PubMed Health⌕ Search

Biomedical subjects

I I Mikhaleva

Publications and source records attributed to I I Mikhaleva.

At least 37 records · Page 2Linked to original sources

[The effect of the intranigral use of the delta sleep-inducing peptide and its analogs on the motor and seizure activities of rats].

The effects of delta-sleep inducing peptide (DSIP) and its analogues (1-4) administered into substantia nigra pars reticulata on locomotor and seizure activity were estimated in experiments in rats. It was shown that intranigral microinjection of DSIP as well as DSIP-1-DSIP-4 caused decreasing of horizontal, vertical locomotor activity and attendance of central sectors of the "open field". Antiseizure effects, i.e. the first and clonic-tonic picrotoxin-induced convulsive latent period lengthening and their intensity decreasing, revealed DSIP, DSIP-2 and DSIP-3. Authors suppose that changes of DSIP structure lead to changes of effects expression on locomotor and seizure activity in conditions of their administration into substantia nigra reticulata. Obtained data concerning protective effects of studied peptides on experimental seizure syndrome allow to conclude that there is interaction between DSIP-induced hypokinesia and DSIP analogues anticonvulsive effectiveness in case of their intranigral administration which is likelihood is one of the component of nigral-dependent seizure-suppressive mechanism.

Animals↗

[Synthesis and biological properties of delta-sleep peptide analogs. 2. Antimetastatic effect].

With the aim to investigate structure-functional relations of DSIP, 11 DSIP analogues were tested on antimetastatic activity, among them five new analogues, differing in positions 2 and 6 of the DSIP amino acid sequence were synthesized by the solid-phase method using Fmoc-approach. Experiments on C57B1 mice with metastatic Lewis lung carcinoma showed some analogues to be more efficient as antimetastatic agents then DSIP after i.v. (50 micrograms/kg) administration. Normalization of neuroendocrine status and activity of peritoneal, alveolar and spleen macrophages after the DSIP and some analogues injections in mice with metastatic Lewis lung carcinoma took place. Antimetastatic action of DSIP derivatives is considerably affected by structural changes, especially in the N-terminal part. Conformational factors rather than enhanced enzymatic resistance are essential for antimetastatic response.

Amino Acid Sequence↗

[Conformation of fragment 66-72 of interleukin-2 complexed with a monoclonal antibody to interleukin-2].

1H-NMR spectra of the interleukin-2 synthetic fragment Ac-Leu66-Glu-Glu-Val-Leu-Asn-Leu72-OCH3 in the presence or absence of the monoclonal antibody were analysed. The data obtained are consistent with an extended unordered conformation of the free peptide. Measurements of NOESY cross-peak intensities allowed us to determine the spatial structure of the peptide bound to the antibody. The peptide has an amphiphilic surface with hydrophobic and hydrophilic amino acid side chains clustered on the opposite sides of its alpha-helical-like structure. The hydrophobic and hydrophilic clusters are located on the opposite sides of the bound peptide's surface. The hydrophobic side chains contact the antibody surface, while the hydrophilic ones are oriented into the solvent (T. A. Balashova et al. (1991) Bioorgan. Khim. (USSR), v. 17, p. 1470-1486). Hydrolysis of the methyl ester slowly ocurs in the presence of the antibody. This process does not alter the conformation of the peptide bounded with the antibody, though decreases the peptide's affinity to the antibody.

Amino Acid Sequence↗

[Synthesis and biological properties of new analogs of delta-sleep peptide. I. Antiepileptic effect].

To study structure-functional relationship in the series of DSIP, eleven DSIP analogues varying in positions 1, 2 and 6 were synthesized by the solid-phase method using both Boc- and Fmoc-approaches. The antiepileptic action of these analogues was compared with that of DSIP. The seizure activity was induced by the corazol or picrotoxin i. p. injection. Some analogues proved more efficient as antiepileptic agents than DSIP after their central (50 micrograms/kg in rats) and peripheral (1.0 mg/kg in mice) administration.

Amino Acid Sequence↗

[The vagotropic action of peptides isolated from the brain of hibernating susliks].

Dipeptide ASP-TYR extracted from the brain of hibernating squirrels was found to potentiate vagal effect on the cardiac rhythm, whereas pentapeptide neokyotorphin--to diminish it. In both cases the effect was due to an alteration of the tonic component's strength in the vagal chronotropic effect. The selective peptidergic modulation of the vagal effect on the cardiac rhythm suggests different physiological roles of the tonic and synchronizing components in regulation of the heart.

Animals↗

[The effect of the delta sleep-inducing peptide on seizure activity].

The delta-sleep-inducing peptide (DSIP) suppressed seizure activity in the cat cortical strychnine-induced seizure foci. The DSIP delayed development of corazol kindling in rats, prevented seizure induced with bicucullin and other agents in mice. The DSIP effect was shown to be realised through the action upon reticular black substance. The DSIP seems to take part in endogenous control of the brain excitability.

Animals↗

[Morphometric evidence of activation of axo-somatic synapses during administration of delta sleep-inducing peptide].

Computed morphometry proved activation of neocortex layer III-V axosomatic synapses. This is evident from an increase in the mean plasmalemma length, that in the active synapse zones on neurone bodies and width of the synaptic cleft, this being induced by a single intraperitoneal administration of delta-sleep-inducing peptide. The activation of the axosomatic synapses correlates with elevated GABA levels in the cerebral hemispheres cortex.

Animals↗

[The effect of a synthetic fragment of human interleukin-2 on the growth and vascularization of sarcoma 180 in mice].

The effect of a modified peptide of the middle part of the human interleukin-2 molecule (C-1-6) on the growth of transplantable sarcoma 180 of mice was studied. C-1-6 injected intraperitoneally in the dose of 0.5, 5 and 50 micrograms 4 times every other day was shown to stimulate tumor growth and enhance angiogenesis induced by the tumor transplanted intracutaneously. Stimulation of tumor growth was most apparent when the agent was given late (on day 4) after transplantation. Supernatants of murine peritoneal macrophages activated by 1 microgram/ml solution of C-1-6 proved capable of stimulating tumor growth, too. It is suggested that the stimulating effect of C-1-6 on tissue regeneration be investigated.

Animals↗

[Study of the interaction of the monoclonal antibody to human interleukin-2 and its Fab-fragment with synthetic peptides --interleukin-2 fragments by (1)H-NMR].

Proton signals for nine synthetic peptide fragments of human interleukin-2 (region 59-78) were assigned for aqueous solutions both of pure peptides and their mixtures with LNKB-2 monoclonal antibody. The nonspecific magnetization transfer (NOE) between the antibody or its Fab-fragment and the peptides was studied upon large excess of free peptide over bound peptide. NOE spectra using modified pulse sequence, enabling to eliminate broad signals and achieve higher (peptide signal)/noise ratio were obtained. The saturation transfer experiments indicated that methyl groups of amino acid residues corresponding to Leu66,70,72, Val69 and Ala73 in interleukin-2 contact with the antibody binding site. Thus, the hydrophobic interactions are of major importance for the LNKB-2-IL-2 peptide complexes. The minimal IL-2 fragment which can still bind to LNKB-2 monoclonal antibody is -Leu70-Asn71-Leu72-.

Amino Acid Sequence↗

[Analysis of the mechanism of the stress-protective action of delta sleep-inducing peptide].

By RIA there were studied the contents of corticosterone, ACTH, beta-endorphin and insulin in the blood plasma, met- and leu-enkephalin in different regions of the rat brain and in the adrenal glands after a 6-hour immobilization. The stress increased the content of corticosterone, ACTH, beta-endorphin, but not insulin in the blood plasma, and the levels of met-enkephalin in the adrenal glands, but decreased the met-enkephalin contents in the striatum. The injection of DSIP (0.1 mg/kg, i/p) blocked partly the elevation of corticosterone only. The authors propose, that stress-protective action of DSIP is realized with the involvements of the hypothalamo-pituitary-adrenal gland system.

Adrenal Glands↗

[Appearance of parkinsonian syndrome after administration of delta sleep-inducing peptide into the rat substantia nigra].

Bilateral microinjection of delta-sleep-inducing peptide (DSIP) (10.0 nmol) into the substantia nigra provoked hypokinesia and rigidity in rats observed during 4.0 hours. Injection of DSIP in dose of 5.0 nmol into the substantia nigra or into the nuclei caudati in dose of 10.0 nmol did not induce such symptoms. The enhanced slow-wave activity was recorded in caudate nuclei during hypokinesia and rigidity which demonstrated the formation of the generator of pathologically enhanced excitation (GPEE). The systemically cyclodol administration resulted in abolishment of rigidity and increase in locomotor activity. The conclusion is that bilateral intranigral DSIP injection caused acute parkinson syndrome in rats due to the formation of cholinergic GPEE in caudate nuclei. The hyperactive caudate nuclei act as the pathologic determinant which induces the parkinson syndrome.

Acute Disease↗

[Synthesis and immunochemical properties of peptides corresponding to sequences 59-72 and 25-36 of human interleukin-2].

Synthesis of peptides corresponding to the 59-72 and 25-36 sequences of human IL-2 is reported. The former peptide, which had been shown to be immunogenic in the protein molecule, was prepared to obtain antipeptide antibodies for isolation and purification of the recombinant IL-2. We located the epitope at the C-terminus of this peptide. In accordance with the IL-2 secondary structure and hydrophilicity profile analysis, the 25-36 fragment was chosen as the potential epitope. The peptides were synthesized by conventional methods in solution, conjugated with a protein carrier, and polyclonal rabbit antisera were obtained. Antibodies against both peptides were shown to be specific to human IL-2 in ELISA. Besides, monoclonal antibodies to IL-2 recognized in ELISA the 59-72 peptide, suggesting the epitope located in this region to be main one in the protein molecule.

Amino Acid Sequence↗

[Antimetastatic effect of the delta-sleep peptide during stress in mice with Lewis' lung carcinoma].

The experiments on C57Bl mice with metastatic Lewis lung carcinoma have shown that peptide delta-sleep (DSIP) lowers the stimulation of metastatic spreading which is observed in combination of the surgical removal of the tumour with the emotional-painful stress. The antimetastatic effect is accompanied by stabilization of neurohumoral indices, by a decrease in the intensity of lipid peroxidation and of the acid cathepsin activity in the blood vessels and in the lung tissue.

Animals↗

[The effect of delta sleep-inducing peptide on the convulsive activity in corasol kindling].

The influence of intraperitoneal delta-sleep inducing peptide (DSIP) injection (100 micrograms/kg) on the epileptic activity was investigated in the experiments on Wistar rats and (CBA X C57B1/6)F1 mice. The model of chronically developing epileptic activity--the model of pharmacological kindling--was created by daily repeated corasole injections in subconvulsive doses (30 mg/kg). It has been shown that DSIP injection delayed the manifestation of generalized seizures during kindling, led to the suppression of seizure activity and reduced the mortality rate of animals that developed kindled seizures. The antiepileptic effect of DSIP was observed throughout the period of 5 minutes to 24 hours after the injection. Naloxone (2.5 mg/kg) did not change the antiepileptic effect of DSIP.

Animals↗