The Effect of the Toxic Dose of Baclofen on Selected Parameters of the Cardiovascular and Respiratory Systems.

The effect of the toxic dose of the muscle relaxant baclofen on the parameters of the cardiovascular and respiratory systems was studied in adult male Wistar rats (n=20). Systolic and diastolic BP, HR, and respiratory rate were measured; histological changes in the lungs 3, 4.5, and 24 h after drug administration. Baclofen was administered orally in a sublethal toxic dose of 85 mg/kg under anesthesia. Cardiac activity was analyzed using RSM physiological indicators monitoring system with MouseMonitor S (Indus Instruments) software. Histological examination was performed by light microscopy. Baclofen significantly decreased the respiratory rate and increased HR and BP. Histological examination of the lungs revealed a complex of general pathological processes, such as local circulatory disorders (venular and capillary fullness, sludge), leukocyte infiltration of the interalveolar septa and their thickening due to edema. These findings can be used to estimate the time elapsed after baclofen treatment.

The Relationship between p53-Positive Neurons and Dark Neurons in the Hippocampus of Rats after Surgical Interventions on the Nasal Septum.

The study evaluates the dependence of p53 protein expression on the appearance of dark neurons (DNs) in the hippocampus in rats during experimental modeling of septoplasty. Septoplasty simulation was carried out on 15 sexually mature male Wistar rats. We studied histological sections of the hippocampus stained with Nissl toluidine blue and antibodies to the p53 protein. In the CA1 subfield, the number of p53-positive neurons significantly increased on the 2nd, 4th (p < 0.001) and 6th days (p < 0.05). In the dynamics, the peak of the growth of p53 protein expression in the cytoplasm of CA1 and CA2 neurons fell on the 2-4th day after the operation, and on the 6th day the number of these neurons decreased (p < 0.001). In the cytoplasm of CA3 neurons in all periods after surgery, an increase in the expression of the p53 protein as compared to the control group was noted. In the CA1 pyramidal layer, the number of DNs decreased on the 6th day (p < 0.001). In CA2, after 2 days, a minimum of DNs as compared with the 4th day (p < 0.001) was noted. In CA3, on the 4th day, there was a peak in DNs as compared with the rest of the days (p < 0.001). A positive strong association was found in all periods of assessment and in all subfields of the hippocampus between an increase in the number of dark and p53-positive neurons. The appearance of dark and p53-positive neurons in the hippocampal formation in rats after simulating septoplasty are typical responses of nervous tissue to stress. It is obvious that the expression of the p53 protein is associated with the basophilia of the cytoplasm of neurons, their morpho-functional state. Presumably, the p53 protein can trigger not only the activation of damaged neurons in the hippocampus but also play a neuroprotective role. Upcoming studies should determine the role of the p53 protein in the further fate of damaged neurons in the pyramidal layer and differentiate the mechanisms of its expression.

[Dynamics of vowel acoustic space indicators in patients with long-term hearing loss]. / Dinamika pokazatelei akusticheskikh treugol'nikov glasnykh zvukov u patsientov, stradayushchikh dlitel'nym narusheniem slukha.

New procedure of vowel acoustic space (VAS) (of vowel acoustic triangles) transformation for the purpose of characterization of vowel production in individuals with long-term hearing loss (HL) was developed. OBJECTIVE: To characterize VAS of adult Russian speakers with long-term HL using newly developed acoustic indicators. MATERIAL AND METHODS: Recordings of sustained Russian cardinal vowels /a/, /i/, /u/ of 10 women and 10 men with long-term HL were acoustically analyzed. For each participant, two first formants of each vowel were measured and log-transformed (logF1, logF2). VAS was transformed into right triangles, their /u/ corners were moved to the origin, and their legs were aligned with axes. VAS was almost symmetrical, equal and have a maximum size in the control group consisted of subjects without hearing impairment while these of long-term HL group VAS size tended to have reduced and VAS stretched along one axis. RESULTS: Our study showed that a new VAS normalization approach can distinguish at least three groups of people with long-term HL. CONCLUSION: There are those with vowel triangles stretched along logF1-axis, with vowel triangles stretched along logF2-axis, and with symmetrical vowel triangles. Causes of the VAS differences require further investigation.

[The effect of music embedded with binaural beats on heart rate parameters during nap]. / Vliyanie muzyki s effektom binaural'nykh bienii na parametry serdechnogo ritma cheloveka v protsesse dnevnogo sna.

OBJECTIVE: To test hypothesis that music embedded with binaural beats can boost activity of parasympathetic part of autonomic nervous system (PPANS) with the development of nap. MATERIAL AND METHODS: The power of high-frequency component of heart rate variability spectrum computed on successive 2-minute intervals during 20-minute nap was a comparison criterion. The criterion was compared during nap accompanied by music with embedded binaural beats (stimulus condition) and nap in silence (control condition). RESULTS AND CONCLUSION: Statistical comparison revealed the increase of PPANS activity during nap in stimulus condition vs. control condition. It is consistent with conclusions of other papers about positive effect of sound stimuli embedded with binaural beats on PPANS.

Influence of Surgical Trauma in the Nasal Cavity on the Expression of p53 Protein in the Hippocampus of Rats.

The aim of the study was to determine the role of the stress effect of septoplasty modeling on p53 protein expression in the hippocampus of rats under conditions of sensory olfactory deprivation. Simulation of septoplasty was carried out on 30 sexually mature male rats. A quantitative assessment of the apoptosis of neurons in the pyramidal layer of the hippocampus in the subfields CA1, CA2, CA3, and dentate gyrus (DG) on days 2, 4, and 6 after surgery was carried out. Histological sections were stained by the immunohistochemical method with antibodies to the p53 protein. An increase in the number of p53-positive neurons was noted in all subfields; the maximum increase in the number of apoptotic neurons was noted on day 4 after surgery. The stress effect of modeling septoplasty in rats, accompanied by sensory deprivation of the peripheral part of the olfactory analyzer, provoked the expression of p53 and the initiation of apoptosis mechanisms in various subfields of the hippocampus.

The Effect of Surgical Trauma in the Nasal Cavity on the Behavior in the Open Field and the Autonomic Nervous System of Rats.

In this article, the effect of surgical damage to the nasal mucosa in rats under the action of general anesthesia was investigated. The motor activity and heart rate variability (HRV) of rats were studied before and 2 days after the surgery. After surgical exposure, motor activity decreased, the time of fading and grooming increased, VLF increased, and HF decreased. Surgical trauma of the nasal septum in rats at the early postoperative stage promotes a pronounced stress response in the form of a sharp shift in the balance of the autonomic nervous system towards the sympathetic level and causes a decrease in exploratory activity, an anxiety, and a depressive-like state in rats.

Effects of circadian restricted feeding on parameters of metabolic syndrome among healthy subjects.

Experimental studies indicate that energy homeostasis to the circadian clock at the behavioral, physiological, and molecular levels, emphasize that timing of food intake may play a significant role in the development of obesity and central obesity. Therefore, resetting the circadian clock by circadian energy restriction via food intake in the morning or evening, may be used as a new approach for prevention of obesity, metabolic syndrome and related diseases. After ethical clearance and written, informed consent, free living subjects were included if they volunteered to take most of the total daily meals (approximately 2000 Kcal./day) in the evening (4 weeks) or morning (4 weeks). Of 22 adults, half were randomly selected by computer generated numbers to eat in the morning and the other half in the evening, after 8.00 PM. The eating pattern was changed after 4 weeks of intervention and a 4-week washout period, those who ate in the morning were advised to eat in the evening and vice versa. Validated questionnaires were used to assess food intakes, physical activity, and intake of alcohol and tobacco. Physical examination included measurement of body weight, height, and blood pressure (BP) by sphygmomanometer. Data were regularly recorded blindly, in all subjects at start of study and during follow-up. Blood samples were collected after an overnight fast for analysis of blood glucose and Hb1c. Feeding in the evening was associated with significant increase in body weight by 0.80 kg (P < .001), body mass index (BMI) by 0.30 kg/m2 (P < .001) and waist circumference by 1.13 cm (P < .05). Feeding the same amount of energy in the morning was not associated with any significant change in weight, BMI or waist circumference (P > .500). Lesser increases in all three variables were associated with AM versus PM feeding (P < .05). Systolic BP slightly increased on PM and decreased on AM feeding, with a difference between the two responses of 1.55 mmHg (P < .05). Fasting blood glucose was lower on AM than on PM feeding (74.86 vs. 77.95 mg/dl, paired t = 4.220, P < .001). Hb1C increased on PM feeding by 0.28 (from 4.45 to 4.73; t = 9.176, P < .001), but decreased on AM feeding by 0.077 (from 4.53 to 4.45; t = -6.859, P < .001). The difference in Hb1C response between AM and PM feeding is also statistically significant (t = -11.599, P < .001). Eating in the evening can predispose to obesity, central obesity and increases in fasting blood glucose and Hb1c that are indicators of the metabolic syndrome. By contrast, eating in the morning can decrease Hb1c and systolic BP, indicating that it may be protective against the metabolic syndrome.

Collagen Hydrolysis Products Reduce the Formation of Stress-Induced Ulcers by Regulating Stress-Associated Activation of the Neuroendocrine and Immune Systems.

We studied the effect of collagen fragments (PGP and AcPGP) on serum content of epinephrine, corticosterone, and IL-1ß in rats subjected to water-immersion stress. The degree of local inflammation accompanying ulceration was assessed by IL-1ß production by ln. gastricus caudalis cells. In 1 h, the sharp increase in hormone concentrations in the blood of stressed animals reflected the high stress intensity. Intranasal administration of PGP reduced the area of stress-induced ulcers by 63%, prevented the increase in the levels of stress hormones and the main proinflammatory cytokine in rat blood. The concentrations of IL-1ß in cell culture from regional lymph node of experimental animals returned to normal in 24 and 48 h after the stress. Acetylation of PGP prevents with gastroprotection, but does not abrogate other properties of the peptide.

[Septoplasty and tonsillectomy: acute stress response as a measure of effectiveness of local anesthetics].

AIM: To compare the effectiveness of lidocaine and articaineused as local anesthetics in septoplasty and tonsillectomy based on the physiological stress response. PATIENTS AND METHODS: The study included 125 patients with nasal septum deviation (NSD) and chronic tonsillitis (CT). The patients presenting with NSD were divided into two groups. Those comprising group 1A (n=32) were treated with a 2% lidocaine solution for local infiltration analgesia (LIA), the patients of group 1B (n=30) were given 2%articaine as LIA. Group 2A contained 32 patients with CT treated with lidocaine, group 2B consisted of 31 patients given articaine. In all the patients, the overall heart rate variability (HRV) including its high, low, and very low components was measured. RESULTS: Evaluation of HRV revealed a certain degree of disadaptation in the patients of groups 1B and 2A. High dispersion of SDANN, SDNN index, andrMSSD in group 1Bas well as SDANN values in group 2A indicates the sympathetic/parasympathetic imbalance. The high-frequency component was augmented in group 2B which suggested the prevalence of parasympathetic tone, but its high dispersion was just aswell indicative of disadaptation. CONCLUSION: Local analgesia with articaine during septoplasty leads tosympathetic/parasympathetic imbalance during the early postoperative period. Lidocaine analgesia for tonsillectomy does not prevent disadaptation induced by surgical stress.

Glyprolines exert protective and repair-promoting effects in the rat stomach: potential role of the cytokine GRO/CINC-1.

Glyprolines have been reported to exert protective effects in the stomach. In this study, we examined the potential effects of intranasal administration of Pro-Gly-Pro (PGP) and N-acetyl-Pro-Gly-Pro (AcPGP) on experimental gastric ulcer formation and healing. We also studied gastric release of the cytokine GRO/CINC-1, and its potential role in ulcer development and healing. Gastric ulcers were induced in rats by applying acetic acid to the serosa of the stomach. PGP and AcPGP were then administered at a dose of 3.7 µmol/kg once daily on either days 1 - 3 (ulcer formation) or days 4 - 6 (ulcer healing). Measurement of ulcer area and histological examination of gastric tissue were carried out on days 4 and 7 after application of acetic acid. In vitro studies involved addition of the glyprolines to cultured rat gastric epithelial cells with or without lipopolysaccharide. Reverse transcription PCR, real-time PCR and ELISA were used for cytokine analysis. PGP and AcPGP significantly reduced ulcer areas on the 4(th) day and accelerated the healing on the 7(th) day compared with the control. After acetic acid-induced ulceration, the expression of GRO/CINC-1 mRNA in gastric tissue was increased 9-fold versus the sham-operated group. Treatment with PGP or AcPGP both significantly suppressed the expression of GRO/CINC-1 mRNA in gastric tissue. However, the glyprolines did not alter LPS-induced mRNA expression or release of GRO/CINC-1 from cultured rat gastric epithelial cells, even though those cells were harvested from rats subjected to the ulcer-induction procedure. The results of this study show that intranasal administration of PGP and AcPGP significantly increased resistance against acetic acid-induced ulceration and accelerated healing in the rats. These effects may be due, at least in part, to their ability to reduce the acetic acid-induced GRO/CINC-1 expression and production in gastric tissue.

[The significance of different 5-HT-receptors in regulation of gastrointestinal motility].

Serotonergic mechanisms are involved in many, if not all digestive functions of the gastrointestinal tract. A special role is played by serotoninergic structures in the neuronal control of motor activity. The study of these structures is of particular interest due to the widespread occurrence of irritable bowel syndrome, covering up to 20% of the adult population, which makes the research in this area up to date and in demand. Acute experiments were performed on 102 Wistar rats in 6 series. Experiments were carried out under general anesthesia (Nembutal, 60 mg/kg) and mechanical lung ventilation. Motor responses of the stomach, duodenum and ascending colon were studied to i.a. Serotonin adipate infusion (1 mg/kg) during joint blockade of sympathetic and parasympathetic chains of ANS, as well as on the background of the blockade of various 5-HT-receptors. Infusions of 5-HT-blockers reduce the magnitude of motor responses in stomach, duodenum and colon in varying degrees. Based on these data found 5-HT(1b)-receptors are mainly located in enteric neurons. The distribution of 5-HT(2b-4)-receptor is heterogeneous: 5-HT(2b)-receptors are located in enteric neurons of the stomach and intestinal myocytes; 5-HT3-receptors localized in the ganglia supplying the stomach and colon and 5-HT4-receptors are mainly located in the smooth muscle of the stomach, duodenal and ascendent colon enteric neurons.

Regulation of hemodynamic parameters under conditions of systemic administration of angiotensin II and angiotensin IV to rats after carotid glomectomy.

Systemic administration of angiotensin II was followed by an increase in systolic BP and HR in rats with carotid glomectomy, the time of attaining maximum values in treated animals was much higher than in sham-operated controls. Injection of angiotensin IV slightly reduced systolic BP in sham-operated animals and increased it in rats with carotid glomectomy. The involvement of the local renin-angiotensin system of the carotid body in systemic mechanisms of hemodynamics regulation is discussed.

Reduction of alcohol dependence in rats after carotid glomectomy.

Carotid glomectomy significantly reduced the degree of alcohol addiction in rats, which was induced over 12 weeks. After glomectomy, the mean weekly volume of alcohol consumed by alcoholic animals over 4 weeks was lower compared to the preoperation level, while water consumption significantly increased by the 3rd and 4th weeks after surgery. Control sham operation had no effect on ethanol and water consumption in alcoholic rats. Possible involvement of the local renin-angiotensin system in chemoreceptor cells of the carotid body into systemic mechanisms of alcohol dependence is discussed.

Comparative analysis of dipsogenic effects of systemic and intracerebral injection of angiotensin II to rats after carotid glomectomy.

Systemic administration of angiotensin II after carotid glomectomy produced a less pronounced dipsogenic effects (consumption of water and NaCl solution) compared to sham-operated control animals. Injection of angiotensin II into the lateral cerebral ventricles of the same glomectomized rats increased water and NaCl consumption to a level surpassing that of sham-operated animals. The number of drinking acts and comfortable grooming acts decreased in glomectomized animals after systemic administration of angiotensin II, but increased after its intracerebral injection compared to the control. The results confirm the hypothesis that carotid chemoreceptors, as the peripheral component of the renin-angiotensin system, participate in the mechanisms of angiotensin-induced thirst, "salt appetite", and associated behavioral forms (comfortable grooming) synergically with the central cerebral receptors.

Water and salt consumption and suppression of Angiotensin-induced thirst in rats after carotid glomectomy.

Carotid glomectomy in rats reduced daily water consumption and increased daily consumption of NaCl solution. Sham operation did not modify water and salt consumption. Intraperitoneal injection of angiotensin-II did not stimulate drinking motivation in the majority of rats subjected to carotid glomectomy. Injection of angiotensin-II to sham-operated and intact animals induced active consumption of both fluids during one hour. These results attest to the involvement of the carotid body in the regulation of consumption of water and sodium ions (the main elements of osmotic blood pressure) and the involvement of angiotensin-sensitive receptors of carotid body cells in the formation of thirst and salt appetite motivation, regulated by the renin-angiotensin system.

[Antihypoxic properties of opiates and substance P]. / Antigipoksicheskie svoistva opiatov i veshchestva P.

Using survival slices of the rat cerebellum, we studied the influence of opiates (alpha- and beta-endorphines, met-enkephalines) as well as substance P (SP) on the impulse activity (IA) of neurons. Low doses of the studied substances (10(-8)-10(-10) M) for the most part increased the IA of the neurons, while high doses (10(6)-10(-5) M) produced biphasic reaction (inhibition-excitation). It is supposed that opiates and SP act as transmitters in the cerebellum. Under increasing hypoxia, opiates and SP manifested antixypoxic properties both in low O22 concentration and under reoxygenation. Opiates and SP proved to be natural antihypoxants involved not only in nociception mechanisms but also in brain adaptation to oxygen deficiency.

Biorhythmologic aspects of seizure activity.

Seasonal and circadian rhythms of neuronal and organism resistance to convulsive effect of strychnine and penicillin were studied in vivo on mice and rats and in vitro on cultured mouse cerebellar sections. Resistance was assessed by the latency of seizures in mice and neuronal response to convulsants in sections. In the night and morning time (0:00-9:00) seizure resistance in mice increased: it manifested in longer latency and lower mortality compared to those in the day and evening time (12:00-21:00). Seizure resistance was minimum in autumn and maximum in winter. Neurons in cerebellar section were most resistant to the convulsive effect of penicillin in autumn and winter and least resistant in spring and summer. Circadian rhythms of cerebellar neuron resistance to convulsants were opposite, which attests to reciprocal relations between epileptogenic and antiepileptic (cerebellar) cerebral structures.

[Role of hypoxia in the development of epileptiform seizures]. / Rol' gipoksii v razvitii épileptiformnykh pristupov.

The article reviews the factors of abiotic and biotic environments liable to provoke convulsions. An assumption is made that the common element of their action on the organism are hypoxic states of varying types and depth. Animals with high individual tolerance of acute hypoxia were found to possess a better resistance to the convulsing effect of penicillin. In these animals the epilepsy-form discharges appear with longer latent periods and the epilepsy-form seizures are generated much more seldom in contrast to rats with poor tolerance of hypoxia. Training of resistless rats in the altitude chamber increases their ability to oppose the convulsing effect of penicillin to the level of animals with moderate but not high hypoxia tolerance.