The inhibitory effects of five novel brominated flame retardants, 1,2-bis(2,4,5-tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP), and β-tetrabromoethylcyclohexane (β-TBECH), on thyroid hormone deiodinase (DIO) and sulfotransferase (SULT) activity were investigated using human in vitro liver microsomal and cytosolic bioassays. Enzymatic activity was measured by incubating active human liver subcellular fractions with thyroid hormones (T4 and rT3 separately) and measuring changes in thyroid hormone (T4, T3, rT3, and 3,3'-T2) concentrations. Only DBDPE showed inhibition of both outer and inner ring deiodination (O and IRD) of T3 and 3,3'-T2 formation from T4, respectively, with an estimated IC of 160 nM; no statistically significant inhibition of SULT activity was observed. ORD inhibition of 3,3'-T2 formation from rT3 was also observed (IC ∼ 100 nM). The kinetics of T4 O and IRD were also investigated, although a definitive mechanism could not be identified as the Michaelis-Menten parameters and maximal rate constants were not significantly different. Concentrations tested were intentionally above expected environmental levels, and this study suggests that these NBFRs are not potent human liver DIO and SULT inhibitors. To our knowledge, DBDPE is the first example of a nonhydroxylated contaminant inhibiting DIO activity, and further study of the mechanism of action is warranted.
The purpose of this study was to develop a method to quantify 4(5)-methylimidazole (4-MEI), a suspected carcinogen, in carbonated beverages by simple sample dilution and isotope-dilution reverse-phase LC-MS/MS. Isotope dilution using hexa-deuterated methylimidazole (d6-4-MEI) was used to quantify native 4-MEI and to assess matrix effects quantitatively. The accuracy of the method was assessed by intentionally fortifying a negative control sample at three doses: low, medium and high (replicates of n = 5 each) with a known amount of 4-MEI. The respective absolute error in each case was 18.7 ± 0.7%, 14.6 ± 2.8% and 21.1 ± 9.7%. Within-day (intra-) and day-to-day (inter-) repeatability, determined as the relative standard deviation by fortifying a negative control sample (n = 5), were 9.5% and 15.4%, respectively. Average ion suppression of d6-4-MEI in beer was 63.9 ± 3.2%, while no suppression or enhancement was seen in non-alcoholic samples. The instrument and method limit of detection were calculated as 0.6 and 5.8 ng ml(-1), respectively. 4(5)-Methylimidazole was quantified in a variety of store-bought consumer beverages and it was found that in many of the samples tested consuming a single can of beer would result in intake levels of 4-MEI that exceed the no significant risk guideline of 29 µg day(-1). Conversely, 4-MEI in the samples was orders of magnitude smaller than the European Food Safety Authority acceptable daily intake threshold value of 100 mg kg(-1) bw day(-1).
Thoracic pseudoaneurysm in the ascending aorta is an uncommon condition associated with significant risk of morbidity and mortality. Treatment is recommended in all cases regardless of symptoms as the mortality rate if left untreated has been documented to be as high as 61%. The current standard of care for managing these lesions is open surgical repair. However, this is associated with significant morbidity. In‐hospital mortality reported for patients undergoing surgical repair of an ascending aortic pseudoaneurysm ranges from 6.7% to 41%. When anatomically suitable, a less invasive approach using amplatzer vascular plug or septal occluder is an attractive approach. We present a case report of repair of a post‐surgical ascending aortic false aneurysm using an amplatzer septal occluder with an Oscor ™ steerable guiding sheath; a novel approach to increase platform stability when engaging an aneurysm neck. Endovascular occluder deployment for closure of aortic false aneurysms remains a relatively novel technique. It is limited by the requirement to develop a stable endovascular platform to deliver the device and avoid system prolapse, particularly when accessing challenging lesions on the inner aortic curvature. We present the first case to utilize a steerable guiding sheath system to improve system stability and facilitate successful device delivery. Given the significant morbidity associated with open repair of these lesions we hope this will further expand the range of lesions viewed as appropriate for endovascular repair.
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