ABSTRACT
The Ca(2+)-calmodulin-activated Ser/Thr protein phosphatase calcineurin and the downstream transcriptional effectors of calcineurin, nuclear factor of activated T cells, have been implicated in the hypertrophic response of the myocardium. Recently, the calcineurin inhibitory agents cyclosporine A and FK506 have been extensively used to evaluate the importance of this signaling pathway in rodent models of cardiac hypertrophy. However, pharmacologic approaches have rendered equivocal results necessitating more specific or genetic-based inhibitory strategies. In this regard, we have generated Tg mice expressing the calcineurin inhibitory domains of Cain/Cabin-1 and A-kinase anchoring protein 79 specifically in the heart. DeltaCain and DeltaA-kinase-anchoring protein Tg mice demonstrated reduced cardiac calcineurin activity and reduced hypertrophy in response to catecholamine infusion or pressure overload. In a second approach, adenoviral-mediated gene transfer of DeltaCain was performed in the adult rat myocardium to evaluate the effectiveness of an acute intervention and any potential species dependency. DeltaCain adenoviral gene transfer inhibited cardiac calcineurin activity and reduced hypertrophy in response to pressure overload without reducing aortic pressure. These results provide genetic evidence implicating calcineurin as an important mediator of the cardiac hypertrophic response in vivo.
Subject(s)
Adaptor Proteins, Signal Transducing , Calcineurin Inhibitors , Calcineurin/physiology , Cardiomegaly/prevention & control , Phosphoproteins/physiology , A Kinase Anchor Proteins , Adenoviridae , Animals , Blood Pressure , Calcineurin/genetics , Cardiomegaly/chemically induced , Cardiomegaly/pathology , Cardiotonic Agents/adverse effects , Carrier Proteins/genetics , Carrier Proteins/physiology , Gene Expression , Genetic Vectors , Heart/physiology , Intracellular Signaling Peptides and Proteins , Isoproterenol/adverse effects , Mice , Mice, Transgenic , Phenotype , Phosphoproteins/genetics , RatsABSTRACT
We report the case of a 47-year-old woman with a large keloid scar on the sternum who was submitted to a simultaneous scar removal with bilateral breast-reduction mammaplasty. Breast reduction was performed to reduce local skin tension and to provide a skin flap for the full reconstruction of the scar-removal site. The association of these surgical procedures stands as a viable alternative for the reconstruction of the sternum region, producing less keloid scarring.
Subject(s)
Breast/pathology , Keloid/surgery , Mammaplasty/methods , Sternum , Surgical Flaps , Breast/surgery , Female , Humans , Keloid/etiology , Middle AgedABSTRACT
Cutaneous injuries of the inferior third of the leg and dorsum of the foot represent a great challenge for plastic surgeons. The poor vascularization and subsequent poor healing encountered in these regions demand detailed knowledge of the local anatomy to select the best surgical alternative for each patient. In patients in whom local or free muscular flaps are not suitable, the fasciocutaneous flaps seem to be a good alternative. The distal pedicled fasciocutaneous flap of the calf was used to cover skin defects of the leg and foot in 22 patients. In 4 patients the authors designed an island flap to prevent a large defect in the donor area and to decrease the time of hospitalization and recovery of the patient. In a severe defect, the flap was used as a cross-leg flap. The results were satisfactory because the flap provided stable coverage for different defects with few complications. The island flap is a good option for achieving a better aesthetic result and can be used in select patients.
