Convenient and straightforward synthesis of ibrutinib labeled by carbon-13 isotope is reported. Isotopically labeled building block is introduced in the last step of reaction sequence affording sufficient isolated yield (7%) of [13 C6 ]-ibrutinib calculated towards starting commercially available [13 C6 ]-bromobenzene.
Bromobenzene is a compound which has contributed much in understanding the mechanisms involved in xenobiotic hepatotoxicity induced by drugs and environment pollutants. In the present study, the protective and ameliorative effect of beta-carotene was investigated against bromobenzene-induced hepatotoxicity and compared with silymarin, a standard hepatoprotective reference drug. Beta-carotene (10 mg/kg b.w. p.o.) was administered to the rats for 9 days before intragastric intubation of bromobenzene (10 mmol/kg b.w.). Liver marker enzymes (aspartate transaminase, alanine transaminase and alkaline phosphatase), total protein content, bilirubin, total cholesterol, high-density lipoproteins, triglycerides, antioxidant status (reduced glutathione, superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase) were assessed along with histopathological analysis. ELISA was performed for analysing the levels of cytokines such as TNF-α, IL-1β and IL-6 in serum and in the liver. Caspase-3, COX-2 and NF-κB were evaluated by Western blotting. Administration of bromobenzene resulted in elevated levels of liver marker enzymes, bilirubin, lipid peroxidation and cytokines but deterioration in total protein content, antioxidant levels and histopathological conditions. Pre-treatment with beta-carotene not only significantly decreased the levels of liver markers, lipid peroxidation and cytokines but also improved histo-architecture and increased antioxidant levels minimising oxidative stress, and reduced factors contributing to apoptosis. This significant reversal of the biochemical changes on pre-treatment with beta-carotene in comparison with rats administered with bromobenzene clearly demonstrates that beta-carotene possesses promising hepatoprotective effect through its antioxidant, anti-inflammatory and antiapoptotic activity and hence is suggested as a potential therapeutic agent for protection from bromobenzene.
- MeSH
- beta-karoten * MeSH
- brombenzeny * otrava škodlivé účinky MeSH
- lékové postižení jater MeSH
- lidé MeSH
- ochranné látky MeSH
- potkani Wistar MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- klinická studie MeSH
The aim of the present study was to investigate the presence and bioaccumulation of new flame retardants (nBFRs), polybrominated diphenyl ethers (PBDEs) and dechlorane plus (DDC-CO) in the marine environment close to an Arctic community. Passive sampling of air and water and grab sampling of sediment and amphipods was used to obtain samples to study long-range transport versus local contributions for regulated and emerging flame retardants in Longyearbyen, Svalbard. BDE-47 and -99, α- and β-tetrabromoethylcyclohexane (DBE-DBCH), syn- and anti-dechlorane plus (DDC-CO) were detected in all investigated matrices and the DDC-COss at higher concentrations in the air than reported from other remote Arctic areas. Water concentrations of ΣDDC-COSs were low (3 pg/L) and comparable to recent Arctic studies. ΣnBFR was 37 pg/L in the water samples while ΣPBDE was 3 pg/L. In biota, ΣDDC-COSs dominated (218 pg/g ww) followed by ΣnBFR (95 pg/g ww) and ΣPBDEs (45 pg/g ww). When compared with other areas and their relative distribution patterns, contributions from local sources of the analysed compounds cannot be ruled out. This should be taken into account when assessing long-range transport of nBFRs and DDC-COs to the Arctic. High concentrations of PBDEs in the sediment indicate that they might originate from a small, local source, while the results for some of the more volatile compounds such as hexabromobenzene (HBBz) suggest long-range transport to be more important than local sources. We recommend that local sources of flame retardants in remote areas receive more attention in the future.
- MeSH
- Amphipoda MeSH
- brombenzeny analýza MeSH
- chlorované uhlovodíky analýza MeSH
- halogenované difenylethery analýza MeSH
- monitorování životního prostředí metody MeSH
- polycyklické sloučeniny analýza MeSH
- retardanty hoření analýza MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Arktida MeSH
- Svalbard MeSH
In this study, 10 polybrominated diphenyl ethers (PBDEs) and 19 alternative halogenated flame retardants (AFRs) were determined in >450 human milk samples across three European countries, representing northern, western and eastern Europe. This study provides first insights into the occurrence of selected AFRs in mother milk samples and compares them among three European countries. Sums of median concentrations of the most frequently detected PBDEs were 2.16, 0.88 and 0.45ngg-1lipid weight (lw) in Norway, the Netherlands and Slovakia, respectively. The sum of the concentrations of AFRs ranged from 0.14 to 0.25ngg-1lw in all countries, which was 2 to 15 times less compared to Σ7PBDEs. The Penta-BDE replacement, bis(2-ethylhexyl) tetrabromophthalate, BEH-TEBP, was present at the greatest concentrations of any of the AFRs and in some samples exceeded concentrations of BDE 47 and BDE 153. Four AFRs including bromobenzenes (hexabromobenzene, pentabromobenzene, pentabromotoluene) and another Penta-BDE replacement (2-ethylhexyl-2,3,4,5-tetrabromobenzoate, EH-TBB) were detected in >42% of all human milk samples. Because of the potential developmental neurotoxicity of the halogenated flame retardants, infant dietary intakes via breastfeeding were estimated; in four cases the intakes of BDE 47 exceeded the reference dose indicating that the present concentrations may pose a risk for children.
- MeSH
- brombenzeny analýza MeSH
- dítě MeSH
- dospělí MeSH
- halogenace MeSH
- halogenované difenylethery analýza MeSH
- kojení MeSH
- lidé MeSH
- mateřské mléko chemie MeSH
- retardanty hoření škodlivé účinky analýza MeSH
- zdraví dítěte * MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
- Nizozemsko MeSH
- Norsko MeSH
- Slovenská republika MeSH
Concentrations of more than 20 brominated flame retardants (FRs), including polybrominated diphenyl ethers (PBDEs) and emerging FRs, were measured in air, dust and window wipes from 63 homes in Canada, the Czech Republic and the United States in the spring and summer of 2013. Among the PBDEs, the highest concentrations were generally BDE-209 in all three matrices, followed by Penta-BDEs. Among alternative FRs, EHTBB and BEHTBP were detected at the highest concentrations. DBDPE was also a major alternative FR detected in dust and air. Bromobenzenes were detected at lower levels than PBDEs and other alternative FRs; among the bromobenzenes, HBB and PBEB were the most abundant compounds. In general, FR levels were highest in the US and lowest in the Czech Republic - a geographic trend that reflects the flame retardants' market. No statistically significant differences were detected between bedroom and living room FR concentrations in the same house (n=10), suggesting that sources of FRs are widespread indoors and mixing between rooms. The concentrations of FRs in air, dust, and window film were significantly correlated, especially for PBDEs. We found a significant relationship between the concentrations in dust and window film and in the gas phase for FRs with log KOA values <14, suggesting that equilibrium was reached for these but not compounds with log KOA values >14. This hypothesis was confirmed by a large discrepancy between values predicted using a partitioning model and the measured values for FRs with log KOA values >14.
- MeSH
- brombenzeny analýza MeSH
- bydlení * MeSH
- halogenované difenylethery analýza MeSH
- látky znečišťující vzduch analýza MeSH
- monitorování životního prostředí MeSH
- prach analýza MeSH
- retardanty hoření analýza MeSH
- znečištění vzduchu ve vnitřním prostředí analýza MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Geografické názvy
- Česká republika MeSH
- Kanada MeSH
- Spojené státy americké MeSH
In order to confirm the possibility that recycled fractions from the waste electrical and electronic equipment (WEEE) stream were illegally entering the European market in black polymeric food-contact articles (FCAs), bromine quantification, brominated flame retardant (BFR) identification combined with WEEE-relevant elemental analysis and polymer impurity analysis were performed. From the 10 selected FCAs, seven samples contained a bromine level ranging from 57 to 5975 mg kg(-)(1), which is lower than expected to achieve flame retardancy. The BFRs that were present were tetrabromobisphenol A (TBBPA), decabromodiphenylether (decaBDE), decabromodiphenylethane (DBDPE) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE). Typical elements used in electronic equipment and present in WEEE were detected either at trace level or at elevated concentrations. In all cases when bromine was detected at higher concentrations, concurrently antimony was also detected, which confirms the synergetic use of antimony in combination with BFRs. This study describes also the measurement of rare earth elements where combinations of cerium, dysprosium, lanthanum, neodymium, praseodymium and yttrium were detected in four of the seven BFR-positive samples. Additionally, polymer purity was investigated where in all cases foreign polymer fractions were detected. Despite the fact that this study was carried out on a very small amount of samples, there is a significant likelihood that WEEE has been used for the production of FCAs.
- MeSH
- antimon analýza MeSH
- brom analýza MeSH
- brombenzeny analýza MeSH
- elektronický odpad analýza MeSH
- halogenované difenylethery analýza MeSH
- obaly potravin * MeSH
- polybrombifenylové sloučeniny analýza MeSH
- polymery MeSH
- recyklace MeSH
- retardanty hoření analýza MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Stabilisation energies of stacked structures of C(6)H(6)...C(6)X(6) (X = F, Cl, Br, CN) complexes were determined at the CCSD(T) complete basis set (CBS) limit level. These energies were constructed from MP2/CBS stabilisation energies and a CCSD(T) correction term determined with a medium basis set (6-31G**). The former energies were extrapolated using the two-point formula of Helgaker et al. from aug-cc-pVDZ and aug-cc-pVTZ Hartree-Fock energies and MP2 correlation energies. The CCSD(T) correction term is systematically repulsive. The final CCSD(T)/CBS stabilisation energies are large, considerably larger than previously calculated and increase in the series as follows: hexafluorobenzene (6.3 kcal mol(-1)), hexachlorobenzene (8.8 kcal mol(-1)), hexabromobenzene (8.1 kcal mol(-1)) and hexacyanobenzene (11.0 kcal mol(-1)). MP2/SDD** relativistic calculations performed for all complexes mentioned and also for benzene[dot dot dot]hexaiodobenzene have clearly shown that due to relativistic effects the stabilisation energy of the hexaiodobenzene complex is lower than that of hexabromobenzene complex. The decomposition of the total interaction energy to physically defined energy components was made by using the symmetry adapted perturbation treatment (SAPT). The main stabilisation contribution for all complexes investigated is due to London dispersion energy, with the induction term being smaller. Electrostatic and induction terms which are attractive are compensated by their exchange counterparts. The stacked motif in the complexes studied is very stable and might thus be valuable as a supramolecular synthon.
