RESUMO
In the ever-aging population of the world, the field of geriatrics continues to grow in importance. As human beings age, the skin undergoes a unique array of changes that predispose it to a specific set of dermatoses, infections, and neoplasms. Some of these physiologic alterations are comparable to the changes that happen in immunosuppressed individuals. Given the importance of immunosuppressive medications in treatment of many common skin conditions, we have reviewed the current literature to assist the practicing clinician in using immunosuppressive medications in the geriatric population.
Assuntos
Produtos Biológicos/uso terapêutico , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/uso terapêutico , Envelhecimento da Pele/imunologia , Dermatopatias Infecciosas/etiologia , Neoplasias Cutâneas/etiologia , Idoso , Idoso de 80 Anos ou mais , Produtos Biológicos/efeitos adversos , Humanos , Imunidade Celular/efeitos dos fármacos , Imunossupressores/efeitos adversos , Dermatopatias Bacterianas/etiologiaRESUMO
OBJECTIVES: The aim of this study was to evaluate the role of tyrosine kinase cellular-Src (c-Src) inhibition on connexin43 (Cx43) regulation in a mouse model of myocardial infarction (MI). BACKGROUND: MI is associated with decreased expression of Cx43, the principal gap junction protein responsible for propagating current in ventricles. Activated c-Src has been linked to Cx43 dysregulation. METHODS: MI was induced in 12-week-old mice by coronary artery occlusion. MI mice were treated with c-Src inhibitors (PP1 or AZD0530), PP3 (an inactive analogue of PP1), or saline. Treated hearts were compared to sham mice by echocardiography, optical mapping, telemetry electrocardiographic monitoring, and inducibility studies. Tissues were collected for immunoblotting, quantitative polymerase chain reaction, and immunohistochemistry. RESULTS: Active c-Src was elevated in PP3-treated MI mice compared to sham at the scar border (280%, p = 0.003) and distal ventricle (346%, p = 0.013). PP1 treatment restored active c-Src to sham levels at the scar border (86%, p = 0.95) and distal ventricle (94%, p = 1.0). PP1 raised Cx43 expression by 69% in the scar border (p = 0.048) and by 73% in the distal ventricle (p = 0.043) compared with PP3 mice. PP1-treated mice had restored conduction velocity at the scar border (PP3: 32 cm/s, PP1: 41 cm/s, p < 0.05) and lower arrhythmic inducibility (PP3: 71%, PP1: 35%, p < 0.05) than PP3 mice. PP1 did not change infarct size, electrocardiographic pattern, or cardiac function. AZD0530 treatment demonstrated restoration of Cx43 comparable to PP1. CONCLUSIONS: c-Src inhibition improved Cx43 levels and conduction velocity and lowered arrhythmia inducibility after MI, suggesting a new approach for arrhythmia reduction following MI.