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It was shown that chronic (over 7 days) intranasal injection of the Pro-Gly-Arg tripeptide to rats in the dose 1 mg/kg before the injection of a diabetogenic dose of alloxan, promotes effective defense against development of insulin dependent diabetes mellitus. At the same time, the tetra-peptide Pro-Gly-Pro-Arg did not show a hypoglycemic affect during diabetes mellitus provocation. Administration of Pro-Gly-Arg and Pro-Gly-Pro-Arg peptides also activates anticoagulation potential.

Dopamine and serotonin are the two important key neurotransmitters, which participate in the formation and regulation of various physiological parameters in the normal and pathological states. It is very interesting and important in both fundamental and practical respect to analyze interactions of dopamine and serotonin with somatostatin--a peptide hormone suppressing the secretion of many other regulatory peptides and various bioactive substances. In the present work, a huge amount of experimental data on the interactions of dopamine and serotonin with somatostatin was collected and analyzed. Literature sources mainly cover the period of 1970 - 2006. Compilation of an information database on dopamine/serotonin--somatostatin interactions has been the next stage. Analysis of the effects of dopamine and somatostatin revealed unilateral influence of these endogenous regulators and also of the induced and/or inhibited peptides on the level of depression, stress, food intake, angiogenesis and cancerogenesis, thus making it possible to increase and prolong their effects via cascade mechanisms. Potentially possible combinations of somatostatin and dopamine analogs, and chimeric somatostatin/dopamine molecules are proposed for the treatment and correction of different pathological states, including acromegaly, prolactinemia, and hyperinsulinism.

The distribution of the glyprolines Pro-Gly-Pro and Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selanc) was analyzed and compared in tissues of rat organs after different ways of their administration using the peptides uniformly labeled with tritium. Comparative data on changes in concentrations of the peptides in the rat organs after their intraperitoneal, intranasal, intragastric, and intravenous administration are given. The intranasal administration of both peptides was shown to be optimal for the delivery of glyproline molecules in the CNS. A high affinity of the studied glyprolines for gastric tissues was found for all the ways of their administration. We suggest that a high efficiency of action of glyprolines on homeostasis of the gastric mucous tunic was partially provided by accumulation of these peptides (to high concentrations) in gastric tissues.

Active immunization against cholecystokinin fragments 31-33 (CCK-3) and 30-33 (CCK-4) results in long-lasting changes of albino rats' behavior. CCK-3 and CCK-4 covalently linked to antigen-carrier evokes the suppression of the anxiety, decreases some signs of depression-like behavior and changes the level of bioamines and their catabolites in striatum at least for two months after immunization. These data can provide a perspective approach to the problem of long term correction of behavior.

Among numerous regulatory peptide (RP) it is possible to presumably indicate the relict, evolutionary ancient RP. They combine three features: formation from non-specialized proteins-precursors, a comparatively high resistance to action of proteases in the organism media, and maximal simplicity of their structure. The examples of them are glyprolines--a recently identified RP family, as well as tuftsin. Several other praline-containing RP in terminal sites also seem to belong to the evolutionary ancient RP. The proposed approach to studies on the RP evolution is additional to those used traditionally in this problem.

The authors studied a vast volume of unsystematized literature data (between 1970 and 2006) on the interaction of the neurotransmitters serotonin and dopamine with the hormonal peptide regulators prolactin, oxytocin, and vasopressin. Analysis of the results of studies made it possible to create a data base and analyze complex induction interactions between serotonin and dopamine and the three regulatory peptides under various physiological conditions: non-pregnancy, early and late stages of pregnancy, lactation, and maternal behavior. The roles of serotonin and dopamine in the formation of reproductive and maternal behavior were determined. The article presents possibilities for research into positive intervention into the hormonal status of a pregnant woman via a range of psychotropic drugs.

The inhibitor of monoaminooxydase isatin and the ligand of B-receptors cholecystokinin-4 play a significant role in the suppression and induction of depressive and anxiety states. We induced the formation of auto-antibodies to these compounds against their conjugates with antigen-carrier by immunization of white rats. The result was long-term (more than 2 months) stimulation of depressive and anxiety behavior after immunization to isatin and, in contrast, the suppression of such behavior after immunization to cholecystokinin. The perspective of immunochemical approach to long-term correction of behavior is discussed.

All physiological processes are regulated by complexes of various endogenous compounds (EC), acting in definite sequences and combinations. The effort to model the regulation by introducing separate ECs provides only partial information. This circumstance also limits the therapeutic efficiency of separate ECs and their stabilized derivatives. Therefore, it is obviously necessary to extensively investigate various EC complexes, for which a conventional name of "synactones" is proposed. It is expedient to use this name only for conjugated EC (or their stabilized derivatives) rather than to various drug combinations with compositions and structures far from those of the endogenous regulators of animal organism. Examples of the most promising synactones (in the form of mixtures of ECs or covalently associated ECs) are presented. Specific methodological difficulties of such investigations, as well as the problems related to various ways of administration and blood-brain barrier penetration are considered.

The big volume of odd literature data (period 1960-2005) was investigated for analysis and estimation of interactions between dopamine (DA), serotonin (5-HT), reward factors and basic members of regulatory peptide (RP) families. Database, which includes information about physiological effect directions, doses and administration types of RP and biological active compounds, organism types, organ-tissues systems and receptor mechanisms was created. The complex cascade interactions between DA, 5-HT, reward factors and RP were investigated and systemized. Based on analysis of correlated functiong of DA and 5-HT-systems, the opponent-reciprocal interactions were established and their integrative characteristics were estimated.

An expert computer system was developed to analyze the effects of regulatory peptides (RPs) and some other biologically active compounds. The database includes information on their structures and physiological and inductive effects taking in account the method of administration, doses, and types of organisms. The developed method of vector representation of RP effects and the software modules provide for the estimation of the role of single RPs and their combinations in the regulatory system of organism. The expert system was used for solving the following tasks: (1) an analysis of the structural and functional organization of the RP continuum and a search for effective RP combinations regulating the levels of anxiety, depression, cognitive processes, etc; (2) design of a network of complicated cross inductive connections of major members of RP families; and (3) an analysis of the peculiar features of functioning of numerous internal reward factors. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

The new glyproline family was distinguished from the regulatory peptides recently. It includes the simplest proline- and glycine-containing peptides: PG, GP, PGP, and respective peptides with hydroxylated proline residues. Glyproline's bioactivity covers many important systems of the body including suppression of some reaction in the blood coagulation and platelet aggregation and gastric mucosal maintenance. It was shown that PGP, PG and GP have a wide spectrum of antiulcer activity with respect to gastric mucosal damages of various aetiology. GHyp and HypGP show also antiulcer action. In vivo glyprolines being fragments of collagen may be generated during synthesis and catabolism of collagen. It is well known that approximately 10-60% of newly synthesized collagen degrade intracellularly with succeeding secretion of small peptides composed of less than 5 aminoacid residues out of cells. Different simplest proline and hydroxyproline fragments of glyprolines are revealed in various type of collagen: GP, GHyp, PG, PPG, PGP, PHypG., GPHyp, GPP, GPG, GHypP, HypGP. It is possible that these fragments may be also secreted out of cells during the stage of degradation of newly synthesized collagen. We showed that the intragastric (per oral) introduction of hydrolyzed gelatin, having 20 small peptide fragments, including PGP and HypGP, also increase gastric stability showing protective and therapeutic antiulcer effect. The corresponding receptors for glyprolines are not completely identified yet but it may be supposed that PGP, GP and other glyprolines interact with the same receptors with which the III type collagen is binding with platelet's receptors. It is supposed that octapeptide sequence KPGGluPGPK of collagen is rather important for binding with receptor. When this sequence in the structure of collagen's molecule binds with the receptor, platelet aggregation is induced. Free octapeptide blocks the receptor and inhibits platelet aggregations. Qualitatve characteristics of parameters of inhibition with intact octapeptide and glyproline, as well as the receptor's structure--that's our concern for the nearest future.

Experimental and theoretical demonstration of different effect of certain regulatory peptides (RPs) on blood coagulation is available. The problem of the role of RPs in hemostatic processes becomes particularly significant since, first, the peptides are widespread in nature both in animal and plant tissues, second, there is a relationship between the peptide structure and function and, third, both natural and synthetic peptides are used in practical medicine to correct functions of some factors of the hemostatic system. Many peptide inhibitors of the primary and plasma hemostasis potentiating anticoagulant effects in the body have been described.

A peptide acidic hydrolysate of collagen (PHC) was obtained under conditions (4 N HCl) ensuring the predominant formation of short peptides, glyprolines. They were separated and their antiulcer activity was studied. Thirty individual peptides with molecular masses of 174-420 amu were isolated from the PHC by HPLC. The PHC was shown to predominantly contain 2- to 4-aa peptides, including PG, GP, and PGP. Experiments on rats demonstrated that, on intragastric administration at a dose of 1 mg/kg, PHC enhances the stability of the gastric mucosa to the action of ulcerogenic factors, such as ethanol and stress, and exhibits a protecting antiulcer effect. Even a lesser dose (0.1 mg/kg), which reduced ulcer area twofold, was effective in the stress model of ulcer formation. The intraperitoneal and intragastric administration of PHC at a dose of 1 mg/kg was found to exhibit a therapeutic effect in the acetate model of ulcer formation.

Regulatory peptides are actively involved in controlling most physiological processes. One such function is regulation of the level of anxiety and panic states. We report here a meta-analysis of data published from 1960 to 2004 on the effects of anxiety-enhancing regulatory peptides. The resulting database was used to investigate the organization and functioning of the anxiogenic regulatory peptide system. Using vector representation of the effects of these peptides, the spectra of physiological effects which might be provoked by each anxiety- and fear-increasing regulatory peptide alone and in combination were evaluated. Complexes of regulatory peptides with anxiogenic profiles with the greatest potential for the further experimental development of inhibitory pharmacological agents were identified.

Functions and possible mechanisms of action of adenosine diphosphate ribose (ADP-ribose) and its cyclic analogue--cycle-ADP-ribose (cADP-ribose)-- substances pretend to role of novel second messengers are reviewed. Possible mechanisms of ADP-ribose and cADP-ribose synthesis regulation and metabolism are analyzed. Prospective mechanisms of ADP-ribose and cADP-ribose transportation into the cell are described. ADP-ribose and cADP-ribose are considered as endogenous regulators of ionic balance (in particular regulators of calcium balance) in different tissues. Effects of ADP-ribose on isolated heart of frog and warm-blooded animal (rat), as well as on rat heart in vivo are discussed. The role of ionic channels and receptors, gated by ADP- and cADP-ribose in regulation of cardiomyocyte ionic balance in normal and pathological condition are analyzed. The possible role of purine receptors in ADP-ribose and cADP-ribose effects on heart are discussed.

Cardiotropic effects of endogenous regulator of intracellular ionic balance adenosine diphosphate ribose (ADP-ribose) was studied on isolated rat heart using standard retrograde perfusion and on rat heart in vivo by means of implanted arterial catheters. Parameters registered were heart rate, pressure developed in left ventricle of isolated heart and blood pressure of rats in vivo. It was shown that ADP-ribose exerted cardiotropic action on isolated rat heart and that its effects did not depend on effects of its metabolite AMP. In concentrations 10-70 microM ADP-ribose caused negative dose dependent chronotropic effect. Amplitude of contraction of isolated heart changed equivocally. In concentration 70 microM ADP-ribose in 50% of cases produced biphasic action: negative inotropic effect was preceded by positive inotropic effect. In other cases this concentration exerted negative inotropic effect. In concentration 10 microM only negative inotropic effect was observed. Contrary to ADP-ribose its metabolite AMP exerted only monophasic positive inotropic effect on isolated heart. The preparations studied differed in dynamics of cardiotropic action. In experiments in vivo ADP-ribose and AMP caused monophasic negative chronotropic and monophasic positive inotropic effects.

The data and hypotheses on the mechanisms of action of ultrasmall doses (USD) and ultralow concentrations (ULC) of endogenous bioregulators and immunoactive compounds (regulatory peptides, cytokines, etc.) are presented. The reliability of the published data on the effectiveness of USD and ULC within the concentration limits 10(-13) - 10(-24) M and lower is considered.

The present concept of relative instability of regulatory peptides (RPs) in organisms must be amended. The recently characterized family of glyprolines and some other prolyl-glycyl-proline (PGP)-containing oligopeptides show the stability quite comparable with those of major pharmacological preparations. The ability of glyprolines to pass gastro-enteric tract barriers opens ways to per-oral administration of this new group of drugs such as semax, selank and their fragments. The most interesting approach is the creation of hybrid ("chimeric") peptide drugs combining the unmodified representatives of various natural RPs that distinctly manifest their inherent physiological activities and cooperate with each other in stabilization of whole peptide in vivo. As the result, the activity of such peptides as semax and selank may have value in a vide variety of pathological processes.

Regulatory peptides (RP) take an active part in managing the majority of physiological processes. One of these functional applications is the monitoring of the anxiety level, of panic state. This work represents the presumptive analysis of literature data of 1960-2004 on the effects of regulatory peptides enhancing anxiety (RP-AT). This information database was used for researching the characteristics of organization and functionality of the system of anxiogenic RP. Taking into account the method of vector representation of RP effects, estimation of spectra of physiological effects that can go with each of RP-AT and their combination, was carried out. The most perspective RP complexes of anxiogenic profile for further experimental development of inhibitory therapeutic agents are proposed.

Influenza A virus M-proteins can cause depression in experimental animals 1 day after administration. HA and NA, on the contrary, activate motor activity in animals under the similar conditions. The effect of viral proteins is dose-dependent.

The pharmacokinetics of glyprolines upon intragastric administration in rats was studied by monitoring the content of tritium-labeled PGP in the blood plasma and protein, in organs (for 5 h), and urine (for 8 h). The maximum radioactivity (2.25% of the introduced level) in the blood plasma was observed 15 min after administration of [3H]-PGP. Then, the radioactivity level gradually decreased, but even in 5 h it exceeded 1%. In contrast, the radioactivity of deposited protein gradually increased. The content of labeled PGP and its metabolites in organs was much lower than in the blood. The radioactivity 15 min after administration was as follows (%): intestine, 1.4; stomach, 0.1; liver, 0.09; brain, heart, and kidney, < 0.05; in 5 h, the radioactivity level was below 0.02% (except for intestine, where it was still greater than 0.1%). No labeled PGP or its metabolites were found in the urine during the 8-h period of observations. It is not excluded that glyprolines introduced with PGP are involved in the synthesis of new peptides and proteins, including collagen.

Peroral administration of peptide Pro-Gly-Pro to 10-11-month-old rats with modeled prethrombotic state normalized functions of the anticoagulation system and produced a potent antiplatelet effect. Peroral administration of Pro-Gly peptide before provocation of thrombin generation and thrombus formation prevented death of animals from thrombosis. Experiments on rats with venous thrombosis induced by stasis and administration of thrombin showed that pretreatment with Pro-Gly peptide decreased the weight of formed thrombi.

The most stable regulatory peptides (RP) including the new family of RP (glyprolines) and derivatives of hybrid peptide MEHFPGP are characterized. High ability of glyprolines to penetrate into the blood-stream through the gastrointestinal tract is demonstrated. Antiulcer, antithrombotic and antidiabetic activities of glyprolines were discovered in experiments on white rats. The activity of oligopeptides PGP, PG and GP is compared. Mechanisms of glycoprolines activities and feasibility of their administration with connective tissue food proteins are discussed. Thus, glyprolines are perspective drugs for treatment of gastric ulcer, correction of hemostasis and thrombosis suppression prepared for preclinical trial.

Ante- and postnatal hypoxia significantly worsened the postnatal development of animals. The posthypoxic behavioral model included hyperactivity and decreased learning ability, these being typical manifestations of attention deficit disorder. A peptide constellation prevented and significantly improved posthypoxic postnatal development and eliminated the majority of negative behavioral changes.

The prolonged effect of thyroliberin in ULD after single intramuscular injection on contractility of lymphatic vessels directly was investigated. The controlled group of animals received injection of 0.2 ml of physiological solution. The experimental group was injected by 0.2 ml of thyroliberin in concentrations of 10(-10) or 10(-16) mol/l (1 x 10(-4) and 1 x 10(-10) micrograms/kg of the body weight respectively). During the experiment the animals were grouped in the following way: 1) directly after the injection; 2) 3 hours later; 3) on the 1st day and then every day during 2 weeks. Lymphatic vessels reactivity of the experimental animals as well as controlled was studied by application of thyroliberin and noradrenalin (in concentrations of 1 x 10(-16) and 1 x 10(-6) mol/l respectively) directly on mesentery lymphatic vessels. The lymphatic vessels reaction in control group of animals on the noradrenalin and thyroliberin was the same during the period of observation. Thyroliberin stimulated contractility at concentration of 1 x 10(-16) mol/l. The reaction of experimental group was dramatically decreased to 10(-4) mol/l on the 1st and the 3rd day (in the case i.m. injected concentration 1 x 10(-10) mol/l) and to 10(-10) mol/l (in the case of i.m. injected concentration 10(-16) mol/l). The lymphatic vessels reactivity to exogenous thyroliberin gradually established at the 6-7th days till 12th day from the moment of thyroliberin injection. The mechanisms of the action of thyroliberin in ULD are discussed.

Thyroliberin (TRH) promoting endogeneous antidepressive effect is the most general regulator of the central mechanisms and visceral functions (especially respiration). Our group pioneered in applying the anticonvulsant action of TRH after local intranasal application). This application of TRH in ultra-low doses contrast the method of systemic TRH administration in the large doses). In our experiments intranasal application of 10(-8), 10(-10) and 10(-12) mol/l TRH significantly inhibited the severe epileptic motor fits in rats induced by PTZ. EEG also confirms beneficent effect of TRH (TRH suppressed SWD in cortex, amygdala and hippocamp). In the experiment that follows compared effects of TRH (pyroGlu-His-Pro-NH2) and its metabolite dipeptide His-Pro (10(-10), 10(-8) mol/l). The experiments make more precise that only TRH but not His-Pro posses the anticonvulsant properties. There is a good believe that medical potentialities of TRH have not been exhausted and its new possibilities of its usage will be revealed in epileptology.

Main pathways of degradation of PGP peptide possessing antiulcer and antithrombotic activities were studied after its intraperitoneal, intragastric, and intraintestinal administration. In experiments on rabbits we showed by HPLC that unmodified PGP is released into the blood after administration by all three routes and is detected in the plasma over 3-5 h. PG dipeptide is a more stable PGP metabolite presumably determining (together with tripeptide) its pharmacological properties.

The study experimentally assessed the approach proposed by the authors to lower alcohol motivation, which involves enhancement of a specific immunity at the stage of alcoholization when acetaldehydemodified ethanol exchange enzymes [alcohol dehydrogenase (ADH)] and acetaldehyde dehydrogenase may be expected to occur. Omega-3 polyunsaturated fatty acid (PUFA) drugs enhance the formation of autoantibodies to modified ADH and decrease the activity of ADH in the stomach and liver. At the same time, PUFA drugs can, under certain conditions, produce an anti-alcoholic activity and a positive effect on the psychoemotional status of animals after the ethanol deprivation period.

We propose new approach to classification of regulatory peptides and proteins. It is based on the complex of their properties: stability, affinity to receptors, existence of specialized percursors, protein-transporters etc. In particular we describe very stable factors such as new peptide family named glyprolines.

Experiments used is combination with traditional preparations (omeprasole, de-nol, and solcoseril), Semax peptide (Met-Glu-His-Phe-Pro-Gly-Pro) possessing nootropic and neuroprotective activity significantly promoted ulcer healing in patients with refractory peptic ulcers. On day 14 of treatment ulcer healing was observed in 89.5% patients receiving intranasal Semax (1% solution, 2-4 drops 3 times a day for 10 days) vs. 30.8% in the control group. Clinical studies of antiulcer activity of Semax in different combinations with usual antiulcer drugs are needed.

During the past decades, bioactive (regulatory) peptides have been identified as the major players in the regulation of many important biological processes. Dozens of peptides have found their application as pharmaceutical agents, which further stimulated research in this field making it one of the most rapidly developing areas on the edge of biological science and medicine. However, the fast accumulation of enormous amounts of experimental data has revealed a great difficulty in their analysis and demanded the development of a systematic approach for generalization of the obtained information. We propose a new computer-based algorithm for studying biological activities of regulatory peptides and their groups based on their representation as vectors in n -dimensional functional space. Our method allows the rapid analysis of databases containing thousands of polyfunctional regulatory peptides with overlapping spectra of physiological activity. The described method permits to perform several types of correlations which, when applied to the large databases, could reveal new important information about the system of regulatory peptides. It can select the groups of peptides with similar physiological role (peptide constellations) and search for the optimal peptide combinations with predetermined spectrum of effects and minimal side effects for their further pharmacological application. It can also reveal the role of regulatory peptides in induction of chain physiological reactions.

The review is devoted to the problem of prenatal hypoxia influence on central and vegetative nervous system, cardio-vascular and respiratory systems, cell metabolism. It is shown that perinatal hypoxia is often resulted in severe non-reversal functional disorders of postnatal development based on significant morphological changes. Regulatory peptide pretreatment is discussed as one of the methods for correction of pre- and postnatal hypoxic consequences.

The role of regulatory peptides is the least explored part in the field of humoral regulation of lymphatics. In this paper we continue a systematic investigation of their effects on the lymphatic vessels of various animals. The effect of thyroliberin was studied on bovine mesenteric lymphatics. The isolated lymphatics contractility and smooth muscle cell electrical activity were investigated. Thyroliberin in ultra low concentrations (1 x 10(-13)-1 x 10(-18) M) exerts a considerable stimulating effect. The mechanism of the theroliberin ultra-low concentrations action and a possibility of the medical usage of the obtained results, are discussed.

Active immunization of white rats with cholecystokinin-4 covalently linked to the antigen carrier BSA evoked long-lasting changes in the rats' behavior, which were in the opposite direction to the anxiogenic effects of cholecystokinin-4 itself, showing that immunization had anxiolytic effects. Immunoenzyme analysis demonstrated the presence of antibodies to cholecystokinin-4 in the serum of immunized rats. These data are interesting from the point of view of correcting pathological anxiety and fear states by inverse immunoregulation.

The experiments in vivo showed that the new nootropic prolyl-containing GVS-111 produces an antithrombotic effect, influencing various stages of the blood coagulation process. GVS-111 exhibits anticoagulant and fibrinolytic properties and enhances fibrin destabilization by reducing the XIIIa factor activity. These effects are manifested upon both intraperitoneal (1 mg/kg) and peroral (10 mg/kg) administration of GVS-111 (in both cases, a single daily treatment over a period of 10 days). The same effects (anticoagulant, fibrinolytic, antifibrin-stabilizing) were observed in in vitro experiments with both GVS-111 (10(-3)-10(-6) M) and its main metabolite cyclo-L-prolylglycine (up to 10(-10) M). In addition, the latter metabolite exhibited an antiaggregant effect. The antithrombotic activity of GVS-111, together with previously established neuroprotector properties, low toxicity, and the absence of complications, makes this compound a promising antistroke drug.

The biological activity of neuropeptides (NP) is extremely wide and, moreover, there are thousands of peptides. Due to the pronounced multifunctionality of each peptide and to the overlapping reduplication of bioactivity spectra of each peptide, a functionally persistent aggregate (i.e. the functional continuum of NP) is formed. The method of vector representation of NP effects is outlined, which makes it possible to classify the multitude of NP according to functional characteristics, to reveal the evolutionary rules of development of the peptide system for regulation of biological parameters, and to indicate the constellations of regulatory peptides that are the most promising to be studied from the medical point of view.

A short review of investigations resulting in determination of a new family of regulatory peptides (glyprolines) participating in modulation of hemostasis and protection of mucous membranes, obtaining of the ACTH4-10 new analogues which are potent neuroprotectors and nootrops, and revealing of unexpected biological activities of some other peptides (behavioural effects of tuftsin, lymph flow stimulation by thyroliberin, etc.). Further investigations into the functional peptide continuum is discussed.

Experimental results have demonstrated a significant decrease in the level of alcohol consumption by albino rats immunized with heterologous horse alcohol dehydrogenase. The role of ADH epitopes 9-14, 93-115, and 265-276 in this phenomenon was examined, and it was established that the latter sequence (265-276) plays the biggest role. The inhibition of ADH activity in the adrenals of immunized rats was much higher compared to the liver. We propose a hypothesis that the effect of alcohol dehydrogenase on alcohol consumption is connected with its role in catecholamine metabolism.

Intranasal administration of Semax, peptide Pro-Gly-Pro, and a mixture of peptides Pro-Gly+Gly-Pro to rats for 5 days enhanced anticoagulant and fibrinolytic potential of the plasma (total fibrinolytic activity and plasmin and plasminogen activator activities) and decreased antiplasmin concentration. Semax and Pro-Gly-Pro decreased the weight of thrombi during experimental thrombosis.

We evaluated the effect of eiconol containing polyunsaturated fatty acids on the behavior and alcohol motivation in rats. Administration of eiconol for 10 days to alcoholized rats against the background of ethanol deprivation produced a sustained suppression of alcohol motivation and corrected deprivation-specific behavior.

This work investigates whether nitric oxide production and lipid peroxidation contribute to the pathophysiology of ischemia and whether glycine and a novel Russian compound, Semax are neuroprotective via a mechanism involving the regulation nitric oxide (NO) and lipid peroxidation. In brief, nitric oxide and indices of lipid peroxidation were elevated following global ischemia. While glycine proved ineffective in reducing NO levels or ameliorating the neurological deficits following global ischemia, Semax proved to be highly effective in abating the rise in nitric oxide and restoring neurologic functioning.

Acute hypobaric hypoxia of pregnant rats led to a significant delay in body weight gain, growth and time of eye opening in newborn rat pups which was paralleled by behavioral changes. Preventive intranasal instillations of peptide mixture (semax and beta-casomorphine-7) to pregnant females prevented the effect of hypoxia on the progeny.