[Creation of registers as one of the mechanisms for improving medical care for patients with chronic heart failure. Problem state].

The annual mortality of patients with clinically pronounced symptoms of chronic heart failure in the Russian Federation reaches 26-29%, i.e., from 880 to 986 thousand patients with heart failure die in the country in one year, which is comparable to the population of a large city. Providing care for patients with heart failure places a heavy burden on the country's health care system, making a significant contribution to mortality rates, hospitalization rates, including readmissions, which in turn requires considerable costs. The article presents an overview of registry studies that are devoted to assessing the effectiveness of diagnostics, the completeness of examinations, as well as the adequacy of ongoing drug treatment.

Oxidative Damage of Proteins Precedes Loss of Cholinergic Phenotype in the Septal Neurons of Olfactory Bulbectomized Mice.

BACKGROUND: The development of cholinergic deficit is considered an early sign of a number of pathological conditions, including Alzheimer's disease. Cholinergic dysfunction underlies cognitive decline associated with both normal aging and Alzheimer's disease. OBJECTIVE: Here, we studied a possible mechanism of functional impairment of cholinergic neurons using an olfactory bulbectomy model. METHODS: Male mice were subjected to olfactory bulbectomy or sham surgery. Three weeks after that they were trained in Morris water maze and then euthanized one month after surgery. The cholinergic indices as well as the indices of oxidative stress were studied using immunohistochemistry, western blot and ELISA. Gene expression was studied using RT-qPCR. RESULTS: The experimental treatment was followed by impaired learning of a standard spatial task in a water maze. This was associated with a decrease in the number of cells containing choline acetyltransferase (ChAT), in relation to total number of neurons in the medial septum and lower ChAT enzymatic activity in the hippocampus. However, the levels of mRNAs of ChAT, vesicular ACh transporter and acetylcholine esterase remained unchanged in bulbectomized mice compared to sham-operated animals. These alterations were preceded by the accumulation of protein-bound carbonyls, indicating oxidative damage of proteins, whereas oxidative damage of nucleic acids was not detected. CONCLUSION: We assume that in olfactory bulbectomy model, oxidative damage of proteins may cause cholinergic dysfunction rather than irreversible neuronal damage. These data indicate that cholinergic neurons of the basal forebrain are very sensitive to oxidative stress, which may be responsible for the appearance of early cognitive decline in Alzheimer's disease.

[Clinical characteristics and quality assessment of the treatment of patients with chronic heart failure with diabetes mellitus].

AIM: A study of the clinical and instrumental characteristics and quality of treatment of patients with chronic heart failure (CHF) with diabetes mellitus. MATERIALS AND METHODS: The study was conducted by using the CHF register method, which is a computer program with remote access, which allows on-line data collection on patients who have been examined and treated in primary care and in hospitals. The study included 8272 patients with CHF IIIV FC (functional class) (New York Heart Association NYHA); among them 62% of patients were treated in hospital. RESULTS: The study showed that the frequency of diabetes was 21%. The main causes of CHF in diabetic patients are coronary artery disease, myocardial infarction (in anamnesis) and hypertension. These patients are more often diagnosed with III and IV CHF FC according to (NYHA) and retained LV (left ventricular) ejection fraction. The reduced ejection fraction was observed in 6.8% of cases, and the frequency of the intermediate LV was significantly higher than among patients with CHF and with diabetes and accounted for 18.9%. At patients with CHF with diabetes in comparison with patients with CHF without diabetes, atherosclerosis of the peripheral arteries, stroke (in anamnesis) and chronic kidney disease of stage III and IV were significantly more common. CONCLUSION: Under the treatment, patients with CHF with diabetes have higher levels of SBP (systolic blood pressure), lipids and glucose in the blood plasma, indicating a lack of quality of treatment and, accordingly, the doctors are not optimally performing the clinical guidelines on treating this category of patients.

[Clinical efficacy of probiotic strains of the Bifidobacterium and Lactobacillus].

The article analyzes the effectiveness of the most studied probiotic strains that are used for prophylactic or therapeutic purposes. The requirements for probiotic microorganisms are described, depending on the form in which they are used. However, their scope most often covers both prevention and treatment of various functional disorders and diseases of the gastrointestinal tract. At the same time, a lot of data has been accumulated on the effectiveness of probiotics for the treatment and prevention of diseases of other organs and organism systems. Most strains are successfully used as dietary supplements, and some of them have found their application in food industry.

Arterial hypertension and chronic obstructive pulmonary disease: clinical characteristics and treatment efficasy (according to the national register of arterial hypertension).

AIM: The objective of the research is studying of demographic and clinical profile as well as treatment effectiveness of patients with AH and COPD based on National Register of Arterial Hypertension. MATERIALS AND METHODS: Among the analyzed selection, consisted of 32 571 patients with AH, who were followed up in the primary medical care, at the average age of 64±7 years old (there were 64% women of them), 5.4% patients with AH had COPD. The analysis of cardiovascular and cerebrovascular diseases frequency as well as treatment effectiveness was made. RESULTS: According to National Register of Arterial Hypertension, cardiovascular [coronary heart disease, Q myocardial infarction, chronic heart failure (CHF), peripheral artery atherosclerosis] and cerebrovascular (stroke/transitory ischemic attack) diseases are accurately more often diagnosed at patients with AH and COPD. CONCLUSION: Male sex and age are the strongest independent factor, contributing into the risk of development of cardiovascular diseases at these patients. COPD considerably increases the risk of CHF development. The conducted analysis has shown that treatment, prescribed to patients with AH and COPD meets modern recommendations.

Features of the clinics and treatment of patients with obesity and hypertension (according to the National register of arterial hypertension).

AIM: The purpose of this study lied in the examination of the clinical characteristics and assessment of the quality of treatment for patients with arterial hypertension (AH) with obesity according to the National Registry of the AH. MATERIALS AND METHODS: The frequency of obesity in a sample of patients with AH, observed in 2010-2016. in polyclinics and cardiological dispensaries for cardiovascular diseases (CVD), was 38.3%, of which the incidence of severe obesity (grade III) was 8%. Women account for the majority of obese AH patients (72%). RESULTS: The study revealed the burden of AH patients with obesity in the following risk factors for CVD: dyslipidemia, hyperglycemia and a history of early cardiovascular disease. Relatively often in patients with hypertension with obesity, there were lesions of target organs (hypertrophy of the left ventricle, chronic kidney disease of the third stage), CVD [ischemic heart disease (CHD), chronic heart failure (CHF) II-IV functional class NYHA] and diabetes mellitus type 2 These data indicate that patients with AH obesity refers to a high and very high cardiovascular risk. CONCLUSION: Conducted antihypertensive and hypolipidemic therapy (statins) in patients with AH obesity was not optimal, only 30% of patients achieved the target level of BP and 23.6% - the target level of total cholesterol.

[The comparative analysis of immunologic techniques of detection of anti-phospholipid antibodies].

The laboratory diagnostic of anti-phospholipid syndrome consists in detection of anti-phospholipid antibodies using technique of enzyme-linked immunosorbent assay namely in detection of anti-cardiolipin antibodies and antibodies to ß2-glycoprotein. In spite of the fact that serological diagnostic plays a key role in diagnosing anti-phospholipid syndrome application of laboratory tests s complicated by their insufficient standardization. The new approach to detection of anti-phospholipid antibodies became application of immune blotting on the basis of polyvinylidenfluoride membrane. As compared with enzyme-linked immunosorbent assay, the advantage of the mentioned technique is in using hydrophobic solid phase for sorption of antigens. The porous structure of polyvinylidenfluoride membrane orientates hydrophilic areas of phospholipids and by that ensures their more dense distribution imitating bi-lipid layer of membranes of living organism. To specify and compare value of different techniques the comparison was implemented concerning the results of measurement of anti-phospholipid antibodies in enzyme-linked immunosorbent assay test-systems of various manufacturers and reagents kits for immune blotting. The collection was assembled including bio-materials from 47 patients with non-cardioembolic ischemic strokes, 20 patients with recurrent thrombosis of deep veins of lower extremities and 50 patients with obstetrics pathology and also 30 healthy donors. In the given serums aKlaIgG, aKlaIgM, aß2glycoprotein I were measured using enzyme-linked immunosorbent assay technique assisted by test-systems of Euroimmun and Orgentes Diagnostica and the samples with the highest titre using immune blotting technique with reagents manufactured by Medipan. On the basis of measurement of anti-phospholipid antibodies by various enzyme-linked immunosorbent assay test-systems the rate of aß2glycoprotein I amounted to 31% in case of Euroimmun reagents kits for enzyme-linked immunosorbent assay, 78% in case of Orgentec Diagnistica test-systems for enzyme-linked immunosorbent assay, aKlaIgG - 2% and 30%, aKlaIgM - 31% and 54% correspondingly. The measurement of anti-phospholipid antibodies using immune blotting technique on Medipan test-systems in bio-samples with the highest titres detected aß2glycoprotein I in all patients, aKlaIgG in 70% and aKlaIgM in 30% of patients. The convergence between three commercial reagents kits varies from 20% to 88%. The standardization of commercial test-systems still to be achieved. The new technique of immune blotting can be appliedjointly with classic techniques ofserological diagnostic of anti-phospholipid syndrome. The absence of algorithms of diagnostic and standardization of different test-systems for detection of anti-phospholipid antibodies prejudices reliability of serological diagnosis of anti-phospholipid syndrome and therefore existence of anti-phospholipid syndrome as a nosologic unit.

[PERSONALIZED MEDICINE IN INTERNAL MEDICINE].

Personalized medicine - a new direction in medicine, which is based on the study of various biomarkers and the use of new methods of molecular analysis (primarily evaluating the activity of isoenzymes of cytochrome P450), allowing individualized approach to the selection of both the drugs and the selection of the dosing regimen for the purpose of maximize the effectiveness and safety of pharmacotherapy. This personalized medicine is to change the development and use of preventive and curative interventions. Genetic polymorphism isozymes of cytochrome P450 may determine the individual activity of a particular isozyme, and thus, to predict the clinical effectiveness, and in some cases, the risk of adverse reactions. The article is an example of the use of information on the activity of cytochrome P450 in clinical practice in matters of diagnosis, treatment and prevention of diseases. The scheme of the five best-known activity of isoenzymes of cytochrome P450 is shown.

[Structure of Response and Dynamics of Preferred Orientation in Cat's V1 Neurons].

Preferred orientation of V1 neurons was changed during the respons time course. In order to reveal mechanisms of such changes, spike trains of single neurons to flashed bars of different orientations were studied by means of principal component and frequency-domain analysis of the spike density functions. There was found out that: 1. contribution of each of the components was dependent on the stimulus orientation. 2. the principal components of V1 neurons responses contain different kinds of transient and sustained parts and rhythmic oscillations in the theta/alpha and beta-bands. 3. There was no correlation between transient parts as well as between rhythmic oscillations within the same frequency band in different components. Taken together, the data obtained allow us to suggest that during generation of response there is a shift of dominance of the components with different orientations which determines the dynamics of the preferred orientations of V1 neurons.

[The Effects of Chronic Combined Stress: Changes in Behavior of Rats with Various Responses to Novelty].

We studied the effect of chronic combined stress (model of experimental neurosis) on behavior of rats with different basal strategies of behavior in novelty conditions. Chronic stress resulted in decreases in the body weight and testosterone contents in the blood and neocortex in all animals. Animals with initially low orient- ing-exploratory response in the "open field" test did not exhibit substantial alterations of behavior during repeated testing in this test of the "dark-light chamber" test; however, the depression-like behavior was more expressed in the second forced swim test. Chronic combined stress did not significantly affect the behavior of this group of rats. Animals with initially high orienting-exploratory response in the "open field" test exhibited decreased locomotor and exploratory activity in the repeated "open field" tests. The decreases in the locomotor and exploratory activity were substantially less expressed in the repeated tests in these rats after chronic combined stress. The indices of depression-like behavior increased one month after the end of exposure to chronic combined stress. Our data demonstrate that different responses to novelty in the "open field" test do not allow predict with reasonable certainty the development of depression-like behavior after exposure to chronic combined stress.

[Effect of a Single Injection of Brain Derived Neurotrophic Factor into Midline Ventral Tegmental Area on Morphine Reinforcing Properties].

Opiate reinforcement is considered as a stimulus inducing addiction, however underlying neurobiological mechanisms remain obscure. According to the literature, BDNF (brain-derived neurotrophic factor) in the lateral ventral tegmental area (VTA) could modulate morphine reinforcement, but the role of BDNF in the midline VTA has not been studied yet. The aim of the study was to investigate the effect of a single intra-mid- line VTA injection on the acquisition and expression of morphine conditioned place preference (CPP). CPP procedure was composed of eight conditioning sessions (one session per day): morphine (i.p., 10 mg/kg) and saline injections were paired to the compartments and counterbalanced.Recombinant human BDNF (0.75 ug) or phosphate-buffered saline (PBS) as a vehicle were injected once into the midline VTA one day before or after conditioning. According to the CPP test rats spent more time in the morphine-paired compartments a scompared to the saline-paired compartments (p < 0.05). After a single BDNF injection into the midline VTA be- fore conditioning, but not after conditioning, differences in time spent in morphine and saline-paired compartments did not reach significance (p > 0.05). Thus, taking into account limitations of the results, we sug- gest that BDNF in the midline VTA may block morphine reinforcement.

[The First Results of the Russian Register of Chronic Heart Failure].

We present in this paper first results of the Russian registry of chronic heart failure (CHF) as well as comparative analysis of available registries and a number of randomized controlled trials and meta-analyses on CHF.

[Slow Formation and Degradation of γH2AX Foci in Human Skin Fibroblasts Exposed to Low-Dose X-Ray Radiation].

It was shown that the kinetics of changes of γH2AX foci number (marker of DNA double-strand breaks) in human skin fibroblasts after exposure to low doses of X-ray radiation (20, 40 and 80 mGy) differs from that observed after exposure to medium-low doses (160 and 240 mGy). After exposure to 160 and 240 mGy the highest number of γH2AX foci was detected at 30 min after exposure (first experimental point) and further their decrease was observed. At the same time we observed a fast phase of repair (upto 4 h), in which there was a decrease of the foci amount to ~50-60% and a slow phase of repair (from 4 h to 24 h). After 24 h only ~3-5% of the foci amount observed at 30 min after irradiation was left. After exposure to low doses, the foci number did not decrease during 2 h and even 24 h after exposure their amount was ~25% from that observed at maximum points (1 h after irradiation at 40 and 80 mGy and 2 h after irradiation at 20 mGy).

[Pulmonary paecilomycosis: Diagnosis and treatment].

AIM: To represent the advances of Russia and Uzbekistan in studying the problem of paecilomycosis. The goal of the investigation was to develop the diagnosis and treatment of pulmonary paecilomycosis (PP). SUBJECTS AND METHODS: Two hundred and twenty-five people, including 200 patients with bronchopulmonary infection with fungi of the Paecilomyces genus and 25 clinically healthy individuals (a control group), were examined. Clinico-anamnestic, laboratory diagnostic, mycological, and immunological studies were conducted; a lymphocyte antigen-binding test was used for differential diagnosis. Paecilomyces infection was diagnosed by microscopically examining the morphology of the fungi in the pathological material (blood, sputum) and by isolating the cultured fungi in the media (Sabouraud's and Czapek's ones). The severe complication of PP - atypical paecilomycosis-associated myocarditis (APAM) - was studied in 112 patients with helminthiasis-complicated paecilomycosis. These patients underwent using the conventional echocardiography. RESULTS: Bronchopulmonary paecilomycosis resulting from primary and secondary infection with fungi of the Paecilomyces genus was clinically manifested as chronic obstructive bronchitis (11.5%), recurrent pneumonia (13.5%), exogenous allergic alveolitis (37%), and asthma (26%) complicated by helminthiasis (12%). Iodine deficiency promotes the prevalence of paecilomycosis and echinococcosis favors Paecilomycosis infection; moreover, the helminth capsule itself serves as a nutrient medium for the development of the mycelial form of the fungus. APAM is a severe complication of PP. Almost 50% of the patients with PP presented with carditis. The patients with APAM occasionally experienced fear and the most severe intermittent pain. The latter first occurred in the chest.and irradiated to the axilla, left hand, and its fingertips, paralyzing the arm. In some patients, the pain manifested itself in both arms with abdominal irradiation, by being accompanied by faints. Current analgesics (meloxicam, tizanidine, nimesulide, morphine, promedole) in combination with fluconazole provided a temporary positive effect. CONCLUSION: Further investigations that must also include neurologists and anesthetists are required to work out effective pain relief regimens for APAM in patients with PP.

Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study.

BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

[THE CLINICAL LABORATORY MARKERS OF ATHEROSCLEROSIS IN PATIENTS WITH ATHEROTHROMBOTIC STROKE].

The laboratory biomarkers can effect on choice of tactics of treatment in patients with atherosclerotic stenosis ofcarotids and high risk of stroke. However, nowadays there is no established laboratory criteria of significant atherosclerotic affection of internal carotid. The purpose of study was to investigate informativeness of biomarkers of atherosclerosis in clinical molecuIar panel of expertise system of determining risk of stroke in patients with significant stenosis of carotid. The study included patients with 50-90% atherosclerotic stenosis of internal carotid in acute period of atherothrombotic stroke or transitory ischemic attack (group 1), patients with stable 50-90% atherosclerotic stenosis of inner carotid having no vascular events during 30 days before engaging into study (group II) and group of healthy volunteers without atherosclerosis of inner carotid. The examination of patients included anamnesis collection, evaluation of neurological status, analysis of serum level of biomarkers of atherosclerosis (lipoprotein-associatedphospholipase A2 (LP-PL A2), serum protein A associated with pregnancy (PA PP-A), lipoprotein (a) (LP(a)), asymmetric dimethylarginine (ADMA), C-reactive protein detected by highly sensitive technique (hsCRP) and lipid spectrum of blood) using enzyme-linked immunosorbent assay, duplex ultrasound scanning of brachiocephalic arteries. The stroke risk factors of other etiology were chosen as exclusion criteria except atherothrombotic one. The Mann-Whitney and Kruskal-Wallis tests were applied to establish group differences. The Data Mining techniques were applied to establish patterns of analyzing sample. Out of 356 examined patients, 30 patients of group 1, 51 patients of group II and 16 healthy volunteers were included in the study. All patients were comparable by gender and age (50-80 years). The serum level of hsCRP and ADMA in the group of patients of acutest period of ischemic stroke was significantly higher than in groups of patients with stable stenosis and healthy volunteers (p < 0.05). The comparison between three groups established no statistically significant differences in serum concentration of PAPP-A, LP-PL A2 and LP(a). The ADMA, hsCRP and PAPP-A can be recommended for including into clinical molecular panel for personalized diagnostic of causes of stroke along with clinical anamnestic data. The serum level of ADMA and hsCRP significantly increases in acute period of atherothrombotic stroke. The analysis of levels of ADMA, hsCR and PPAPP-A interpreted with regard to clinical anamnestic data can be proposed for enhancing quality of diagnostic of causes of stroke.

[Creation of a Russian Federation's register for assessing the physician adherence to the guidelines for the diagnosis and treatment of chronic heart failure].

The paper reviews existing chronic heart failure (CHF) registers, a number of randomized trials, and meta-analyses on CHF. It provides a rationale for the need to create a CHF register in the Russian Federation, which will be able to assess the physician adherence to the guidelines for the guidelines for and the quality of medical care.

[Comparison of its and orientation tuning dynamics in neurons located in different functional domains of cat's primary visual cortex].

Orientation tuning and its dynamics of cat's primary visual cortex neurons located in pinwheel centers and orientation columns were studied during development of response in time. Functional domains in the Cortex were revealed by intrinsic signal optical imaging on functional and vascular maps of cortex. Both maps were used for precise placement of electrodes during recordings. Orientation tuning dynamic of each neuron was analyzed by temporary slices technique. Several types of neurons were observed in different functional domains: neurons with stable preferred orientation (14.5%); cells with preferred orientation dynamically shifted by 102 +/- 5 degrees (40.8%) and neurons with mixed dynamics type (44.7%). In pinwheel centers neurons with stable preferred orientation are differed from neurons with unstable preferred orientation in their features. In particular, they are showing greater response strength for preferred orientation. In orientation columns neurons with stable tuning are demonstrating larger latent periods for all orientations including preferred and non-preferred in comparison to cells with unstable response dynamics. We observed better detection quality of stable orientation neurons than in unstable preferred orientation neurons. Further coding features of neurons belonging to one functional type but located in different domains were compared. In general, located in pinwheel centers stable neurons have shorter latencies and stronger responses than for the stable cells located in orientation columns. Detection features were similar for this functional type of neurons. Unstable neurons located in different functional domains don't differ from each other in orientation tuning characteristics. Functional significance of neurons with stable and unstable preferred orientation located in pinwheel center and orientation columns in visual information processing are discussed.

[The value of quantitative analysis of procalcitonine in diagnostics of septic complications in patients with autoimmune rheumatic diseases].

The infections very often complicate the course of autoimmune rheumatic diseases. In diagnostic of septic complications in rheumatic patients the new biomarkers of infections can have a decisive importance. The procalciotonine test is one of them. The issue was to evaluate the diagnostic informativity of this test. The sample included 93 patients. The examination was applied to 65 patients with rheumatic diseases. Among them, 13 patients had bacterial infections. The group consisted of 33 patients with rheumatoid arthritis, 11 patients with systemic lupus erythematous, 6 patients with systemic angiitis, and 15 patients with other rheumatic diseases. The comparative group included 27 patients of cardio-therapeutic profile and 8 of these patients had bacterial infections. The procalcitonine test was applied with quantitative electrochemiluminescent technique. In patients with rheumatoid arthritis the mean levels of procalciotonine test consisted 0.10 +/- 0.13 ng/ml; with systemic lupus erythematous--0.08 +/- 0.06 ng/ml; with systemic angiitis--0.22 +/- 0.2 ng/ml; with other rheumatic diseases--0.12 +/- 0.15 ng/ml; of cardio-therapeutic profile without infections--0.08 +/- 0.06 ng/vl/ With threshold of procalcitonine test higher than 0.5/ml the sensitivity to diagnostic of infections consisted of 58%, specificity--94% in the group with rheumatic diseases. The procalciotonine test in case of no infection process with values higher than 0.5 ng/ml was detected in three patients. The evaluation of dependence of sensitivity and specificity for procalciotonine test and C-reactive protein the area under curve of procalcitonine test was larger in patients with rheumatic diseases (0.85 against 0.79) and in patients of cardio-therapeutic profile (0.92 against 0.90). The quantitative procalcitonine test is the best technique to detect septic complications in rheumatic patients.

[Neurodegenerative changes in rat hippocampal areas during the pentylenetetrazole kindling development].

The development of pentylenetetrazole-induced kindling is accompanied by neurodegeneration and neuronal loss in different areas of the hippocampus. However, the data on neurodegeneration development in the dentate gyrus remain controversial. In our study that was performed on 20 Wistar male rats, it was found that the process of neuronal loss was expressed unequally along the dentate gyrus. By the end of pentylenetetrazole kindling development, degenerating cells were present in the superior and inferior blades of the dentate gyrus, whereas the neuronal density in these areas was not reduced. On the other hand, in the angle of the dentate gyrus neuronal loss was already detected at the very early stages of kindling development. These findings allow to suggest a functional heterogeneity of a population of granule cells in relation to their susceptibility to seizure-induced injury.