Biomedical subjects

N F Miasoedov

Publications and source records attributed to N F Miasoedov.

54 records · Page 3Linked to original sources

PubMedDate not supplied

[Behavioural effects of beta-casomorphin-7 in its intranasal administration].

Intranasally administrated natural opioid peptide beta-casomorphin-7 (doses 0.001, 0.005, 0.02, and 0.1 mg/kg) was shown to produce alterations in behavior of male albino rats. The anxiolytic effect of the peptide tested in two "open field" modifications was most pronounced. Besides, two higher doses of promoted learning under conditions of negative reinforcement. The beta-casomorphin-7 effects on pain sensitivity and locomotion were insignificant. The obtained results only in part coincide with the effects of intraperitoneal peptide injection described earlier. This suggests that the specific effects of beta-casomorphin-7 considerably depend on the way of its penetration into a body; in case of intranasal administration they are apparently determined by primarily influence of the peptide on hypothalamic structures.

Administration, Intranasal↗

PubMedDate not supplied

[Pharmacokinetics of glyprolines (PGP) upon intragastric administration].

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.

Animals↗

PubMedDate not supplied

[Thermoregulatory activity of dermorphin fragments].

We studied the effect of C-terminal truncation of the dermorphin (DM) molecule and analogs of its N-terminal tetrapeptide, [DOrn2]-DM(1-4), [DArg2]-DM(1-4), [DAla4]-DM(1-4), [DArg2, DAla4]-DM(1-4), Arg-DM(1-4), Arg-[DArg2]-DM(1-4), Arg-[DAla4]-DM(1-4), and Arg-[DArg2, DAla4]-DM(1-4), on the functional status of the thermoregulation system in rats at different ambient temperatures. For the first time, we demonstrate that the N-terminal tetrapeptide is the minimal fragment with the hypothermic effect. Only the N-terminal octapeptide exerted the vasomotor effect. Amino acid substitutions in the tetrapeptide affected its hypothermic effect. [DArg2]-DM(1-4) and [DArg2, DAla4]-DM(1-4) had the greatest effect. Addition of Arg to the N-terminus of DM(1-4) analogs changed their thermoregulatory activity. The greatest thermoregulatory effect was observed for Arg-[DArg2]-DM(1-4) and Arg-[DArg2, DAla4]-DM(1-4).

Analgesics, Opioid↗

PubMedDate not supplied

[Study of thermoregulatory activity of a fragment of natural dermorphin precursor Arg-dermorphin and its analogs].

We studied the effect of a fragment of natural dermorphin (DM) precursor Arg-DM and its analogs (Pro-DM, 4Amino-Pro-DM, Mike et-DM, Kre-DM, Arg-[DArg2]-DM, and Arg-[DAla4]-DM after intraperitoneal administration on the functional status of the thermoregulation system in rats. The obtained data demonstrated that the hypothermic and vasomotor effects of Arg-DM were temperature-dependent and had the same pattern as DM (Emel'yanova et al., 1996). In the thermoneutral and room environment, the peptide induced a two-phase vascular response. The first phase was vasodilation; it was twice as strong as for DM and was not removed by naloxone pretreatment. The second phase was vasoconstriction; it was blocked by naloxone. Replacement of Arg with 4Amino-Pro, Met, and Kre as well as DAla2 to DArg2 or Gly4 to DAla4 replacements in the Arg-DM molecule affected the thermoregulatory activity of the peptide. For instance, only the vasodilation response was observed for Arg-[DAla2]-DM and Arg-[DAla4]-DM while only the vasoconstriction response was observed for 4Amino-Pro-DM.

Amino Acid Substitution↗

PubMedDate not supplied

[Long-lasting behavioral effects of chronic neonatal treatment with ACTH (4-10) analogue semax in white rat pups].

It is well known that ACTH/MSH-like peptides (melanocortins) have neurotrophic and neuroprotective effects on the central and peripheral nervous systems in the early postnatal life. The aim of present work was to study consequences of the ACTH (4-10) analogue Semax influence on the developing brain. The work was carried out in white rat pups. The peptide (0.05 mg/kg, i/p) was injected daily on the 8th-21st postnatal days. Delayed long-lasting effects of such treatment on animal behavior were revealed. At the age of four to eight weeks, Semax-treated rats displayed elevated exploratory activity, decreased anxiety level and improved passive avoidance conditioning. The results suggest that neonatal Semax administration modulates the development of the central nervous system.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

[Analgesic activity of dermorphin and its proline analogs].

Dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2; DM) and its analogs obtained via stereochemical transformation of L-Pro6 to D-Pro6 peptide in DM ([Dpro6]DM) and via dehydration of L-Pro6 peptide ([dHPro6]DM) were characterized with respect to the analgesic activity in rats tested under conditions corresponding to various levels of pain sensitivity organization. The drugs were introduced by intraperitoneal injections in various doses (0.1, 1.0, and 10 mg/kg). In the case of acetic-acid induced convulsions (writhing), DM and [Dpro6]DM produced analgesic action in the minimum dose, while the analogous effect of [dHPro6]DM was observed only in greater doses. In the tail-clamp (Haffner) test, DM and [Dpro6]DM also inhibited nociception while the latter compound was ineffective. In the grid-shock test, [Dpro6]DM showed a higher activity than [dHPro6]DM, whereas DM did not produce analgesic action. Thus, all the studied peptides exhibit pronounced analgesic activity, and the replacement of L-Pro6 in DM by its stereomer D-Pro is more effective than the substitution of dHPro6.

Amino Acid Substitution↗

PubMedDate not supplied

[Comparative study of the physical dependence on proline analog of dermorphin and morphine].

On the model of acute physical dependence, naloxone treatment of animals dependent on D-Pro6 peptide ([D-Pro6]DM) (a demorphin analog) led to tremor, shaking, convulsions, and rare jumps typical of morphine-dependent animals. The variety and intensity of reactions depended on the naloxone dose and the interval between naloxone and peptide injections. In the state of reject syndrome upon peptide and morphine subchronic treatments according to identical schedules, the symptoms in [D-Pro6]DM dependent animals were much less pronounced than in morphine-dependent ones.

Animals↗

PubMedDate not supplied

[Effect of modification of the N-terminal region of molecule on the expression of neotropic effect of semax analogues].

A comparative study of neotropic activity of semax (MEHFPGP), an analogue of the ACTH(4-10), and some of its derivatives in which the N-terminal methionine was modified or substituted with other amino acid residues was performed. The effect of these peptides on learning of albino rats in tests with positive (alimentary) and negative (pain) reinforcement was studied. In the case of modification of methionine by attachment of the gluconic-acid residue or substitution of methionine with lysine, the neotropic effect of the peptide was retained. The substitution of methionine with tryptophan or serine resulted in a decrease in the neotropic activity. The substitution of methionine with glycine, threonine, or alanine caused a complete loss of the neotropic activity of the peptide. Therefore, the amino acid residue located at position 1 of the heptapeptide analogue semax, plays a key role in retaining the neotropic effects of the peptide and determines the degree of their expression.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

[Comparison of anticoagulant effects of regulatory proline-containing oligopeptides. Specificity of glyprolines, semax, and selank and potential of their practical application].

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.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

[Study of the relationship between analgesic activity and structure of synthetic melanocortin analogs].

Melanocortins, peptides of the family of adrenocorticotropic (ACTH) and melanocyte-stimulating (MSH) hormones, have a wide range of physiological activity. Heptapeptide semax (MEHFPGP) is an analog of the ACTH4-10 fragment. Previously, pronounced nootropic and neuroprotective activities were shown for this peptide; in addition, it decreases pain sensitivity in animals. In this work, the relationship between analgesic activity of the peptide and its structure was studied. The following analogs of the N-terminal ACTH fragments were used: rMEHFPGP, where r is glucuronic acid, KEHFPGP, GEHFPGP, EHFPGP, HFPGP, and ERP. The peptides were administered intraperitoneally at doses of 0.015, 0.05 and 0.5 mg/kg. Rat pain sensitivity was assessed using the paw-withdrawal test. Truncations of the N-terminal residues eliminated the analgesic activity. The peptide analgesic effect was observed after the replacement of the N-terminal methionine with lysine or after the attachment of glucuronic acid to the methionine, while the peptide with glycine instead of the methionine had no effect on pain sensitivity. Hence, the amino acid at position 1 of semax analogs plays a key role in mediating the analgesic effects of the peptides.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

[Evenly tritium-labeled peptides and their in vivo and in vitro biodegradation].

Biologically active peptides evenly labeled with tritium were used for studying the in vitro and in vivo biodegradation of the peptides. Tritium-labeled peptides with a specific radioactivity of 50-150 Ci/mmol were obtained by high temperature solid phase catalytic isotope exchange (HSCIE) with spillover tritium. The distribution of the isotope label among all amino acid residues of these peptides allows the simultaneous determination of practically all possible products of their enzymatic hydrolysis. The developed analytical method includes extraction of tritium-labeled peptides from organism tissues and chromatographic isolation of individual labeled peptides from the mixture of degradation products. The concentrations of a peptide under study and the products of its biodegradation were calculated from the results of liquid scintillation counting. This approach was used for studying the pathways of biodegradation of the heptapeptide TKPRPGP (Selank) and the tripeptide PGP in blood plasma. The pharmacokinetics of Selank, an anxiolytic peptide, was also studied in brain tissues using the intranasal in vivo administration of this peptide. The concentrations of labeled peptides were determined, and the pentapeptide TKPRP, tripeptide TKP, and dipeptides RP and GP were shown to be the major products of Selank biodegradation. The study of the biodegradation of the heptapeptide MEHFPGP (Semax) in the presence of nerve cells showed that the major products of its biodegradation are the pentapeptide HFPGP and tripeptide PGP. The enkephalinase activity of blood plasma was studied with the use of evenly tritium-labeled [Leu]enkephalin. A high inhibitory effect of Semax on blood plasma enkephalinases was shown to arise from its action on aminopeptidases. The method, based on the use of evenly tritium-labeled peptides, allows the determination of peptide concentrations and the activity of enzymes involved in their degradation on a tg scale of biological samples both in vitro and in vivo.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

[Short peptide fragments with antiulcer activity from a collagen hydrolysate].

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.

Animals↗

PubMedDate not supplied

[Synactones--functionally conjugated complexes of endogenous regulators].

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.

Amino Acid Sequence↗

PubMedDate not supplied

[Introduction of a radioactive label into Escherichia coli cells].

A labeled cell culture was obtained by treating Escherichia coli cells with diluted tritium in the presence of rhodium catalysts and by incubating them with sodium [14C]acetate. Most of the cells retained their ability for division. The rate of cell growth declined with increasing the molar radioactivity of sodium acetate.

Acetates↗

PubMedDate not supplied

[The reaction of pepsin and pepsinogen with dicyclohexylcarbodiimide].

The reaction of pig pepsin and pepsinogen with 3H-dicyclohexylcarbodiimide (DCC-T) is studied. It is found that about three residues of DCC-H incorporate into pepsin molecule and about four residues--into pepsinogen molecule under the excess of carbodiimide. The incorporation of DCC-T into protein results in a deep enzyme and zymogen inactivation: pepsine retains 20% of the proteolytic activity with respect to hemoglobin, and pepsinogen completely loses its potential proteolytic activity. It is found that a part of DCC-T residues attaches to N-terminal part of pepsinogen, which splits off under the activation of proenzyme in acid medium. It is demonstrated that the interaction of DCC-T with carboxyl groups of dicarbonic amino acids results in the change of isoelectric point of pepsin and pepsinogen.

Animals↗

PubMedDate not supplied

[A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its design and study)].

Semax is one of the rare analogues of regulatory peptides which underwent all stages from fundamental investigations to practical usage. It has been demonstrated that this peptide is capable to stimulate operative memory and attention, to increase resistance to hypoxia and to improve brain circulation in experimental animals and human beings over prolonged period (20-24 h after intranasal administration in doses 0.015-0.050 mg/kg). Semax significantly improves memory and attention in healthy men under extreme conditions of activities. Moreover at present semax is successfully used in treatment of patients with different diseases of CNS. In the majority of cases the peptide exhibited positive effects and in no case it produced negative side actions or complications connected with its administration. There is good reason to believe that medical potentialities of semax have not been exhausted and in future new possibilities of its usage will be revealed.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

[The anxiolytic action of an analog of the endogenous peptide tuftsin on inbred mice with different phenotypes of the emotional stress reaction].

The anxiolytic effect of the synthetic analogue of the endogenous peptide tuftsin (Thr-Lys-Pro-Arg-Pro-Gly-Pro) was studied in inbred mice Balb/c (C) and C57B1/6 (B6) with different heritable types of emotional-stress reaction. In C strain with genetically high level of anxiety and "passive" type of behaviour under conditions of avoidable and unavoidable stress (open field, elevated plus-maze, light-dark chamber) the heptapeptide prevented manifestations of anxiety being administered intraperitoneally in a wide range of active doses (200-3000 mcg/kg). The drug did not change the behaviour of B6 mice with low level of anxiety and active type of emotional-stress reaction. The described effect is comparable with tranquilizing-activatory action of low doses of benzodiazepine tranquillizers, however, in contrast to the latter, the heptapeptide has no side inhibitory behavioural effects even in high doses. The heptapeptide may be considered as a promising new anxioselective drug without side inhibitory behavioural effects which are typical for benzodiazepine tranquillizers.

Animals↗

PubMedDate not supplied

[The pharmacokinetics and metabolism of heptapeptide--a prospective synthetic analog of tuftsin with psychostimulating action in rats].

The pharmacokinetics of a new heptapeptide with psychotropic activity was studied in rats in experiments in vitro and in vivo by means of high-performance liquid chromatography. The heptapeptide was detected in its natural form in rat blood plasma for 7-10 min; its T1/2 exceeded that of other oligopeptides of similar structure. The structure of the main pharmacologically active heptapeptide metabolite was identified by high performance liquid chromatography; it proved to be tetrapeptide Thr-Lys-Pro-Arg (taphtsin). The heptapeptide was distributed in well vascularized organs of rats: liver > kidneys > heart.

Animals↗