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E I Gusev

Publications and source records attributed to E I Gusev.

162 records · Page 9Linked to original sources
PubMedDate not supplied

Levels of neurotransmitter amino acids in the cerebrospinal fluid of patients with acute ischemic insult.

The dynamics of excitatory (glutamate, aspartate) and inhibitory (GABA, glycine) neurotransmitter amino acid contents in the cerebrospinal fluid were studied in 110 patients with hemispheric ischemic insult. These studies revealed significant increases in the levels of glutamate and aspartate in the first six hours of illness, and the level and duration of these changes correlated with the severity of the insult. Peak GABA and glycine levels were seen at the end of the first day after strokes, reflecting the delayed activation of the mechanisms of protective inhibition. The insufficiency of GABAergic mediation in strokes located in the hemispheres to a significant extent mirrored the severity of clinical features and the potential of restorative processes. Early significant biochemical criteria were identified for objective assessment of the severity of brain ischemia, and these had prognostic value for the course and outcome of strokes. The most unfavorable prognostic signs were the presence of low (or undetectable) GABA levels in the first days after insult and progressive increases in aspartate levels to the third day on the background of sharp reductions in glutamate levels (after initial elevation on the first day).

Aspartic Acid↗
PubMedDate not supplied

Neuroprotective effects of glycine for therapy of acute ischaemic stroke.

The aim of this randomized, double-blind, placebo-controlled trial was to assess the safety and the efficacy of the pharmaceutic drug glycine in 200 patients with acute (<6 h) ischaemic stroke in the carotid artery territory. Fifty patients received placebo, 49 glycine 0.5 g/day, 51 glycine 1.0 g/day and 50 glycine 2.0 g/day for 5 days in each group. The efficacy of glycine was assessed by clinical analysis, by an enzyme-linked immunosorbent assay of levels of blood serum autoantibodies to NMDA-binding proteines, by detection of excitatory (glutamate, aspartate) and inhibitory (glycine, GABA) amino acid concentrations and lipid peroxidation products (TBARS) in CSF. The trial confirmed the safety profile of the glycine treatment. Slight sedation was observed in 9 patients (4. 5%) as a side-effect. Other marked side-effects or adverse events were absent. The glycine treatment at the dose of 1.0-2.0 g/day was accompanied by a tendency to a decreased 30-day mortality (5.9% in 1. 0 g/day glycine and 10% in 2.0 g/day glycine groups vs. 14% in the placebo and 14.3% in 0.5 g/day glycine groups), to an improved clinical outcome on the Orgogozo Stroke Scale (p < 0.01) and the Scandinavian Stroke Scale (p < 0.01) and to a favourable functional outcome on the Barthel index (p < 0.01 in 1.0 g/day glycine vs. placebo group in patients with no or mild disability). An early normalization of autoantibody titres to NMDA-binding proteins in serum was found (p < 0.01 vs. placebo), a reduction of glutamate and aspartate levels (p < 0.05 vs. placebo), an increase in GABA concentrations (p < 0.01 vs. placebo in severe stroke patients) and also a reduction of TBARS levels (p < 0.05 vs. placebo) in CSF by day 3. Thus, the trial suggests that sublingual application of 1.0-2. 0 g/day glycine started within 6 h after the onset of acute ischaemic stroke in the carotid artery territory is safe and can exert favourable clinical effects. These results will be verified in further trials with a larger number of patients.

Acute Disease↗
PubMedDate not supplied

[Polymorphism A/G in position +49 of CTLA4 exon 1 in multiple sclerosis in Russians].

The association of multiple sclerosis (MS) with alleles A and G of the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, a candidate gene for autoimmune disorders, was studied. The allele polymorphism results from single nucleotide substitution (A/G) in position +49 of exon 1 and leads to substitution Thr-->Ala in the leader peptide. The case-control study involved two groups of ethnic Russians: 168 MS patients and 209 healthy subjects from central Russia. Genotype frequencies were in agreement with the Hardy-Weinberg equilibrium in both groups (P > 0.05). The controls significantly differed in CTLA4 allele and genotype frequencies from Mongoloids but not from other Caucasians. No association was observed between MS and CTLA4. In addition, the combined association with MS was analyzed for both the CTLA4 alleles and allele groups of HLA DRB1. The results showed that the CTLA4 dimorphism does not affect susceptibility to MS in ethnic Russians, be these stratified or not with regard to DRB1 alleles corresponding to serologic specificities DR1 to DR16.

Abatacept↗
PubMedDate not supplied

[Glutamate neurotransmission and calcium metabolism in cerebral ischaemia and under normal conditions].

This article is dedicated to the mechanisms of ischaemic brain damage. The processes of glutamate-calcium cascade connected with formation of focal brain necrosis within the period of therapeutic window (the first 3-6 h after the induction of cerebral ischaemia) are discussed. The basis mechanisms of energy-dependent ionic pumps failure, development of glutamate excitotoxicity, disorders of calcium metabolism are analyzed. The results of own investigations are presented. The significant increases in the concentrations of excitatory aminoacidergic neurotransmitters (glutamate and aspartate) in the cerebrospinal fluid were demonstrated in patients with acute ischaemic strokes from the first hours of illness with no dependency on vascular origin of strokes. The extent and duration of these increases were of prognostic value for determining the severity and outcome of the stroke. It was showed that along with "excitotoxicity", the pathogenesis of ischaemic stroke also involves a deficiency of protective inhibitory GABAergic mechanisms and developing imbalance between the excitatory and inhibitory neurotransmitters systems. The significant increase of the level of the specific autoantibodies to phencyclidine-binding protein of glutamate NMDA-receptors was found out in blood serum of patients beginning from the first 3 h after stroke onset and it directly correlated with the severity of ischaemic stroke. The great attention is paid to the role of astroglia in energy metabolism and glutamate neurotransmission, to the mechanisms of regulation of concentrations of neurotransmitter amino acids in the synaptic cleft, as well as to the mechanisms of spreading depression waves and zinc neurotoxicity.

Aspartic Acid↗
PubMedDate not supplied

[Immunogenetics of optic neuritis in children with multiple sclerosis].

The aim of the work was to study immunogenetic peculiarities of optic neuritis in children with MS. Using PCR-SSP technique genomic typing was performed on HLA DRB1 gene (chromosome 6p21) of 56 unrelated children with ON registered at least once in clinically verified MS. 264 adult MS patients and 328 healthy controls from the same stratum of population were also genotyped. A very strong correlation of MS with DR15 (DRB1*150 ... alleles) was observed in comparison with healthy cases in the above population. In 39 cases of children with ON and MS both parents were also genotyped and the rate of their DRB1 haplotypes transmitted (patients) and non-transmitted (control cases) to their sick children were compared in accordance with affected family-based (AFBAC) method. A very strong correlation of demielinating disease with DRB1*150 ... alleles was verified. Transmission/disequilibrium test (TDT) was carried out to analyze correlation in selected families consisting of one sick child and two parents at least one of whom was heterozygous for DR15. The difference observed in transmission from these parents of DR15 alleles and alternative DRB1 alleles was extremely great providing obvious evidence for correlation of DR15 (DRB1*150...) alleles and susceptibility of children to ON and MS.

Adolescent↗
PubMedDate not supplied

[Dynamics of the functional state of the brain in acute focal ischemia].

Complex clinical-neurophysiological investigation of 200 patients with cerebral acute focal ischemia was carried out. It included polymodal monitoring of brain functional activity: monitoring of electroencephalography (EEG), compressed spectral array and toposelective mapping of somatosensory evoked potentials, acoustic short-latency evoked potentials, transcranial cortical electric stimulation, electromyo- and electroneuromyography. The development of acute focal cerebral ischemia was shown to be independent of its location, kind and prognosis, accompanied by functional reorganization of whole brain: its supersegmented specialized motor and sensory functional systems, nonspecific formations of segmental peripheral system. These changes in cerebral functional activity can be found already during first hours of ischemia and they remain generalized during 3-5 days.

Brain↗
PubMedDate not supplied

[Polymorphism of length of tetranucleotide repeat from the 5'-side from the myelin basic protein gene in multiple sclerosis in Russians].

The myelin basic protein gene (MBP) can confer the susceptibility to multiple sclerosis, because its protein product is the main protein component of myelin of the central nervous system and a potential autoimmune antigen in the disease. A possible association of multiple sclerosis with alleles and genotypes of a microsatellite repeat (TGGA)n, located to the 5' side from the first exon of MBP in ethnic Russians (126 patients with reliable multiple sclerosis and 142 healthy controls from Central Russia) was analyzed using the case-control method. Upon separation of the tetranucleotide repeat site amplification products in 1.5% agarose gel, one can see two distinct bands that can be analyzed as two allele groups (A and B). The distribution of allele A and B group frequencies as well as frequency of allele group B and genotype A/A reliably differs in multiple sclerosis patients and healthy controls. Alleles A and the A/A genotype are associated with the development of multiple sclerosis. We also analyzed the association of multiple sclerosis with combined bearing of alleles and genotypes A and B of MBP and groups of alleles of the DRB1 gene of the major histocompatibility complex that correspond to serospecificities DR1-DR18. The comparison of subgroups of multiple sclerosis patients and healthy individuals, formed on the basis of the DRB1 phenotype, has shown a reliable increase in the frequency of allele B in healthy individuals and the genotype A/A frequency in patients, only among DR4- and DR5-positive individuals. No reliable difference was found in the MBP allele and genotype distribution between multiple sclerosis patients and healthy individuals in combined groups of (DR4,DR5)-negative individuals, i.e., no carriers of any phenotype except DR4 and DR5 were revealed. Thus, MBP or some other nearby gene is involved in the multiple sclerosis development in Russians, predominantly (or exclusively) among DR4 and DR5 carriers. In this case, without stratification of analyzed individuals by the MBP alleles, multiple sclerosis is reliably associated only with DR2(15), but not of DR4 and DR5 alleles of DRB1. The results obtained are in favor of the genetic heterogeneity of multiple sclerosis, and suggest the possibility of epistatic interactions between the MBP and DRB1 genes.

Base Sequence↗