Topographic and zonal distribution of tenascin in human articular cartilage from femoral heads: normal versus mild and severe osteoarthritis

AbstractObjective: The extracellular matrix glycoprotein tenascin (TN) is upregulated in articular cartilage with severe osteoarthritis (OA). This study gives a detailed description of TN expression in areas of articular cartilage from femoral heads with mild OA showing structural lesions and in structurally normal areas of the same femoral heads compared with normal cartilage and cartilage with severe OA.Methods: Immunohistochemical evaluation was performed on cryosections stained with antibodies against TN. Sections were selected as follows: from each macroscopically normal femoral head (n=6) a normal central and peripheral biopsy; from each femoral head with macroscopically mild OA (n=8) a central biopsy that showed structural lesions and a peripheral normal biopsy; from each femoral head with severe OA (n=9) a central and a peripheral biopsy with structural lesions. Central biopsies represent load bearing areas, whereas peripheral biopsies are non-load bearing.Results: Central cartilage with mild OA contains significantly higher levels of TN in the superficial zone than structurally normal, peripheral cartilage from the same femoral heads. Normal cartilage and cartilage with severe OA do not display this topographic variation. Central cartilage with mild OA shows significantly higher levels of TN than normal, central cartilage. Peripheral, normal cartilage with mild OA shows significantly less TN than peripheral cartilage with severe OA.Conclusions: In femoral heads with mild OA, TN is accumulated in areas displaying structural damage. This proposes mild OA to be a localized disorder. Extreme caution is necessary for sampling of articular cartilage, especially from joints with mild OA

Insulin Degludec in Clinical Practice: A Review of Japanese Real-World Data

Article full text The full text of this article can be found here. Provide enhanced digital features for this article If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact [email protected]. The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content. Other enhanced features include, but are not limited to: • Slide decks • Videos and animations • Audio abstracts • Audio slides</p

Efficacy and safety of once‐daily insulin degludec dosed flexibly at convenient times vs fixed dosing at the same time each day in a Japanese cohort with type 2 diabetes: A randomized, 26‐week, treat‐to‐target trial

AIMS/INTRODUCTION: This trial assessed the efficacy and safety of the possibility of varying the daily injection time of once‐daily, long‐acting basal insulin degludec (IDeg) in Japanese patients with type 2 diabetes inadequately controlled with insulin glargine. MATERIALS AND METHODS: This was a 26‐week, multicenter, open‐label, randomized, treat‐to‐target trial, with a 2 × 2 factorial design comparing IDeg flexible (allowing dosing ±8 h from an agreed dosing time) with IDeg fixed dosing (at the same time each day). It was carried out in 458 adult patients who were inadequately controlled on insulin glargine with or without oral antidiabetic drugs. RESULTS: The majority of doses were taken within 2 h of the agreed dosing time, showing a high level of adherence among Japanese patients. After 26 weeks, IDeg flexible was non‐inferior to IDeg fixed with respect to change in glycated hemoglobin from baseline, estimated treatment difference 0.08% points (95% confidence interval −0.05; 0.22). Fasting plasma glucose decreased to a similar level with IDeg flexible and IDeg fixed, estimated treatment difference −0.18 mmol/L (95% confidence interval −0.48; 0.12). The rates of confirmed and nocturnal confirmed hypoglycemia were numerically, but not significantly, higher with IDeg flexible vs IDeg fixed dosing. The rates of adverse events with IDeg flexible and IDeg fixed dosing were similar. CONCLUSIONS: These results showed the efficacy and safety of allowing patients to vary the time they dosed IDeg, when necessary, in Japanese patients with type 2 diabetes. Dosing of IDeg at a time convenient to the patient was non‐inferior, with respect to glycated hemoglobin, to dosing at the same time each day