Synthesis and biological evaluation of dual action cyclo-RGD/SMAC mimetic conjugates targeting α(v)ß(3)/α(v)ß(5) integrins and IAP proteins.

The rational design, synthesis and in vitro biological evaluation of dual action conjugates 11-13, containing a tumour targeting, integrin αvß3/αvß5 ligand portion and a pro-apoptotic SMAC mimetic portion (cyclo-RGD/SMAC mimetic conjugates) are reported. The binding strength of the two separate units is generally maintained by these dual action conjugates. In particular, the connection between the separate units (anchor points on each unit; nature, length and stability of the linker) influences the activity of each portion against its molecular targets (integrins αvß3/αvß5 for cyclo-RGD, IAP proteins for SMAC mimetics). Each conjugate portion tolerates different substitutions while preserving the binding affinity for each target.

Considerations on 100 cases of free microsurgical flaps in the reconstruction of the soft tissues of the lower limb.

The authors evaluate the results for 100 cases of severe loss of substance of the lower limb treated by microvascular free flaps at the Division of Plastic Surgery, Bellaria Hospital in Bologna, between 1994 and 2001. The cases involved recent traumatic loss of substance in 48 cases, post-traumatic defects such as osteomyelitis, ulcers, unstable scarring, sequelae of burns in 40, and neoplasms in 12. Muscular flaps were used in 89 cases, skin flaps in 9, a flap of the omentum in 1; the latissumus dorsi flap was that most frequently used (50 cases). A total of 87 cases had favorable results, while in 13 cases there was failure of the flap. Based on the results obtained, and experience, current indications and causes of failure are discussed.