Repeated application of incremental landing impact loads to intact knee joints induces anterior cruciate ligament failure and tibiofemoral cartilage deformation and damage: A preliminary cadaveric investigation.

Anterior cruciate ligament (ACL) injury is a major problem worldwide and prevails during high-impact activities. It is not well-understood how the extent and distribution of cartilage damage will arise from repetitive landing impact loads that can lead to ACL failure. This study seeks to investigate the sole effect of repetitive incremental landing impact loads on the induction of ACL failure, and extent and distribution of tibiofemoral cartilage damage in cadaveric knees. Five cadaveric knees were mounted onto a material testing system at 70 degrees flexion to simulate landing posture. A motion-capture system was used to track rotational and translational motions of the tibia and femur, respectively. Each specimen was compressed at a single 10Hz haversine to simulate landing impact. The compression trial was successively repeated with increasing actuator displacement till a significant compressive force drop was observed. All specimens underwent ACL failure, which was confirmed via magnetic resonance scans and dissection. Volume analysis, thickness measurement and histological techniques were employed to assess cartilage lesion status. For each specimen, the highest peak compressive force (1.9-7.8kN) was at the final trial in which ACL failure occurred; corresponding posterior femoral displacement (7.6-18.0mm) and internal tibial rotation (0.6 degrees -4.7 degrees ) were observed. Significant compressive force drop (79.8-90.9%) was noted upon ACL failure. Considerable cartilage deformation and damage were found in exterior, posterior and interior femoral regions with substantial volume reduction in lateral compartments. Repeated application of incremental landing impact loads can induce both ACL failure and cartilage damage, which may accelerate the risk of developing osteoarthritis.

Van der Woude syndrome: a report of two cases.

Van der Woude syndrome is a rare autosomal dominant condition with high penetrance and variable expression. It consists of a cleft lip and/or palate pits on the vermilion of the lower lip, and hypodontia. Two cases of congenital lip pits with cleft lip and alveolus and an isolated cleft palate are described to illustrate the variable presentation of the clinical features and the importance of early recognition of Van der Woude syndrome because of the genetic implications.

3-Deazaadenosine analogues inhibit the production of tumour necrosis factor-alpha in RAW264.7 cells stimulated with lipopolysaccharide.

The effects of 3-deazaadenosine (DZA), 3-deaza(+/-)-aristeromycin (DZAri) and 3-deazaneplanocin (DZNep) on tumour necrosis factor-alpha (TNF-alpha) production were examined in the mouse macrophage cell line, RAW264.7, stimulated with lipopolysaccharide (LPS). The 3-deazaadenosine analogues inhibited the TNF-alpha production and the inhibition was dependent upon the concentration of the analogue. DZA reduced the level of TNF-alpha mRNA suggesting that DZA acts at a transcriptional step. In contrast, DZAri and DZNep had little effect on mRNA levels for TNF-alpha, implying that these compounds inhibit a post-transcriptional or translational biosynthetic step of TNF-alpha synthesis. The observation that homocysteine (Hcy) potentiated the DZA inhibition of TNF-alpha production and of TNF-alpha mRNA levels suggests that the inhibition of TNF-alpha production may be caused by elevated levels of 3-deazaadenosylhomocysteine (DZAHcy). The results show that the 3-deazaadenosine analogues are potent inhibitors of TNF-alpha production in the RAW264.7 cell line stimulated with LPS and suggest that these analogues may be effective agents for the treatment of diseases in which TNF-alpha plays an important pathogenic role.