[C-peptide physiological effects].

In the recent years there were numerous evidences that C-peptide, which was previously considered as a product of insulin biosynthesis, is one of the key regulators of physiological processes. C-peptide via heterotrimeric G(i/o) protein-coupled receptors activates a wide range of intracellular effector proteins and transcription factors and, thus, controls the inflammatory and neurotrophic processes, pain sensitivity, cognitive function, macro- and microcirculation, glomerular filtration. These effects of C-peptide are mainly expressed in its absolute or relative deficiency occurred in type 1 diabetes mellitus and they are less pronounced when the level of C-peptide is close to normal. Replacement therapy with C-peptide prevents many complications of type 1 diabetes, such as atherosclerosis, diabetic peripheral neuropathy, and nephropathy. C-peptide interacts with the insulin hexamer complexes and induces their dissociation and, as a result, regulates the functional activity of the insulin signaling system. At the same time, C-peptide at the concentrations above physiological may demonstrate pro-inflammatory effects on the endothelial cells and cause atherosclerotic changes in the vessels, which should be considered in the study of pathogenic mechanisms of complications of type 2 diabetes mellitus, where the level of C peptide is increased, as well as in the development of approaches for C-peptide application in clinic. This review is devoted contemporary achievements and unsolved problems in the study of C-peptide, as an important regulator of physiological and biochemical processes.

Comparative experimental evaluation of the efficacy of Prostamol Uno and Samprost on rat model of chronic aseptic prostate inflammation.

Comparative experimental evaluation of the efficiency of prostatotropic drugs Prostamol Uno and Samprost on the model of the chronic aseptic prostate inflammation in rats was performed. It was established that peptide drug Samprost decelerates sclerotic processes in the prostate gland to a greater extent than herbal preparation Prostamol Uno. Both products equally stimulate secretory activity of the gland. Prostamol Uno, unlike Samprost, prevents the development of reduced sexual motivation, one of the complications of chronic prostatitis.

[Evaluation of antiepileptic effects of cortexin in a model of convulsions].

We studied antiepileptic effects of cortexin administered in doses 0,015, 0,15 and 1,0 mg/kg intraperitoneally in solution or intranasally in the complex with nanoparticles in a model of acute and chronic convulsions in rats induced by pentylenetetrazole. In the model of epileptic status, the long-term preliminary administration of cortexin had no effect on convulsions while in the model of chronic convulsions (temporal epilepsy), cortexin had a marked dose-dependent antiepileptic effect. The influence of cortexin on neuroplasticity and its clinical potential are discussed.

[Experimental hemorrhagic stroke: the effect of the peptide preparation cortexin in the formation of Hb-NO-complexes and other blood paramagnetic centers].

Using electronic paramagnetic resonance (EPR), we studied the effect of the peptide cortexin on the content of hemoglobin nitrozyl complexes (Hb-NO-complexes) and other paramagnetic centers (transferrin, methemoglobin) in the blood of rats of Krushynsky-Molodkina line in the experimental hemorrhagic stroke induced by acoustic stress. After the acoustic exposure, the level of Hb-NO-complexes have increased by more than 6 times. The intensity of the EPR signal of the plasma peptide transferrin increased by 1,5 times. The level of blood methemoglobin was also elevated, though not significantly, after the acoustic stress. Cortexin substantially reduces the formation of Hb-NO-complexes and, therefore, the level of nitride oxide while the contents of transferrin and methemoglobin remain intact.

[S100B protein and autoantibodies to S100B protein in diagnostics of brain damage in craniocerebral trauma in children].

Levels of antibodies AB (AB) to S100B and S100B protein were studied in the blood serum of children with different severity and outcomes of traumatic brain injury (TBI) from the 1st to 15-75th days after TBI. Severity and outcomes were assessed using the Glasgow Coma Scale (GCS). Patients were stratified by outcomes into the following groups: complete recovery (group 1), moderate disability (group 2), high disability (group 3), vegetative state (group 4) and fatal outcome (group 5). In patients of groups 1-3, the changes of S100B in the blood serum didn't depend on the severity of brain's damage; the significant increase of S100B protein levels in the 1st day was accompanied by the decrease to the normal range in the following 2-3 days. On the contrary, the levels of nAB in these groups increased starting from 3-5 days corresponding to the severity of brain's damage. The development of vegetative state was accompanied by low S100B and high AB to S100B levels in the blood serum. The maximal level of S100B protein and increased levels of AB were observed in patients with fatal outcome. In most patients with combined TBI, the levels of both parameters were higher compared to those with separate TBI.

Autoantibodies to glutamate receptors and products of nitric oxide metabolism in serum in children in the acute phase of craniocerebral trauma.

Levels of serum autoantibodies (aAb) to glutamate receptors and products of nitric oxide (NO) metabolism, i.e., nitrates and nitrites, were assayed in children with recent craniocerebral trauma (CCT) of different levels of severity. All the children showed increases in serum aAb to both AMPA and NMDA receptor subtypes from day 1 to day 10 after trauma. The highest levels of serum aAb were to the NMDA subtype of glutamate receptor, which was characteristic of children with mild CCT (MCCT), with Glasgow Coma Scale (GCS) scores of 14-15 points. Levels of aAb to NMDA (NR2A) receptors in children with severe CCT (SCCT, GCS < 9 points) were lower than in children with MCCT, the lowest levels being seen in the group of children with lethal CCT (SCCT-2). Serum concentrations of NO metabolites increased by large factors in the group of children with SCCT, indicating marked brain hypoxia.

[Autoantibodies to glutamate receptors and metabolic products of nitric oxide in blood serum of children in the acute period of brain trauma].

Autoantibodies (AB) to glutamate receptors of AMPA (Glur1) and NMDA (NR2A) types and nitric oxide metabolites, nitrates and nitrites (NOx), were studied in the blood serum of children with brain trauma of different severity. The level of both AB types increased from the 1st to the 10th day after trauma. The level of NMDA (NR2A) AB was higher comparing to AMPA (Glur1). Patients with mild brain trauma, scoring 14-15 on the Coma Glasgow Scale, had the highest AB concentration while patients with severe brain trauma (scores <9), had the lower level of NMDA (NR2A) AB. The lowest level of AB and the highest level of NOx in the blood serum were found in a group of children with the fatal outcome of severe brain trauma. The many-fold increase of NOx concentration in this group points to marked hypoxia after severe brain trauma.

Effect of antibodies against AMPA glutamate receptors on brain neurons in primary cultures of the cerebellum and hippocampus.

Rabbit antibodies against GluR1 subunit of AMPA glutamate receptors in a concentration of 1 mug/ml significantly increased intracellular Ca(2+)concentration and decreased mitochondrial potential in hippocampal neurons, i.e. produced changes typical of the influence of glutamate in toxic concentrations. In cerebellar neurons rabbit antibodies potentiated glutamate-induced increase in intracellular Ca(2+)concentration and significantly decreased the mitochondrial potential (compared to the level observed after application of glutamate alone). The exposure of cultured cerebellar neurons to antibodies in a concentration of 0.1 mug/ml for 24 h was followed by a 50% decrease in ATP concentration and development of neuronal necrosis. Our results attest to an important role of autoimmune damage to neurons during hyperstimulation of glutamate receptors.

[Determination of antibodies to opiate receptors by latex agglutination and immunoenzyme analysis]. / Opredelenie antitel k opiatnym retseptoram metodami latex-aggliutinatsii i immunofermentnogo analiza.

Adsorption ability of few kinds of latex covered by synthetic peptide fragments of mu- and delta-opiate receptors (OR) is investigated. The levels of autoantibodies to opiate receptors fragments in the blood serum of patients with drug abuse are detected by latex agglutination and ELISA. The patients with drug abuse demonstrated positive latex agglutination reaction for level specific antibodies from 10.4 mg/ml and higher in the 71.4% of cases. The levels of autoantibodies to OR in the blood of patients with drug abuse was in 2.8 times higher of control data. The correlation between levels of autoantibodies to opiate receptors obtained by methods of latex agglutination and ELISA is revealed. The obtained data confirms our hypothesis concerning existence of specific changes in immune system linked with some CNS disorders like drug abuse. Thus, the level of autoantibodies to opiate receptors could be used as new criterion for diagnostics of opiate abuse.

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.

[Levels of autoantibodies to glutamate receptors and immunological blood parameters in patients with epilepsy]. / Uroven' autoantitel k sub''edinitsam glutamatnykh retseptorov i immunologicheskie pokazateli krovi u bol'nykh épilepsiei.

The role of glutamate receptors in the brain spiking activity was evaluated. The electroencephalographic (EEG) spiking activity was monitored and autoreactive antibodies (aAbs) to subunits of glutamate receptors were assessed in the blood serum of epileptic and ischemic stroke patients. We showed that the level of GluR autoantibodies in blood serum of patients correlates to the intensity of the brain paroxysmal activity. These data confirm our previous observations. The level of GluR1 aABs has been proposed as a specific biomarker typical for epilepsy. This approach could be recommended as an additional criterion for diagnostic of nervous diseases such as epilepsy and ischemic stroke.

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.