Concentrations of indomethacin and its metabolite desmethylindomethacin in plasma and urine after repeated indomethacin topical application to Thoroughbreds.

BACKGROUND: Repeated topical application of indomethacin is common in Japanese racehorses, despite the lack of pharmacokinetic data. OBJECTIVES: To determine the concentrations of indomethacin and its metabolite, desmethylindomethacin, in plasma and urine of Thoroughbreds topically treated repeatedly with indomethacin. STUDY DESIGN: In vivo experimental. METHODS: Seven female Thoroughbreds were topically treated with 50 g of 1% indomethacin cream per horse to the back and hips (500 mg of indomethacin/head/2400 cm2 , 0.21 g/cm2 ) for 3 consecutive days. Samples were pretreated by protein precipitation for plasma and liquid-liquid extraction with ethyl acetate after hydrolysis with hydrochloric acid for urine. The concentrations of indomethacin and desmethylindomethacin in plasma and urine were measured by liquid chromatography-mass spectrometry. RESULTS: Indomethacin was quantifiable in plasma up to 48-72 h and in urine up to 96 h after the final application. Desmethylindomethacin was quantifiable in plasma up to 48 h and in urine up to 72-96 h after the final application. MAIN LIMITATIONS: The relationship between the local and systemic indomethacin concentrations after the topical application was not clarified. CONCLUSIONS: Pharmacokinetic data were acquired for repeated topical administration of 1% indomethacin cream to Thoroughbreds. Hydrolysing urine samples with hydrochloric acid was effective for the analysis of indomethacin and its metabolite, and indomethacin may be an excellent marker analyte for doping tests. The estimated withdrawal time based on the limit of detection was 342 h.

Endothelial and inflammatory markers in relation to progression of ischaemic cerebral small-vessel disease and cognitive impairment: a 6-year longitudinal study in patients with type 2 diabetes mellitus.

BACKGROUND: Progression of silent brain infarctions (SBIs) and white-matter lesions (WMLs) seen on brain MRI is associated with an increased risk of cognitive impairment, but their relation to endothelial and inflammatory markers is unknown in type 2 diabetes mellitus. METHODS: In 190 type 2 diabetic outpatients (mean age 62.7 years), the authors related baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1) and high-sensitivity C-reactive protein (hs-CRP) to subsequent brain MRI findings and cognitive function. The authors assessed incident SBIs and changes in periventricular and subcortical WMLs (PVWMLs and SCWMLs) on MRI performed at baseline and 3 and 6 years. Neuropsychological tests were administered to 83 patients older than 65 years at 6 years. This present study represents an extension of the authors' previously published study. RESULTS: SBIs were observed in 46 patients (24.2%), PVWMLs in 93 (48.9%) and SCWMLs in 87 (45.8%) on baseline MRI. After adjustment for age, gender, hypertension, duration of diabetes, baseline MRI findings and medication use, the relative odds associated with a 1SD increase in sICAM-1 levels at baseline were 1.67 (95% CI 1.02 to 3.05) for SBI progression and 2.17 (95% CI 1.29 to 3.62) for PVWML progression at 6 years. In contrast, baseline hs-CRP levels were significantly associated with SBI progression only at 3 years. Significant trends were observed between quartiles of sICAM-1 at baseline and scores in Digit Symbol substitution (p for trend=0.01). CONCLUSIONS: The findings suggest that higher sICAM-1 levels are associated with SBI and PVWML progression, and may predict impairment in psychomotor function in type 2 diabetes.

[Evaluation of CRT images of digitized film angiographs].

X-ray sheet film images of the test chart, the vascular phantom and angiography were digitized at sampling pitch of 0.2 mm and 0.15 mm using film digitizer TFR-01 (Toshiba) and transferred to a device for image storage and display system with 1635-line display monitor (TDF-500AS, Toshiba). Comparison of image qualities between film- and CRT-images was performed in fundamental and clinical studies. Resolution of the test chart image of conventional radiography was worse on CRT than on the original film, although it was improved when film image was digitized at resolution of 0.15 mm/pixel in comparison with that at resolution of 0.2 mm/pixel. Moiré stripes which occurred due to interference were found on CRT images taken using a grid technique. On CRT images of X-ray sheet film using direct magnification technique moiré stripes were not produced because of non grid technique, and the resolution approached that of the original film. In the study using vascular phantom, the optimal image on CRT could be obtained by various image processing procedures, and image quality on CRT with resolution of 0.15 mm approached that of original film. In case of direct magnification CRT images were superior to film images. Subtraction image of the vascular phantom at resolution of 0.2 mm/pixel was obtained on CRT and compared with film subtraction image. On conventional subtraction CRT image moiré stripes impaired the image quality in comparison with the film subtraction. However, magnification subtraction image of the vascular phantom on CRT was superior to the film subtraction. The results obtained in the test chart studies and phantom studies were also confirmed in clinical studies using various kind of angiograms. In addition, ROC study using clinical angiograms showed no significant statistical differences between the original film and CRT image even with 0.2 mm matrix size. Angiographic image on CRT at resolution of 0.15 mm/pixel or less is available for clinical use in place of conventional film image.

Ethyl 2-cyanoacrylate as an embolic agent for cranial arteriovenous malformations. An experimental study.

Physical properties of ethyl 2-cyanoacrylate (Aron Alpha) were studied in comparison with isobutyl 2-cyanoacrylate (IBCA). Aron Alpha is characterized by high viscosity, a short polymerization time, low spreadability and low fragmentability. On the other hand, IBCA had low viscosity, a relatively long polymerization time, high spreadability and high fragmentability. Based on these findings, it is suggested that IBCA is suitable for transcatheter embolization, and Aron Alpha for intraoperative embolization. Mixture of IBCA with 5% Aron Alpha suppressed the spreadability and the fragmentability of IBCA, resulting in reduction of distal migration of IBCA into the venous system.

[The comparative study of renogram both in case of dehydration and hydration (author's transl)].

In order to study the merit or demerit of the dehydration or hydration as the preparation of renographic examination, the following 25 cases--11 cases of uterine cancer, 2 cases of breast cancer, a case of esophageal cancer, pharyngeal cancer, maxillary cancer, salivary gland tumor, leiomyosarcoma of uterus and others are examined by renography using 131I-hippurate. Renogram is performed in case of patient's dehydration and followed in case of patient's hydration with 600 ml of water intake. Renographic findings such as Tmax, T1/2, HB/HA and step-like pattern are studied as a parameter. Following 600 ml water intake, Tmax is significantly shortened and the step-like pattern is disappeared. This study is strongly suggested that patient's hydration is significantly necessary in the performance of renogram as the preparatory procedure.