Multiparametric assessment of acute and subacute ischemic neuronal damage: A small animal positron emission tomography study with rat photochemically induced thrombosis model

We evaluated sequential changes in rat brain function up to 14 days after focal ischemic insult with a small animal positron emission tomography (PET). Unilateral focal ischemic cerebral damage was induced by left middle cerebral artery occlusion with a photochemically induced thrombosis (PIT) method. PET scans were conducted with [¹¹C](R)‐PK11195 ([¹¹C](R)‐PK) for peripheral benzodiazepine receptor (PBR), [¹¹C]flumazenil ([¹¹C]FMZ) for central benzodiazepine receptor (CBR), and [¹⁸F]fluoro‐2‐deoxy‐D ‐glucose ([¹⁸F]FDG) for glucose metabolism at before (as “Normal”) and after PIT. At 1 and 3 days after PIT, [¹⁸F]FDG indicated lower uptake in the infarct area. Interestingly, unexpectedly high‐[¹⁸F]FDG uptake was observed in the peri‐infarct area surrounding the infarct area at day 7. The high‐[¹⁸F]FDG uptake region completely overlapped with the high‐[¹¹C](R)‐PK uptake region at day 7, which resulted in the underestimation of neuronal damage. Immunohistochemical data also suggested that the high‐[¹⁸F]FDG uptake peak at day 7 was caused by inflammation including microglial cell activation. In contrast, imaging with [¹¹C]FMZ indicated cortical neuronal damage on days 7 and 14 without any disturbance by microglial formation. These results indicated that [¹⁸F]FDG might not be a suitable ligand for ischemic neuronal damage detection from acute to subacute phases. Synapse, 2010. © 2010 Wiley‐Liss, Inc.     

Ultrasonic probe is useful for in vivo quantitative assessment of medial femoral condyle articular cartilage

Purpose  

Although objective evaluation of articular cartilage is important for assessing the outcome of surgical treatment, no reliable method has yet been developed. It has recently been reported that quantitative ultrasound is applicable for assessment of living human cartilage. The purpose of this study was to investigate whether quantitative ultrasound is able to detect subtle changes in articular cartilage, as well as age-related changes in normal cartilage during arthroscopic surgery.     

Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate

Objective

To compare the efficacy, safety, and tolerability of 4 doses of oral tofacitinib (CP‐690,550) with placebo in Japanese patients with active rheumatoid arthritis (RA) receiving stable background methotrexate (MTX) who had an inadequate response to MTX alone.

Methods

A total of 140 patients were randomized to receive tofacitinib 1, 3, 5, and 10 mg twice a day or placebo in this 12‐week, phase II, double‐blind study. All patients remained on background MTX. Efficacy and safety were assessed at weeks 1, 2, 4, 8, and 12. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12.

Results

ACR20 response rates at week 12 were significant (P < 0.0001) for all tofacitinib treatment groups: 1 mg twice a day, 64.3%; 3 mg twice a day, 77.8%; 5 mg twice a day, 96.3%; and 10 mg twice a day, 80.8% versus placebo, 14.3%. A significant dose‐response relationship for the ACR20 was observed (P < 0.0001). Low disease activity was achieved by 72.7% of patients with high baseline disease activity for tofacitinib 10 mg twice a day at week 12 (P < 0.0001). Significant improvements in the ACR50, ACR70, Health Assessment Questionnaire Disability Index, and Disease Activity Score 28‐3 (C‐reactive protein) were also reported. The most commonly reported adverse events (AEs) were nasopharyngitis (n = 13) and increased alanine aminotransferase (n = 12) and aspartate aminotransferase (n = 9) levels. These AEs were mild or moderate in severity. Serious AEs were reported by 5 patients. No deaths occurred.

Conclusion

In Japanese patients with active RA with an inadequate response to MTX, tofacitinib in combination with MTX over 12 weeks was efficacious and had a manageable safety profile.     

Endovascular coil embolization for ruptured aneurysm associated with persistent primitive anterior choroidal artery--case report

An 18-year-old man presented with a rare case of a ruptured internal carotid artery (ICA)-persistent primitive anterior choroidal artery (PPAchA) manifesting as sudden onset of headache. Computed tomography (CT) showed subarachnoid hemorrhage. Three-dimensional CT angiography showed a saccular aneurysm at the right ICA-AchA region. Right internal carotid angiography showed a PPAchA and saccular aneurysm. Endovascular treatment of the aneurysm achieved complete aneurysm occlusion.     

Construction of osteochondral-like tissue graft combining β-tricalcium phosphate block and scaffold-free centrifuged chondrocyte cell sheet

Background  

The combination of a β-tricalcium phosphate (βTCP) block with a scaffold-free chondrocyte sheet formed by the centrifugation of chondrocytes in a well was investigated with the aim of constructing an osteochondral-like structure.