[The impact of immunoactive drugs on passive avoidance response].

AIM: The objective of this project was to explore the influence of immunoactive drugs (tactivin, thymulin, and thymosin fraction 5) on the development of the passive avoidance conditioned reflex. MATERIALS AND METHODS: Two types of passive avoidance boxes were used--a regular two-chamber box and a modified three-chamber box, comprising a dark chamber in which rats were exposed to electrical shock, a safe dark chamber, and a light chamber in the center. RESULTS: The project has established that the memory trace persists longer under the influence of the immunoactive drugs in both models, which is consistent with the reference nootropic piracetam test results. Notably, the immunoactive drugs' mnemotropic effect was more pronounced in the modified three-chamber box than in the standard two-chamber box. Using the modified box helped to establish the influence of tactivin, thymulin, and thymosin fraction 5 on the spatial memory component. Immunotropic preparations from thymus caused the animals to select the safe chamber 24 hours later and in subsequent tests. CONCLUSION: The project's results indicate that the drugs tested do possess mnemotropic properties, so their range of clinical use can be broadened.

[Effect of tactivin on the behaviour and learning in rats].

The action of the immunocorrective agent tactivin on CNS functional activity was studied in an experiment using outbred white rats. The drug was shown to affect the animals' behaviour in an elevated cross-shaped maze including learning capacity and ability to overcome functional disorders of conditioned active avoidance response. The data obtained suggest anti-stress activity of tactivin.

[Immunobiologically active compounds from skin].

This paper describes physiochemical and biological properties of 3 immunologically active compounds extracted by acetone from porcine skin. High pressure gel chromatography confirmed their heterogeneity. RP-HPLC of compound 2 (C2 or K-activin) also characterizes it as a heterogeneous entity. It was shown to inhibit proliferation of cultured fibroblasts from human fetuses and exhibit weak activity in general anaphylactic reaction (anaphylactic shock) and skin anaphylactic reaction. A summary of data on immunologically active compounds are presented with special emphasis laid on acetone-extractable K-activin.

[Autolytic degradation of RNA; the effect of various factors on the dynamics of the process]. / Avtoliticheskaia degradatsiia RNK: vliianie razlichnykh faktorov na dinamiku protsessa.

As found earlier RNA preparations from different eukaryotic tissues followed by thorough deproteinization contain "masked" RNases, that cause autolytic degradation. The present paper indicates that the autolytic degradation of a deproteinized preparation of RNA from Ehrlich's cells by gel electrophoresis under denaturated conditions and ultracentrifugation in sucrose gradient is submitted by definite regularities and is essentially dependent on the concentration change of Mg2+, Na+, K+, NH4+ ions and also GTP and guanosine. It is proposed the activity of "masked" RNases is the manifestation of ribozyme properties of RNA molecules. Similar processes may take place in processing and catabolism of RNA in vivo.

[Discovery of "masked" ribonucleases in highly purified preparations of RNA]. / Obnaruzhenie "skrytykh" ribonukleaz v vysokoochishchennykh preparatakh RNK.

It was found that RNA preparations isolated with the help of various inhibitors of RNAses from different eukariotic tissues, followed by thorough deproteinization contain particular ribonucleases ("masked" RNAses). These RNAses were supposed to be connected with RNA molecules and are not active. They may be activated by changes of RNA molecule conformation. Apparently the "marked" RNAses can take part in (a) processing of large precursor RNA molecules; (b) regulation of gene expression by means of specially cut RNA fragments.

[From transplantation of the thymus to molecular reconstruction of the immune system]. / Ot peresadki timusa k molekuliarnoi rekonstruktsii immunnoi sistemy.

The results of the first global grafting of the thymus and a thymus-sternum block are given. The grafting of immunocompetent organs in children with the Louis-Bar syndrome is shown to cause to a partial and in some cases significant recovery of immunological parameters. Thus, blast-cell transformation showed 10-40% increases, the titers of antibodies to Staphylococcus and Escherichia coli rose, and immunoglobulin A that was generally absent in these children before surgery appeared. The clinical effect of grafting was noticeably observed 20-30 days after surgery. The most significant parameters were as follows: cessation of sinusitis, rhinitis, bronchitis, and purulent skin lesions. Neurological syndromes improved: tremor and staggering gait diminished, ocular convergence normalized. Thereafter such operations were made in 27 patients with Bruton's disease and in 3 patients with lymphogranulomatosis. The grafting of immunocompetent organs led to the design of agents derived from the thyroid gland (Tactivin) and bone marrow (myelopid). The immunobiological and clinical effects of Tactivin in the past 15-20 years are given in detail. The basic principles in immunomodulating therapy with thymic agents are presented.

[Effect of different temperature fractions of RNA on allogenic inhibition of hematopoietic stem cells of mouse bone marrow and embryonal liver]. / Vliianie razlichnykh temperaturnykh fraktsii RNK na allogennuiu ingibitsiiu stvolovykh krovetvornykh kletok kostnogo mozga i émbrional'noi pecheni myshei.

In the system of non-syngeneic transfer of stem hemopoietic cells, the preliminary incubation of the cells of bone marrow or embryonic liver of the C57BL mice with different temperature RNA fractions isolated from the spleen of (CBAXC57BL) F1 was shown to lead to the complete or partial restoration of the colony forming ability of the donor cells. The 63 degrees RNA fraction was shown to have the greatest restorative effect.

[Activation of gamma-interferonogenesis]. / Aktivatsiia gamma-interferonogeneza.

Production of gamma-interferon was increased considerably by priming with homologous gamma- or alpha-interferons as well as by T-activin or vitamins of group B. The factors under study were effective both in the population of mononuclears and in the total fraction of nucleated cells of the donor blood. The maximal yields of gamma-interferon, up to 10,000 IU/ml, could be obtained by priming with gamma-interferon in a dose of 5 IU/ml or alpha-interferon in a dose of 1000 IU/ml. T-activin and vitamin B12 also enhanced production 8-10-fold. The combined use of priming, T-activin, and vitamin B12 in various combinations gave no further increase in the yield of activity.

[Abolishment of allogeneic inhibition of colony formation with the aid of various RNA classes]. / Otmena allogennoi ingibitsii kolonieobrazovaniia s pomoshch'iu razlichnykh klassov RNK.

The authors analysed the capacity of various temperature fractions of RNA isolated from the spleen of donors of the bone marrow cells (of mice C57BL/6I) and recipients--hybrids (CBA X C57BL/6I) F1 to abolish the depression of colony formation in the nonsyngenous organism. In the administration of bone marrow cells of mice of parental genotype C57BL/6I of the irradiated recipients F1 there is observed a sharp depression of the number of colony forming units in the spleen F1. This depression can be eliminated by preliminary incubation of the bone marrow cells of mice of parental genotype with a 63 degrees fraction of the recipient's RNA. Preliminary inculation of the bone marrow cells of mice of parental genotype with 85 degrees and cytoplasmic fractions of recipient's RNA led to a partial restoration of colony formation only. The 45 degrees and 55 degrees RNA fractions of the recipient's RNA produced no restoring action. None of the temperature RNA fractions of the RNA of donor bone marrow cells were capable of abolishment of the colony formation depression in the nonsyngenous organism. It is supposed that restoration of the colony forming capacity in the nonsyngenous organism was connected with the activity of matrix RNA of the 63 degrees fraction obtained from the recipient's spleen.

[Changes in the blood immunological indices of newborn infants as affected by T-activin in vitro]. / Izmenenie nekotorykh immunologicheskikh pokazatelei krovi u novorozhdennykh detei pod deistviem T-aktivina in vitro.

T-activin, introduced into the culture of mononuclear cells obtained from the blood of healthy newborn infants, does not induce any essential changes in the levels of E-, Ea- and EAC-rosette-forming cells. An overwhelming majority of healthy infants has shown a decrease in the functional activity of lymphocytes in the blast transformation test in response to the optimal dose of ConA and an increase in their functional activity in response to the suboptimal dose of this mitogen. After stimulation with phytohemagglutinin, both the increase of the stimulation index and its decrease have been observed in an equal number of cases. The introduction of the preparation into the culture of mononuclear blood cells isolated from newborn infants with sepsis leads to a considerable increase in the detection rate of Ea-rosette-forming cells with a tendency to an increase in that of E- and EAC-rosette-forming cells. The final values of the stimulation indexes, no matter what the mitogens used, are in conformity with the values characteristic of the normal parameters for healthy newborns, due to a specific pattern of changes in the T-lymphocyte functional activity in the blast-transformation test.

[Interaction of T-activin with peritoneal macrophages]. / Vzaimodeistvie T-aktivina s peritoneal'nym makrofagami.

The action of T-activin on peritoneal macrophages of CBA mice after its introduction into the animals has been studied. In intact mice the phagocytic activity of macrophages and their resistance to the cytopathogenic action of Salmonella typhimurium live cells remains unchanged. The injection of corpuscular pertussis vaccine into mice leads to a decrease in the resistance of macrophages to the action of salmonellae. The simultaneous injection of T-activin into mice in doses of 0.1 and 1.0 microgram per animal abolishes the damaging action of the vaccine. The analysis of the in vitro action of T-activin on macrophages of intact mice revealed that the preliminary incubation of cells with the preparation sharply increases their resistance to the action of salmonellae, while its introduction simultaneously with bacteria or after them rapidly leads to the death of macrophages. The action of T-activin is supposed to be linked with triggering the biosynthetic processes mediating the resistance of macrophages to the cytopathogenic action of salmonellae.

[Immunotherapy with taktivin and myelolipid in experimental influenzal infection]. / Immunoterapiia taktivinom i mielopidom éksperimental'noi grippoznoi infektsii.

In experiments on mice the influence of thymic and medullary immunomodulators on the character of fatal influenza infection, the reproduction of influenza virus in pulmonary and thymic tissues and the level of MIF production was studied. Tactivin and myelolipid, used both separately and in combination, proved to be immunotherapeutic preparations capable of decreasing mortality rate by 70-95%. The immunological effects of these preparations were manifested by an increase in the functional activity of the T-link of immunity in the absence of the stimulation of antibody formation.

[Experience in using T-activin in multiple sclerosis patients]. / Opyt primeneniia T-aktivina u bol'nykh rasseiannym sklerozom.

Forty patients with multiple sclerosis of a differing course, duration and severity were treated in this series. T-activin was employed as an immunocorrective agent (AFT-6 fraction). The immunological status was assessed in all patients observed prior to, during and after the treatment. Good clinical response was noted in patients with a secondary progressive course; the effect of a short course of treatment with T-activin on the state of patients with a prolonged progressive course or at the stage of stabilization in the presence of severe organic symptomatology was less prominent. AFT-6 showed a beneficial effect on the immunological status of patients, largely on the T-immunity system. Following the treatment, most patients displayed the normalization of the total lymphocyte count and of the proportional content of T-cells with their activity rising.

[The use of T-activin for the prevention of congenital influenzal infection in mice and the correction of the immune deficiency]. / Ispol'zovanie T-aktivina dlia profilaktiki vrozhdennoi grippoznoi infektsii u myshei i korrektsii immunodefitsita.

Viremia accompanying influenza infection and the possibility of transplacental passage of the virus into the fetus make it expedient to develop measures for the prophylaxis of intrauterine infection of the fetus in case of influenza during pregnancy. The work presents the optimum scheme of administration of T-activin for prophylactic purposes to pregnant mice with acute influenza infection. Besides, the use of T-activin for immunocorrection in case of established congenital influenza infection in mice is proposed.

[Analysis of immunoregulatory peptides of the thymus using high performance liquid chromatography]. / Analiz immunoreguliatornykh peptidov timusa metodom vysokoéffektivnozhidkostnoi khromatografii.

High performance liquid chromatography (gel filtration and chromatography in the reverse phase) was applied to analyse a composition of the heterogenous immunoregulating peptide preparation T-activine isolated from calf thymus. Gel chromatography at high pressure on the column TSK G2000 SW enabled to separate T-activine into 3 subfractions at a preparative scale. Physico-chemical properties and biological activity of these fractions were studied in vitro. Subfraction B with molecular mass of 1.0-3.5 kD and pI below 5.9 proved to be the most active.

[Effect of T-activin on enzymes in the metabolism of xenobiotics]. / Vliianie T-aktivina na fermenty metabolizma ksenobiotikov.

Effect of T-activin on some xenobiotic metabolizing enzymes and several immunity parametres in secondary immune deficiency (subacute and chronic benzene intoxication) were investigated. T-activin was shown to regulate the xenobiotic metabolizing enzyme system. The compound decreased the enzymatic activity in subacute benzene intoxication, approaching their values up to the control level. In chronic benzene intoxications, which were accompanied by decrease in xenobiotic metabolizing enzymes activity, except of glutathione-S-transferase, T-activin stimulated these enzymes. At the same time, T-activin increased some immunological parameters in these models. Thymus-tropic peptides appear to be the bioregulators of some in vivo systems.

[Chronic nonspecific lung diseases, immunological deficiency and the means of its correction]. / Khronicheskie nespetsificheskie zabolevaniia legkikh, immunologicheskaia nedostatochnost' i puti ee korrektsii.

Ninety-eight patients with different patterns of chronic nonspecific pulmonary diseases (CNPD) were examined for thymus-dependent immunity. The clinical manifestations of T lymphocyte dysfunction included a torpid recurrent inflammatory process in the respiratory system, respiratory viral infections, short-term efficacy of antibacterial drugs. The patients demonstrated a decrease in the number of T lymphocytes, in production of immune interferon, and in secretion of serum thymic humoral factor. Application of tactivin, a new immunomodulator, is an effective approach to correction of the disorders enumerated. The drug has a beneficial effect on inflammatory process, reduces the symptoms of virus-induced intoxication. Administration of repeated tactivin treatment made it possible to shorten the time of repeated tactivin treatment made it possible to shorten the time of staying at hospital, to reduce the frequency of CNPD relapses from 80 to 36% within the period from 2 months to 1.5 years. This permits recommending the drug during resistance to antibiotic therapy.

[Leukocytic index of intoxication and immunologic disorders in diffuse suppurative peritonitis]. / Leikotsitarnyi indeks intoksikatsii i immunologicheskie narusheniia pri razlitom gnoinom peritonite.

Expression of total T- and B-population, T-subpopulation lymphocyte receptors and secretion of IgM, IgG and IgA were measured in 112 patients with diffuse purulent peritonitis and 81 healthy donors. Expression of receptors was correlated with the disease severity identified by leukocytic index of intoxication (LII). The latter appeared to accurately reflect the pattern of immunological impairment. Reduced absolute and proportional values of total pools of T-, B-cells and T-helpers, but elevated ones of T-suppressors and T-amplifiers occurred in LII less than 2.0. In LII greater than 7.0 there was total suppression of all the cellular populations due to deep lymphopenia. At the terminal stage of peritonitis paralysis of T-helper receptors and B-cells went in parallel with high secretion of serum immunoglobulins.

[Immunodiagnosis of retinoblastoma]. / Ob immunodiagnostike retinoblastomy.

To improve the accuracy of early diagnosis of retinoblastoma, the authors have examined a number of cellular and humoral immunity parameters in 188 children with retinoblastomas, in 57 ones with nontumorous conditions of the eyes, and in healthy controls. Stages III-IV retinoblastoma was found associated with reduced blood levels of IgG and IgA and a still more marked reduction of both in the lacrimal fluid (4-fold), with reduced blood T lymphocyte count (by 1.5 times), decreased lymphocyte blastogenesis response to phytohemagglutinin (by 8-9 times), reduced leukocyte migration activity (MI = 79 +/- 10%), reduced serum thymic activity (by 2.5 times). The early (I-II) stage of the disease involves a lowering of only lacrimal fluid IgA (2-fold) and of the leukocyte migration index (MI) (89 +/- 2%). This index was found to be an important specific indicator for the early preoperative diagnosis of retinoblastoma. Leukocyte migration inhibition (MI less than 95%) by retinoblastoma antigens was observed only if this tumor was present. In cases with the nontumorous conditions and in health retinoblastoma antigens as a rule stimulated the leukocyte migration (MI over 95%).

[Tactivin in the combined treatment of acute inflammatory diseases of the maxillofacial area]. / Taktivin v kompleksnom lechenii ostrykh vospalitel'nykh zabolevaniiakh cheliustno-litsevoi oblasti.

Examinations of 46 patients with acute inflammatory diseases of the maxillofacial area revealed a reduction of some immunity parameters. Thymic activity of the saliva and blood was found to reduce still more after surgery (opening of the phlegmon). The ratio of thymic activities of the saliva and blood may be an indirect evidence of a tendency in development of an inflammatory process. The authors demonstrated the efficacy of correcting immunity parameters by tactivin, which was particularly effective in grave cases. Tactivin concentrations in the blood and saliva, their time course and ratio may be considered as additional criteria for assessing the status of patients and the risk of complications.