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Background and Purpose: Aspirin eugenol ester (AEE) is a new drug compound synthesized by combining aspirin with eugenol. It was reported to possess anti‐thrombotic, anti‐atherosclerotic, and anti‐oxidative effects. However, its molecular mechanism against oxidative injury is unclear. This study investigated how AEE affected the oxidative injury of vascular endothelial cells in vivo and in vitro. Experimental Approach A hamster model of atherosclerosis induced by a high fat diet (HFD) and an in vitro model of oxidative stress, H2O2‐induced apoptosis of HUVECs, were used to investigate the anti‐oxidative effects of AEE. Key Results: AEE significantly reduced the stimulatory effect of HFD on malondialdehyde, the inhibitory effect of HFD on SOD activity and GSH/GSSG ratio, and the overexpression of inducible NOS (iNOS) in the aorta. In vitro, incubation of HUVECs with H2O2 led their apoptosis, dysfunctions of the NO systems (including increased iNOS activity, decreased endothelial NOS activity, and increased production of NO), an imbalance in calcium homeostasis and energy metabolism with an increase in intracellular free calcium and decrease in ATP, and a down‐regulation of Nrf2. In contrast, in the HUVECs pretreated with 1 μM AEE for 24 hr, the above adverse effects induced by H2O2 were significantly ameliorated. Moreover, the decrease in NO production and activity of iNOS induced by AEE was significantly attenuated in Nrf2‐inhibited HUVECs. Conclusion and Implication: AEE protects vascular endothelial cells from oxidative injury by regulating NOS and Nrf2 signalling pathways. This suggests that AEE is a novel potential agent for the prevention of atherosclerosis. [ABSTRACT FROM AUTHOR]

A rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify tilmicosin in pig plasma. Plasma samples were prepared by liquid-liquid extraction. Chromatographic separation was achieved on a C18 column (2.1 × 30 mm, 3.5 μm) using acetonitrile-water (90:10, v/v; water included 0.1% formic acid) as the mobile phase. Mass detection was carried out using positive electrospray ionization in multiple reaction monitoring mode. The calibration curve was linear from 0.5 to 2000 ng/mL ( r2 = 0.9998). The intra- and inter-day accuracy and precision were within the acceptable limits of ±10% for all tilmicosin concentrations. The recoveries ranged from 95 to 99% for the three tested concentrations. The LC-MS/MS method described herein was simple, fast and less laborious than other methods, achieved high sensitivity using a small sample volume, and was successfully applied to pharmacokinetic studies of tilmicosin enteric granules after oral delivery to pigs. In comparison with tilmicosin premix, tilmicosin enteric granules slowed the elimination rate of tilmicosin, prolonged its period of action and significantly improved its bioavailability. [ABSTRACT FROM AUTHOR]

Early and accurate noninvasive means of identifying right ventricular ( RV) dysfunction in children with tetralogy of Fallot ( TOF) are needed. RV function was examined using tissue Doppler imaging ( TDI), strain rate ( SR), and strain analysis ( SA) in children before ( N = 37) and after (6-12 months; N = 32) TOF repair, and in a control group of children ( N = 37). Plasma concentrations of N-terminal pro-brain natriuretic peptide ( NT- proBNP) and matrix metalloproteinase 9 ( MMP-9) were measured. TDI, SR, and SA revealed that RV systolic and diastolic function indices were lower preoperatively in the TOF group compared with the control group, and did not improve after TOF repair. Plasma NT- proBNP concentrations were significantly higher in the TOF group pre- and postoperatively compared with the control group. In the preoperative TOF group, NT- proBNP concentration was significantly correlated with peak systolic SR and systolic strain in the mid segments of RV free wall. Plasma MMP-9 concentrations were significantly increased in the preoperative TOF group compared with the control group, and significantly correlated with plasma NT- proBNP and logNT- proBNP concentrations. RV function correlated with plasma NT- proBNP concentrations in children with TOF. Assessment of this noninvasive measure may help identify RV dysfunction in patients with TOF before they become clinically symptomatic. [ABSTRACT FROM AUTHOR]

An LC–MS/MS method with internal standard tolfenamic acid for determining diclofenac sodium (DCF) in dairy cow plasma was developed and validated. Samples were processed with protein precipitation by cold formic acid–acetonitrile. Determination of DCF was performed using LC–ESI+–MS/MS with the matrix‐matched calibration curve. The results showed that the method was sensitive (LOD 2 ng mL−1, LOQ 5 ng mL−1), accurate (97.60 ± 5.64%), precise (<10%) and linear in the range of 5–10,000 ng mL−1. A single intravenous (i.v.) or intramuscular (i.m.) administration of 5% diclofenac sodium injection at a dose of 2.2 mg kg−1 was performed in six healthy dairy cows according to a two‐period crossover design. The main pharmacokinetic (PK) parameters after a single i.v. administration were as follows: t1/2β, 4.52 ± 1.71 h; AUC, 77.79 ± 16.76 h μg mL−1; mean residence time, 5.16 ± 1.11 h. The main PK parameters after a single i.m. administration were as follows: Tmax, 2.38 ± 1.19 h; Cmax, 7.46 ± 1.85 μg mL−1; t1/2β, 9.46 ± 2.86 h; AUC 67.57 ± 13.07 h μg mL−1. The absolute bioavailability was 87.37 ± 5.96%. The results showed that the diclofenac sodium injection had PK characteristics of rapid absorption and slow elimination, and high peak concentration and bioavailability in dairy cows, and that the recommended clinical dosage of diclofenac sodium injection is 2.2 mg kg−1. [ABSTRACT FROM AUTHOR]

There are two independent and conformationally dissimilar mol-ecules (A and B) in the asymmetric unit of the title compound, C11H6F3N3O3S; the dihedral angles between the benzene and thia-zole rings are 33.8 (2)° in A and 59.7 (2)° in B. The similarity of the C-N bond lengths in the amide group [1.379 (5) and 1.358 (5) Å for A, and 1.365 (5) and 1.363 (5) Å for B] indicates the presence of conjugation between the two rings. In the crystal, mol-ecules are linked by N-H⋯N hydrogen bonds, forming chains extending along [010]; weak N-H⋯Oamide inter-actions are also present in the structure.

The title compound, C(10)H(5)ClF(2)N(2)OS, was obtained by linking an amino heterocycle and a substituted benzoyl chloride. The dihedral angle between the two rings is 41.2 (2)° and the equalization of the amide C-N bond lengths reveals the existence of conjugation between the benzene ring and the thia-zole unit. In the crystal, pairs of N-H⋯N hydrogen bonds link mol-ecules into inversion dimers. Non-classical C-H⋯F and C-H⋯O hydrogen bonds stabilize the crystal structure.

In the title compound, C(19)H(18)O(5), the ester group is twisted with respect to the acetyl-salicylic acid and eugenol rings at dihedral angles of 22.48 (2) and 81.07 (1)°, respectively. The dihedral angle between the two benzene rings is 60.72 (1)°. The crystal packing exhibits no significantly short inter-molecular contacts.

The title compound, C(11)H(13)ClO(3), has been obtained in the reaction of 2, 4-dihydroxy-lacetonephenone, potassium carbonate and 1-bromo-3-chloro-hexane. The hydr-oxy group is involved in an intra-molecular O-H⋯O hydrogen bond. The crystal packing exhibits no significantly short inter-molecular contacts.