Comparative analysis of two mathematical algorithms for the calculation of computed tomography perfusion parameters in the healthy and diseased pancreas.

BACKGROUND: The maximum slope (MS) and deconvolution (DC) algorithms are commonly used to post-process computed tomography perfusion (CTP) data. This study aims to analyze the differences between MS and DC algorithms for the calculation of pancreatic CTP parameters. METHODS: The pancreatic CTP data of 57 patients were analyzed using MS and DC algorithms. Two blinded radiologists calculated pancreatic blood volume (BV) and blood flow (BF). Interobserver correlation coefficients were used to evaluate the consistency between two radiologists. Paired t-tests, Pearson linear correlation analysis, and Bland-Altman analysis were performed to evaluate the correlation and consistency of the CTP parameters between the two algorithms. RESULTS: Among the 30 subjects with normal pancreas, the BV values in the three pancreatic regions were higher in the case of the MS algorithm than in the case of the DC algorithm (t = 39.35, p < 0.001), and the BF values in the three pancreatic regions were slightly higher for the MS algorithm than for the DC algorithm (t = 2.19, p = 0.031). Similarly, among the 27 patients with acute pancreatitis, the BV values obtained using the MS methods were higher than those obtained using the DC methods (t = 54.14, p < 0.001). Furthermore, the BF values were higher with the MS methods than the DC methods (t = 8.45, p < 0.001). Besides, Pearson linear correlation and Bland-Altman analysis showed that the BF and BV values showed a good correlation and a bad consistency between the two algorithms. CONCLUSIONS: The BF and BV values measured using MS and DC algorithms had a good correlation but were not consistent.

Improvement of pharmacokinetics behavior of apocynin by nitrone derivatization: comparative pharmacokinetics of nitrone-apocynin and its parent apocynin in rats.

Apocynin, a potent inhibitor of NADPH-oxidase, was widely studied for activities in diseases such as inflammation-mediated disorders, asthma and cardiovascular diseases. In our recent study, a novel nitrone derivative of apocynin, AN-1, demonstrated potent inhibition to oxidative injury and to high expression of gp91(phox) subunit of NADPH-oxidase induced by tert-butyl hydroperoxide (t-BHP) in RAW 264.7 macrophage cells, and displayed promising preclinical protective effect against lipopolysaccharide (LPS)-induced acute lung injury in rats. In this work, the pharmacokinetic behaviors of AN-1 in Sprague-Dawley rats with single intravenous and intragastric doses were investigated for further development. Furthermore, apocynin's pharmacokinetics remain lacking, even though its pharmacological action has been extensively evaluated. The pharmacokinetics of parent apocynin were also comparatively characterized. A simple HPLC method was developed and validated to determine both AN-1 and apocynin in rat plasma. The chromatographic separation was achieved on an Agilent HC-C18 column (250 mm×4.6 mm, 5 µm) at an isocratic flow rate of 1.0 mL/min, with the mobile phase of methanol and water (53∶47, v/v) and the UV detection set at 279 nm. Good linearity was established over the concentration range of 0.1-500 µg/mL for AN-1 and 0.2-100 µg/mL for apocynin. The absolute recovery, precision and accuracy were satisfactory. Compared with the parent compound apocynin, AN-1 yielded a much longer T1/2 (AN-1 179.8 min, apocynin 6.1 min) and higher AUC0-t (AN-1 61.89 mmol/L·min, apocynin 2.49 mmol/L·min) after equimolar intravenous dosing (0.302 mmol/kg). The absolute bioavailability of oral AN-1 was 78%, but that of apocynin was only 2.8%. The significant improvement of pharmacokinetic behavior might be accounted for the effective pharmacodynamic results we documented for the novel nitrone derivative AN-1.