Scientific reports
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In July 2018, certain valsartan-containing drugs were voluntary recalled in Japan owing to contamination with N-nitrosodimethylamine (NDMA), a probable human carcinogen. In this study, an HPLC method was developed for the quantitative detection of NDMA simultaneously eluted with valsartan. Good linearity with a correlation coefficient (R2) > 0.999 was achieved over the concentration range of 0.011-7.4 µg/mL. ⋯ When the recalled valsartan samples were subjected to this method, the observed NDMA contents were in agreement with the reported values, indicating that our method achieved sufficient linearity, accuracy, and precision to detect NDMA in valsartan drug substances and products. Moreover, six samples (valsartan drug substances and tablet formulations), which had a possibility for NDMA contamination, were analyzed; none of the samples contained NDMA at detectable levels. Our method would be useful for the rapid screening and quantification of NDMA impurity in valsartan drug substances and products.
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Impedance, or oscillometry, measurements of the respiratory system can generate information about the function of the respiratory system not possible with traditional spirometry. There are currently several instruments on the market using different perturbations. We have compared a new respiratory oscillometry instrument, the tremoflo, with Impulse Oscillometry (IOS). ⋯ Testing both instruments against a respiratory phantom unit confirmed that the resistance measured by the tremoflo compares closely with the known resistance of test loads, whereas the IOS' resistance correlated with a test load of 0.19, kPa.s. L-1 at higher loads it deviated significantly from the known resistance (p < 0.0028). We conclude that the absolute values measured with the two devices may not be directly comparable and suggest that differences in the calibration procedures might account for the differences.
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Tamoxifen (TAM) is the standard anti-hormonal therapy for estrogen receptor-positive breast cancer. However, long-term TAM therapy can make acquisition of TAM resistance and there are still no solutions to treat TAM-resistant breast cancer. In this study, we found that protein and mRNA expression of the P2X purinoreceptor 7 (P2X7) was higher in tamoxifen resistant MCF-7 (TAMR-MCF-7) cells than in control MCF-7 cells. ⋯ The migration of TAMR-MCF-7 cells was increased in a concentration-dependent manner by purified sEV treatment. The number of secreted sEVs and the protein levels of CD63 in TAMR-MCF-7 cells were decreased by the P2X7 antagonist, showing that P2X7 influences the production of sEV. Our results suggest that inhibiting the P2X7 could be considered for metastasis prevention in TAM-resistant cancer patients.
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Multicenter Study
Supratentorial Cerebral Arterial Territories for Computed Tomograms: A Mapping Study in 1160 Large Artery Infarcts.
We recently generated a high-resolution supratentorial vascular topographic atlas using diffusion-weighed MRI in a population of large artery infarcts. These MRI-based topographic maps are not easily applicable to CT scans, because the standard-reference-lines for axial image orientation (i.e., anterior-posterior commissure line versus orbito-meatal line, respectively) are 'not parallel' to each other. Moreover, current, widely-used CT-based vascular topographic diagrams omit demarcation of the inter-territorial border-zones. ⋯ We then mapped the three vascular territories collectively, generating a dataset of Certainty-Index (CI) maps to reflect the likelihood of a voxel being a member of a specific vascular territory. Border-zones could be defined by using either relative infarct frequencies or CI differences. The topographic vascular territory atlas, revised for CT, will allow for easier and more accurate delineation of arterial territories and borders on CT images.
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Sterile inflammation is a key determinant of myocardial reperfusion injuries. It participates in infarct size determination in acute myocardial infarction and graft rejection following heart transplantation. We previously showed that P2Y11 exerted an immunosuppressive role in human dendritic cells, modulated cardiofibroblasts' response to ischemia/reperfusion in vitro and delayed graft rejection in an allogeneic heterotopic heart transplantation model. ⋯ P2Y11R stimulation following H2O2-induced oxidative stress reduced mitochondria-derived ROS production and damages through PKCε signaling pathway activation. Our results suggest a novel protective role of P2Y11 in cardiomyocytes against reperfusion injuries. Pharmacological post-conditioning targeting P2Y11R could therefore contribute to improve myocardial ischemia/reperfusion outcomes in acute myocardial infarction and cardiac transplantation.