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1.
J Orthop Res ; 37(11): 2429-2436, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31304988

RESUMEN

Knee injuries cause structural damage and acute inflammation that initiates the development of post-traumatic osteoarthritis (PTOA). NADPH oxidase 4 (Nox4), a member of a family of enzymes that generates reactive oxygen species (ROS), plays a pivotal role in normal development of the musculoskeletal system, but may increase ROS production to harmful levels after joint injury. The role of ROS in both normal joint homeostasis and injury is poorly understood, but inhibition of excessive ROS production by Nox4 after joint injury could be protective to the joint, decreasing oxidative stress, and initiation of PTOA. Knee injuries were simulated using inflammatory cytokines in cultured primary human chondrocytes and a non-invasive mouse model of PTOA in C57BL/6N and Nox4 knockout mice. There is an acute decrease in Nox4 activity within 24 h after injury in both systems, followed by a subsequent sustained low-level increase, a novel finding not seen in any other system. Inhibition of Nox4 activity by GKT137831 was protective against early structural changes after non-invasive knee injury in a mouse model. Nox4 knockout mice had significant differences in structural and mechanical properties of bone, providing further evidence for the role of Nox4 in development of joint tissues and biochemical response after joint injury. Nox4 plays a significant role in the acute phase after joint injury, and targeted inhibition of inflammation caused by Nox4 may be protective against early joint changes in the pathogenesis of PTOA. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2429-2436, 2019.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior/complicaciones , Condrocitos/enzimología , NADPH Oxidasa 4/metabolismo , Osteoartritis de la Rodilla/enzimología , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Adolescente , Adulto , Animales , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Peróxido de Hidrógeno/metabolismo , Masculino , Ratones Noqueados , Persona de Mediana Edad , NADPH Oxidasa 4/antagonistas & inhibidores , NADPH Oxidasa 4/genética , Osteoartritis de la Rodilla/etiología , Osteoartritis de la Rodilla/prevención & control , Cultivo Primario de Células , Pirazoles/farmacología , Pirazolonas , Piridinas/farmacología , Piridonas , Adulto Joven
2.
Instr Course Lect ; 66: 367-377, 2017 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-28594513

RESUMEN

Minimally invasive lateral releases for the correction of lumbar scoliosis are becoming an increasingly common treatment alternative to posterior osteotomies or surgery via an open anterior approach. Minimally invasive approaches minimize blood loss and morbidity, which may be important in older patients who often have substantial comorbidities. Anterior column realignment allows lumbar lordosis to be restored via a minimally invasive lateral approach, which restores sagittal balance and is correlated with improvements in health-related quality of life. Surgeons should understand the development of, the indications for, the surgical technique for, and the complications and early clinical outcomes of the minimally invasive lateral approach to the spine.


Asunto(s)
Escoliosis , Fusión Vertebral , Adulto , Humanos , Vértebras Lumbares , Procedimientos Quirúrgicos Mínimamente Invasivos , Calidad de Vida , Estudios Retrospectivos , Escoliosis/cirugía , Resultado del Tratamiento
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