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Biomedical subjects

S A Dambinova

Publications and source records attributed to S A Dambinova.

At least 19 recordsLinked to original sources

Detection of antibodies to opioid and glutamate receptors by latex agglutination and enzyme immunoassay.

We studied adsorption capacity of 5 latexes to synthetic peptide fragments of mu- and delta-opioid receptors and to GluR1 and NR2A subunits of glutamate receptor. Levels of autoantibodies to opioid receptors in the latex agglutination test and enzyme immunoassay were in good correlation. The level of autoantibodies to opioid receptors measured by these methods was increased in patients with opium narcomania, while the content of autoantibodies to the glutamate receptor subunits was increased in epileptics.

Autoantibodies↗

The effects of substance P after central administration on the activity of the mesolimbic system of the rat brain as studied by microdialysis.

In vivo microdialysis was used to study the effects of substance P on dopamine, dihydroxyphenylacetic acid, and homovanillic acid levels in the nucleus accumbens in rats. Each animal received sequential injections of physiological saline, 0.1 microg of substance P, and 1 microg of substance P into the lateral ventricle over three days. Dialysates showed increases in dopamine levels in response to neuropeptide, by 41% for the 0.1 microg dose and 71% for the 1 microg dose. The dynamics of these changes also depended on the concentration of the agent. Administration of 1 microg of substance P gave a peak dopamine level at 50 min; the neurotransmitter level remained significantly elevated 75 min after dosage with substance P. The dopamine level was increased only at 75 min when the 0.1 microg dose of neuropeptide was used. Changes in metabolite levels were also dose-dependent. After the 1 microg dose, the dihydroxyphenylacetic acid level increased by 28%, while the 0.1 microg dose produced no significant change in the level of this metabolite. The homovanillic acid level did not respond to administration of substance P at either dose. These data support the suggestion that the influence of substance P on the internal compensation system is to a significant extent mediated by dopaminergic mechanisms and provides a possible explanation for the effects of the neuropeptide seen in a conditioned place preference reflex.

3,4-Dihydroxyphenylacetic Acid↗

Expression of NMDA neuroreceptors in experimental ischemia.

The role of NMDA receptors in molecular mechanisms of neurotoxicity was investigated using rat models of global and focal cerebral ischemia. Expression of NR2A and NR2B receptor mRNAs up-regulated in cortex after 3 h of reperfusion following middle cerebral artery occlusion (MCAo). This effect was accompanied by an increase in NR2A and NR2B immunoreactivity. At six hours of reperfusion, drastic activation of NR2A mRNA expression was observed in the penumbra that returned to the control level at 24 h of reperfusion. The monitoring of NR2A autoantibodies in the blood of the experimental rats showed its reliable increase to the 5-6th day of reperfusion that maintained elevated to the 20th day of the experiment. The data indicate that NR2A and 2B receptor subunits and NR2A autoantibodies are biochemical markers of the neurotoxicity underlying cerebral ischemia.

Animals↗

Mechanisms of the influences of the central administration of substance P on ethanol consumption in chronically alcoholic rats.

The effects of central administration of substance P (SP) on alcohol consumption and dopamine metabolism in the projections of the mesocorticolimbic and nigrostriatal systems of the brain were studied in chronically alcoholic rats. Rats received 15% ethanol solution for 6 months without choice. Intraventricular administration of SP (1 microg/rat) decreased consumption of 10% ethanol solution by 41% compared with controls in an alcohol free choice test lasting one day. After chronic alcoholism, there was a decrease in the ratio of dihydroxyphenylacetic acid (DOPA) and homovanillic acid (HVA) to dopamine in the nucleus accumbens and striatum in rats subjected to alcoholism, as compared with intact controls. Chronically alcoholic rats treated with SP showed increases in DOPA, HVA, and the DOPA:dopamine and HVA:dopamine ratios in the nucleus accumbens as compared with animals given physiological saline, by 17%, 23%, 9% and 19% respectively. The only increases in the striatum were in the absolute levels of DOPA and HVA, by 28% and 29%, while the ratios of these metabolites to dopamine remained unchanged. Thus, central administration of SP decreased the voluntary consumption of ethanol in the ethanol free choice test and enhanced dopamine metabolism in structures of the mesolimbic and nigrostriatal systems in chronically alcoholic rats.

3,4-Dihydroxyphenylacetic Acid↗

[Effect of centrally administrated substance P on the brain mesolimbic system activity in rats as measured by microdialysis].

Action of substance P on the contents of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens of rats was investigated with microdialysis procedure. During 3 days, each animal daily received i.v. the saline (the 1st day), 0.1 mcg of substance P (the 2nd day), 1 mcg of substance P (the 3rd day). Elevation of accumbal dopamine was observed amounting up to 41% and 71% for 0.1 mcg and 1 mcg of substance P, resp. Rates and duration of these changes also depended on neuropeptide concentration. 1 mcg of substance P produced the dopamine elevation with a peak by the 50th min. Moreover, in 75 min. after infusion of the neuropeptide, the levels of dopamine still remained increased. Response of metabolites also proved to be dose-related. With 1 mcg of substance P, the contents of dihydroxyphenylacetic acid increased by 28%, while with 0.1 mcg of substance P, this parameter did not change. Contents of homovanillie acid was unaffected by central substance P at the above doses. The data obtained corroborate the assumption of influence of the substance P on the reward system arising from its dopaminergic properties and provide a possible explanation of the neuropeptide effects observed in the conditioned place preference paradigm.

3,4-Dihydroxyphenylacetic Acid↗

[The influence of substance P central administration on ethanol intake in rats chronically exposed to alcohol].

The influence of central substance P (SP) administration on alcohol intake and brain dopamine metabolism within mesocortico-limbic and nigrostiatal systems of rats exposed to ethanol, was studied. During 6 months, the rats consumed 15% ethanol solution instead of water. Central administration of SP (3 mcg/kg) decreased alcohol consumption by 41% in alcohol-preference animals. After long-term ethanol exposure ratios DOPAC/DA and HVA/DA were reduced in striatum and accumbens. SP in dose 3 mcg/kg increased content of DOPAC by 17% and HVA by 23% as well as DOPAC/DA by 9%, HVA/DA by 19% in accumbens. Whereas in striatum only increased DOPAC (28%) and HVA (29%) were observed as compared with saline-treated rats.

3,4-Dihydroxyphenylacetic Acid↗

[Significance of the level of auto-antibodies for the NMDA type glutamate receptors in diagnosis of chronic cerebral circulation disorders].

For studying diagnostic possibilities of a new laboratory test for cerebral ischemia (CIS-test), thirty patients have been examined. The level of autoantibodies to NMDA type glutamate receptors is shown to increase significantly (3-5 times) in patients with stage 2 dyscirculatory encephalopathy. Parallel measurements of free glutamate and homocysteine levels in the patients blood plasma did not reveal any substantial changes of the given parameters, comparing to indices of autoantibodies to NR2a glutamate receptor. The titer of autoantibodies to this receptor type did not change significantly in patients with epilepsy; the titer dependence on dyscirculatory encephalopathy severity level and its decrease during treatment have been found as well. The possibilities of CIS using for diagnosis and therapy control in patients with chronic cerebral circulation disorders are discussed.

Adult↗

Intracerebroventricular administration of substance P increases dopamine content in the brain of 6-hydroxydopamine-lesioned rats.

The interactions existing between substance P- and dopamine-positive neurons, notably in the basal ganglia, suggest that substance P may have therapeutic use in treatment of Parkinson's disease characterized by impaired dopaminergic transmission. The effects of intracerebroventricularly administered substance P were tested on the levels of dopamine and its metabolites in the striatum, nucleus accumbens and frontal cortex of 6-hydroxydopamine-lesioned rats. Intracerebroventricular injection of 6-hydroxydopamine decreased the levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the brain structures under investigation. Administration of substance P in low dose (0.35 nmol/kg) had no effect on the 6-hydroxydopamine-induced reduction of the dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid contents in the brain. However, treatment with substance P in higher dose (3.5 nmol/kg) increased the concentrations of dopamine and its metabolites in the striatum, nucleus accumbens and frontal cortex relative to saline-treated group. Additionally, 6-hydroxydopamine lesions significantly increased 3,4-dihydroxyphenylacetic acid/dopamine and homovanillic acid/dopamine ratios in the striatum and nucleus accumbens. Substance P (3.5 nmol/kg) partially reversed lesion-induced increases in 3,4-dihydroxyphenylacetic acid/dopamine and homovanillic acid/dopamine ratios in the striatum, but did not alter these ratios in nucleus accumbens. To test whether substance P fragmentation is responsible for this phenomenon, substance P(5-11), which is one of the main substance P fragments in rat CNS, was administered in equimolar dose. Substance P(5-11) was found to have no effect on the content of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the striatum and nucleus accumbens. In the frontal cortex, substance P(5-11) produced decreases in dopamine levels and increases in homovanillic acid/dopamine ratio. The results of this study suggest that substance P helps to restore dopamine deficit in the brain in an animal model of Parkinson's disease, with the positive effects being more prominent on the nigrostriatal than on the mesocorticolimbic dopaminergic system, but substance P(5-11) is not responsible for this effect.

Animals↗

[Neuroprotective effects of glycine in the acute period of ischemic stroke].

Both the efficiency of glycine in the acute period of hemispheric ischemic stroke and mechanisms of its action were studied in a double blind placebo-controlled trial including 200 patients. Orgogozo's and Scandinavian scales for objective assessment of the condition severity and of a degree of neurologic deficiency, and Bartel's scale--for evaluation of functional recovery were used and measurements were made of the levels of autoantibodies to the structural component of glutamate NMDA-receptors in blood serum and concentrations of neurotransmitter amino acids and of the products of lipid peroxidation in cerebrospinal fluid. Sublingual glycine application in daily dose of 1-2 g was found effective beginning with the first 6 hours of the stroke development during 5 days. Multicomponent neuroprotective action of glycine was established directed at correction of the unbalance between stimulating and inhibiting aminoacidergic neurotransmitters, as well as at a decrease of excitotoxicity and oxidant stress.

Acute Disease↗

[The use of the clinical biochemical Epitest kit in children with epilepsy].

57 children aged 3-15 years were examined: children with epilepsy (n = 26), children with epileptic syndrome (n = 16) and children with other neurologic pathology (n = 15). Control group included 25 healthy children. Diagnostic efficiency of the epileptic test was investigated on the basis of the detection of autoantibodies (aAb) to glutamate receptor of AMPA type in blood serum of the patients. It was shown that children with epilepsy had elevated level of aAb to AMPA receptors in blood in comparison with that of the healthy children. The level of aAb to AMPA receptors correlated with severity of the disease and location of the epileptic focus. The authors recommend the "Epitest" as an additional biochemical tool for differential diagnosis of children's epilepsy.

Adolescent↗

Monitoring of brain spiking activity and autoantibodies to N-terminus domain of GluR1 subunit of AMPA receptors in blood serum of rats with cobalt-induced epilepsy.

We have monitored EEG spontaneous spiking activity and analyzed serum from rats with cobalt-induced epilepsy for the presence of autoreactive antibodies to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) glutamate receptor subunits. The presence and the level of autoantibodies were assessed using immunoblot and ELISA with synthetic peptide specific to the N-terminus domain of the GluR1 subunit of the AMPA receptor. Rats with cobalt-induced epilepsy exhibited strong GluR1 immunoreactivity at the end of the first week after surgery compared with vehicle-treated rats. We showed that GluR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy preceded the spiking activity maximum in the EEG. Levels of autoantibodies to GluR1 detected in blood of these rats remained elevated when EEG spiking activity was significantly reduced and seizures disappeared. The EEG monitoring of spiking activity showed a correlation with accumulation of GluR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy.

Animals↗

The presence of autoantibodies to N-terminus domain of GluR1 subunit of AMPA receptor in the blood serum of patients with epilepsy.

We have analyzed the serum from patients with refractory epilepsy for the presence of autoreactive antibodies to AMPA glutamate receptor subunits. The presence and the level of autoantibodies were assessed using immunoblot and ELISA with synthetic peptides specific for subregions of AMPA glutamate receptor subunits. Patients with refractory epilepsy exhibited strong immunoreactivity to GluR1 subunit compared to healthy donors and patients with Parkinson's disease and Alzheimer's disease. Weak immunoreactivity to other AMPA glutamate receptor subunits was also detected and the signal was diminished in the raw GluR4>GluR3>GluR2. The occurrence of autoantibodies to specific neurotransmitter subunits in the sera of patients with refractory epilepsy suggest that autoimmune process may underlie this disorder.

Autoantibodies↗

[Autoantibodies to NMDA-type glutamate receptors in the blood of patients with acute ischemic and hemorrhagic stroke].

The characteristics of accumulation of autoantibodies (aAbs) on NMDA-type glutamate receptors were studied in blood of patients at different stages (1-4 days, 5-7 days, 8-14 days, up to 28 days) of acute period of ischemic or hemorrhagic stroke. The stability of low values (1.29 +/- 0.31 ng/ml) of the titer of aAbs to NMDA-receptors was revealed in patients with acute cerebral hemorrhage. Two types of titer of Abs to NMDA-receptors were revealed in case with cerebral ischemia. The undulating nature of Abs titer changes was revealed in acute ischemic strokes caused by hypertension and cerebral atherosclerosis (from 2.23 +/- 0.53 ng/ml on the 1-st day with increase up to 3.23 +/- 0.90 ng/ml and up to the 3-4 day), following fluctuations with less pronounced increase on 7-8th day were found out. High titer of aAbs to NMDA-receptors (up to 10.0 ng/ml) were observed on 3-4th day in cases of acute ischemic strokes on the background of chronic alcohol encephalopathy caused by intoxication or dysmetabolism with their retention up to 10-14th day.

Acute Disease↗

[Clinico-biochemical study in epilepsy].

Diagnostic opportunities of the test of paroxysmal activity (TPA) were examined in 253 epileptic patients of different age and duration of disease. It was established that the changes of autoantibodies (aAB) titers in the control group were about 64-110% (mean value 85%). Meanwhile in epileptic patients there was elevation of the same indices 2.1 times (182%). The correlation was observed between the levels of aAB titers and duration of the disease, frequency and character of paroxysmal disorders. The conclusion was made that TPA may be used quite successfully in diagnosis of epilepsy, especially in difficult cases. The level of accumulation of aABs in blood of patients with the fits may be used as new immunological index which may facilitate essentially objective of diagnosis of epilepsy.

Adolescent↗

[The diagnosis of epilepsy by using blood analysis for the content of autoantibodies to glutamate neuroreceptors].

The glutamate receptor autoantibody level was studied in blood of 170 epileptic patients as well as of 114 control donors (64 patients with nonepileptic cerebral pathology and 50 healthy individuals). The elevation of autoantibodies level (higher than 140%) was observed in 63.5% of patients with paroxysmal epileptic disturbances. This elevation was observed more frequently in the initial period of the disease as well as in generalized (convulsive or nonconvulsive) fits irrespective of disease etiology. Combined application of the test with EEG method permitted to confirm the epileptic nature of the disease in 83.5% of cases. The results of repeated analysis of glutamate receptor autoantibody level in blood proved to be a significant criterion of the effectiveness of anticonvulsive therapy. It also allowed to predict the development of posttraumatic epilepsy in individuals with craniocerebral trauma in the past.

Adult↗

[The level of autoantibodies to glutamate receptors in the blood serum of patients in the acute period of ischemic stroke].

The level of autoantibodies (aAB) to main structural component of glutamate NMDA-receptors--phencyclidin-binding protein--was measured in blood serum of 70 patients during first 3, 6, 9, 12, 24 hours, and 3, 5 days after ischemic stroke development. 200 healthy individuals formed the control group. The elevation of titers of aAB to glutamate receptors was observed in all patients with severe or moderate disease from the very first hours of stroke. It was especially pronounced by 9-12 hours after stroke. The highest increase of aAB titers was found in severe cases. The tendency to normalization of aAB titers was observed by the end of the first twenty four hours. The degree of aAB elevation had the prognostic importance. The most favourable course of stroke with good restoration of damaged functions was predicted when stable normalization of the aAB level was observed by the third day of the disease development. Patients in stupor-coma condition did not show the phenomenon of aAB level's elevation during the first days of stroke, that reflected, probably, the development of immuno-deficient state. The decrease of aAB level down to subnormal values was extremely unfavourable prognostic sign proceeding patient's death as a rule.

Acute Disease↗