Quantitative X-ray microradiography for high-throughput phenotyping of osteoarthritis in mice.

OBJECTIVE: To investigate and validate digital X-ray microradiography as a novel, high-throughput and cost-effective screening approach to identify abnormal joint phenotypes in mice. METHOD: Digital X-ray microradiography was used to quantify the subchondral bone mineral content (BMC) in the medial tibial plateau. Accuracy and reproducibility of the method were determined in 22 samples from C57BL/6(B6Brd;B6Dnk;B6N-Tyr(c-Brd)) wild-type mice. The method was then validated in wild-type mice that had undergone surgical destabilisation of medial meniscus (DMM) and in a genetically modified mouse strain with an established increase in trabecular bone mass. RESULTS: The measurement of subchondral BMC by digital X-ray microradiography had a coefficient of variation of 3.6%. Digital X-ray microradiography was able to demonstrate significantly increased subchondral BMC in the medial tibial plateau of male mice 4 and 8 weeks after DMM surgery and in female mice 8 weeks after surgery. Furthermore, digital X-ray microradiography also detected the increase in subchondral BMC in a genetically modified mouse strain with high trabecular bone mass. CONCLUSION: Quantitation of subchondral BMC by digital X-ray microradiography is a rapid, sensitive and cost-effective method to identify abnormal joint phenotypes in mice of both genders at several ages.

Comparative bioavailability of sustained-release and uncoated aspirin tablets.

Plasma salicylate concentrations during multiple-dose administration of an uncoated and a sustained-release aspirin preparation were compared. Eight healthy adult subjects were given aspirin 2.6 g/day as sustained-release and uncoated tablets in two and four divided doses, respectively, for five-day periods in a crossover design. Treatment regimens were compared on the basis of five plasma salicylate concentrations measured during the fourth and fifth days of drug administration. Although there was considerable intersubject variation, no significant differences in salicylate concentrations (p less than or equal to 0.05) were found between treatments at any sampling time using the Wilcoxon signed-rank test or analysis of variance. Sustained-release aspirin preparations are capable of producing plasma salicylate concentrations comparable with those produced by uncoated aspirin tablets administered more frequently.