Interaction of the chemotherapeutic agent oxaliplatin and the tyrosine kinase inhibitor dasatinib with the organic cation transporter 2.

Oxaliplatin (OHP) is effective in colorectal cancer treatment but induces peripheral neurotoxicity (OHP-induced peripheral neurotoxicity, OIPN), diminishing survivor quality of life. Organic cation transporter 2 (OCT2) is a key OHP uptake pathway in dorsal root ganglia. Competing for OCT2-mediated OHP uptake, such as with the tyrosine kinase inhibitor dasatinib, may mitigate OHP side effects. We investigated OHP and dasatinib interaction with OCT2 in human embryonic kidney 293 (HEK293) cells expressing OCT2 within a 10-3 to 10-7 M concentration range. Uptake competition experiments using fluorescent organic cation 4-(4-dimethylaminostyryl)-N-methylpyridinium (ASP+, 1 µM) and mass spectrometry (MS) to determine cellular platinum content indicated that OHP (100 µM) is an OCT2 substrate, mediating OHP cellular toxicity. ASP+ and MS analysis revealed dasatinib as a non-transported inhibitor of hOCT2 (IC50 = 5.9 µM) and as a regulator of OCT2 activity. Dasatinib reduced transporter Vmax, potentially via Y544 phosphorylation suppression. MS analysis showed cellular dasatinib accumulation independent of hOCT2. Although 3 µM dasatinib reduced 100 µM OHP accumulation in hOCT2-HEK293 cells, co-incubation with dasatinib and OHP did not prevent OHP toxicity, possibly due to dasatinib-induced cell viability reduction. In summary, this study demonstrates OHP as an OCT2 substrate and dasatinib as a non-transported inhibitor and regulator of OCT2, offering potential for OIPN mitigation.

Detection of inorganic arsenic in rice using a field-deployable method with Cola extraction.

Rice is a staple food and known to accumulate inorganic arsenic (iAs), which is a class 1 carcinogen to humans. Arsenic field-deployable method kits, designed for water testing, are able to screen iAs in rice, to assure food safety and quick decision-making without the need for laboratory analysis. For the arsenic extraction within the field method, nitric acid is used. To make the field method on-site safer, cost-effective and easier to handle, the method was adapted using a Cola in the extraction process. The adapted field-deployable method was tested by screening a total of 30 rice and rice products from the Austrian market. To verify the results obtained by the Cola extraction field-deployable method, the obtained iAs concentration was compared to HPLC-ICP-MS results. The Cola extraction field method obtained an LOD of 39 µg iAs kg-1 rice, and with an average reproducibility of 14% RSD, the method was capable of recording no false-negative but 7% false-positive values at the 2023 updated European Commission (EC) limits for rice. All, but one, screened rice samples were within the EU limits for iAs in rice and rice products.

Arsenic, cadmium, and lead in rice and rice products on the Austrian market.

Fifty-one rice samples, i.e. 25 rice varieties, 8 rice products, and 18 rice containing baby foods from the Austrian market were surveyed for arsenic, cadmium, and lead. Inorganic arsenic (iAs) is most toxic to human health, and its mean concentrations in rice were 120 µg kg-1, 191 µg kg-1 in rice products, and 77 µg kg-1 in baby foods. The average dimethylarsinic acid and methylarsonic acid concentrations were 56 µg kg-1 and 2 µg kg-1, respectively. The highest iAs concentration was found in rice flakes (237 ± 15 µg kg-1), close to the Maximum Level (ML) set by the EU regulation for husked rice (250 µg kg-1). The levels of cadmium (12 to 182 µg kg-1) and lead (6 to 30 µg kg-1) in the majority of rice samples were below the European ML. Upland grown rice from Austria showed both, low inorganic arsenic (<19 µg kg-1) and cadmium (<38 µg kg-1) concentrations.

Utility of Hounsfield unit in the diagnosis of tandem occlusion in acute ischemic stroke.

BACKGROUND: Tandem occlusions can complicate medical and endovascular stroke treatment. To identify these occlusions, computed tomography angiography (CTA) represents the best imaging modality. However, CTA is still not initially performed in some patients not admitted directly to stroke centers. Early identification of an additional occlusion of the proximal extracranial internal carotid artery may improve the best suitable treatment strategy. The purpose of this study was to find a valuable threshold of thrombus attenuation in a non-contrast head CT (NCCT) scan to facilitate a safe diagnosis of tandem occlusions. MATERIALS AND METHODS: Consecutive patients with acute middle cerebral artery (MCA) occlusions who underwent endovascular treatment were identified from our registry of neuroendovascular interventions. Thrombus attenuations of the affected MCA and contralateral vessel were measured by NCCT. To compare individual baseline blood attenuations, the difference between the thrombus attenuation and the contralateral MCA attenuation (referred to as ΔTM) was calculated. RESULTS: Three hundred and twenty-five patients were included. There was a highly significant difference between mean thrombus attenuation with isolated MCA occlusion and additional extracranial internal carotid artery (ICA) occlusion (49.9 ± 8 vs. 56.2 ± 10 Hounsfield units (HU); P < 0.001). The area under the receiver operating characteristic curve of ΔTM was 0.72. The optimal threshold value was 13.5 HU, with a sensitivity of 67.5% and a specificity of 68.6%. CONCLUSION: Despite a significant difference in thrombus attenuation in MCA occlusions with an additional extracranial ICA occlusion compared with isolated MCA occlusions, a relevant threshold of thrombus attenuation was not found.