Immunocorrective therapy of the traumatic syndrome

The effect of combined application of thymalin and plaferon in the prophylaxis and treatment of traumatic syndrome has been investigated in rats. The survival rate was taken as the criterion of efficiency, the mechanism of the effect obtained being estimated at the level of immunological protective factors. Traumatic shock was induced by Kennon's method in Wistar male rats weighing 200-250 g. Post-traumatic syndrome has been observed within 7 days. The combined application of thymalin and plaferon has increased the survival rate twice within the first 7 days. Immunomodulating effect of the combined application of thymalin and plaferon on the 7th day of traumatic syndrome was most marked at the level of total T-lymphocyte population, theophylline-sensitive T suppressors and lysozyme blood serum activity.     

Morphofunctional status of the thymus in guinea pigs exposed to thymus and bone marrow preparations

Study of the effect of the polypeptide thymic factor (thymalin) and the polypeptide bone marrow factor (hemalin) on the morphofunctional status of the thymus in guinea-pigs has shown that injection of thymalin into animals increases the count of small lymphocytes whereas injection of hemalin the count of medium-sized lymphocytes and lymphoblasts. Injection of thymalin magnifies the size of the nuclei of the reticuloendothelial cells.     

Differentiation characteristics of circulating and bone marrow hematopoietic stem cells and the effect of thymus factors

Circulating hemopoietic stem cells (HSC) considerably differ from bone marrow HSC in active erythroid differentiation. After thymectomy of adult animals the number and differentiation of blood HSC remain unchanged, whereas during the cloning of bone marrow cells, a decrease in the number of granulocytic colonies is revealed. In in-vitro experiments, thymalin does not influence the number or differentiation of circulating HSC. On the contrary, in experiments made in vivo, it dramatically lowers erythroid specialization of blood HSC in thymectomized and sham-operated mice, which is followed by the diminution of the total number of circulating HSC. Differentiation of thymectomized mice bone marrow stem cells is completely normalized after thymalin injection. Sham-operated and thymectomized animals' HSC stimulated by thymalin injection become similar to bone marrow cells of normal mice as regards the trend of differentiation. Thymalin injection is likely to change the bone marrow HSC differentiation profile, thereby preventing the release of the cells with erythroid-oriented differentiation from the bone marrow to blood. The influence of thymalin on HSC is mediated by the environmental component which is present in the bone marrow and absent from the peripheral blood.     

Effect of thymalin on the immunological indices and morphofunctional structure of the uterus in guinea pigs with endometrial hyperplasia

The efficiency of usage of the preparations of thymalin in hyperplasia of endometrium has been studied in the experiment on 125 female guinea pigs. Indicated pathology was caused by the introduction of oil solution of synestrol during 19 weeks. It is determined that marked hyperplasia of endometrium is developing as a result of prolonged introduction of synestrol in experimental animals and the decrease of the amount of T- and B-lymphocytes takes place. The use of thymalin results in normalization of indexes of immune system and in partial normalization of morphologic structure of endometrium.     

Dynamics of immunological indices in patients with chronic viral hepatitis B and the effect of thymalin therapy

The work deals with the results of the study of T-lymphocytes and their subpopulations (active, thermostable, theophylline-sensitive and theophylline-resistant) in 102 children with chronic viral hepatitis B, depending on the effectiveness of thymalin therapy. The sensitization of lymphocytes to specific antigens was studied. Among patients with chronic viral hepatitis B and cirrhosis of the liver the homozygous phenotype of haptoglobin is registered essentially more frequently (63.6% and 82.4% respectively) than among healthy persons (44.0%). The patients of this group showed a decrease in the number of T-lymphocytes, disturbances in the suppressor/helper ratio: hypersuppression in persisting hepatitis and hyposuppression in active hepatitis. In 71.6% of cases thymalin therapy produced an effect manifested by clinico-biochemical remission, an increase in the number of T-lymphocytes, thermostable cells and the normalization of the T-suppressor/T-helper ratio. In these patients sensitization to HBsAg essentially decreased (from 30.5% to 13.9%), while sensitization to human liver lipoprotein retained its high level even after treatment with thymalin.     

Nonspecific and antigen-specific adhesiveness of circulating lymphocytes in dysentery patients undergoing combined therapy using thymalin and indomethacin

Nonspecific adhesiveness of lymphocytes to polyacrylonitrile fiber and the antigen-specific adhesiveness of T-lymphocytes to Shigella flexneri pellicular immunosorbent have been studied in dysentery patients. Short courses of treatment with indomethacin, but not with thymalin (the preparation of thymic hormones), used for immunomodulation, have accelerated the normalization of nonspecific lymphocyte adhesiveness during regression of the disease, while indomethacin, in contrast to thymalin, inhibits antigen-specific T-lymphocyte adhesiveness which increases with the development of immune response.     

Effect of thymagen, thymalin and vilosen on the cAMP and cGMP levels and phosphodiesterase activity in spleen lymphocytes during sensitization and anaphylactic shock]

It is established that the effect of thymus-derived species is connected with the cyclic nucleotide system. The action of thymus-derived immunocorrectors (thymalin, thymagen, vilosen) on catabolic processes of cyclic nucleotides has been observed under conditions of anaphylaxy and sensibilization. They show that sensibilization of the animal is bound up with a decrease of the cAMP/cGMP ratio. Anaphylaxis induces levelling of the cAMP/cGMP ratio up to the reference level. So, activity of enzymes of cyclic nucleotide catabolism grows due to the influence of thymogen, thymalin and vilosen in lymphocytes of sensibilized guinea pigs and tends to an increase in lymphocytes of anaphylaxis-treated animals.     

Colony-forming units of the bone marrow and spleen of immunodeficient mice after stimulation of the cells with thymalin

It has been previously demonstrated by the authors that histological characteristics of colony-forming units (CFUs) in normal mice prove a certain shift in their differentiation in erythroid direction comparing to the bone marrow CFUs. Thymectomy of mature animals is accompanied with weakening growth of granular colonies at cloning of the bone marrow CFUs and with loss of stability in direction of splenic CFUs differentiation. Polypeptide preparation of the thymus--thymalin stimulates growth of the granulocytic colonies from the splenic CFUs in thymectomized mice both in in vivo and in vitro experiments. Differentiation of the bone marrow CFUs is normalized under the effect of thymalin in in vivo experiment only. The data obtained confirm the suggestion made by R. V. Petrov on existence of T-cell clone, enhancing CFUs differentiation in granulocytic direction. Activation of this clone in the spleen is revealed at thymectomy and stimulation of the cells with thymalin both in in vivo and in vitro experiments. Thus, affirmations are obtained on differences of clonic T-cell regulation of the CFUs differentiation in the bone marrow and in the spleen.     

Effect of thymus polypeptide fractions on the development of rat thymus and spleen in organ culture

Peptides of the thymus--vilon, thymogen and thymalin, alone or in combination with concanavalin A, were used to investigate their effect on organotypic culture of thymus and spleen explants from 1- and 21-day old rats. Vilon, thymogen and thymalin in concentrations of 2 and 10 ng/ml and 5 ng/ml, resp., exerted stimulating effects in thymus and spleen tissue cultures from 21-day old rats as compared to the control explants. Vilon and thymogen showed inhibiting effect in the thymus tissue cultures from 1-day old rats as compared to the control explants. However, the peptides together with concanavalin A in concentration of 10 mkg/ml resulted in decreasing the action of concanavalin A alone. The polypeptide fractions of thymus and their synthetic analogs play different roles in the regulation of thymus and spleen development in rats of different age.     

Effect of thymalin on protein synthesis in the brain and conditioned-reflex activity of the progeny of neurosensitized female rats

Thymalin administration to two-week-old offspring of neurosensitized female rats prevented the development of protein synthesis disturbances in the central nervous system and the retention of conditioned reflex of passive avoidance. Thymalin injection to the offspring of intact female rats improved conditioned reflex retention and did not affect brain protein synthesis. A possible mechanism of thymalin effect in conditions of congenital neuroimmunopathology is discussed.     

Effect of thymalin on the cyclic nucleotide system in the mouse spleen

The effect of the thymus preparation thymalin (1000 micrograms/mouse, i.p.) on the system of cyclic nucleotides in the spleen has been studied. The preparation produced two-phasic changes in the content of cAMP and cGMP, as well as in the activity of cAMP phosphodiesterase. The changes in the spleen cAMP content are consequent on those in the activity of phosphodiesterase.     

Type-II alveolocytes in the treatment of the pulmonary form of oxygen poisoning (electron microscopic and morphometric research)

The effect of cytochrome C, thymalin and their combination has been studied concerning morphofunctional state of alveolocytes of the II type (A II) in the lungs of 33 non-inbred white rats at the pulmonary form of oxygen poisoning. The phenomenon develops, when the animals are in pure oxygen under pressure of 0.25 MPa for 10 h. The ultrastructural stereological analysis demonstrates that after exposure of the mice in the barochamber, immediately after decompression and during the 1st and the 3d day in the animals not given the pharmacological preparations in the A II diffuse and local edema develops in hyaloplasm, certain changes develop in mitochondria and endoplasmic reticulum. Comparing to intact animals, a relative volume of the lamellar bodies decreases nearly two times, the volume of mitochondria increases by 1.5 times, amount of A II drops. While treating the pulmonary form of oxygen poisoning with cytochrome C or thymalin, in 3 days after beginning to administer the preparations, the relative volume of the lamellar bodies increase by 1.5 times in comparison with those in the group of untreated animals, and at the combined administration-by 2.5 times. This demonstrates stimulation of the pulmonary surfactant synthesis. When the preparations are applied together, by the 3d day the relative volume of mitochondria and amount of A II do not differ from the corresponding indices in intact animals.     

Regulating properties of peptides of the thymus and bursa of Fabricius in immunodepression in birds

The intensity of nucleic acids and protein synthesis in the cells of the thymus and the bursa of Fabricius was studied in chickens against the background of an immunodepression induced by administration of hydrocortisone and cyclophosphamide. It was found out that hydrocortisone causes in chicken a marked lowering of the intensity of inclusion of 3H-thymidine, 3H-uridine and 14C-glycine in thymic cells, and cyclophosphamide--in the cells of the bursa of Fabricius. Under the conditions of selective immunodepression the preparations on the basis of the peptides of the thymus (thymalin) and of the bursa of Fabricius (bursilin) regulate the processes of nucleic acids and protein synthesis chiefly in the cells of organs which produce them.     

Prolongation of the effect of immunostimulators as means of increasing resistance to causative agents of infection

Possible prolongation of the biological effect of some available immunostimulators such as prodigiozan, salmozan, polyribonate and thymalin by their sorption on aluminium hydrate was studied. It was shown that in comparison to the native immunostimulators the sorbed ones had a more pronounced biological action and provided a more prolonged increase in the host resistance to the causative agents of gas gangrene and typhoid fever. Using prodigiozan as an example it was demonstrated that the observed increase in the anti-infective activity of the sorbed drugs was associated with more intensive stimulation of some immunological factors involved in regulation of host nonspecific resistance. The results of the study are likely to indicate that it was experiment to further investigate the drugs to reveal their efficacy in other infection models and to optimize the schemes of their use.     

Differentiation and a change in the sensitivity to antibrain serum of circulating colony-forming units under the action of thymic factors

The rabbit anti-mouse brain serum (RAMBS) that interacts with SC-1 marked cells, rather than with thymocytes and bone marrow cells, inhibits most of the blood and bone marrow colony-forming unit (CFU) population. A commercial thymus preparation thymalin increases the granulocytopoietic activity of the circulating CFU and decreases their sensitivity to RAMBS in thymectomized and normal animals. Differentiation of circulating CFU remains unchanged in thymalin-treated mice after RAMBS administration, while CFU erythroid activity of nontreated animals is lowered. The revealed changes in the CFU differentiation and sensitivity to RAMBS confirm the assumption that SC-1 antigen may mark Thy-1 lymphocytes of their microenvironment, rather than CFU.     

The effect of therapy with cytostatics and immunomodulators on mitotic pathology in Lewis tumor cells in mice]

The effect of cytostatics (methylnitrosourea and methotrexate), immunomodulators (thymalin and reaferon) and their combinations on the mitotic pathology of mice Lewis tumour cells was studied. It was revealed that chemotherapy with these agents changed the interrelation between mitotic phases and somewhat enhanced the incidence of pathologic mitoses mainly connected with the damage of mitotic apparatus. Immunomodulators differently affected the cytostatic activity of antitumour agents that may be associated with their mechanisms of action.     

Effect of immunomodulators of varying nature on the expression of lymphocyte markers in melanoma patients]

The influence of immunomodulators such as tactivin, thymalin, gangliin and translam on expression of lymphocyte markers in patients with melanoma was studied. It was shown in vitro that sensitivity of the lymphocyte receptors of melanoma patients to the immunomodulators was individual and depended on the initial level of the marker expression and the drug properties. Preliminary determination of sensitivity of the immunoregulatory cells to the immunomodulators lays the basis for the use of adequate immunocorrecting therapy in the complex treatment of oncologic patients. Gangliin and translam are membrane active compounds influencing the structure and function of lymphocytic membranes. They are considered as a promising class of immunomodulators with diverse spectra of immunotropic action and various fields of practical use.     

Effect of cytomedins on development of organotypic culture of various tissues from the internal organs of rats

Some natural peptides, referred to as cytomedines, were isolated from different organs: cortexin and epithalamin (both from the brain), cordialin (heart), hepalin (liver) and thymalin (thymus),--to test their stimulating effects on the growth in organotypic culture of different tissue explants taken from 3 day old rats. It has been found that these peptides exerted their obvious stimulating effects on the growth of the cultured explants, compared to the control, if taken in the respective concentrations: 100, 50, 50, 100 and 5 ng/ml. Thus, these cytomedins can be used in the clinical practice for stimulating reparative processes in the appropriate tissues.     

The dynamics of thymalin localization in human thymus cells in embryogenesis

Immunofluorescence methods were applied to study the localization of the thymalin-containing cells in human thymic epithelium of 6-23-wk-old fetus and 2-3-yr-old infants. The study of the fetal thymus (6 weeks) showed the presence of thymalin in reticuloepithelial framework. These cells were present in both in the cortex (in subcapsular regions) and in the medulla; Thymalin-containing cells presence--in the Hassall's corpuscles (23 weeks). The same results were obtained with the infants thymus (3-yr-old).     

The prevention of suppurative-septic complications in severe burns by using immunotropic drug preparations in an experiment

The prophylactic and therapeutic action of immunotropic preparations in different doses on the development of Pseudomonas infection of experimental animals with thermal burns was evaluated. Natural marrow and thymic regulatory peptides (myelopid, tactivin and thymalin), as well as the synthetic immunopreparation polyoxydonium, were used for immunocorrection. The study revealed that the injection of these immunomodulators in doses recommended by instructions for use did not affect the course of the infectious process, antibody production by immunocompetent cells and the death rate of experimental animals. The use of the course dose of any of these substances, introduced in a single injection, prevented the generalization of infection. The death rate of experimental animals dropped from 80.3% to 47.2%.