0000000000053951
AUTHOR
Larisa Baumane
Endothelium- and nitric oxide-dependent vasorelaxing activities of gamma-butyrobetaine esters: possible link to the antiischemic activities of mildronate.
Mildronate [3-(2,2,2-trimethylhydrazine) propionate (THP)] is an antiischemic drug acting mainly via inhibition of fatty acid beta-oxidation. Some effects of the drug cannot be explained by the latter mechanism. We tested the eventual nitric oxide (NO) dependence of the mildronate action. Mildronate, gamma-butyrobetaine (GBB) and GBB methyl ester induced transient increases in nitric oxide (NO) concentrations in rat blood and myocardium. In vitro, these compounds neither modified the activities of purified neuronal and endothelial recombinant nitric oxide synthases (NOSs) nor were able to interact with their active site. GBB induced vasodilatation at high concentrations only (EC50 = 5 x 10(…
The anti-inflammatory and antinociceptive effects of NF-κB inhibitory guanidine derivative ME10092
The guanidine compound ME10092 (1-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine) is known to possess anti-radical and anti-ischemic activity but its molecular targets have not been identified. This study investigated whether ME10092 regulates the nuclear factor kappa B (NF-kappaB)-mediated signal transduction in vivo. The effect of ME10092 treatment (1-100 pmol/mouse) on nuclear translocation of NF-kappaB, activation of expression of inflammatory mediators and production of nitric oxide were measured in the lipopolysaccharide (LPS)-induced brain inflammation model in mice in vivo. The antinociceptive activity of ME10092 was tested in the formalin-induced paw licking test. ME10092 dose-…
Study of interaction of antimutagenic 1,4-dihydropyridine AV-153-Na with DNA-damaging molecules and its impact on DNA repair activity
Background1,4-dihydropyridines (1,4-DHP) possesses important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. It was shown that the antimutagenic 1,4-dihydropyridine AV-153-Na interacts with DNA. The aim of the current study was to test the capability of the compound to scavenge peroxynitrite and hydroxyl radical, to test intracellular distribution of the compound, and to assess the ability of the compound to modify the activity of DNA repair enzymes and to protect the DNA in living cells against peroxynitrite-induced damage.MethodsPeroxynitrite decomposition was assayed by UV spectroscopy, hydroxyl radical scavenging—by EPR spectroscopy. DNA b…
Putative role of nitric oxide synthase isoforms in the changes of nitric oxide concentration in rat brain cortex and cerebellum following sevoflurane and isoflurane anaesthesia.
We have previously observed an increase in nitric oxide (NO) content in rat brain cortex following halothane, sevoflurane or isoflurane anaesthesia. This study was undertaken in order to determine whether isoform-specific nitric oxide synthase (NOS) inhibitors and inducers could modify these increases in NO contents. Rats were subjected to isoflurane and sevoflurane anaesthesia with concomitant administration of neuronal nitric oxide synthase (nNOS) inhibitor 7-Nitro-indazole (7-NI), inducible nitric oxide synthase (iNOS) inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) or lipopolysaccharide. NO concentration in different organs was measured by electron paramagnetic resonance (E…
P5
Background Pathogenic action of nitric oxide (NO) is responsible to a large extent for development of complications of the diabetes mellitus (DM). NO overproduction is largerly responsible for development of diabetic nephropathy. Thus search for compounds modifying NO production appears to be important for development of pharmacological remedies for treatment of DM complications. Dihydropiridines (DHP) appear to be prospective compounds from this point of view. The goal of the present work was to study alterations of NO production in streptozotocin model of DM in rats and ability of several DHPs and to normalize NO synthesis in kidneys of these animals. Methods Diabetes mellitus was induced…
Functional Evaluation of THIQ, a Melanocortin 4 Receptor Agonist, in Models of Food Intake and Inflammation
The central melanocortinergic system plays an important role in regulating different aspects of energy homeostasis and the immunomodulatory response. In the present study, we evaluated the in vivo activities of food intake suppression and anti-inflammatory activity of THIQ, which has been proposed to possess high and selective melanocortin-4 receptor agonistic activity in vitro. The results showed that THIQ (0.1, 0.3 and 1 nmol/rat, intracerebroventricularly) is less effective in reducing food intake and body weights of rats than the non-selective melanocortin receptor agonist melanotan II. Electron paramagnetic resonance measurements in mice brain tissue showed that THIQ at doses of 0.001 …
Spectrometric analysis of inner divertor materials of JET carbon and ITER-like walls
Abstract One of main reasons of the Joint European torus (JET) transformation from the carbon (JET-C) to ITER-like (JET-ILW) wall was high tritium retention of carbon. In order to compare the tritium retention, samples of analogous positions of the plasma-facing side of vertical tiles No. 3 of two campaigns: JET-C (2008–2009) and JET-ILW (2011–2012) were cut out. Temperature-programmed tritium desorption spectrometry in He + 0.1% H2 gas flow showed that JET-C sample without a tungsten coating had by a factor of >20 higher surface concentration of tritium than JET-ILW tungsten-coated sample: 4.9 × 1013 and 1.7–2.2 × 1012 T atoms/cm2 respectively. Installation of metallic plasma facing wall i…
Behaviour of advanced tritium breeder pebbles under simultaneous action of accelerated electrons and high temperature
The authors greatly acknowledge the technical and experimen-tal support of O. Valtenbergs and L. Avotina (Institute of Chemical Physics, University of Latvia). The work is performed in the frames of the University of Latvia financed project No. Y9-B044-ZF-N-300, “Nano, Quantum Technologies, and Innovative Materials for Eco-nomics”.
Characterisation and radiolysis of modified lithium orthosilicate pebbles with noble metal impurities
Modified lithium orthosilicate (Li4SiO4) pebbles with additions of titanium dioxide (TiO2) are suggested as an alternative tritium breeding ceramic for the European solid breeder test blanket module. The noble metals – platinum (Pt), gold (Au) and rhodium (Rh), can be introduced into the modified Li4SiO4 pebbles during the melt-based process, due to the corrosion of Pt-Rh and Pt-Au alloy crucible components. In this study, the surface microstructure, chemical and phase composition of the modified Li4SiO4 pebbles with different contents of the noble metals was analysed. The influence of the noble metals on the radiolysis was evaluated after irradiation with accelerated electrons (E = 5 MeV),…
Radiation stability of long-term annealed bi-phasic advanced ceramic breeder pebbles
Abstract Advanced ceramic breeder pebbles consisting of Li4SiO4 and additions of Li2TiO3 were tested regarding their long-term thermal and to their radiation stability. As-prepared and long-term annealed pebbles were irradiated with accelerated electrons (up to 6 MGy) to investigate the formation of radiation-induced defects and radiolysis products caused by ionizing radiation. By using Raman spectroscopy the formation of significant amounts of radiolysis products can be excluded. Electron spin resonance spectrometry revealed several paramagnetic radiation-induced defects, such as HC2 centres ( SiO 4 3 - and TiO 3 - ), E’ centres ( SiO 3 3 - and TiO 3 3 - ), Ti 3 + centres and peroxide radi…
New 1,4-Dihydropyridines Down-regulate Nitric Oxide in Animals with Streptozotocin-induced Diabetes Mellitus and Protect Deoxyribonucleic Acid against Peroxynitrite Action.
Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic actions of nitric oxide (NO) are responsible to a large extent for development of complications of DM. Search for compounds regulating NO production in patients with DM is thus important for the development of pharmacological drugs. Dihydropyridines (1,4-DHPs) are prospective compounds from this point of view. The goals of this study were to study the in vivo effects of new DHPs on NO and reactive nitrogen and oxygen species production in a streptozotocin (STZ)-induced model of DM in rats and to study their ability to protect DNA against nocive action of peroxynitrite. STZ…
Formation and accumulation of radiation-induced defects and radiolysis products in modified lithium orthosilicate pebbles with additions of titanium dioxide
Abstract Lithium orthosilicate (Li4SiO4) pebbles with 2.5 wt.% excess of silicon dioxide (SiO2) are the European Union's designated reference tritium breeding ceramics for the Helium Cooled Pebble Bed (HCPB) Test Blanket Module (TBM). However, the latest irradiation experiments showed that the reference Li4SiO4 pebbles may crack and form fragments under operation conditions as expected in the HCPB TBM. Therefore, it has been suggested to change the chemical composition of the reference Li4SiO4 pebbles and to add titanium dioxide (TiO2), to obtain lithium metatitanate (Li2TiO3) as a second phase. The aim of this research was to investigate the formation and accumulation of radiation-induced …
Effects of Kaempferol and Myricetin on Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production in Rats
Abstract: When administered as drugs or consumed as food components, polyphenolic compounds synthesized in plants interfere with intracellular signal transduction pathways, including pathways of nitric oxide synthase expression. However, effects of these compounds in vivo do not always correlate with nitric oxide synthase-inhibiting activities revealed in experiments with cultured cells. The initial goal of this work was to compare effects of flavonoids kaempferol and myricetin on inducible nitric oxide synthase mRNA and protein expression monitored by real-time RT-PCR and immunohistochemistry and to evaluate the impact of these effects on nitric oxide production in rat organs measured by …
Strong, Rapid and Reversible Photochromic Response of Nb doped TiO2 Nanocrystal Colloids in Hole Scavenging Media
Understanding photochromicity is essential for developing new means of modulating the optical properties and optical response of materials. Here, we report on the synthesis and exciting new photochromic behavior of Nb5+ doped TiO2 nanoparticle colloids (NCs). We find that in hole scavenging media, Nb5+ doping significantly improves the photochromic response time of TiO2 nanoparticles. In the infrared regime, Nb-doped TiO2 NCs exhibit an order of magnitude faster photoresponse kinetics than the pristine TiO2. Enhanced photochromic response is observed in the visible light regime as well. The transmittance of Nb-doped TiO2 NCs drops to 10% in less than 2 minutes when irradiated by UV light in…
The MC3 receptor binding affinity of melanocortins correlates with the nitric oxide production inhibition in mice brain inflammation model
Melanocortins possess strong anti-inflammatory effects acting in the central nervous system via inhibition of the production of nitric oxide (NO) during brain inflammation. To shed more light into the role of melanocortin (MC) receptor subtypes involved we synthesized and evaluated some novel peptides, modified in the melanocyte-stimulating hormone (MSH) core structure, natural MCs and known MC receptor selective peptides - MS05, MS06. Since the study included both selective, high affinity binders and the novel peptides, it was possible to do the correlation analysis of binding activities and the NO induction-related anti-inflammatory effect of the peptides. beta-MSH, gamma1-MSH, gamma2-MSH…
Nitric oxide metabolism is impaired by type 1 diabetes and diabetic nephropathy
Diabetes leads to reduced nitric oxide bioavailability, resulting in endothelial dysfunction. However, overproduction of nitric oxide due to hyperglycaemia is associated with oxidative stress and tissue damage. The objective of this study was to characterise nitric oxide production (NO) and added nitrite and nitrate (NO(2)(-)+NO(3)(-)) concentration in the blood and urine of patients with and without diabetic nephropathy. A total of 268 patients with type 1 diabetes and 69 healthy subjects were included. Diabetic nephropathy was defined as macroalbuminuria and/or estimated glomerular filtration rate below 60 ml/min/1.73 cm(2). NO(2)(-)+NO(3)(-) concentration was measured by Griess reaction.…
Radiation-induced effects in neutron- and electron-irradiated lithium silicate ceramic breeder pebbles
Abstract Ceramic breeder (CB) pebbles consisting of lithium orthosilicate (Li4SiO4) as the main phase and lithium metasilicate (Li2SiO3) as a secondary phase were analysed with respect to radiation-induced defects and radiolysis products. Therefore, pebbles that were irradiated with neutrons in the so-called HICU experiment ( H igh neutron fluence i rradiation of pebble sta c ks for f u sion) were compared to pebbles irradiated with accelerated electrons and to an unirradiated sample. Fourier transformation infrared spectroscopy was used to investigate changes in the phase composition. Beside an expected increase in the second phase in the neutron-irradiated samples, no further significant …
DNA-binding studies of a series of novel water-soluble derivatives of 1,4-dihydropyridine
Aim. to determine DNA interaction modes for a series of 1,4-dihydropyridines with different biological activities synthesized in the Latvian Institute of Or-ganic Synthesis. Methods. Affinity of the compounds to DNA was detected by UV/VIS spec-trometry and re-proofed by means of spectrofluorimetry, EBr extrusion assay, cyclic voltammetry and DNA melting. Radical scavenging was tested by electron paramagnetic resonance spectros-copy, peroxynitrite binding was monitored spectrophotometrically, protection of DNA against hydroxyl radical was determined by gel electrophoresis. Results. In a series of water-soluble monocyclic derivatives of 1,4-dihydropyridine with carboxylate groups in position-…
Influence of chemisorption products of carbon dioxide and water vapour on radiolysis of tritium breeder
Abstract Lithium orthosilicate pebbles with 2.5 wt% excess of silica are the reference tritium breeding material for the European solid breeder test blanket modules. On the surface of the pebbles chemisorption products of carbon dioxide and water vapour (lithium carbonate and hydroxide) may accumulate during the fabrication process. In this study the influence of the chemisorption products on radiolysis of the pebbles was investigated. Using nanosized lithium orthosilicate powders, factors, which can influence the formation and radiolysis of the chemisorption products, were determined and described as well. The formation of radiation-induced defects and radiolysis products was studied with …
Modifications of expression of genes and proteins involved in DNA repair and nitric oxide metabolism by carbatonides [disodium-2,6-dimethyl-1,4-dihydropyridine- 3,5-bis(carbonyloxyacetate) derivatives] in intact and diabetic rats
Abstract Studies on the pathogenesis of diabetes mellitus complications indicate that the compounds reducing free radicals and enhancing DNA repair could be prospective as possible remedies. Carbatonides, the disodium-2,6-dimethyl-1,4- dihydropyridine-3,5-bis(carbonyloxyacetate) derivatives, were tested for these properties. EPR spectroscopy showed that metcarbatone was an effective scavenger of hydroxyl radicals produced in the Fenton reaction, etcarbatone, and propcarbatone were less effective, styrylcarbatone was ineffective. UV/VIS spectroscopy revealed that styrylcarbatone manifested a hyperchromic effect when interacting with DNA, while all other carbatonides showeda hypochromic effec…
Effects of γ-Butyrobetaine and Mildronate on Nitric Oxide Production in Lipopolysaccharide-Treated Rats
Production of nitric oxide was measured in lipopolysaccharide-treated rats (10 mg/kg, 4 hr) using the electron paramagnetic resonance method. As compared to the control animals, the nitric oxide level in liver of lipopolysaccharide-treated rats increased from 27.6+/-4.7 to 1485+/-129 ng/g tissue, in heart from 4.8+/-0.7 to 271+/-26 ng/g tissue, in blood from 33.6+/-12.4 to 638+/-136 ng/g tissue, in kidney from 3.3+/-0.5 to 356+/-31 ng/g tissue, in brain cortex from 46.0+/-3.4 to 227+/-27 ng/g tissue, in cerebellum from 27.7+/-2.6 to 218+/-30 ng/g tissue, and in testes from 13.8+/-1.1 to 86+/-8 ng/g tissue. Administration of the antiischaemic drug, mildronate (120 mg/kg) caused a significant…
X-ray induced defects in advanced lithium orthosilicate pebbles with additions of lithium metatitanate
Abstract Advanced lithium orthosilicate (Li4SiO4) pebbles with additions of lithium metatitanate (Li2TiO3) as a secondary phase have attracted international attention as an alternative solid-state candidate for the tritium breeding in future nuclear fusion reactors. In this research, the generation of radiation-induced defects in the Li4SiO4 pebbles with various contents of Li2TiO3 was analysed in-situ by X-ray induced luminescence technique. After irradiation with X-rays, the accumulated radiation-induced defects in the Li4SiO4 pebbles were studied by electron spin resonance, thermally stimulated luminescence and absorption spectrometry. On the basis of the obtained results, it is conclude…
Effects of Lycopene, Indole-3-Carbinol, and Luteolin on Nitric Oxide Production and iNOS Expression are Organ-Specific in Rats
Effects of Lycopene, Indole-3-Carbinol, and Luteolin on Nitric Oxide Production and iNOS Expression are Organ-Specific in RatsNatural compounds are known to modify NO content in tissues; however, the biological activity of polyphenol-rich food often does not correspond to the effects of individual polyphenols on NO synthase activity. The aim of this study was to see how natural compounds luteolin, indole-3-carbinol, and lycopene modify NO production in rat tissues and change the expression of the iNOS gene and protein. Indole-3-carbinol produced multiple effects on the NO level; it significantly decreased NO concentration in blood, lungs, and skeletal muscles and increased it in the liver. …
Rapid Catalytic Water Disinfection from Earth Abundant Ca 2 Fe 2 O 5 Brownmillerite
Water disinfection is a crucial challenge for humanity. Approaches that are effective, cheap, environmentally friendly, and do not promote gene exchange between bacteria are urgently required. Strongly oxidizing radicals are highly promising to achieve this as they lead to bacterial activation at high efficiencies. However, sources to consistently generate these radicals are limited to high energy UV/H2O2 treatments requiring a large energy input. Here the use of abundant, cheap, brownmillerite (Ca2Fe2O5) is demonstrated as an efficient radical generation material under dark conditions, showing a seven order of magnitude decrease in bacterial concentration over 10 min. This decrease is attr…
Effects of Indole-3-Carbinol and Flavonoids Administered Separately and in Combination on Nitric Oxide Production and iNOS Expression in Rats
Beneficial effects of natural compounds are often attributed to modulation of NO production; however effects produced by plant extracts do not correlate with effects of purified components. The goal of our work was to study ability of flavonoids and indole-3-carbinol, as well as their combinations to modify NO production, iNOS gene and protein expression in rat tissues. Baicalein and luteolin decreased NO concentration in both intact and LPS-treated animals. Baicalein decreased iNOS gene expression. Luteolin decreased NO production in the liver and heart and number of iNOS-positive cells in the liver of LPS-treated animals. Combination of the two substances did not decrease the NO synthesis…
Luminescence of X-ray induced radiation defects in modified lithium orthosilicate pebbles with additions of titanium dioxide
The authors greatly acknowledge the technical and experimental support of O. Leys, M. H. H. Kolb, and R. Knitter (Karlsruhe Institute of Technology, Germany). The work is performed in the frames of the University of Latvia financed project No. Y9-B044-ZF-N-300, “Nano, Quantum Technologies, and Innovative Materials for Economics”.
Beta-MSH inhibits brain inflammation via MC(3)/(4) receptors and impaired NF-kappaB signaling.
The anti-inflammatory effects of melanocortin peptides have been demonstrated in different inflammation models. This is the first report describing the molecular mechanisms for the beta-MSH-induced suppression of bacterial lipopolisaccharide (LPS)-caused brain inflammation. We found that beta-MSH suppresses LPS-induced nuclear translocation of the transcription factor NF-kappaB, and inhibits the expression of inducible nitric oxide synthase, and the following nitric oxide overproduction in the brain, in vivo. Moreover, administering the preferentially MC(4) receptor selective antagonist HS014 blocked completely these effects, suggesting a tentative MC(4) receptor mediated mechanism of actio…
Comparison of tritium measurement techniques for a laser cleaned JET tile
Abstract Over the last 7–8 years, two quantitative analyzing methods—accelerator mass spectrometry (AMS) and full combustion (FC) followed by scintillation detection have been applied for determining the tritium activity concentrations in JET divertor tiles. These methods have two main differences – the range of detection and the spatial resolution – and are thus complementary. However, these differences can also complicate the comparison of the two techniques for typical JET divertor samples. Therefore a cross comparison exercise for tritium measurements was performed between the two methods using specially produced identical standard samples. The cross comparison measurements were perform…
Blood levels of nitric oxide and DNA breaks assayed in whole blood and isolated peripheral blood mononucleated cells in patients with multiple sclerosis
Abstract Oxidative stress, especially overproduction of nitric oxide (NO), is considered to be one of the crucial factors in the pathogenesis of multifactorial multiple sclerosis (MS). DNA breaks could be one of the consequences of oxidative stress; however, data on DNA breakage in MS are very few and contradictory. There are no data on direct measurements of NO production in the blood of MS patients. The goal of this study was to determine the level of single-stranded DNA breaks in whole blood or isolated peripheral blood mononuclear cells (PBMNCs) by means of alkaline single cell gel electrophoresis (comet assay) and to evaluate production of NO in the human blood by applying electron par…
Interaction of antimutagenic 1,4-dihydropyridine AV-153-Na with DNA and DNA-damaging molecules and its impact on DNA repair activity
1,4-dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. Interaction of some 1,4-DHP with DNA was recently reported. AV-153-Na, an antimutagenic and DNA-repair-enhancing compound appeared to be able to interact with DNA by intercalation. The aim of the current study was to characterize DNA’s capacity for the binding of AV-153-Na, and using different approaches, to test intracellular distribution of the compound, to test the ability of the compound to scavenge peroxynitrite and hydroxyl radical and to assess the ability of the compound to modify the activity of DNA repair enzymes. The DNA binding activity…
Beta- and gamma-melanocortins inhibit lipopolysaccharide induced nitric oxide production in mice brain.
The pro-opiomelanocortin-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH) mediates many diverse physiological actions, including anti-inflammatory and immunomodulatory effects. However, little is known about the physiological roles of the other melanocortins, beta- and gamma-MSH. Here, we investigated the effects of melanocortin peptides in an in vivo neuroinflammation model. Six hours following intracisternal (i.c.) administration of 10 microg lipopolysaccharide (LPS) to mice a five-fold increase in the nitric oxide (NO) level was seen in the animals' brains, when detected by electron paramagnetic resonance (EPR). All tested melanocortins, alpha-, beta-, gamma1- and gamma2-…
Accumulation of radiation defects and products of radiolysis in lithium orthosilicate pebbles with silicon dioxide additions under action of high absorbed doses and high temperature in air and inert atmosphere
Abstract One of the technological problems of a fusion reactor is the change in composition and structure of ceramic breeders (Li 4 SiO 4 or Li 2 TiO 3 pebbles) during long-term operation. In this study changes in the composition and microstructure of Li 4 SiO 4 pebbles with 2.5 wt% silicon dioxide additions, fabricated by a melt-spraying process, were investigated after fast electron irradiation ( E = 5 MeV, dose rate up to 88 MGy h −1 ) with high absorbed dose from 1.3 to 10.6 GGy at high temperature (543–573 K) in air and argon atmosphere. Three types of pebbles with different diameters and grain sizes were investigated. Products of radiolysis were studied by means of FTIR and XRD. TSL …