Activation of Cardiac δ2-Opioid Receptors Increases Heart Tolerance to Reperfusion.

Coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats in vivo, as well as total ischemia (45 min) of an isolated rat heart followed by reperfusion (30 min) were reproduced. The selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg and 152 nmol/liter) was administered intravenously 5 min before reperfusion in vivo or added to the perfusion solution at the beginning of reperfusion of the isolated heart. The peripheral opioid receptor antagonist naloxone methiodide and δ2-opioid receptor antagonist naltriben were used in doses of 5 and 0.3 mg/kg, respectively. It was found that the infarct-limiting effect of deltorphin II is associated with the activation of δ2-opioid receptors. We have demonstrated that deltorphin II can improve the recovery of the contractility of the isolated heart after total ischemia.

Morphological and Neurological Impairments Induced by Chronic Administration of Dimethyl Sulfoxide in Mice.

We studied the influence of DMSO administered ad libitum with drinking water in concentrations of 0.01, 0.1, and 1% for 4 and 6 weeks on pain sensitivity, motor coordination, and myelin content in the corpus callosum of C57BL/6 mice. After 6-week administration, DMSO in all studied concentrations decreased myelin content in the corpus callosum. Moreover, 4-week administration of 0.1% DMSO and 6-week administration of 1% DMSO increased the latency to fall in the rotarod test by 3.1 (p<0.05) and 5.1 (p<0.001) times, respectively. After 4-week administration of DMSO in concentrations of 0.01 and 0.1%, the latency of the tail flick response increased by 2.1 (p<0.05) and 1.8 times (p<0.001), respectively. Administration of DMSO in concentrations of 0.01 and 1% for 6 weeks led to a decrease of this parameter by 2.7 (p<0.05) and 3.8 times (p<0.01), respectively. Thus, DMSO in all studied concentrations decreased myelin content in the corpus callosum of C57BL/6 mice and modified motor coordination and pain sensitivity of animals.

Comparative Analysis of Infarct-Limiting Activity of Peptide and Non-Peptide δ- and κ-Opioid Receptor Agonists during Heart Reperfusion In Vivo.

A comparative analysis of the infarct-limiting activity of δ- and κ-opioid receptors (OR) agonists was carried out on a model of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used selective δ2-OR agonist deltorphin II (0.12 mg/kg), δ-OR agonists BW373U86 and p-Cl-Phe DPDPE (0.1 and 1 mg/kg), selective agonists of δ1-OR DPDPE (0.1 and 0.969 mg/kg), κ1-OR U-50,488 (0.1 and 1 mg/kg), κ2-OR GR-89696 (0.1 mg/kg), and κ-OR ICI-199,441 (0.1 mg/kg). All drugs were administered intravenously 5 min before reperfusion. Deltorphin II, BW373U86 (1 mg/kg), p-Cl-Phe DPDPE (1 mg/kg), U-50,488 (1 mg/kg), and ICI-199,441 had a cardioprotective effect. The most promising compounds for drug development are ICI-199,441 and deltorphin II.

[Formation and Unique Experience of the Center For the Treatment of Cerebrovascular Pathology in Children and Adolescents Located in a Multidisciplinary Pediatric Hospital, as the Only Primary Center of Pediatric Stroke in the Russian Federation].

Stroke is in the top ten causes of children death, ahead of brain tumors. Х-ray diagnostics development has significantly improved the detectability of pediatric stroke. The average incidence of cerebrovascular diseases in children was 13 per 100,000 children annually. The main feature of children's stroke is its multifactorial character, which complicates diagnostic process and requires involvement of doctors of different specialties to determine the leading etiological factors and choose optimal therapy and management tactics. The Center for the Treatment of Cerebrovascular Pathology in Children and Adolescents was established on the basis of Morozov Children City Clinical Hospital by Moscow Healthcare Department, Order No. 169, dated February 27, 2014. The main task was to create a pediatric stroke center on the basis of multidisciplinary Morozov Children City Clinical Hospital, which met the main international requirements of the primary center for pediatric stroke. It was done to improve early diagnostic process, refine the algorithm for maintaining patient data in acute periods, develop preventive measures, maintain city pediatric stroke register, introduce family consultations, coordinate medical care for children with cerebrovascular pathology at various levels in Moscow, and improve medical care quality for children with cerebrovascular pathology and their families. Since April 2014 more than 800 children have undergone inpatient treatment and more than 420 have been treated in outpatient departments of Morozov Children City Clinical Hospital.

Effect of Chronic Continuous Normobaric Hypoxia on Functional State of Cardiac Mitochondria and Tolerance of Isolated Rat Heart to Ischemia and Reperfusion: Role of µ and delta2 Opioid Receptors.

Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to ischemia/reperfusion injury in vivo and this effect is mediated via µ and delta2 opioid receptors (ORs) activation. CNH has also been shown to be cardioprotective in isolated rat heart. In this study, we hypothesize that this cardioprotective effect of CNH is mediated by activation of µ and delta2 ORs and preservation of mitochondrial function. Hearts from rats adapted to CNH (12 % oxygen) for 3 weeks were extracted, perfused in the Langendorff mode and subjected to 45 min of global ischemia and 30 min of reperfusion. Intervention groups were pretreated for 10 min with antagonists for different OR types: naloxone (300 nmol/l), the selective delta OR antagonist TIPP(psi) (30 nmol/l), the selective delta1 OR antagonist BNTX (1 nmol/l), the selective delta2 OR antagonist naltriben (1 nmol/l), the selective peptide µ OR antagonist CTAP (100 nmol/l) and the selective delta OR antagonist nor-binaltorphimine (3 nmol/l). Creatine kinase activity in coronary effluent and cardiac contractile function were monitored to assess cardiac injury and functional impairment. Additionally, cardiac tissue was collected to measure ATP and to isolate mitochondria to measure respiration rate and calcium retention capacity. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the postischemic recovery of contractile function. Additionally, CNH improved mitochondrial state 3 and uncoupled respiration rates, ADP/O, mitochondrial transmembrane potential and calcium retention capacity and myocardial ATP level during reperfusion compared to the normoxic group. These protective effects were completely abolished by naloxone, TIPP(psi), naltriben, CTAP but not BNTX or nor-binaltorphimine. These results suggest that cardioprotection associated with adaptation to CNH is mediated by µ and delta2 opioid receptors activation and preservation of mitochondrial function.

The Role of NO Synthase in the Cardioprotective Effect of Substances of Humic Origin on the Model of Ischemia and Reperfusion of Isolated Rat Heart.

The cardioprotective and inotropic effects of standardized active natural substance based on high-molecular-weight compounds of humic origin were studied on the model of global ischemia (40 min) and reperfusion of isolated perfused rat heart. Preventive administration of the test substance (0.1 mg/ml) before ischemia/reperfusion modeling reduced reperfusion contracture and necrotic death of cardiomyocytes and promoted recovery of myocardial contractility. Blockade of NO synthase with L-NAME (100 µM) abolished the above effects of the test substance. It was hypothesized that NO synthase plays an important role in the development of the cardioprotective and inotropic effects of the test natural substance.

Author Correction: Long-range non-diffusive spin transfer in a Hall insulator.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Long-range non-diffusive spin transfer in a Hall insulator.

We report on optical visualization of spin propagation more than 100 µm. We present an electronic system in a new state of aggregation, the magnetofermionic condensate, in which the lowest-energy spin excitations - photoexcited spin-triplet magnetoexcitons - freely propagate over long distances, in the order of a millimeter, which implies non-diffusion spin transport. Our results open up a completely new system suitable for spintronic devices.

Role of Endogenous Agonists of Opioid Receptors in the Regulation of Heart Resistance to Postischemic Reperfusion Injury.

Intravenous injection of nonselective antagonists of opioid receptors (OR) naltrexone (5 mg/kg) and naloxone methiodide (5 mg/kg), selective δ1-OR antagonist BNTX (0.7 mg/kg), selective δ2-OR blocker naltriben (0.3 mg/kg), selective κ-OR antagonist norbinaltorphimine (2 mg/kg), and selective blocker of ORL1 opioid receptors JTC-801 (0.1 mg/kg) produced no effect on reperfusion injury to the heart in rats narcotized with α-chloralose. In contrast, selective µ-OR antagonist CTAP (1 mg/kg) limited the infarct size, although this effect was not observed at a lower CTAP concentration of 0.1 mg/kg. Probably, the myocardial infarct size-limiting effect of CTAP was associated with activation of the non-opioid receptors. It was hypothesized that endogenous OR agonists did not affect heart resistance to reperfusion injury in unadapted rats.

Cardiovascular Effects of High-Molecular-Weight Compounds of Humic Nature.

The active ingredient extracted from the peat humic substances was characterized by physicochemical parameters evaluated by UV- and IR-spectroscopy, titration, and elemental (C, H, N) analysis. The cardiovascular effects of this ingredient were examined on isolated Langendorff-perfused rat heart. It was found that the active substance in a concentration range of 0.01-0.1 mg/ml produced a vasodilating effect; in addition, it decreased the end-diastolic and left-ventricular developed pressures.

Polarization loss in the organic ferroelectric trialkylbenzene-1,3,5-tricarboxamide (BTA).

We investigate the polarization loss in the archetypical molecular organic ferroelectric trialkylbenzene-1,3,5-tricarboxamide (BTA). We prove that the polarization loss is due to thermally activated R-relaxation, which is a collective reversal of the amide dipole moments in ferroelectric domains. By applying a weak electrostatic field both the polarization loss and the R-relaxation are suppressed, leading to an enhancement of the retention time by at least several orders of magnitude. Alternative loss mechanisms are discussed and ruled out. By operating the thin-film devices slightly above the crystalline to liquid crystalline phase transition temperature the retention time of one compound becomes more than 12 hours even in absence of supportive bias, which is among the longest reported so far for organic ferroelectric materials.

[INDIVIDUAL SURGICAL ТАCTICS IN PATIENTS, SUFFERING CHRONIC PANCREATITIS].

Results of surgical treatment for various clinic-morphological forms of chronic pancreatitis were presented. Efficacy of surgical treatment of the patients, using elaborated individual tactics, was analyzed. There was noted, that morphological changes in the pancreatic gland tissue determines peculiarities of surgical tactics for individual patient. Оperative interventions must be performed for the pain syndrome, for the foregut and common biliary duct impaction, as well as acidic affection of pancreatic gland, fibrous pancreatitis. Indications for miniinvasive operations for chronic pancreatitis were substantiated. While estimating efficacy of miniinvasive and radical operative interventions for chronic pancreatitis a lesser postoperative morbidity and lethality rate was noted, when miniinvasive procedures were applied.

[LIFTING LAPAROSCOPY IN SIMULTANT SURGERY].

Results of treatment of 84 patients, to whom simultant operative interventions on abdominal, the small pelvis and retroperitoneal organs were performed for concomitant somatic diseases, were analyzed. The author's technology of laparolifting was applied in 36 patients, and classical technology with carboxyperitoneum adjustment - in 48. Variants of optimal operative accesses were determined, structure and rate of postoperative complications, peculiarities of the early postoperative period course studied. Indisputable advantages of the lifting laparoscopic operations were established, including reduction of the postoperative complications rate and severity, the postoperative pain syndrome intensity, the concurrent chronic diseases exacerbation rate, and postoperative stationary stay.

CB-Receptor Agonist HU-210 Mimics the Postconditioning Phenomenon of Isolated Heart.

CB receptor agonist HU-210 exhibits an infarction-limiting effect during in vitro reperfusion of the heart after focal ischemia. This effect is paralleled by a decrease in left-ventricular developed pressure and double product. In addition, HU-210 reduces end-diastolic pressure during the reperfusion period, which indirectly attests to reduced Ca2+ overload of cardiomyocytes.

Magnetofermionic condensate in two dimensions.

Coherent condensate states of particles obeying either Bose or Fermi statistics are in the focus of interest in modern physics. Here we report on condensation of collective excitations with Bose statistics, cyclotron magnetoexcitons, in a high-mobility two-dimensional electron system in a magnetic field. At low temperatures, the dense non-equilibrium ensemble of long-lived triplet magnetoexcitons exhibits both a drastic reduction in the viscosity and a steep enhancement in the response to the external electromagnetic field. The observed effects are related to formation of a super-absorbing state interacting coherently with the electromagnetic field. Simultaneously, the electrons below the Fermi level form a super-emitting state. The effects are explicable from the viewpoint of a coherent condensate phase in a non-equilibrium system of two-dimensional fermions with a fully quantized energy spectrum. The condensation occurs in the space of vectors of magnetic translations, a property providing a completely new landscape for future physical investigations.

Involvement of Protein Kinase C-δ in the Realization of Cardioprotective Effect of Ischemic Postconditioning.

Experiments on isolated perfused rat heart modeled 45-min global ischemia followed by 30-min reperfusion. Ischemic postconditioning was modeled by 3 cycles of reperfusion (30 sec) and ischemia (30 sec). Cardiomyocyte necrosis was assessed by the level of creatine phosphokinase in the perfusate. Postconditioning reduced the release of creatine phosphokinase from the heart by 30%. The cardioprotective effect of ischemic postconditioning was eliminated after inhibition of protein kinase C with cheleritrin or after blockade of δ-isoform of protein kinase C with rottlerin. These findings attest to participation of protein kinase C-δ in the realization of the cardioprotective effect of postconditioning.

True ferroelectric switching in thin films of trialkylbenzene-1,3,5-tricarboxamide (BTA).

We have investigated the ferroelectric polarization switching properties of trialkylbenzene-1,3,5-tricarboxamide (BTA), which is a model system for a large class of novel organic ferroelectric materials. In the solid state BTAs form a liquid crystalline columnar hexagonal phase that provides long range order that was previously shown to give rise to hysteretic dipolar switching. In this work the nature of the polar switching process is investigated by a combination of dielectric relaxation spectroscopy, depth-resolved pyroelectric response measurements, and classical frequency- and time-dependent electrical switching. We show that BTAs, when brought in a homeotropically aligned hexagonal liquid crystalline phase, are truly ferroelectric. Analysis of the transient switching behavior suggests that the ferroelectric switching is limited by a highly dispersive nucleation process, giving rise to a wide distribution of switching times.

[PHENOMENON OF REMOTE PRECONDITIONING THE HEART AND ITS MAIN MANIFESTATIONS].

Remote ischemic preconditioning prevents reperfusion cardiomyocyte apoptosis and has the infarct-limiting effect which is maintained in the experiments on the isolated perfused heart. Remote preconditioning promotes to recovery the contractility of the heart during reperfusion, but did not affect the incidence of occlusion and reperfusion of ventricular arrhythmias. Remote preconditioning has a mild anti-inflammatory effect. Presented article is a review and formulated conclusions based on the published literature data.

[THE CARDIORESPIRATORY PLASTICITY IN CHILDREN DURING THE PROCEDURE OF PACED BREATHING].

The cardiorespiratory plasticity in healthy children 9-10 years old (n = 72) was studied during the procedure of paced breathing. The observations of a child after an informed consent taken from him, his parents and teachers were carried out by a psychologist, a physiologist and a doctor after the lessons. In a preliminary series 1 minute trials of pace breathing with various frequencies (22-5.5 times/minute) were used which showed a good endurance of slow breathing. Inthemain series a 3 minute baseline recording and 4-5 periods of 1.5 minute duration with a stepwise reduction of breathing rate of 12, 8, 7, 6 times/minute and in 10 children - 5.5 times/minute were registered. Computer-aided pacer set the durations of inspiration, expiration, pause. The main parameters of heart-rate variability (HRV) and corresponding FFT spectra were analyzed by ANOVA. In children a high cardiorespiratory plasticity of heart rhythm according to frequency of pace breathing is observed. During the stepwise reduction of breathing rate a quasilinear growth of HRV and peak power of FFT spectra of RR-intervals are registered, reaching the maximum level in a HF-band at 12 breaths/min and in LF-band at frequencies of 6-5.5 that are critical to the sustained volitional control of cardiorespiratory processing in children. At 6-5.5 breaths/min a growth of HF-band power of heart rhythm modulation is also registered.

THE FUNCTIONAL STATE OF THE SMALL INTESTINE IN THE EARLY STAGES OF GALL STONE FORMATION.

Complex studying of functional condition of small intestine at bile stone disease and analyzing connection of small intestine functional disorders with formation of lithogenic bile. 123 patients with Bile stone disease were examined at pre-stone stage. Examinations done include ultrasonic exam of gallbladder, biochemical examination of bile, studying of bile acids in the bile by method of mass-spectrometry, morphological examination of duodenal mucous membrane, functional examination of small intestine with loading test. RESULTS: As the survey showed, a biliary sludge was found at 86,2% of the patients at ultrasonic examination of gallbladder In the patients' bile there were noticed changes of both general pool of bile acids and of ratio of their separate fractions. 82% of patients with bile stone disease at pre-stone stage had disorders of digestive and absorbing functions of small intestine, connected with reducing of general pool of bile acids in bile.