Additional experiments were performed following pre-treatment with the P-glycoprotein modulator tariquidar.
Results: [C-11]quinidine was metabolized rapidly, whereas [C-11]laniquidar was more stable. Brain concentrations of both radiotracers remained at relatively low levels at baseline conditions. Tariquidar pre-treatment resulted in significant increases of [C-11]quinidine and [C-11]laniquidar brain concentrations. In the epileptic EPZ004777 solubility dmso subgroup “”non-responders”", brain uptake of [C-11]quinidine in selected brain regions reached higher levels than in electrode-implanted control rats. However, the relative response to tariquidar did not differ
between groups with full blockade of P-glycoprotein by 15 mg/kg of tariquidar. For [C-11]laniquidar differences between epileptic and control animals were only evident at baseline conditions but not after tariquidar
pretreatment.
Conclusions: We confirmed that both [C-11]quinidine and [C-11]laniquidar are P-glycoprotein substrates. At full P-gp blockade, tariquidar pre-treatment only demonstrated slight differences for [C-11]quinidine between drug-resistant and drug-sensitive animals. (C) 2013 Elsevier Inc. All rights reserved.”
“Objective: Computed tomography (CT) scans are routinely used for graft surveillance in patients who have had endovascular repair (EVAR) of an abdominal aortic aneurysm. There is a growing concern for cancers associated with inadvertent use of CT scans. We report the estimated risk of radiation associated solid organ malignancy caused by routine surveillance CT after
EVAR using the Biological AG-120 chemical structure Effects of Ionizing Radiation (BEIR VII) model created by U.S. National Institute of Science and National Research Council.
Methods: Our study estimated the excess relative risk (ERR) of a patient acquiring a solid organ malignancy secondary to radiation exposure from postoperative EVAR surveillance CT imaging. The radiation dose was calculated in sieverts (Sv). The ERR of solid organ malignancy, as given by the BEIR VII model, is = beta(s) D exp gamma e* (a/60)(n), where beta(s), gamma, and eta are data-derived parameters, SSR128129E e is age at exposure, and e* = (e-30)/10 for e < 30 and zero for e >= 30, a is attained age, and D is dose in sieverts. Dose-weighted ERRs were calculated to allow a comparison of malignancy risk when using a CT at all time points (model 1: 0, 1, 6, 12, and 18 months, 2, 3, and 4 years, and yearly thereafter) vs replacing the CT scan with two other models (model 2: CT once in 3 years) and (model 3: CT once in 5 years). The risk was stratified by age groups, sex, and use of two different radiation doses (15 or 31 mSv) per CT scan. Statistical analysis used the paired t test.
Results: There were significant differences between the ERR of solid organ malignancy in those patients who would undergo surveillance CTs at all time points vs those whose surveillance consisted of alternative modalities at some time points (P < .0001).