STRUCTURAL AND FUCNTIONAL PARAMETERS OF THE CARDIOVASCULAR SYSTEM DURING ATRIAL FIBRILLATION IN PATIENTS AFTER STROKE.

OBJECTIVE: The aim: To evaluate the structural and functional parameters of the cardiovascular system during atrial fibrillation (AF) in patients after a stroke. PATIENTS AND METHODS: Materials and methods: In the main group, we selected 28 patients with non-valvular AF who had previously suffered an ischemic stroke (IS). The comparison group (30 people) included patients with AF without a stroke, comparable in age and gender. RESULTS: Results: As a result of the study, we discovered an increase in the risk of stroke with an increase in the thickness of the intima-media complex>0.9mm. The thickness of the interventricular septum was 1.19 (1.1; 1.25) in the group of patients with IS, and in the group of patients without IS - 1.09 (1.0; 1.19) cm (p = 0.019), the thickness of the LV posterior wall is greater in the main group 1.14 (1.05; 1.24) and 1.09 (1.01; 1.18) cm in the comparison group (p = 0.038). The myocardial mass index is 123.3 in the main group and 107.4 g/m2 in the comparison group (p = 0.41), which indicates left ventricle (LV) hypertrophy in the main group. CONCLUSION: Conclusions: thus, during AF in stroke patients, changes in the following structural and functional parameters of the cardiovascular system were discovered: an increase in the thickness of the interventricular septum, thickness of the posterior wall of the LV, and in the thickness of the intima-media complex.

Characterization of a New Positive Allosteric Modulator of AMPA Receptors - PAM-43: Specific Binding of the Ligand and its Ability to Potentiate AMPAR Currents.

BACKGROUND: Currently, the most dynamic areas in the glutamate receptor system neurobiology are the identification and development of positive allosteric modulators (PAMs) of glutamate ionotropic receptors. PAM-based drugs are of great interest as promising candidates for the treatment of neurological diseases, such as epilepsy, Alzheimer's disease, schizophrenia, etc. Understanding the molecular mechanisms underlying the biological action of natural and synthetic PAMs is a key point for modifying the original chemical compounds as well as for new drug design. OBJECTIVE: We are trying to elaborate a system of molecular functional screening of ionotropic glutamate receptor probable PAMs. METHODS: The system will be based on the radioligand - receptor method of analysis and will allow rapid quantification of new AMPAR probable PAMs molecular activity. We plan to use a tritiumlabeled analogue of recently elaborated ionotropic GluR probable PAM ([3H]PAM-43) as the main radioligand. RESULTS: Here, we characterized the specific binding of the ligand and its ability to potentiate ionotropic GluR currents. The existence of at least two different sites of [3H]PAM-43 specific binding has been shown. One of the above sites is glutamate-dependent and is characterized by higher affinity. "Patchclamp" technique showed the ability of PAM-43 to potentiate ionotropic GluR currents in rat cerebellar Purkinje neurons in a concentration-dependent manner. CONCLUSION: The possibility of using PAM-43 as a model compound to study different allosteric effects of potential regulatory drugs (AMPAR allosteric regulators) was shown. [3H]PAM-43 based screening system will allow rapid selection of new AMPAR probable PAM structures and quantification of their molecular activity.