ABSTRACT
Ischemia reperfusion injury (IRI) has long-term sequelae on kidney allograft function. Early initiation of rapamycin can retard surgical wound healing and recovery from IRI. In contrast, rapamycin may paradoxically retard long-term fibrotic effects of kidney IRI. We, therefore, hypothesized that delayed initiation of rapamycin after kidney ischemia, started after the initial week of wound healing, would decrease the long-term inflammation and fibrosis caused by IRI. C57BL/6 male mice were subjected to either 45 or 60 minutes of unilateral kidney ischemia or a sham operation. Mice were given rapamycin (subcutaneous, 1.5 mg/kg/d) or vehicle starting at 1 week after IRI surgery for 3 weeks. Urine albumin excretion, kidney histology, and kidney cytokine proteins were examined at 4 weeks after surgery. The 3-week treatment course of rapamycin significantly reduced body weight gain in all 3 groups and reduced postischemic kidney weight in both the 45- and 60-minute ischemia groups, but unexpectedly increased urine albumin excretion in all rapamycin-treated sham or IRI mice compared with vehicle-treated mice. Rapamycin treatment showed minimal effects on postischemic kidney fibrosis with variable effects on various cytokine/chemokine protein expressions, namely, decreasing interleukin (IL)-1alpha, IL-6, tumor necrosis factor (TNF)-alpha, and regulated on activation normal T cell expressed and secreted (RANTES) while increasing IL-4, keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP-1alpha), and IL-10 in the ischemic kidney. These data demonstrated that rapamycin reduced mouse body weight and ischemic kidney weight, while increasing urinary albumin excretion. Delayed initiation of rapamycin after IRI had a minimal effect on renal fibrosis and mixed effects on proinflammatory mediator production. These data do not support delayed initiation of rapamycin after IRI to attenuate IRI-induced progressive fibrosis and inflammation, and They raise further caution regarding rapamycin and albuminuria.
Subject(s)
Fibrosis/drug therapy , Kidney Diseases/drug therapy , Reperfusion Injury/drug therapy , Sirolimus/therapeutic use , Albuminuria , Animals , Body Weight/drug effects , Cytokines/metabolism , Fibrosis/immunology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Injections, Subcutaneous , Kidney/anatomy & histology , Kidney/immunology , Kidney/pathology , Kidney Diseases/immunology , Male , Mice , Mice, Inbred C57BL , Organ Size/drug effects , Sirolimus/administration & dosage , Sirolimus/blood , Weight GainABSTRACT
La medición de la longitud de los miembros inferiores forma parte de la evaluación y diagnóstico del dolor lumbo-sacro, y/o de miembros inferiores. En el presente estudio se determinó la concordancia inter e intra observador, e inter-métodos usando dos métodos clínicos de medición de la longitud de los miembros inferiores (real y aparente) y uno radiológico. Dos médicos entrenados en las técnicas a usar realizaron todas las mediciones. Se incluyeron pacientes con capacidad de extensión completa de los miembros inferiores y con peso que no excediera al 20 por ciento para el peso ideal. Se calcularon el coeficiente de correlación (r), y el intervalo de confianza de 95 por ciento (IC), test de una cola (Ho=0.75). Se estudiaron 17 pacientes (15 mujeres, dos hombres) con edades promedio de 35.8 años (13.0 de desviación estándar). A. Inter-observadores: 1. Medición aparente: r=0.99 (IC=0.98) y para la diferencia de longuitud entre los miembros inferiores fue r=0.88 (IC=0.10). 2. Medición real: r=0.77 (IC=0.95) y para la diferencia r=0.99 (IC=0.85). B. Intra-observador: r=0.95 (IC=0.85). C. Inter-observadores, método radiológico: r=0.98 (IC=0.92). D. Intra-método:1. Medición real/radiológico: r=0.80 (IC=0.70). 2. Medición aparente/radiológico: r=0.75 (IC=0.57). Los resultados obtenidos nos permiten concluir que todos los métodos dan resultados similares. La medición de la diferencia obtenida con ambos métodos clínicos es reproducible pero no al nivel esperado en una técnica que se usa de rutina en la evaluación y diagnóstico de síntomas músculo-esqueléticos lumbo-sacros
