Iron Overload in a Murine Model of Hereditary Hemochromatosis Is Associated with Accelerated Progression of Osteoarthritis Under Mechanical Stress

OBJECTIVE: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. DESIGN: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. RESULTS: Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. CONCLUSIONS: HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA

A Transposição Valvular nos Doentes com Úlceras dos Membros Inferiores Consequentes a Síndromes Pós-Trombóticos

Venous ulcers in patients with post thrombotic syndromes are complex situations with multiple therapeutic options. They are responsible for high morbidity rates, conservative treatment is very slow and recurrences are very common. Deep venous reconstructive surgery is an alternative, but it should be based on the morphologic and functional aspects of the venous system and only adopted after a very careful study, including venography. The authors describe a morphological "pattern", found in some of these patients and related to the competence of the saphenous femoral junction, rendering possible to perform a valvular transposition. Seven patients with post thrombotic ulcers who have been treated during the last 6 years in which the pattern already described was detect, underwent a transposition of the superficial femoral vein, to the great saphenous vein and when necessary complemented with skyn grafts. Before the operation all patients had ulcers with more than 3 cm in size (3.2-5.4 cm) and with more than 4 months duration (4-16 months). All ulcers healed in the postoperative period (mean time 28 days). All patients have been reevaluated in 2003 and it was diagnosed the thrombosis of two procedures, one of them with the recurrence of the ulcer who healed with conservative treatment. The authors consider this method as a very easy technique to perform, although rarely used, and a valid alternative in a highly selected group of patients.