Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

BACKGROUND/AIMS: Only moderate to severe Crohn's Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria. METHODS: A retrospective analysis was conducted in nine medical centers in Taiwan and we collected the results of CD patients receiving adalimumab from Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI (Crohn's Disease Activity Index), adverse events and survival status were recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI decrease of 70, 100 or 150 points compared with baseline. RESULTS: A total of 103 CD patient records were used in this study. Sixty percent of these patients received combination therapy of adalimumab together with immunomodulators. CR-70 was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of patients, respectively. In considering the mucosal healing, only 25% patients achieve mucosal healing after treatment for 6 to12 months. Surgery was still needed in 16.5% of patients. Combination treatment of adalimumab with immunomodulators further decreased the level of CDAI at week 8 when compared with the monotherapy. CONCLUSIONS: Even under the stringent criteria for using adalimumab, the response rate was comparable to those without stringent criteria.

Aquaporin-1 and aquaporin-3 expressions in the temporo-mandibular joint condylar cartilage after an experimentally induced osteoarthritis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Over 70% of the total tissue weight in the cartilage matrix consists of water, and the early-stage osteoarthritic cartilage is characterized by swelling. Water transport in the cartilage matrix and across the membranes of chondrocytes may be important in normal and pathological conditions of cartilage. The purpose of this study was to identify aquaporin-1 (AQP1) and aquaporin-3 (AQP3) expressions in the mandibular condylar cartilage after experimentally induced osteoarthritis (OA) in rats.</p><p><b>METHODS</b>An experimental temporomandibular joint OA was induced by partial discectomy in rats. The pathological characteristics of the normal, early-stage, and late-stage osteoarthritic TMJ cartilages were verified by histological techniques. The AQP1 and AQP3 gene expressions in the normal and osteoarthritic cartilages were measured using quantitative real-time reverse-transcription PCR analysis. The cartilage sections were incubated in primary polyclonal antibodies to AQP3; immunofluorescent microscopy was used to examine the AQP3 expression shown by its protein level.</p><p><b>RESULTS</b>The mRNA expression levels of AQP1 and AQP3, analyzed using quantitative PCR, revealed that AQP3 mRNA was highly up-regulated in the OA cartilage, which was considered significant. There was no notable difference in the expression of AQP1 mRNA between OA and normal controls. With the progressing of the OA, the localization of the AQP3 protein was quite different from that of the normal cartilage. Compared to the normal cartilage, the expressions of AQP3 protein were observed mainly in the proliferative zone and the upper mid-zone chondrocytes at the early-stage of OA, and were observed to appear frequently throughout the mid- and deep zone during the late-stage of OA.</p><p><b>CONCLUSIONS</b>The high expression of AQP3 mRNA in the OA cartilage and the different localization of the AQP3 protein suggest that it may play a particular role in OA pathogenesis. Further study of AQP3 function may provide new insight into the understanding of the molecular mechanisms underlying OA.</p>

Study on the characteristics of apoptosis in the condyles of osteoarthritic temporomandibular joints / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the characteristics of apoptosis in the condyles of osteoarthritic temporomandibular joints, and investigate its role in the pathogenesis of the disease.</p><p><b>METHODS</b>Temporomandibular joint osteoarthrosis model of rabbits was created by partial resection of joint disc. The animal models were sacrificed in the 15th day, the 1st month, the 2nd month, the 3rd month, the 4th month, the 5th month, and the 6th month chronologically. Then the pathological condyles were sectioned and detected with TUNEL method to investigate the apoptosis within the tissue.</p><p><b>RESULTS</b>In the reactive repairing state of osteoarthrosis, the apoptosis cells mainly located in the superficial fibrous layer of articular cartilage. With the remodeling of articular cartilage and bone, the apoptosis cells gradually appeared in the proliferating layer, especially in the "clusters of chondrocytes". Accompanied with the severe damage and loss of articular cartilage, the phenomena of apoptosis decreased in the lower zone of cartilage and increased in the hypertrophic and calcified zone.</p><p><b>CONCLUSION</b>There were abundant phenomena of apoptosis within the condylar cartilage of osteoarthritic temporomandibular joint. Abnormal proliferation and abundant apoptosis would disturb the regulation mechanism in the cartilage matrix and lead to the osteoarthrosis.</p>

Bone formation in vitro and in vivo by human bone marrow-derived mesenchymal stem cells / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To culture and study the osteogenic characteristics of human bone marrow-derived mesenchymal stem cells (hBMMSCs).</p><p><b>METHODS</b>hBMMSCs were separated and cultured from human iliac crest marrow. Growth kinetics of hBMMSCs was studied by growth curve. Under the osteoinductive culture, osteogenic differentiation of hBMMSCs was tested by alkaline phosphatase (ALP). Osteogenic functions of hBMMSCs in vitro and in vivo were also respectively detected by von Kossa stain and by transplanting hydroxyapatite/tricalcium phosphate ceramics (HA/TCP) with hBMMSCs.</p><p><b>RESULTS</b>hBMMSCs were cultured successfully. The growth curve of the second passage of BMMSCs indicated that the time of population doublings was about 3.5 days. The results of ALP stain were evident by the significant increase in ALP activity after hBMMSCs cultured in osteoinductive medium. Some mineralized nodules were detected by von Kossa stain at nineteenth day of osteoinductive culture. In vivo assay, histological evalution showed bone formation in 3 months after grafts of HA/TCP with hBMMSCs.</p><p><b>CONCLUSIONS</b>Osteoinductive solution can induce hBMMSCs to differentiate osteogenetic cell lines. Mineralized nodules and bone formation were found in vitro and in vivo assay. The results demonstrate that hBMMSCs have the potential for osteogenesis.</p>