Biomedical subjects
Publications and source records attributed to M I Grutman.
Results are reported of a study of relationship of complement level, unspecific adaptative reactions, number of circulating immune complexes and some cellular parameters of the immunogram in patients with different forms of streptococcal infection. Different changes were found in acute and chronic forms of the disease. The possible mechanisms of development of these disorders are discussed.
It was established that administration of S. typhimurium lysate causes activation of the processes of free-radical oxidation. Introduction of unithiol in combination with magnesium sulfate returns the intensity of these processes to the initial level. Unithiol and alpha-tocopherol acetate protect the animals form lethal effects of S. sonnei lysate. Use of a combination of pharmacological agents consisting of unithiol, magnesium sulfate and alpha-tocopherol acetate in the treatment of patients with acute intestinal infections due to gram-negative pathogens (shigellae, salmonellae, proteus, klebsiellae, pseudomonas) resulted in decrease of the length of the intoxication and diarrhea syndrome, decrease of the frequency of repeat bacteria elimination and protracted forms of these infections, more rapid normalization of immune system functions.
The authors studied the activity of complement, nonspecific adaptive reactions of the body, the presence of antibodies to cross-reacting antigens of Streptococcus, the concentration of circulating immune complexes, some cellular characteristics of the immunogram in patients with different forms of streptococcal infection. The changes revealed allow a conclusion about the presence of autoimmune processes, most pronounced in chronic and recurrent forms of diseases. In the formation of streptococcal infection relapses, of the role is pathology of the complement system in combination with disorders in other components of nonspecific anti-infection resistance.
The morphological study of various types of liver cells revealed early reaction of sinusoid endothelial cells during the development of gram-negative infection (Salmonella typhimurium). The reaction of sinusoid endothelial cells is obviously connected with the direct effect of endotoxin because the first increase of endotoxin level in the blood is detected 60 min after injection of bacteria. The initial signs of Kupffer's cell activation are revealed at the same time. One of the manifestations of endothelial cell reaction is the increase of porosity of the barrier between the blood and Disse's space. It is accompanied by ultrastructural changes in hepatocytes. The second sharp rise of endotoxin level occurs 24 hours after the administration of bacteria and is accompanied by necrobiotic changes in the endothelial cells. It is assumed that the intensity of sinusoidal endothelial cell reaction and Kupffer's cell activation determine the degree of liver damage during the development of infection.
The experiments were carried out on mice of CBA strain. The animals received lysate of S. typhimurium in the dose of LD50. The injection of lysate was followed by an increase in the level of malonic dialdehyde (MDA) suggesting the lipid peroxidation (LPO) activation in the liver. At the same time the concentration of cyclic adenosine monophosphate (cAMP) in the liver and the lungs was decreasing, which was indicative of the decrease in the activity of prostaglandins. The injections of unithiol prevented both the activation of LPO and the decrease in the concentration of cAMP, that effect having been caused by the antioxidant action of unithiol. The repeated injection of unithiol protected the animals from death in intoxication by lysate of S. typhimurium and Shigella sonnei; the protection manifested itself in the 4.2 and 3.7-fold increase in LD50 respectively. Magnesium sulphate enhanced the protective action of unithiol.
An early response (activation) of the microcirculatory bed endothelial cells precedes other changes in the lung in the course of development of gram-negative infection. This response is manifested at various degree in different endotheliocytes and taking into consideration the microenvironment (alveolar macrophages, stromal elements, etc) is one of the main mechanisms in the development of infectious process.
Investigation of the changes of the mouse liver cells revealed early reaction of endothelial sinusoid cells and Kupffer cells after endotoxin application. During first 60 min. after endotoxin injection there were certain bulge of nuclear zone, changes of nuclear shape, appearance of microfilaments in the cytoplasm of endothelial cells. An increase in the number of the pores and fenestrae grouped in sieve plates was discovered in the endothelial cells. Their luminal surface formed the bubbles. Such changes of the endothelial cells can be described as their activation. Reaction of the endothelial cells of hepatic sinusoids and activation of the Kupffer cells were revealed at the same time.
The process of L-transformation of S. typhi was studied under conditions of diffusion chambers implanted into the abdominal cavity of rabbits with different immunological status. The process of L-transformation of S. typhi in vivo was induced by the action of humoral immunity factors. No unbalanced growth forms and L-forms of S. typhi were found to appear in the organism of nonimmune animals.
Experiments were conducted on 117 rabbits and cells of the macrophage cultures in vitro by the methods of clinico-laboratory, quantitative microbiological, immunological, electron microscopic and microcinematographic examination; a study was made of the interaction of the typhoid causative agent with the cells of the organism and the macrophage cultures and also of some aspects of the immune response during acute typhoid infection and carrier state. Infection was modelled by the enteral, subconjunctival and intrabonemarrow infection with 24-hour culture of the typhoid bacillus (strain Ty2 4446). Experiments demonstrated that structural reconstruction of both the causative agent and of the cells of the organism, of the culture macrophages and their organoids occurred in the course of the first hour after the infection. Homogenates of the lymphoid and myeloid tissues and also of the macrophages and polymorphonuclears possessed bactericidal activity against S. typhi. The degree of this activity largely depended on the pH of the medium. It was also shown that under conditions of the macrophage culture sodium aside inhibited the bactericidal activity of macrophages obtained from the intact and immune animals.
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It is shown that unithiol protects mice from death in intoxication by S. typhimurium and S. Sonnei lysates and in infection caused by S. typhimurium. Magnesium sulfate strengthens the protective effect of unithiol. It is suggested that the protective effect of unithiol is due to its antioxidant action.
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