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BACKGROUND AND PURPOSE Soluble epoxide hydrolase inhibitors (sEHIs) possess anti-inflammatory, antiatherosclerotic, antihypertensive and analgesic properties. The pharmacokinetics (PK) and pharmacodynamics in terms of inhibitory potency of sEHIs were assessed in non-human primates (NHPs). Development of a sEHI for use in NHPs will facilitate investigations on the role of sEH in numerous chronic inflammatory conditions. EXPERIMENTAL APPROACH PK parameters of 11 sEHIs in cynomolgus monkeys were determined after oral dosing with 0.3 mg·kg−1. Their physical properties and inhibitory potency in hepatic cytosol of cynomolgus monkeys were examined. Dose-dependent effects of the two inhibitors 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) and the related acetyl piperidine derivative, 1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl) urea (TPAU), on natural blood eicosanoids, were determined. KEY RESULTS Among the inhibitors tested, TPPU and two 4-(cyclohexyloxy) benzoic acid urea sEHIs displayed high plasma concentrations (>10 × IC50), when dosed orally at 0.3 mg·kg−1. Although the 4-(cyclohexyloxy) benzoic acid ureas were more potent against monkey sEH than piperidyl ureas (TPAU and TPPU), the latter compounds showed higher plasma concentrations and more drug-like properties. The Cmax increased with dose from 0.3 to 3 mg·kg−1 for TPPU and from 0.1 to 3 mg·kg−1 for TPAU, although it was not linear over this range of doses. As an indication of target engagement, ratios of linoleate epoxides to diols increased with TPPU administration. CONCLUSION AND IMPLICATIONS Our data indicate that TPPU is suitable for investigating sEH biology and the role of epoxide-containing lipids in modulating inflammatory diseases in NHPs. [ABSTRACT FROM AUTHOR]

The intrahepatic non-tumorous arterioportal shunt (APS) is one of the important causes of transient hepatic enhancement differences (THED) on dynamic CT or MRI. Most small APSs are located in the peripheral portion of the liver. Because of the parenchymal distortion in the advanced cirrhotic liver, many small APSs tend to show an amorphous or nodular appearance, making them difficult to distinguish from hypervascular tumors. In addition to the use of dynamic CT or MRI, iso-attenuation densities or iso-intensities on pre-contrast and equilibrium phases, MRI using a liver-specific contrast agent can be useful to characterize the hypervascular pseudolesions. Because there is no difference in water diffusion in the hepatic parenchyma in the region of the APS, diffusion-weighted MRI also has great potential to distinguish non-tumorous shunts from true focal lesions. Larger (>2 cm) APSs of direct arterio-portal venous fistulas from extrinsic insults show typical subcapsular wedge-like THEDs that are only temporarily depicted several months after the traumatic event; most of these THEDs gradually decrease in size or vanish completely. By understanding the nature of non-tumorous APSs, radiologists will be able to provide a more accurate assessment of many THEDs during daily interpretations of CT or MR images of the liver. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the natural history of transcatheter arterial chemoembolization (TACE)-induced, transient hepatic attenuation difference (THAD). Among the patients who underwent TACE for treatment of hepatocellular carcinomas during a 32-month period, 32 patients with 40 newly developed THADs defined as localized, transient, peripheral hepatic parenchymal enhancement during the hepatic arterial phase of dynamic CT (axial dimension, 1.9-8.8 cm; mean, 4.9 cm) in the vicinity of iodized-oil accumulation were subjected to a retrospective analysis of serial follow-up CT examinations. Among the 40 TACE-induced THADs, 18 (45%) and 9 (23%) were accompanied with arterial-portal venous fistula (APF) and portal venous stenosis (PVS), respectively, while 2 (5%) THADs showed both APF and PVS simultaneously. Thirty-eight (95%) THADs disappeared spontaneously during the follow-up period (range, 4-26 months; mean, 9 months), and 11 (29%) of them showed progressive atrophy of the corresponding hepatic parenchyma. Regardless of the presence of APF, 10 (91%) of 11 THADs of following parenchymal atrophy had shown PVSs (P<0.001). During the long-term follow-up period after TACE, almost all of the TACE-induced THADs spontaneously disappeared and either had or did not have corresponding parenchymal atrophy, which is strongly related to the presence of PVS. Understanding the nature of these CT features would be helpful for radiologists in determining the prognosis of the TACE-induced hepatic injuries as well as in distinguishing them from the recurrent tumour. [ABSTRACT FROM AUTHOR]

Ceramic liner fractures are rare after ceramic-on-ceramic THA. This article describes a case of an early ceramic liner fracture caused by impingement with a tilted acetabular screw head 2 months after cementless ceramic-on-ceramic THA. A 59-year-old man underwent primary THA for avascular necrosis of his right femoral head. The implant used was an Osteonics Secur-Fit HA ceramic-on-ceramic bearing system. The metal shell was fixed with 1 cancellous bone screw. During the index procedure, the acetabular screw seemed tilted in the metal shell hole, but the liner was fully seated in the metal shell without difficulty. However, 2 months later he re-presented due to pain and crepitation in the right hip. Radiographs taken at the time showed that the ceramic acetabular insert had fractured. At revision, ceramic insert had fractured into large and numerous comminuted fragments, and the acetabular screw head was slightly tilted and protruded over the inner surface of the metal shell, which had worn eccentrically. The ceramic inner head and metal shell were visibly intact. Because the metal shellDSbone fixation was firm, a new identical design ceramic liner and head were fitted, and no adverse event has occurred since. [ABSTRACT FROM AUTHOR]