A simple and sensitive method for the determination of fibric acids in the liver by liquid chromatography.

Fibrates are used in biochemical and pharmacological studies as bioactive tools. Nevertheless, most studies have lacked information concerning the concentrations of fibric acids working inside tissues because a simple and sensitive method is not available for their quantitation. This study aimed to develop a simple and sensitive bioanalytical method for the quantitation of clofibric, bezafibric and fenofibric acids in samples of very small portions of tissues. Fibric acids were extracted into n-hexane-ethyl acetate from tissue homogenates (10 mg of liver, kidney or muscle) or serum (100 µL) and were derivatized with 4-bromomethyl-6,7-dimethoxycoumarin, followed by HPLC with fluorescence detection. These compounds were separated isocratically on a reversed phase with acetonitrile-water. Standard analytical curves were linear over the concentration range of 0.2-20 nmol/10 mg of liver. Precision and accuracy were within acceptable limits. Recovery from liver homogenates ranged from 93.03 to 112.29%. This method enabled the quantitation of fibric acids in 10 mg of liver from rats treated with clofibric acid, bezafibric acid or fenofibrate. From these analytical data, it became clear that there was no large difference in ratio of acyl-CoA oxidase 1 (Acox1) mRNA level to fibric acid content in the liver among the three fibric acids, suggesting that these three fibric acids have similar potency to increase expression of the Acox1 gene, which is a target of peroxisome proliferator-activated receptor α. Thus, the proposed method is a simple, sensitive and reliable tool for the quantitation of fibric acids working in vivo inside livers.

Fibrates reduce triacylglycerol content by upregulating adipose triglyceride lipase in the liver of rats.

Hepatic triacylglycerol (TAG) homeostasis is maintained by carefully regulated balance between its synthesis and disposal. Impairment in this balance causes steatosis. The aims of this study were i) to uncover whether fibrates control TAG concentration through the action of adipose triglyceride lipase (ATGL) and ii) to compare the potency of the effects on ATGL expression and TAG concentration among fenofibrate, bezafibrate, and clofibric acid in the liver of rats. Treatments of rats with the three fibrates induced ATGL and concomitantly decreased hepatic TAG concentration. The upregulation of ATGL was likely mediated through the activation of peroxisome proliferator-activated receptor α. Fibrates also expanded capacity of fatty acid ß-oxidation. Importantly, three fibric acids (fenofibric, bezafibric, and clofibric acids) that are active metabolites formed in the liver exhibited almost the same potency to elevate ATGL expression in vivo, despite the fact that there were considerable differences in this regard among fenofibrate, bezafibrate, and clofibric acid when compared on the basis of their dosage. These results suggest that ATGL represents a potential therapeutic target for ameliorating hepatic steatosis and that fibric acids are promising agents to ameliorate and/or protect against hepatic steatosis.

Correction to: Causes, background, and characteristics of binocular diplopia in the elderly.

In the original publication, the second paragraph under the heading "Results" has been mistakenly published as.

Causes, background, and characteristics of binocular diplopia in the elderly.

PURPOSE: We evaluated the background and characteristics of elderly patients with binocular diplopia including diseases caused by abnormalities in orbital pulleys. STUDY DESIGN: Retrospective. METHODS: The participants were 236 patients aged 60 years or older who visited Kitasato University Hospital complaining of binocular diplopia. We classified strabismus by types and investigated the causes for each group. We diagnosed orbital pulley disorders using magnetic resonance imaging (MRI). Patients with orbital pulley disorders exhibited esotropia and/or vertical strabismus and did not present with cranial nerve palsy, systemic illness, or ocular injury. RESULTS: Classification of strabismus types was: exotropia (24.2%); esotropia (25.0%); vertical strabismus (30.1%), combined strabismus (20.8%). There were 50.9% cases of strabismus associated with vertical deviation. The causes of disease in each group were as follows: in the exotropia group, 50.9% convergence insufficiency exotropia, 21.1% basic exotropia; in the esotropia group: 35.6% orbital pulley disorder 33.9% sixth cranial nerve palsy; in the vertical strabismus group: 32.4% forth cranial nerve palsy, 31.0% orbital pulley disorder; in the combined strabismus group: 28.6% orbital pulley disorder, 28.6% forth cranial nerve palsy. CONCLUSIONS: About half of the elderly patients with binocular diplopia exhibited vertical deviation. In addition, binocular diplopia was often caused by orbital pulley disorders. It is the first epidemiological study focusing on orbital pulley disorders diagnosed on the basis of MRI.

Diagnostic Ability and Repeatability of a New Supra-Threshold Glaucoma Screening Program in Standard Automated Perimetry.

PURPOSE: We assess the diagnostic ability and repeatability of a new suprathreshold glaucoma screening test (GST) comprising 28 test points and a 1-of-3 sampling strategy at 95% of the normal limit for standard automated perimetry (SAP) in early to advanced glaucoma. METHODS: This prospective cross-sectional study included 96 eyes of patients with early, moderate, or advanced glaucoma and 37 eyes of normal controls. Participants were evaluated by the G-Dynamic threshold test once and the GST twice, in random order, using the Octopus 600 perimeter. The diagnostic ability of GST was assessed by comparison with the G-Dynamic threshold obtained by receiver operating characteristic analysis. Repeatability was assessed by κ statistics for agreement on glaucoma diagnosis and each test point. RESULTS: Although the G-Dynamic test exhibited significantly higher areas under the curve (AUC) than the GST1st (P = 0.009) in early glaucoma, there were no significant differences in any other AUCs between the two methods. The κ values for repeatability of glaucoma diagnosis and each test point were 0.747 to 1.0 and 0.537 to 1.0, respectively. The duration of the GST in the control and early glaucoma groups was less than a minute, while that in the moderate and advanced glaucoma groups was within 1.5 minutes. CONCLUSION: The diagnostic ability of the new suprathreshold GST for early to advanced glaucoma was high, with moderate to strong repeatability and short test duration. TRANSLATIONAL RELEVANCE: There currently are no prominent suprathreshold screening strategies using SAP. The GST would be an effective clinical method for glaucoma screening.