteria by means of the Fc-dependent mechanism. In addition, about 4.9% of leukocytes may bind endotoxin as the result of the treatment of blood smears with the preparation of glycolipid of chemotype Re. At the acute period of bacterial cerebrospinal meningitis leukocytes capable of binding endotoxin in the body or during the treatment of blood smears are practically absent. The conclusion was made that the binding of endotoxins by leukocytes had a protective character.
Literature and own data on endotoxin- induced injuries to endothelium are reviewed. It is shown that endotoxin can cause, hyperactivation of granulocytes, activation of complements, local endothelial injuries and some increase of vascular cell wall permeability, oxidation of low-density lipoproteins (LDL) and LDL-LPS complexes, binding of LPS with high-density lipoproteins (HDL) and some decrease of HDL ability to bind cholesterol, stimulation of endothelial and smooth muscle cell replication in local injuries to vessel wall. Low doses of endotoxin were found in blood plasma and on granulocytes surface in healthy and sick subjects. It is concluded that intestinal microflora endotoxin may play an essential role in pathogenesis of atherosclerosis.
The role of gram-negative bacteria endotoxin in infectious and non-infectious pathology is reviewed. It is shown that endotoxin may induce some injuries to the lungs, liver, kidney and blood vessels. It is suggested that intestinal microflora endotoxin may take part in the development of many pathological processes. The basis of the endotoxin effect is its capacity to interact with cell membrane. Intravascular blood coagulation and endotoxin shock resulting in the patient's death may occur at high doses of endotoxin.
The state of immunity to endotoxin of gram-negative bacteria in 45 patients with purulent meningitis caused by meningococci and Escherichia was studied. For comparison, similar characteristics in 35 practically healthy persons were studied. The state of immunity was evaluated by antibody titers in the passive hemagglutination inhibition test with chemotype Re glycolipid and by the content of polymorphonuclear leukocytes, capable of binding endotoxin in the blood of the examinee (in vivo determination), and leukocytes, capable of binding endotoxin during the treatment of thin blood smears (in vitro determination). Leukocytes bound with endotoxin were detected in blood smears in the enzyme immunoassay with the use of the conjugate of horse-radish peroxidase with antibodies to chemotype Re glycolipid. The study revealed that the acute period of bacterial meningitis was characterized by considerable suppression of antiendotoxin immunity. Leukocytes, binding endotoxin in vivo, as well as leukocytes, capable of binding endotoxin in vitro, were practically absent in the patients at the time of their admittance to the hospital. After treatment the characteristics of antiendotoxin immunity restored practically to normal values.
As shown in this work, antisera obtained after the immunization of animals with vaccines, prepared from Salmonella minnesota strain R595 (Re mutant) or Escherichia coli O14 having enterobacterial common antigen (ECA), as well as human antisera with elevated titers of antibodies to Re glycolipid or to LPS O14 (ECA), inhibited the development of experimental intestinal dysbacteriosis in white mice, induced by the administration of ampyox in large doses. The degree of the inhibiting action of the antisera was proportional to antibody titers, which was indicative of the fact that antibodies possibly played some role in the regulation of the amount of intestinal microflora.