[Immunological aspects of Parkinson's disease]. / Immunovospalitel'nye aspekty bolezni Parkinsona.

The review summarizes information on immunological disorders in Parkinson's disease (PD). The data on neuroinflammation associated with degeneration of the medial substantia nigra cells are presented. It is pointed out that innate and adaptive immunity cells are involved in the process of neuroinflammation. The authors analyze the cytokine level in the brain, cerebrospinal fluid and peripheral blood as well as the relationship between neuroinflammation and neuron dysfunction and provide information on immunological disorders in people with PD and animal models of PD. Specific features of PD models and data on blood-brain barrier damage and evidence of autoimmune inflammation in PD are presented. Identification of PD preclinical markers, including cytokines, HLA-DR and HLA-DQ antigens, autoantibodies, etc, is discussed. Pre-symptomatic diagnosis of PD, prevention and treatment at the pre-symptomatic stage could lead to interruption or slowdown the neurons death.

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.

[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.

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.

[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.

[Xylanase and cellulase of fungus Cerrena unicolor VKM F-3196: production, properties, and applications for the saccharification of plant material].

Under the conditions of submerged cultivation in a medium containing microcrystalline cellulose, the Cerrena unicolor VKM F-3196 basidiomycete is capable of producing xylanase and cellulase. Electrophoretically homogeneous cellulase and xylanase were obtained using ion exchange and hydrophobic chromatography. The molecular weight of both cellulase and xylanase was -44 kDa. It was shown that xylanase catalyzed the hydrolysis of xylan with the production of xylose, xylobiose, and xylotetrose and it exhibited properties of endoxylanases. Cellulase hydrolyzed carboxymethylcellulose, xylan, and microcrystalline cellulose with the formation of cellotriose and cellotetraose. For both enzymes, the pH optimum was -4.0. The enzymes exhibited moderate thermostability: xylanase retained 35% of the initial activity for an hour at 60 degrees C; cellulase, 10% under the same conditions. Xylanase, cellulose, and a mixture of these enzymes saccharified plant material (wheat, rye, wheat middling, and oat), indicating the possible use of these enzymes in biotechnology.

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.

[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.

New properties of immunotropic preparation from porcine skin.

We studied new immunological and physicochemical properties of K-activin, immunotropic preparation from porcine skin isolated by the acetone method. The preparation restored the sensitivity of background rosette-forming cells in the spleen of thymectomized mice to the inhibitory effect of azathioprine in vivo and practically normalized serum thymic activity reduced in thymectomized mice. The molecular weight of proteins present in K-activin and previously detected by SDS-PAAG electrophoresis was determined by MALDI mass spectrometry

Some pharmacological properties of immunotropic preparation from porcine skin.

We studied pharmacological properties of immunotropic preparation from porcine skin (skin resorption effect and acute and chronic toxicity). It was demonstrated that the preparation did not damage the skin during evaluation of skin-resorption effect; evaluation of acute and chronic toxicity revealed no changes in the general state of experimental animals and histological structure of visceral organs and skin; evaluation of chronic toxicity showed that the preparation induced no changes in blood biochemical parameters compared to the control.

[Laccase of the lignolytic fungus Trametes hirsuta: purification and characterization of the enzyme, and cloning and primary structure of the gene].

The main physicochemical characteristics of the major isoform of the laccase secreted by the fungu, Trametes hirsuta 072 were studied. The enzyme belongs to the group of high redox potential laccases (E(T1) = 790 +/- 5), and it oxidizes with high efficiency various substrates of phenolic nature. The gene of this isoform was cloned, and its nucleotide sequence was determined. The length of the complete gene is 2134 bp. It comprises 11 exons and 10 introns. Analysis of the amino acid sequence of T. hirsuta 072 laccase demonstrated a high homology (to 96.9%) to the other laccases secreted by fungi of the genus Trametes.

Enzymes of a new modified ortho-pathway utilizing 2-chlorophenol in Rhodococcus opacus 1CP.

Chlorocatechol 1,2-dioxygenase (CC 1,2-DO), chloromuconate cycloisomerase (CMCI), chloromuconolactone isomerase (CMLI), and dienolactone hydrolase (DELH), the key enzymes of a new modified ortho-pathway in Rhodococcus opacus 1CP cells utilizing 2-chlorophenol via a 3-chlorocatechol branch of a modified ortho-pathway, were isolated and characterized. CC 1,2-DO showed the maximum activity with 3-chlorocatechol; its activity with catechol and 4-chlorocatechol was 93 and 50%, respectively. The enzyme of the studied pathway had physicochemical properties intermediate between the pyrocatechase of ordinary and chlorocatechase of modified pathways described earlier for this strain. In contrast to the enzymes investigated earlier, CMCI of the new pathway exhibited high substrate specificity. The enzyme had Km for 2-chloromuconate of 142.86 microM, Vmax = 71.43 U/mg, pH optimum around 6.0, and temperature optimum at 65 degrees C. CMCI converted 2-chloromuconate into 5-chloromuconolactone. CMLI converted 5-chloromuconolactone into cis-dienolactone used as a substrate by DELH; this enzyme did not convert trans-dienolactone. DELH had Km for cis-dienolactone of 200 microM, Vmax = 167 U/mg, pH optimum of 8.6, and temperature optimum of 40 degrees C. These results confirm the existence of a new modified ortho-pathway for utilization of 2-chlorophenol by R. opacus 1CP.

[Biologically active substances from the skin that influence the proliferation and differentiation of cultured human keratinocytes]. / Biologicheski aktivnye veshchestva kozhi, vliiaiushchie na proliferatsiiu i differentsirovku kul'tiviruemykh keratinotsitov cheloveka.

Three fractions of biologically active substances of human skin varying in molecular weight (F1 > 15 kD, F2 1.4-15 kD, F3 < 1.4 kD) were tested in primary and regenerating cultures of human epidermal keratinocytes. F1 and F3 caused stimulation of keratinocyte proliferation, F2 inhibited proliferation and enhanced terminal differentiation of epidermal cells.