[The role of neutrophils in ischemic and reperfusion myocardial injury].
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Biomedical subjects
Publications and source records attributed to D N Maianskiĭ.
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A method for evaluating the serum leukocyte-modulating activity (LMA) in patients with unstable angina pectoris (UAP) and acute myocardial infarction (AMI) is proposed. The method consists in measuring the total phlogogenic potential of the blood serum from increase or decrease in the chemiluminescence of donor leukocyte suspension after its incubation with patient's serum. LMA sufficiently accurately reflects the imbalance between the pro- and anti-inflammatory activities of the serum in patients with UAP and AMI. Predominance of the stimulating components in the serum predicts a more acute course and rapid development of AMI with complications. Inhibition of the leukocyte activity by patient's serum predicts a torpid protracted course of the acute coronary syndrome, indicative of an extremely low phlogogenic potential of the serum. The course of the acute coronary syndrome is complicated in both cases, requiring additional correction with anti-inflammatory drugs.
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The state of hemopoietic system at different stages of CCL4-induced liver fibrosis in mice and its reaction to stimuli was examined. At early stages of liver fibrosis (2 weeks of CCL4-administration) we observed a disinhibition of granulo-monocytopoiesis. This is manifested in an increase of the number of immature granulocytes, monocytes/macrophages and CFU-GM in the bone marrow. After 24 h of zymosan injection in this stage an increase of both bone marrow CFU-GM and CFU-E, and the rate of serum colony stimulating activity (CSA) occurred. On the contrary, in advanced liver fibrosis (16 weeks of CCL4 administration), the rate of both granulo-monocytopoiesis and erythropoiesis were decreased as compared with the preceding stage of the process and the response to zymosan became perverted: the number of CFU-GM was paradoxically decreased, while the number of CFU-E remained practically unchanged. The rate of serum CSA increased very poorly too. Thus, in advanced liver fibrosis the hemopoietic system is functionally defective and this factor may be important in development of fibrotic process in the liver.
The main attention in diagnosis of chronic exudative-destructive inflammation resulting from tissue injury should be focused on responsiveness and functional reserves of polymorphonuclear leukocytes (PML) from blood and lesion, the key effectors of inflammatory reaction. The ability of phagocytes to migrate into the lesion site and generate phlogogenic substances is to be analysed. Basing on the initial state of PML system and its functional limits one can predict the effectiveness of the treatment with antiinflammatory drugs and immunostimulators. In the diagnosis of mononuclear infiltrative inflammation the reliable assessment of macrophage responsiveness and their relations with lymphoid cells is of great importance.
The male (CBA X C57BL) FI mice received 125 mg of hydrocortisone per kg body weight intraperitoneally. The functional activity of neutrophils has been evaluated by means of nitroblue terazolium test (NBT-test) values taken before or after heat-killed S. marcescens cell stimulation in vitro by 2, 12, 24 h 3, 7 or 14 days post hormonal treatment. Throughout the 1st day after hydrocortisone administration the NBT-test values taken prior to as well as post microbial neutrophil stimulation were steadily increased. This effect could be seen as early as 2 h post hormone administration and it was linked with growing leukopenia and total decrease of blood granulocyte content. By the 3rd day the same very values turned up to become normal. The NBT-test values after microbial stimulation of neutrophils were 1.7 or 2.4 lower after hydrocortisone had been added to blood in vitro in a dose 3.5 X 10(-6) M or 7 X 10(-5) M.
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Bactericidal and migration activity of neutrophils was investigated in 53 patients with chronic bronchitis by means of a spontaneous and induced (6 stimulators) NBT-test and in 18 patients by means of skin fenestrae. A spontaneous NBT-test (sNBT-test) was shown to reflect the activity of an inflammatory bronchial process and to decrease by the end of therapy indicating complete remission. A stimulation index was in reverse correlation with sNBT-test indices. Response of neutrophils to various stimuli leveled down with an increase in sNBT-test indices. In an inflammatory bronchial process inhibition of neutrophil migration into a zone of inflammation was noted, particularly in patients with lingering exacerbation. Dependence of a stimulating effect on a sNBT-test value and disorder of neutrophil migration activity should be taken into account in administration of one or another immunostimulator.
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In rats with CCl4-induced liver cirrhosis the clearance rate of colloid carbon particles was more than 2 times lower than in control animals. Simultaneously the uptake capacity of liver Kupffer calls falls. The number of phagocytizing liver macrophages decreased. Along with the diminished functional activity of liver macrophages in cirrhotic liver, the total number of lung and spleen macrophages increased 1.5-fold, with their uptake capacity increasing 10- and 3-fold, respectively. The nitroblue tetrazolium dye reduction and methacrylate particles uptake by alveolar macrophages in vitro rises. The liver, lung, spleen and peritoneal macrophages during liver fibrosis become less sensitive to zymosan stimulation. The incidence of zymosan-induced liver infiltrates decreases 50-fold, while in the lungs they do not develop at all. Such a decreased macrophage reactivity may be closely linked with progressing, poorly reversible liver fibrosis.
Antitoxic effect of lysozyme was shown on a model of experimental acute toxic hepatitis of rats and mice. Administration of lysozyme to the animals in a dose of 5 mg/kg 24 hours before administration of carbon tetrachloride markedly decreased the level of morphological damages in the liver tissue and promoted a decrease in increased levels of alanine aminotransferase in blood serum. Higher levels of lysozyme in blood serum and cells of mouse peritoneal exudate 3 hours after administration of lysozyme were observed. The role of lysozyme as one of the main products secreted by activated macrophages in providing the general and antitoxic resistance of hepatocytes is discussed. Possible use of lysozyme as a hepatoprotective agent is suggested.