Stress-protective effect of thymic peptides.

Experiments on Wistar rats showed that thymic peptides produce a stress-protective effect that manifested in prevention of functional impairment of conditioned active avoidance response and a decrease in generalized motor activity typical of higher nervous activity failure. We concluded that thymic peptides significantly modulate integrative functions of the brain and produce a stress-protective effect.

Thymus Polypeptide Preparation Tactivin Restores Learning and Memory in Thymectomied Rats.

We studied the effects of tactivin and splenic polypeptides on learning and memory of thymectomized animals. In 3-week rats, thymectomy blocked active avoidance conditioning. Injections of tactivin (0.5 mg/kg) during 1 month after surgery restored learning capacity; splenic polypeptides were ineffective.

[Neuropeptides, Cytokines and Thymus Peptides as Effectors of Interactions Between Thymus and Neuroendocrine System].

The review presents data on mutual influence of nervous system and thymus, realized through the neuroendocrine-immune interactions. The pres- ence of adrenergic and peptidergic nerves in thymus creates conditions for implementation of the effect of neuropeptides secreted by them. These neuropeptides induce activation of thymus cells receptors and influence on the main processes in thymus, including T-lymphocyte maturation, cytokine and hormones production. In turn, thymuspeptides and/or cytokines, controlled by them, enter the brain and exert influence on neuro- nalfunction, which creates the basis for changes of behavior and homeostasis maintenance in response to infection. Ageing and some infectious, autoimmune, neurodegenerative and cancer diseases are accompanied by distortion of interactions between thymus and central nervous system. Mechanisms of signaling pathways, which determine these interactions, are not revealed yet, and their understanding will promote the development of effective therapeutic strategies.

[The influence of the thymus peptides on analgesia caused by acute and chronic immobilization].

OBJECTIVE: Our aim was to investigate the influence of thymic polypeptides on pain sensitivity and to analyze a possible role of the opioid system in the implementation of the analgesia caused by immobilization stress. METHODS: The study was performed on male Wistar rats at the Moscow state University named after M. V. Lomonosov. We studied effects of thymus peptides: thymuline (0.15 mg/kg), fraction 5 thymosin (0.25 microgram/kg) and cattle thymus extracted product (CTEP) (0.5 mg/kg) on pain sensitivity in rats using test "tail flick" without stress, with acute (3 h) and sub acute (12 h) immobilization stress. The comparison groups were animals treated with saline and spleen polypeptides. RESULTS: It is shown that preparations of thymus increase the threshold of pain sensitivity in the intact animals. Immobilization stress duration 3 and 12 h in thymus peptides treated rats caused a less pronounced increase in pain threshold than in the control groups (immobilization stress 3 h: CTEP--p = 0.025, thymuline--p = 0.022, fraction 5 thymosin--p = 0.033; immobilization stress 12 h: CTEP--p = 0.034, thymuline--p = 0.027, fraction 5 thymosin--p = 0.036). The opioid receptor blocker naloxone (1 mg/kg) did not completely block the stress-induced analgesia, indicating the presence of both opioid and non -opioid components in this state. In thymus peptides treated rats, opioid component was less pronounced than in the control groups (CTEP--p = 0.031, thymuline--p = 0.026, fraction 5 thymosin--p = 0.029). CONCLUSION: Pre-activation of the opioid system by the thymus polypeptides leads to an increase in the share of non-opioid component of the stress-induced analgesia and prevents the depletion of the opioid system in immobilization stress.

Purification of high-molecular-weight subfraction from porcine skin inhibiting proliferation of A431 human carcinoma epidermoid cells.

Subfraction with a molecular weight >250 kDa isolated from porcine skin and inhibiting the proliferation of A431 human carcinoma epidermoid cells was purified by DEAE 32 anion exchange chromatography with NaCl concentration step-gradient. The effects of the initial subfraction and fractions obtained by separation in DEAE 32 on the proliferation of A431 human carcinoma epidermoid cells were studied in vitro in two tests (MTT and fluorescent test). The more sensitive fluorescent test showed the highest inhibitory activity of fraction No. 2 released from the column at 0.15 M NaCl. One major protein component and a series of minor protein components were detected in this fraction by vertical PAAG-SDS electrophoresis.

[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.

Corrigendum to: Recent Developments in the Field of Tumor-Inhibiting Metal Complexes.

An article was published in the journal "Current Pharmaceutical Design", Volume 9, No. 25, 2003, pp: 2078-2089 [1]. The first author is requesting an alteration in the name. Details of a correction are provided here. The original name published was Markus Galanski. The request is to change the name to Mathea Sophia Galanski. The original article can be found online at: https://www.eurekaselect.com/article/8545 We regret the error and apologize to readers.

Optical properties of Bismuth-doped silica core photonic crystal fiber.

Optical properties of a Bismuth-doped pure silica sol-gel core photonic crystal fiber (PCF) were investigated. We report on the absorption, CW luminescence and time resolved luminescence spectra at different excitation wavelengths at room temperature. Complex structure of the energy levels of Bismuth-connected centers in pure silica glass is put in evidence.

[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.

Recent Developments in the Field of Tumor-Inhibiting Metal Complexes

25 years after the first approval of cisplatin in the clinic against a number of cancer diseases, cisplatin and related compounds continue to be among the most efficient anticancer drugs used so far. Efforts are focused to develop novel platinum- and non-platinum-based antitumor drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. In the field of non-platinum compounds exhibiting anticancer properties, ruthenium complexes are very promising, showing activity on tumors which developed resistance to cisplatin or in which cisplatin is inactive. Furthermore, general toxicity was found to be very low. The first ruthenium compound NAMI-A entered phase I clinical trials in 1999 as an antimetastatic drug, whereas the ruthenium complex KP1019 will enter phase I clinical trials in 2003 as an anticancer drug which is among others very active against colon carcinomas and their metastases. Remarkable progress is also seen in developing tumor inhibiting gallium compounds. One of them, KP46, will also enter phase I clinical trials in 2003. This article reviews briefly the achievements in the field of anticancer metal complexes focusing the discussion onto the impact of the group of Bioinorganic Chemistry at the Department of Inorganic Chemistry at the University of Vienna. The development of pH sensitive platinum prodrugs, platinum-based drug targeting strategies with low-molecular-weight carriers, kinetically inert platinum(IV) complexes, as well as tumor inhibiting non-platinum anticancer drugs based on ruthenium and gallium is covered in the following sections.

[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.

[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.

[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.

[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.

[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.

[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.