Sleep disorders and vascular responsiveness in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is the most common systemic autoimmune disease characterized by chronic systemic inflammation. Half of the deaths of patients with RA are due to cardiovascular diseases (CVD), considered to be 1.5 to -2.0-fold that in the general population. Patients with RA also experience poor sleep, which by itself is associated with endothelial dysfunction, CVD events and sudden death. Our aim was to study the mechanistic pathways and the correlations between sleep efficiency and vascular reactivity of patients with RA. METHODS AND RESULTS: A prospective study that evaluated quality of sleep using ACTi Graphs, vascular inflammation and endothelial function of 18 patients with RA. Inflammation was studied by levels of E-selectin, intercellular adhesion molecule 1 (ICAM-1) and NO in serum. Endothelial function was studied using the brachial artery plethysmography method. Eighteen RA patients (aged 57.56 ± 13.55 years; 16 women) with a long-standing active RA: Eight patients had impaired sleep efficiency and 10 had a good sleep efficiency. Those who had an impaired sleep had larger baseline diameters of the brachial artery (0.39 ± 0.08 cm vs. 0.32 ± 0.04 cm; P = 0.02). Negative correlations were found between baseline brachial artery diameter and sleep efficiency (P = 0.01), and with NO level (P = 0.04). Stepwise regression found that brachial artery diameter at baseline and NO level could predict sleep efficiency (r2  = 0.543, P = 0.01). CONCLUSION: Vascular reactivity could predict quality of sleep in patients with RA. Quality of sleep may serve as an independent CVD risk factor in patients with RA.

IMPACT OF THE RIVNE NPP ACTIVITY ON NATURAL AND SOCIAL ENVIRONMENT OF THE CONTROL AREA. / VPLYV DIIaL'NOSTI RIVNENS'KOÏ AES NA PRYRODNE TA SOTsIAL'NE SEREDOVYShchE ZONY SPOSTEREZhENNIa.

OBJECTIVE: To assess an impact of the Rivne Nuclear Power Plant (RNPP) activity on the control area (CA) environ- ment according to environmental and radiation monitoring data over time of 2011-2017 as a component of the radiation safety system. MATERIALS AND METHODS: Review of geographical and natural features of the territory of the «Rivne NPP¼ manufac- turing facility was carried out to assess its CA environment. Assessment of environmental and radiation situation of the CA was carried out according to the data of RNPP monitoring systems and a number of state institutions of Rivne oblast over time of 2011-2017. Opinion of the CA population about the RNPP environmental impact was studied. The sampled population of respondents was calculated based on the total population living in CA. The sampling error no more that 7.0%. Data from sociological survey of population were calculated using the statistical programs. RESULTS: The radiation impact of RNPP on environment is related to emissions and discharges of radioactive sub- stances generated in the production cycle. Over time the total index of radionuclide discharge to the Styr River since 2011 is of a marked downward trend from 2.11 % to 0.18 %. The maximum concentrations of 60Co and 137Cs radionuclides at the three sampling points along the Styr River over time of 2011-2016 were about one thousandth of a percent, and of 131I - one hundredth of a permissible value according to the Radiation Safety Standards of Ukraine (RSSU). Emissions of inert radioactive gases and long-lived nuclides into the atmosphere were less than 0.2 % and iodine emissions were 0.01 % to the emission limit. Average radionuclide concentrations in the natural air of the RNPP CA settlements did not exceed the admissible concentration limit (ACL). Concentrations of chem- ical pollutants in discharges of the RNPP to the Styr River over time of 2012-2017 did not exceed the ACL. Integral wastewaters of municipal enterprises of the CA and RNPP result in an increased index of biochemical oxygen uti- lization and ammonium salt content in the Styr River, exceeding the ACL in fishery reservoir water. No exceedance of ACL of repugnant substances in the open air of settlements was observed regarding the pollutants under study. According to population survey the radiation contamination of territories as a result of the ChNPP accident and RNPP activities, which cause anxiety, are the key factors determining an environmental situation at the place of residence. The correlation coefficients between anxiety index and public estimates of environmental situation are established. CONCLUSIONS: Content of radionuclides in emissions and discharges generated in the RNPP production cycle under everyday conditions does not exceed the allowed RSSU-97 values. The combined discharges of collective enterpri- ses and RNPP are the main sources of chemical pollution of surface waters in CA. There is a higher correlation coef- ficient between the anxiety and somatization rates and environmental sphere parameter in rural population com- pared to urban one. The combined effect of environmental, radiation and psychological factors on the RNPP CA population makes the health studies necessary in the latter.

Airborne concentrations and chemical considerations of radioactive ruthenium from an undeclared major nuclear release in 2017.

In October 2017, most European countries reported unique atmospheric detections of aerosol-bound radioruthenium (106Ru). The range of concentrations varied from some tenths of µBq·m-3 to more than 150 mBq·m-3 The widespread detection at such considerable (yet innocuous) levels suggested a considerable release. To compare activity reports of airborne 106Ru with different sampling periods, concentrations were reconstructed based on the most probable plume presence duration at each location. Based on airborne concentration spreading and chemical considerations, it is possible to assume that the release occurred in the Southern Urals region (Russian Federation). The 106Ru age was estimated to be about 2 years. It exhibited highly soluble and less soluble fractions in aqueous media, high radiopurity (lack of concomitant radionuclides), and volatility between 700 and 1,000 °C, thus suggesting a release at an advanced stage in the reprocessing of nuclear fuel. The amount and isotopic characteristics of the radioruthenium release may indicate a context with the production of a large 144Ce source for a neutrino experiment.

[PREDICTION OF RECURRENT PYELONEPHRITIS BY AN INDEX OF OXIDATIVE STRESS].

We examined the indicators of oxidant/antioxidant (O/A) balance in the blood of, 118 women with chronic pyelonephritis. (PN), aged 18 to 69 years (mean 36.0 +/- 7.9 years) and 30 conventionally healthy donors: 82 (69.5%) of patients had the recurrent PN, 36 (30.5%) of women had the sporadic PN. The malondialdehyde in serum, ceruloplasmin, transferrin and the number of sulfhydryl groups, which allowed to calculate the index of oxidative stress (IOS) were included into the complex research of O/A balance. IOS was significantly increased in patients with recurrent PN 4.27 2.06 vs. 2.30 +/- 1.06 for sporadic PN (P < 0;001). It allowed us to conduct the multivaiate analysis using binary logistic regression. The analysis demonstrated alhigh quality (>80 %) of regression model chi2 = 74.3; P < 0.001, odds ratio (OR) = 7.5, 95% CI 3.3-7.1. We have created an additional examinational sample to confirm the adequacy of this model which included the test results of 23 pa- tients with acute PN in 6 (26%) of them have developed recurrent PN. We defined a high quality of examinational model chi2 = 11.2; P = 0.0008, OR =3.34, 95% CI 1.3-10.3. The optimal criteria for IOS was > 3, sensitivity 100%, and for specificity 94%. Thus, for the prediction of recurrent PN can be evaluated the IOS. The development of recurrent PN can be predicted with probability 97.6% if value of IOS > 2.5; this will optimize the rehabilitation program of patients Vith acute PN.

[Effect of 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl)thiazole chloride on nystatin-created K(+)-current across bilayer lipid membrane].

The application of 0.1 mM of vitamin B1 (thiamine) structural analogue, 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl)thiazole chloride (DMHT) from the cis-side of cholesterol-containing phospholipid bilayer membrane in symmetric solution of 100 mM KCl reversibly reduced the conductance of nystatin channels, reconstituted from the same side of membrane, by 67 +/- 3%. The conductance of nystatin channels applied to the cis-side of bilayer membrane remained unaffected, when DMHT was introduced separately to the opposite trans-side of modified membrane. The kinetics of nystatin channels inhibition with DMHT showed no cooperativity allowing to expect that negatively charged ionogenic groups of these channels formed one DMHT binding site per channel. Relatively high pK of binding with nystatin channels (5,17) suggests that this site provides specific interaction with DMHT.

[Effect of vitamin B1 structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl) thiazole chloride on transmembrane current via ion channels formed by amphotericin B in bilayer lipid membrane].

The structural analogue of vitamin B1 (thiamine)-3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl) thiazole chloride (DMHT) introduced from the cis-side of cholesterol-containing phospholipid bilayer membrane reversibly reduced the conductance induced by amphotericin B channels reconstituted from the same side of membrane. Introduction of DMHT (0.1 mM) from the cis-side of membrane blocked the amphotericin B-created conductance in symmetric solution of 100 mM KCI by 84 +/- 2%. The conductance of one-sided amphotericin B channels remained unaffected, when DMHT was introduced separately to the opposite trans-side of membrane. The kinetics of amphotericin B channels inhibition with DMHT showed no cooperativity allowing to expect that negatively charged ionogenic groups of these channels formed one DMHT binding site per channel as the slope of blocking rate determined in double-log coordinates was 1.5. Relatively high pK of binding with amphotericin B channels (5.13) suggests that this site provides high-affinity interaction with DMHT. The comparative analysis of inhibition kinetics with the other blockers of amphotericin B channels--tetraethylammonium and tetramethylammonium has proved that DMHT is a comparable though much more potent substitute for both tetraalkylammonia. Hence, the DMHT was proposed as a novel powerful blocker for cation-selective channels with the size of the pore ranging between 0.28 nm and 0.385 nm.

[Blocking action of pyridoxal-5'-phosphate on nonadrenergic synaptic inhibition of human small intestine smooth muscle].

We investigated the inhibitory synaptic potentials (ISP) in isolated smooth muscle strips of the human duodenum circular layer from the ulcer adjacent region (I group) as well as ileum and distal part of small intestine, which were on a distance of some dozen centimeters from the place of disturbance under the different gastrointestinal diseases (II group). ISP amplitude was several times smaller in the muscle strips of the I group compare to the II group. It could depend on the alterations of smooth muscles cable properties, increase of connective tissue mass, changes in the intestinal nervous system and synaptic transmission in the region adjacent to duodenum ulcer. Pyridoxal-5'-phosphate effectively decreased amplitude and increased ISP latent period in the muscle strips from both groups. N(omega)-nitro-L-arginine, the blocker of NO-synthase did not affect pyridoxal-5'-phosphate activity in smooth muscles. Phosphate group was essential for realization of its influence on ISP in smooth muscles because pyridoxal did not influence both ISP amplitude and ISP latent period.

[Clinical and immunological features of the course of tuberculosis concurrent with HIV infection].

The clinical and immunological features of the course of tuberculosis concurrent with HIV infection were studied in 109 patients. Thirty-eight patients were found to have active tuberculosis to HIV infection; 22 patients were diagnosed to have HIV infection and tuberculosis, and 49 patients developed tuberculosis in the presence of HIV infection. The most acute course of the disease with severe infection-toxic and asthenovegetative syndromes was observed in patients with simultaneous detection of HIV infection and tuberculosis, and, when tuberculosis joins as a secondary disease in the presence of HIV infection, the bronchopulmonary syndrome, body weight loss, lymphoadenopathy, and skin lesion were pronounced at most. The most severe clinical forms of tuberculosis were observed in a group where tuberculosis manifested itself as an opportunistic disease in the presence of moderate and severe immunodeficiency.

[Molecular aspects of pharmacological activity of naltrexone and naloxone]. / Molekuliarnye aspekty farmakologicheskoi aktivnosti naltreksona i naloksona.

Naltrexone and naloxone, being competitive antagonists of opioid receptors, have found therapeutic applications in medicine. The experiments with mutant receptors showed that many amino acid residues within transmembrane domains play an important role in binding these drugs. Using the site-directed mutagenesis technique, it was established that even single mutations (replacing single amino acid residues) can significantly modify the affinity of antagonists to receptors, sometimes even imparting agonist-like properties to the compounds studied. Chronic administration of naltrexone and naloxone leads to an increase in the density of opioid receptors and in the sensitivity to agonists. This hypersensitivity and overdose risk in heroin abusers after chromic naltrexone treatment are discussed.

[Neurochemical basis of ultra rapid opioid detoxication]. / Neirokhimicheskie osnovy ul'trabystroi opiatnoi detoksikatsii.

Ultra rapid opioid detoxification (UROD) is a new technique with the use of mu-opioid receptor antagonists to precipitate withdrawal. The scientific literature on UROD techniques in opiate addicts are reviewed, but little has been published on its neurochemical aspects. It is discussed that exposure to naloxone ore naltrexone during UROD is associated with development of increasing in opioidergic neurotransmission. On the other hand, ultra rapid opioid detoxification can be accompanied by normalization of joined brain neurotransmitter systems: noradrenergic, serotoninergic, GABAergic, cholinergic and glutamatergic neurotransmission systems. The neurochemical aspects of the new method detoxification are discussed.

[Experience in treating patients with postvagotomy syndromes]. / Opyt lecheniia bol'nykh s postvagotomicheskimi sindromami.

The article generalizes experiences with treatment of 257 patients with postvagotomy syndromes (PVS). The patients were distributed according to the character of the syndromes. Main causes of the development of PVS are discussed. The authors describe the specific methods of diagnosis allowing individualized approach to option of the program of treatment. Criteria of decision in favor of various methods of reconstructive-restorative procedures are proposed. The individualized approach to treatment allowed to get considerably better condition in 95% of patients with PVS.

[Long-term results of pylorus-preserving gastric resections]. / Otdalënnye rezul'taty pilorosokhraniaiushchikh rezektsii zheludka.

An analysis of long-term results of pylorus-preserving resections of the stomach performed on 540 patients has shown that 44 patients (8.1%) had different postgastroresectional syndromes. Operations were made on 20 patients with severe manifestations of the postgastroresectional syndromes. An analysis of the causes of complications was made as well as the substantiation of the methods of reconstructive interventions. Indications and contraindications for pylorus-preserving resections of the stomach are proposed.

Effect of cross-tolerance between endotoxin and TNF-alpha or IL-1beta on cellular signaling and mediator production.

Endotoxin [lipopolysaccharide (LPS)] tolerance suppresses macrophage/monocyte proinflammatory-mediator production. This phenomenon also confers cross-tolerance to other stimuli including tumor necrosis factor (TNF) alpha and interleukin (IL)-1beta. Post-receptor convergence of signal transduction pathways might occur after LPS, IL-1beta, and TNF-alpha stimulation. Therefore, it was hypothesized that down-regulation of common signaling molecules induces cross-tolerance among these stimuli. LPS tolerance and cross-tolerance were examined in THP-1 cells. Phosphorylation of MAP kinases and degradation of inhibitor kappaBalpha (IkappaBalpha) DNA binding of nuclear factor-kappaB (NF-kappaB), and mediator production were examined. In naive cells, LPS, TNF-alpha, and IL-1beta induced IkappaBalpha degradation, kinase phosphorylation, and NF-kappaB DNA binding. LPS stimulation induced production of TNF-alpha or TxB2 and degradation of IRAK. However, neither TNF-alpha nor IL-1beta induced IRAK degradation or stimulated TNF-alpha or TxB2 production in naive cells. Pretreatment with each stimulus induced homologous tolerance to restimulation with the same agonist. LPS tolerance also suppressed LPS-induced TxB2 and TNF-alpha production. LPS pretreatment induced cross-tolerance to TNF-alpha or IL-1beta stimulation. Pretreatment with TNF-alpha induced cross-tolerance to LPS-induced signaling events and TxB2 production. Although pretreatment with IL-1beta did not induce cross-tolerance to LPS-induced signaling events, it strongly inhibited LPS TNF-alpha and TxB2 production. These data demonstrate that IL-1beta induces cross-tolerance to LPS-induced mediator production without suppressing LPS-induced signaling to MAP kinases or NF-kappaB activation.

[Functional state of glutamate receptors during treatment with ethanol]. / Funktsional'noe sostoianie retseptorov glutamata pri vozdeistviiakh étanolom.

A growing bulk of experimental data indicates that change of certain neurotransmitter receptors and voltage-dependent ion cannels are characteristic manifestations accompanying ethanol consumption. A likely target for ethanol effects is the glutamate receptors. Glutamate is one of major excitatory neurotransmitter in the mammalian brain. While the acute application of ethanol inhibits glutamate-induced cationic currents, chronic treatment with ethanol leads to an up-regulation of glutamate receptors.

Interaction between antibodies and hapten-protein conjugates of different composition: theoretical predictions and experimental data.

Mathematical models of competitive ELISAs with labelled antibody and with labelled antigen taking into account bivalent interactions between antibodies and hapten-protein conjugates were developed and analyzed. It was shown that in the kinetic model of the immunochemical reaction the conjugate composition influenced the amplitude of detected signal but not ELISA sensitivity. In the equilibrium model decreased sensitivity correlated with bivalent complexes formation. The predictions were tested experimentally using 2,4-dichlorophenoxyacetic acid (2,4-D) and testosterone as haptens. It was confirmed that increasing of the hapten : protein ratio resulted in formation of bivalent complexes with antibodies. The equilibrium binding constants for these complexes were two orders of magnitude higher than for monovalent ones. Optimal conjugate compositions have been chosen for ELISA of these haptens.

[Solid-phase methods of immunoenzyme analysis of the herbicides simazine and atrazine]. / Tverdofaznye metody immunofermentnogo analiza gerbitsidov simazina i atrazina.

Competitive methods of enzyme immuno assay (EIA) for detecting simazine and atrazine were developed, and conditions providing optimal performance were found. EIA sensitivity was shown to increase by an order of magnitude if samples were preincubated with antibodies; chloride ions were omitted; a herbicide-peroxidase conjugate was treated with urea. In EIA using labelled antibodies sensitivities thresholds towards simazine and atrazine were 0.05 and 0.1 ng/ml, respectively. EIA took 1-2 h to be done. The methods developed might be applied for quality control of water.

[Solid phase methods of immunoenzyme analysis of the herbicides 2,4-dichlorophenoxyacetic and 2,4,5-trichlorophenoxyacetic acids]. / Tverdofaznye metody immunofermentnogo analiza gerbitsidov 2,4-dikhlorfenoksiuksusnoi i 2,4,5-trikhlorfenoksiuksusnoi kislot.

Competitive solid-phase enzyme immunoassays for the detection of 2,4-dichlorophenoxyacetic (2,4-D) and 2,4,5-trichlorophenoxyacetic (2,4,5-T) acids have been developed and optimized. The sensitivity of the assay is 3 ng/ml for 2,4-D and 5 ng/ml for 2,4,5-T. The time of the assay is 1.5 h. The sensitivity of the assays increases after immobilization of antibodies on staphylococcus protein A, in the case of using monovalent derivatives of antibodies, and as a result of chemical modification of hapten. The detection limit for the pesticides is 0.1 ng/ml in this case, which is close to the sensitivity of the assay for the haptens conjugated with proteins.

A new visual enzyme immunoassay of methamphetamine using linear water-soluble polyelectrolytes.

A new visual enzyme immunoassay (EIA) technique has been developed. Oppositely charged synthetic linear water-soluble polyelectrolytes (poly-N-ethyl-4-vinyl-pyridine as polycation and polymethacrylate as polyanion) were used as carriers for reagent immobilization. The ability of these molecules to form an insoluble complex was applied for the separation of bound and free components of the immunoassay reaction mixture. This approach was realized in methamphetamine visual EIA. In the first stage of the assay two specific reactions took place during incubation of the analytical reagents with the probe to be analyzed: (1) competition between methamphetamine and hapten conjugated with peroxidase for the interaction with specific antibodies and (2) interaction of these antibodies with the protein A-polymethacrylate conjugate. As a result of these reactions the (polyanion-protein A)-antibody-(hapten-peroxidase) complex was formed. Then the reaction mixture was filtered through an Ultrabind membrane (0.45 microns) with adsorbed poly-N-ethyl-4-vinylpyridine, and the immunological complexes were immobilized to the membrane by electrostatic interaction. The level of peroxidase binding on the membrane was measured by diaminobenzidine substrate. The system described was optimized to achieve both high rapidity (20 min) and an appropriate sensitivity (0.4 micrograms/ml) for methamphetamine assay.