2-Benzisothiazolylimino-5-benzylidene-4-thiazolidinones as protective agents against cartilage destruction.

We report the synthesis, the antioxidant and the inhibitory activity (IC50) on metalloproteinases (MMPs) 3 and 13 of 2-benzo[d]isothiazolylimino-5-benzylidene-4-thiazolidinones. Their potential as protective agents in osteoarthritis (OA) was evaluated by biological assays on chondrocytes cultures, stimulated by IL-1ß. The chondroprotective capability, related both to antioxidant activity and to inhibition of MMPs, was studied in vitro, by determining nitric oxide production and glycosaminoglycans release. Moreover, selected derivatives 1h and 1g was studied for nuclear factor kappaB (NF-κB) inhibition by Western Blot analysis and for MMP-3 protein release using ELISA test. The structure-activity relationship of tested compounds demonstrates a favorable effect of the para substitution on the 5-benzilydene ring. Compound 1g shows a potent and selective activity on MMP-3 versus MMP-13. Accordingly, 1g possesses high antioxidant effect, NO lowering and GAGs restoring capability and also reduces the production of MMPs and NF-κB expression. Thus 1g can be considered as new potential chondroprotective agents.

Treatment of Developmental Dysplasia of Hip With Tubingen Hip Flexion Splint.

BACKGROUND: Developmental dysplasia of the hip is an anomaly of the hip joint. In patients with early diagnosis, within 3 to 6 months of life, the treatment is essentially conservative and involves the use of dynamic harness. The indication for the use of the Tubingen hip flexion splint is a dysplastic hip. The aim of this study is to report the experience of the Orthopaedic Clinic of the "University of Catania" regarding conservative treatment with the Tubingen harness of dysplastic hips diagnosed in children within 3 months of life. METHODS: From January 1997 to July 2012, 5137 infants (10,274 hips) aged within 3 months of life were submitted to ultrasonographic hip assessment. Start, duration of treatment, and outcome were investigated. RESULTS: A total of 351 (6.83%) patients affected by developmental dysplasia of the hip for a total of 544 dysplastic hips (5.3%) were treated with the Tubingen hip flexion splint. Treatment was started on average 39 days of life. Harness were dressed for 24 hours a day and applied for a mean of 3.8 months. Mean follow-up was 6.4 years (range, 2.2 to 14 y). We obtained the following results: 482 (90.44%) dysplastic, unstable, or dislocated hips were successfully converted into type I hips with an α-angle of >64 degrees in the splint. Complications were reported in 3 (0.55%) hips.No statistically significant relationship was found between the duration of therapy and the time when treatment was started, early or late within the first week of life (P=0.152). CONCLUSIONS: Dysplastic, unstable, and dislocated hips can be successfully treated with the Tubingen hip flexion splint, reporting good clinical and ultrasonographic outcomes.

Hypophosphatemic rickets: etiology, clinical features and treatment.

Hypophosphatemic rickets (HR) is a genetic disorder, which prevents sufficient reabsorption of phosphate in the proximal renal tubule, with increased phosphate excretion, resulting in rickets. The more common form of HR is an X-linked inherited trait, with a prevalence of 1/20,000. The defective gene is located on the X chromosome, but females may present with a wide variety of clinical manifestations. The less common form of HR is caused by autosomal-dominant transmission. Activating mutations of the fibroblast growth factor 23 (FGF-23) gene and inactivating mutations in the phosphate regulating gene (PHEX gene with homologies to endopeptidases on the X chromosome), involved in the regulation of FGF-23, have been identified and have been implicated in the pathogenesis of these disturbances. A review of etiopathogenesis and clinical, differential diagnostic and therapeutic aspects of HR, with a particular emphasis on bone impairment, is reported.

The natural history of focal fibrocartilaginous dysplasia in the young child with tibia vara.

BACKGROUND: Focal fibrocartilaginous dysplasia is an uncommon disorder that affects young children causing unilateral deformity of the tibia. The lesion is seen in other similar conditions but this anomaly shows peculiar clinical characteristic. METHODS: Eleven young patients have been seen between the years 2002-2010 and followed up clinically and radiographically from 3 to 9 years. Family history, previous episode of trauma, infections, and bone disease in the children were not recountered. RESULTS: All cases were treated conservatively and self-corrected by the last follow-up. One case (9.09%) displayed a 4° of varus, and one case (9.09%) displayed a 5° of varus and one (9.09%) a slight leg length discrepancy. CONCLUSION: According to our results and those reported in the literature, focal fibrocartilaginous dysplasia is a benign affection that does not need treatment with a Levine and Drennan angle of <30°.

Biomarkers of Osteosarcoma, Chondrosarcoma, and Ewing Sarcoma.

Osteosarcoma is the most frequent malignant bone neoplasm, followed by chondrosarcoma and Ewing sarcoma. The diagnosis of bone neoplasms is generally made through histological evaluation of a biopsy. Clinical and radiological features are also important in aiding diagnosis and to complete the staging of bone cancer. In addition to these, there are several non-specific serological or specific molecular markers for bone neoplasms. In bone tumors, molecular markers increase the accuracy of the diagnosis and assist in subtyping bone tumors. Here, we review these markers and discuss their role in the diagnosis and prognosis of the three most frequent malignant bone neoplasms, namely osteosarcoma, chondrosarcoma, and Ewing sarcoma.