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Biomedical subjects

I P Ashmarin

Publications and source records attributed to I P Ashmarin.

At least 19 recordsLinked to original sources

A functional continuum of regulatory anxiety-enhancing peptides. The search for complexes providing the optimal basis for developing inhibitory therapeutic agents.

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.

Anti-Anxiety Agents↗

[Reversible inhibitory action of adenosine diphosphate ribose on isolated rat heart and rat heart in vivo].

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.

Adenosine Diphosphate Ribose↗

Natural and hybrid ("chimeric") stable regulatory glyproline peptides.

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.

Journal Article↗

[Functional continuum of the regulatory peptides enhancing anxiety. Search for the optimal complexes as a basis for developing inhibitory therapeutic agents].

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.

Animals↗

The effects of ante- and postnatal hypoxia on the central nervous system and their correction with peptide hormones.

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.

Adrenocorticotropic Hormone↗

Metabolism of PGP peptide after administration via different routes.

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.

Animals↗

Prevention of thrombus formation with glyprolines on various models of prethrombotic state and thrombosis in rats.

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.

Administration, Oral↗

Functional continuum of regulatory peptides (RPs): vector model of RP-effects representation.

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.

Amino Acid Motifs↗

Therapy of peptic ulcer with semax peptide.

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.

Adrenocorticotropic Hormone↗

[Effect of thyroliberin on contractility and electrical activity of isolated bovine lymphangions].

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.

Animals↗

[Rules of interactions and functional continuum of neuropeptides (on the way to the common conception)].

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.

Mathematics↗

Novel synthetic analogue of ACTH 4-10 (Semax) but not glycine prevents the enhanced nitric oxide generation in cerebral cortex of rats with incomplete global ischemia.

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.

Adrenocorticotropic Hormone↗

Comparative study of modulatory effects of Semax and primary proline-containing peptides on hemostatic reactions.

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.

Adrenocorticotropic Hormone↗

[Long-term correction of brain function. Prospects of immunologic approaches].

Among various approaches to long-term correction of the highest functions of the brain there are two methods that are particularly promising. These included: 1) induction of autoantibodies against the enzymes involved in the metabolism of neuroregulators by means of immunization of respective heterologous enzymes; 2) immunization by covalent conjugates of monomolecular neurotropic compounds and neuropeptides with antigen carriers. The investigations of both methods are reviewed and illustrated in experiments on albino rats during alcoholization and some other processes of pathological behavior formation. Evidence is provided for that behavior can be corrected for several months or longer.

Alcoholism↗