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Comparative data regarding the effect of percutaneous and thoracoscopic ablation of atrial fibrillation (AF) on cognitive function are very limited. The aim of the study was to determine and compare the effect of both types of ablations on patient cognitive functions in the mid-term.Patients with AF indicated for ablation procedure were included. Forty-six patients underwent thoracoscopic, off-pump ablation using the COBRA Fusion radiofrequency system, followed by a catheter ablation three months afterward (Hybrid group). A comparative cohort of 53 AF patients underwent pulmonary vein isolation only (PVI group). Neuropsychological examinations were done before and nine months after the surgical or catheter ablation procedure. Neuropsychological testing comprised 13 subtests of seven domains, and the results were expressed as post-operative cognitive dysfunction (POCD) nine months after the procedure.Patients in both groups were similar with respect to the baseline clinical characteristics; only non-paroxysmal AF was more common in the hybrid group (98% vs. 34%). Major POCD was present in 8 (17.4%) of hybrid patients vs. 3 (5.7%) of PVI patients (p = 0.11), combined (major/minor) worsened cognitive decline was present in 10 (21.7%) hybrid patients vs. 3 (5.6%) PVI patients (p = 0.034). On the other hand, combined (major/minor) improvement was present in 15 (32.6%) hybrid patients vs. 9 (16.9%) patients in the PVI group (p = 0.099).Hybrid ablation, a combination of thoracoscopic and percutaneous ablation, is associated with a higher risk of cognitive decline compared to sole percutaneous ablation. This article is protected by copyright. All rights reserved.

Patients with type 1 diabetes mellitus (T1DM) develop microvascular complications during the course of the disease. Oxidative stress is the main mechanism of the microvascular damage. Currently no specific and reliable laboratory tests are available for screening of early microvascular changes. 56 patients with T1DM were included. We measured their serum levels of malonyl dialdehyde and reactive aldehydes with chain lengths C6–C12, which are known to be generated during lipid peroxidation, a process associated with oxidative stress. Serum levels of aldehydes were compared with the parameters of microvascular reactivity (MVR) examined by laser Doppler flowmetry and with the parameters of blood glucose control (glycated hemoglobin, glycemic variability using continuous glucose monitoring). In this cross-sectional observational study, higher levels of reactive aldehydes were associated with impaired skin MVR in T1DM. However, the parameters of glucose control were not associated with lipid peroxidation or MVR in our study. Therefore, we suggest that other than simple glycemic mechanism may be more important in the process of reactive aldehyde generation in T1DM.

X-ray powder diffraction data, unit-cell parameters, and space group for a C9H9I3N2O4 are presented [a = 17.000 (1) Å, b = 13.896 (1) Å, c = 12.597 (1) Å, unit-cell volume V = 2975.9 Å3, MW = 589.89, Tm (melting point) = 300(1) °C, ρc = 2.641 g cm−3, ρm = 2.66(3) g cm−3, Z = 8, space group Pbca]. All measured lines were indexed and are consistent with the Pbca space group. No detectable impurities were observed.

Liraglutide is the glucagon-like peptide-1 receptor agonist widely used for the treatment of type 2 diabetes mellitus. Recently, it has been demonstrated to decrease cardiovascular morbidity and mortality in patients with type 2 diabetes and high cardiovascular risk. Although the major modes of liraglutide action are well-known, its detailed action at the metabolic level has not been studied. To this end, we explored the effect of 2-week liraglutide treatment in C57BL/6 male mice with obesity and diabetes induced by 13 weeks of high-fat diet using NMR spectroscopy to capture the changes in urine metabolic profile induced by the therapy. The liraglutide treatment decreased body and fat pads weight along with blood glucose and triglyceride levels. NMR spectroscopy identified 11 metabolites significantly affected by liraglutide treatment as compared to high-fat diet-fed control group. These metabolites included ones involved in nicotinamide adenine dinucleotide metabolism, β-oxidation of fatty acids and microbiome changes. Although majority of the metabolites changed after liraglutide treatment were similar as the ones previously identified after vildagliptin administration in a similar mouse model, the changes in creatinine, taurine and trigonelline were specific for liraglutide administration. The significance of these changes and its possible use in the personalization of antidiabetic therapy in humans requires further research.

Context: The role of neuroinflammation in methanol-induced toxic brain damage has not been studied.Objective: We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors.Methods: Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge.Results: The acute maximum (Cmax) LT concentrations were higher than concentrations in survivors: Cmax for LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p

Life span and aging are substantially modified by natural selection. Across species, higher extrinsic (environmentally related) mortality (and hence shorter life expectancy) selects for the evolution of more rapid aging. However, among populations within species, high extrinsic mortality can lead to extended life span and slower aging as a consequence of condition-dependent survival. Using within-species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter intrinsic life spans and a greater increase in mortality with age, more pronounced cellular and physiological deterioration (oxidative damage, tumor load), and a faster decline in fertility than populations from wetter regions. This parallel intraspecific divergence in life span and aging was not associated with divergence in early life history (rapid growth, maturation) or pace-of-life syndrome (high metabolic rates, active behavior). Variability across four study species suggests that a combination of different aging and life-history traits conformed with or contradicted the predictions for each species. These findings demonstrate that variation in life span and functional decline among natural populations are linked, genetically underpinned, and can evolve relatively rapidly.

New chiral imide-oxazoline derivatives of Kemp’s acid were synthesized with the aim to produce new ligands suitable for catalytic asymmetric reactions. Compound 1 is C18H28N2O3, systematic name (1R, 5S, 7R)-7-[(S)-4-tert-butyl-4,5-dihydrooxazole-2-yl]-1,5,7-trimethyl-3-azabicyclo-[3.3.1]-nonane-2,4-dione. Compound 2 is C21H26N2O3, systematic name (1R,5S,7R)-7-[(S)-4-benzyl-4,5-dihydrooxazole-2-yl]-1,5,7-trimethyl-3-azabicyclo-[3.3.1]-nonane-2,4-dione. Both compounds contain two molecules with very similar conformations in the asymmetric unit. The two structures were characterized by single crystal X-ray diffraction. DFT calculations of two possible distinct conformations were performed to elucidate the differences between the preferred conformation in vacuo and the one observed in the single crystal. Also, charges on the key atoms of the compounds were compared with a common ligand used for asymmetric transfer hydrogenation.

Simvastatin and other statins (HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors) are extensively used in clinical practices and are very effective in decreasing serum low-density lipoprotein cholesterol. However, their effect on cholesterol synthesis in central nervous system and its behavioral consequences have not been fully understood yet. We have studied selected biologic traits potentially affected by statin treatment - serotonin (5-HT) uptake in platelets, membrane microviscosity in erythrocytes, cholesterol level in the brain (amygdala; hippocampus and prefrontal cortex), as well as behavioral changes in an elevated plus maze and open field test in male Long-Evans rats, which were treated by simvastatin (30mg/kg per day) for 2 or 4weeks. We demonstrated: 1) a decrease in both serotonin transporter (SERT) activity and membrane microviscosity after treatment with simvastatin, 2) lower cholesterol content in all tested brain regions in animals from the simvastatin treated group, and 3) longer time spent in the open arms and a higher number of entrances to the closed arms in the elevated plus maze by animals from the simvastatin group compared to animals from the control group, but no differences in behavior in the open field test. Taken together, our results confirmed complex alterations, including behavioral changes, after the cholesterol lowering treatment. Furthermore, we discuss the possibility that the behavioral changes, traditionally interpreted as an anxiolytic effect, may be interpreted as increased impulsivity. We also confirmed that such behavioral changes may be attributed to changes in serotonergic neurotransmission.

X-ray powder diffraction data, unit-cell parameters, and space group for a new memantine analogue of a Platinum (Pt) (II) complex labelled LA-13, C12H24Cl2N2Pt, are reported [a = 8.324(1) Å, b = 27.838(2) Å, c = 7.113(1), β = 111.25(1), unit-cell volume V = 1536.26 Å3, Z = 4, and space group P21/n]. All measured lines were indexed and are consistent with the P21/n space group. No detectable impurity was observed.

The role of the sulfonamide moiety of Noyori-Ikariya [Ru(II)Cl(η 6-p-cymene)(S,S)-(N-arylsulfonyl-DPEN)] (where DPEN = 1,2-diphenylethylene-1,2-diamine) half-sandwich complexes in the asymmetric transfer hydrogenation (ATH) of imines (1-methyl-3,4-dihydroisoquinoline and 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline) was investigated. Nine complexes were synthesized and characterized, most of which have not been previously reported and a majority of the corresponding ligands (N-arylsulfonyl-DPEN) have not been described in imine ATH. The study demonstrates that the structure of the sulfonamide fragment strongly affects the catalytic activity. By monitoring the reaction kinetics, it was found that the reactivity of certain complexes was moderately enhanced and the enantioselectivity was affected as well, albeit to a lesser extent. No simple structure–activity pattern was found, suggesting that extensive screening experiments are necessary in order to obtain the optimal catalyst for a particular substrate. The study complements other previously reported works on structure–activity relationships concerning Ru(II)-catalyzed ATH by adding a new dimension of investigation.

A method for enantioselective hydrogenation of cyclic imines with gaseous hydrogen has been developed. Easily accessible Noyori-Ikariya Ru(II) and Rh(III) complexes can be used directly without an inert atmosphere. Substrate activation has been achieved by trifluoroacetic acid. A new hydroxyl-functionalized complex is reported, showing high activity in transfer hydrogenation.

In addition to dopamine, endocannabinoids are thought to participate in neural reward mechanisms of opioids. Number of recent studies suggests crucial involvement of ghrelin in some addictive drugs effects. Our previous results showed that ghrelin participates in morphine-induced changes in the mesolimbic dopaminergic system associated with reward processing. The goal of the present study was to test whether the growth hormone secretagogue receptor (GHS-R1A) antagonist JMV2959 was able to influence morphine-induced effects on anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) in the nucleus accumbens shell (NACSh). We used in vivo microdialysis to determine changes in levels of AEA and 2-AG in the NACSh in rats following (i) an acute morphine dose (5, 10 mg/kg s.c.) with and without JMV2959 pretreatment (3, 6 mg/kg i.p.) or (ii) a morphine challenge dose (5 mg/kg s.c.) with and without JMV2959 (3, 6 mg/kg i.p.) pretreatment, administered during abstinence following repeated doses of morphine (5 days, 10–40 mg/kg). Co-administration of ghrelin (40 ug/kg i.p.) was used to verify the ghrelin mechanisms involvement. Pretreatment with JMV2959 significantly and dose-dependently reversed morphine-induced anandamide increases in the NACSh in both the acute and longer-term models, resulting in a significant AEA decrease. JMV2959 significantly intensified acute morphine-induced decreases in accumbens 2-AG levels and attenuated morphine challenge-induced 2-AG decreases. JMV2959 pretreatment significantly reduced concurrent morphine challenge-induced behavioral sensitization. JMV2959 pretreatment effects were abolished by co-administration of ghrelin. Our results indicate significant involvement of ghrelin signaling in morphine-induced endocannabinoid changes in the NACSh.

Severe refractory asthma (SRA) is characterized by prominent airway inflammation and oxidative stress. Inadequate production of anti-inflammatory arachidonic acid product lipoxin was described in severe phenotype of asthma. Aims: We sought to investigate whether concentration of lipoxin A4 (LXA) and leukotrien B4 (LTB) in exhaled breath condensate differs in various phenotypes of SRA. Methods: We harvested EBC of 59 SRA patients and 38 healthy controls (HC) by standardized protocol (EcoScreen). LXA and LTB were compared between subgroups of eosinophilic (EA, n=29) and non-eosinophilic (NEA, n=30) phenotype defined by exhaled nitric oxide > 30ppb despite high dose of inhaled corticosteroid therapy. LXA and LTB in EBC were analyzed by liquid chromatography and mass spectrometry. Measured results were analyzed together with FEV1, FeNO50, PBE and subgroups statistically evaluated. Results: EA and NEA were comparable by FEV1, ACT, peripheral blood eosinophilia (all p>0.05). LXA and concentration in SRA were markedly lower than in HC (27.65 vs. 59.89 pg/ml, p Conclusion: We showed imbalance of anti-inflammatory and pro-inflammatory arachidonic acid products in SRA in comparison to HC. SRA is associated with decreased production of LXA4, which is significantly lower in non-eosinophilic asthma phenotype (NEA). NEA phenotype could be associated with prolonged resolving of airway inflammatory damage.

Nanoscale titanium dioxide (nanoTiO2) is a commercially important nanomaterial. Animal studies have documented lung injury and inflammation, oxidative stress, cytotoxicity and genotoxicity. Yet, human health data are scarce and quantitative risk assessments and biomonitoring of exposure are lacking. NanoTiO2 is classified by IARC as a group 2B, possible human carcinogen. In our earlier studies we documented an increase in markers of inflammation, as well as DNA and protein oxidative damage, in exhaled breath condensate (EBC) of workers exposed nanoTiO2. This study focuses on biomarkers of lipid oxidation. Several established lipid oxidative markers (malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, 8-isoProstaglandin F2α and aldehydes C6–C12) were studied in EBC and urine of 34 workers and 45 comparable controls. The median particle number concentration in the production line ranged from 1.98 × 104 to 2.32 × 104 particles/cm3 with ∼80% of the particles

Only four types of dimeric precursors [RuCl2(η6-arene)]2 for the synthesis of Noyori’s half sandwich diamine catalysts [RuCl(TsDPEN)(η6-arene)] are commercially available, yet so far no study has tried to systematically evaluate how these systems perform during the asymmetric transfer hydrogenation of various 3,4-dihydroisoquinolines (i.e., the typical substrates for Noyori asymmetric transfer hydrogenation benchmarking). Experiments combined with molecular modeling allowed us to assess their properties and formulate a hypothesis clarifying the difference in enantioselectivity of these systems.

Background: Methamphetamine (METH) abuse is a growing health problem worldwide, and METH use during pregnancy not only endangers the mother’s health but also the developing fetus. To provide better insight into these risks, we performed the following experiments. Method: First, we investigated how sex influences the pharmacokinetics of METH and amphetamine (AMP) in male and female rats. Subsequently, we simulated chronic exposure of prenatal infants to METH abuse by investigating brain and plasma levels of METH and AMP in dams and pups. Finally, we modeled chronic exposure of infants to METH via breast milk and investigated sex differences in pups with regard to drug levels and possible sensitization effect of chronic prenatal METH co-treatment. Results: We observed significantly higher levels of METH and AMP in the plasma and brain of female rats compared to males. Additionally, brain concentrations of METH and AMP in pups exposed to METH prenatally were equivalent to 62.13% and 37.78% relative to dam, respectively. Plasma concentrations of AMP where equivalent to 100% of the concentration in dams, while METH was equivalent to only 36.98%. Finally, we did not observe a significant effect relative to sex with regard to METH/AMP levels or sensitization effects linked to prenatal METH exposure. Conclusion: We demonstrated that female rats display higher levels of METH and AMP, thus indicating a greater risk of addiction and toxicity. Furthermore, our data show that pups are exposed to both METH and AMP following dam exposure.

The asymmetric transfer hydrogenation (ATH) of imines catalyzed by the Noyori-Ikariya [RuCl(η6-arene)(N-arylsulfonyl-DPEN)] (DPEN = 1,2-diphenylethylene-1,2-diamine) half-sandwich complexes is a research topic that is still being intensively developed. This article focuses on selected aspects of this catalytic system. First, a great deal of attention is devoted to the N-arylsulfonyl moiety of the catalysts in terms of its interaction with protonated imines (substrates) and amines (components of the hydrogen-donor mixture). The second part is oriented toward the role of the η6-coordinated arene. The final part concerns the imine substrate structural modifications and their importance in connection with ATH. Throughout the text, the summary of known findings is complemented with newly-presented ones, which have been approached both experimentally and computationally.

An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine and nicotine abuse. However, the role of ghrelin in opioid effects has rarely been examined. Recently we substantiated in rats that ghrelin growth hormone secretagogue receptors (GHS-R1A) appear to be involved in acute opioid–induced changes in the mesolimbic dopaminergic system associated with the reward processing. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit morphine-induced biased conditioned place preference and challenge-morphine-induced accumbens dopaminergic sensitization and behavioral sensitization in adult male rats. In the place preference model, the rats were conditioned for 8 days with morphine (10 mg/kg s.c.). On the experimental day, JMV2959 (3 and 6 mg/kg i.p.) or saline were administered before testing. We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens in rats following challenge-morphine dose (5 mg/kg s.c.) with or without JMV2959 (3 and 6 mg/kg i.p.) pretreatment, administered on the 12th day of spontaneous abstinence from morphine repeated treatment (5 days, 10–40 mg/kg). Induced behavioral changes were simultaneously monitored. Pretreatment with JMV2959 significantly and dose dependently reduced the morphine-induced conditioned place preference and significantly and dose dependently reduced the challenge-morphine-induced dopaminergic sensitization and affected concentration of by-products associated with dopamine metabolism in the nucleus accumbens. JMV2959 pretreatment also significantly reduced challenge-morphine-induced behavioral sensitization. Our present data suggest that GHS-R1A antagonists deserve to be further investigated as a novel treatment strategy for opioid addiction.

A new [Ru(II)( η 6 - p -cymene)(1 R ,2 R )- N -((1 S ,2 S )-borneol-10-sulfonyl)-1,2-diphenylethylenediamine] catalyst for the asymmetric transfer hydrogenation of both 1-alkyl and 1-aryl dihydroisoquinolines has been isolated. For the first time in this type of reaction, the catalyst employs an N-alkylsulfonyl group instead of N-arylsulfonyl.

The asymmetric transfer hydrogenation of five dihydroisoquinolines (DHIQs) was studied by NMR spectroscopy. The DHIQs differed by substitution with methoxy groups, which had a significant effect upon the reaction performance in terms of reaction rate and enantioselectivity. The differences are most probably related to the basicity of DHIQs.

We present, to the best of our knowledge, the first parametric study of the asymmetric transfer hydrogenation of imines catalyzed by a Noyori-type catalytic complex based on ruthenium. A model imine for this study was 1-methyl-3,4-dihydroisoquinoline, and a well-known complex RuCl(η 6 - p -cymene)((1 S ,2 S )- N - p -toluenesulfonyl-1,2-diphenylethylenediamine) was chosen as the model catalyst. The reactions were performed in the presence of a formic acid–triethylamine mixture as the source of hydrogen. The parameters examined include general parameters, for example, concentration, temperature, and substrate-to-catalyst molar ratio, as well as parameters specific to this particular reaction, such as the amount of the hydrogenation mixture used, the ratio of its components, or the inhibitive effect of carbon dioxide. During this study, several unexpected parameters worth further investigation have emerged.

We have examined the potential of vapor-phase hydrogen peroxide (VPHP) for degradation of 21 structurally different pharmaceutical substances. Our results show that VPHP can be used to degrade pharmaceuticals, but it was not universally applicable to all the drugs tested. Structural analysis revealed a significant correlation of the molecular structure of a compound with its susceptibility to VPHP. Tertiary amino groups seem to be the initiation centers, although the overall susceptibility of a substance depends on other factors also. Several tested substances underwent significant structural changes, suggesting a possible decrease in their biological activity. As far as we are aware, this is one of the first reports of application of VPHP to the decontamination of hazardous chemicals.

A method for the analysis of the optical purity of a series of chiral substituted tetrahydroisoquinolines (THIQs) was developed. The method is based on pre-column derivatization of the analytes with the derivatization reagent (–)-(1R)-menthyl chloroformate. The derivatization reaction selectively gives diastereomeric carbamates that are resolvable on an achiral non-polar GC column. The developed technique covers variously substituted THIQs, which differ significantly in volatility, steric and electronic properties. In all cases, the resolution factors (R) exceeded the value of 1.5. The method represents a robust way of analysis of mixtures of THIQs, which are often present in various matrixes such as body fluids, tissues and reaction mixtures.

A chiral precursor of Mivacurium chloride, (R)-5′-methoxylaudanosine, was prepared using two different methods. The chiral resolution of racemic 5′-methoxylaudanosine, typically used in industry, was carried out in parallel with a procedure consisting of asymmetric transfer hydrogenation (ATH) and reductive methylation. A novel one-pot synthetic step was developed for the synthesis of racemic 5′-methoxylaudanosine. In both routes, the enantioselectivity was high but further purification was necessary to reach the level of a pharmaceutical standard. The individual synthetic steps reported herein can also be used for the synthesis of analogous bistetrahydroisoquinoline-based skeletal muscle relaxants.

Interactions of two neurosteroids, inhibiting membrane-bound N-Methyl-d-aspartate receptors, with phospholipid membranes are studied. Namely, endogenous pregnanolone sulfate is compared with pregnanolone glutamate, the latter being a novel synthetic steroidal inhibitor of these receptors with potential pharmaceutical use. Molecular-level details of steroid-phospholipid membranes interactions are scrutinized employing molecular dynamics simulations supported by quantum chemical calculations to assess steroid lipophilicity. Moreover, permeability of both species across membranes is experimentally evaluated by immobilized artificial membrane chromatography. We demonstrate that while there is no significant difference of lipophilicity and membrane permeability between the two steroids, they differ significantly regarding detailed localization in phospholipid membranes. The bulky glutamate moiety of pregnanolone glutamate is flexible and well exposed to the water phase while the sulfate group of pregnanolone sulfate is hidden in the membrane headgroup region. This dissimilarity of behavior in membranes can potentially account for the observed different activities of the two steroids toward membrane-bound N-Methyl-d-aspartate receptors.

Chronic obstructive pulmonary disease (COPD) is linked to increased oxidative and nitrative stress (RNOS) in the airways and systemic circulation. RNOS causes damage of fosfolipids and proteins in cellular membrane including airway epithelium. Exhaled breath analysis (EBC) can reflex intensity of RNOS in COPD. We compared concentration of RNOS biomarkers and anti-inflammatory lipoxin A4 (LXA4) in EBC in COPD patients and healthy controls before and after incremental shuttle walk test (ISWT), actigraphy was used to follow average daily steps 1 week before ISWT. In 29 patents with severe COPD (age 62±1,7, FEV1 48,8 ± 15,6%) and 17 age matched healthy controls were during 1 day performed EBC collection, EBC samples were frozen and analyzed by mass spectrometry with liqid chromatography. After EBC sampling subjects underwent ISWT, and then again gave EBC. Results: We tested 8-isoprostane (8-ISO), cysteinyl leucotriens (LTB4, LTC4) and LXA4. In COPD was 8-ISO 48.2±3.5, LTB4 45.8±2.3, LTC4 56.4±14.9 pg/mL and LXA4 18.5±8.9 pg/mL, in control group were results of RNOS lower, and LXA4 higher (all differences p Conclusion: The higher RNOS in EBC the lower ISWT and daily acitivity. COPD patients with lower oxidative stress production had better tolerance of physical activity.

Background: NanoTiO 2 is used in many applications as a high volume commercially important engineered nanomaterial. Experimental studies documented oxidative stress, inflammation, and lung injury. Human health data are extremely limited (1, 2). Methods: In exhaled breath condensate (EBC) of 36 workers occupationally exposed to TiO 2 we studied post-shift a panel of biomarkers of lipid oxidation: malondialdehyde (MDA), 4-hydroxy-trans-hexenale (HHE), 4-hydroxy-trans-nonenale (HNE), 8-isoProstaglandin F2α (8-isoprostane) and aldehydes C 6 -C 12 in 2012 and 2013. Identical examination was done in 45 controls. Results: Median particle number concentration in the production area ranged from 1.98x10 4 to 2.32x10 4 particles/cm 3 with 80-85% of the particles 3 . All 11 markers of lipid oxidation were elevated in workers comparing to controls (p 2 and markers of lipid oxidation in the EBC. No association was found with age or lifestyle factors. Conclusion: Lipid oxidation in EBC of workers following nanoTiO 2 exposures is consistent with the oxidative stress hypothesis and suggests, at the molecular level, sustained lung injury. Markers of oxidation of lipids in EBC, in addition to oxidative products of nucleic acids and proteins (1) appear a useful and sensitive technique for non-invasive monitoring of workers exposed to engineered nanoparticles of nanoTiO 2 similarly as to Fe oxides (2). Acknowledgement: P25/1LF/2, P28/1LF/6. References: 1. Pelclova D et al. Occup Environ Med. 2016;73:110-8. 2. Pelclova D, et al. J Breath Res. 2016 1;10(1):016004.

Background: NanoTiO 2 is widely used as a high volume engineered nanomaterial, however human health data for exposed workers are scarce. Experimental and in vitro studies found lung inflammation and injury. Methods: In 30 workers occupationally exposed to TiO 2 in 2012/2013, post-shift spirometry, fractional exhaled nitric oxide (FeNO) and leukotrienes (LTs) as markers of inflammation in exhaled breath condensate (EBC) were examined: LT B4 and cysteinyl-LTs C4,D4 and E4. Identical examination was done in 22 office employees from the same factory; and in 45 unexposed controls. Results: The aerosol TiO 2 exposure mildly lowered from 2012 to 2013; respirable mass concentration was 0.4 and 0.65 mg/m 3 and the median particle number concentration in the production area 1.98x10 4 and 2.32x10 4 particles/cm 3 in 2012 and 2013, respectively. In both years, 80-85% of the particles had Conclusion: These findings are consistent with the inflammation in the respiratory tract and suggest a lung injury. LTs in EBC appear a useful and sensitive technique for non-invasive monitoring of workers exposed to engineered nanoTiO 2 , similarly as oxidation products of nucleic acids and proteins(1). FeNO and lung functions are not sensitive enough. Acknowledgement: P25/1LF/2, P28/1LF/6. Reference: 1. Pelclova D et al. Occup Environ Med 2016;73:110-8.

Human health data regarding exposure to nanoparticles are extremely scarce and biomonitoring of exposure is lacking in spite of rodent pathological experimental data. Potential markers of the health-effects of engineered nanoparticles were examined in 30 workers exposed to TiO2 aerosol, 22 office employees of the same plant, and 45 unexposed controls. Leukotrienes (LT) B4, C4, E4, and D4 were analysed in the exhaled breath condensate (EBC) and urine via liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Fractional exhaled nitric oxide (FeNO) and spirometry was also measured. The median particle number concentration of the aerosol in the production ranged from 1.98 × 10(4) to 2.32 × 10(4) particles cm(-3); about 80% of the particles were

Life span and aging are substantially modified by natural selection. Across species, higher extrinsic (environmentally related) mortality (and hence shorter life expectancy) selects for the evolution of more rapid aging. However, among populations within species, high extrinsic mortality can lead to extended life span and slower aging as a consequence of condition-dependent survival. Using within-species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter intrinsic life spans and a greater increase in mortality with age, more pronounced cellular and physiological deterioration (oxidative damage, tumor load), and a faster decline in fertility than populations from wetter regions. This parallel intraspecific divergence in life span and aging was not associated with divergence in early life history (rapid growth, maturation) or pace-of-life syndrome (high metabolic rates, active behavior). Variability across four study species suggests that a combination of different aging and life-history traits conformed with or contradicted the predictions for each species. These findings demonstrate that variation in life span and functional decline among natural populations are linked, genetically underpinned, and can evolve relatively rapidly.

Several recent hypotheses consider oxidative stress to be a primary constraint ensuring honesty of condition-dependent carotenoid-based signalling. The key testable difference between these hypotheses is the assumed importance of carotenoids for redox homeostasis, with carotenoids being either antioxidant, pro-oxidant or unimportant. We tested the role of carotenoids in redox balance and sexual signalling by exposing adult male zebra finches (Taeniopygia guttata) to oxidative challenge (diquat dibromide) and manipulating carotenoid intake. As the current controversy over the importance of carotenoids as antioxidants could stem from the hydrophilic basis of commonly-used antioxidant assays, we used the novel measure of in vivo lipophilic antioxidant capacity. Oxidative challenge reduced beak pigmentation but elicited an increase in antioxidant capacity suggesting resource reallocation from signalling to redox homeostasis. Carotenoids counteracted the effect of oxidative challenge on lipophilic (but not hydrophilic) antioxidant capacity, thereby supporting carotenoid antioxidant function in vivo. This is inconsistent with hypotheses proposing that signalling honesty is maintained through either ROS-induced carotenoid degradation or the pro-oxidant effect of high levels of carotenoid-cleavage products acting as a physiological handicap. Our data further suggest that assessment of lipophilic antioxidant capacity is necessary to fully understand the role of redox processes in ecology and evolution.

IgA nephropathy is diagnosed by renal biopsy, an invasive procedure with a risk of significant complications. Noninvasive approaches are needed for possible diagnostic purposes and especially for monitoring disease activity or responses to treatment. In this pilot project, we assessed the utility of urine samples as source of biomarkers of IgA nephropathy. We used spot urine specimens from 19 healthy controls, 11 patients with IgA nephropathy, and 8 renal-disease controls collected on day of renal biopsy. Urine samples were analyzed using untargeted metabolomic and targeted proteomic analyses by several experimental techniques: liquid chromatography coupled with mass spectrometry, immunomagnetic isolation of target proteins coupled with quantitation by mass spectrometry, and protein arrays. No single individual biomarker completely differentiated the three groups. Therefore, we tested the utility of several markers combined in a panel. Discriminant analysis revealed that combination of seven markers, three metabolites (dodecanal, 8-hydroxyguanosine, and leukotriene C4), three proteins (α1-antitrypsin, IgA-uromodulin complex, and galactose-deficient IgA1), and heparan sulfate, differentiated patients with IgA nephropathy from patients with other renal diseases and healthy controls. Future studies are needed to validate these preliminary findings and to determine the power of these urinary markers for assessment of responses to therapy.

Asymmetric transfer hydrogenation of the acyclic imine acetophenone N-benzylimine was studied by means of computational chemistry. Calculated transition states offer an explanation of why this proc...

Behavioral, neurochemical and pharmaco-EEG profiles of a new synthetic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats were examined.Locomotor effects, prepulse inhibition (PPI) of acoustic startle reaction (ASR), dopamine and its metabolite levels in nucleus accumbens (NAc), EEG power spectra and coherence in freely moving rats were analysed. Amphetamine was used as a reference compound.2C-B had a biphasic effect on locomotion with initial inhibitory followed by excitatory effect; amphetamine induced only hyperlocomotion. Both drugs induced deficits in the PPI; however they had opposite effects on ASR. 2C-B increased dopamine but decreased 3,4-dihydroxyphenylacetic acid (DOPAC) in the NAc. Low doses of 2C-B induced a decrease in EEG power spectra and coherence. On the contrary, high dose of 2C-B 50 mg/kg had a temporally biphasic effect with an initial decrease followed by an increase in EEG power; decrease as well as increase in EEG coherence was observed. Amphetamine mainly induced an increase in EEG power and coherence in theta and alpha bands. Increases in the theta and alpha power and coherence in 2C-B and amphetamine were temporally linked to an increase in locomotor activity and DA levels in NAc.2C-B is a centrally active compound similar to other hallucinogens, entactogens and stimulants. Increased dopamine and decreased DOPAC in the NAc may reflect its psychotomimetic and addictive potential and monoaminoxidase inhibition. Alterations in brain functional connectivity reflected the behavioral and neurochemical changes produced by the drug; a correlation between EEG changes and locomotor behavior was observed.

Bread represents an important source of trace elements in the human diet. This study is focused on home prepared bread in the Czech Republic. The amounts of Cu, Mo, Mn, Ni and Zn (total and soluble...

A rapid and precise method for the identification and quantification of cysteinyl leukotrienes (leukotriene C(4), leukotriene D(4) and leukotriene E(4)), essential markers of bronchial asthma, in exhaled breath condensate was developed. The protocol consists of immunoaffinity separation and a detection step, liquid chromatography combined with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). In particular, the selected reaction monitoring mode was used for its extremely high degree of selectivity and the stable-isotope-dilution assay for its high precision of quantification. The developed method was characterized with a high precision (≤ 7.7%, determined as RSD), an acceptable accuracy (90.4-93.7%, determined as recovery), a low limit of detection (≤ 2 pg/ml EBC) and a low limit of quantification (≤ 10 pg/ml EBC). It was compared to other simple, clinically appropriate combinations of pre-treatment methods (solid phase extraction and lyophilization) with LC/MS. Finally, the method (a combination of immunoaffinity separation with LC-MS) was successfully tested in a clinical study where a significant difference was found in the concentration levels of cysteinyl leukotrienes between patients with occupational bronchial asthma and healthy subjects.