RESUMEN
We studied the vulnerability of the spinal cord to extracorporeal shock wave treatment (ESWT). In this experiment, 12 rabbits were divided into three groups (4 in each group). All animals underwent a preceding lumbar laminectomy at L4 1 week before ESWT. In group 1, 2000 impulses of high dose (0.62 mJ/mm2 energy flux density) shockwave energy were applied to the spinal cord at the laminectomy site. In group 2, 2000 impulses of low dose (0.18 mJ/mm2 energy flux density) shockwave energy were applied to the same site as group 1. Group 3 did not receive ESWT and served as a control. None of the rabbits in the study groups (groups 1 and 2) showed weakness or paralysis of the hind limbs throughout the entire post-ESWT period. The spinal cord at the L4 level of all animals was harvested on day 13 after laminectomy. On gross morphology, the cord from the study groups and the control group showed normal surface appearance. On microscopic examination, the cord from the control group was normal, whereas the cords from the study groups showed varying degrees of myelin damage and neuronal loss. These microscopic findings were dose-dependent. For the low-energy group (group 2), neuronal loss was insignificant compared to that in the control group. ESWT produced varying degrees of microscopic changes of the treated cords, but no neurological symptoms. The neuronal injury was dose-dependent and mild in the low-energy group.
Asunto(s)
Ondas de Choque de Alta Energía/uso terapéutico , Traumatismos de la Médula Espinal/terapia , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta en la Radiación , Miembro Posterior/fisiopatología , Miembro Posterior/efectos de la radiación , Laminectomía/métodos , Masculino , Conejos , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/fisiopatología , Sinaptofisina/metabolismoRESUMEN
Albuminuria is indicative of nephropathy. However, little literature has focused on the role of albumin in renal distal tubule fibrosis. We used a well-defined distal tubule cell, Madin-Darby Canine Kidney (MDCK). Proliferation and cytotoxicity were examined. The conditioned supernatant was collected and subjected to ELISA assay for detection of fibronectin and TGF-beta1. Reverse transcription-PCR and Western blot assay were performed to evaluate the expression of mRNA and protein of two types of TGF-beta receptors (TbetaR). Flow cytometry assay and phosphotyrosine (pY)-specific antibodies were used to assay the phosphorylation status of TbetaR. We showed that albumin dose dependently (0, 0.1, 1, or 10 mg/ml) inhibited cellular growth in MDCK cells without inducing cellular cytotoxicity. In addition, albumin significantly upregulated the secretion of both fibronectin and TGF-beta1 at dose over 1 mg/ml. Moreover, 24 h pretreatment of albumin significantly enhanced exogenous TGF-beta1-induced secretion of fibronectin. These observations were reminiscent of the implications of TbetaR since TbetaR appears to correlate with the susceptibility of cellular fibrosis. We found that albumin significantly increased protein levels of type I TbetaR (TbetaRI) instead of type II receptors (TbetaRII). In addition, phosphorylation level of TbetaRII of both pY259 and pY424 was significantly enhanced instead of pY336. The novel observation indicates that extreme dose of albumin upregulates TGF-beta autocrine loop by upregulating TGF-beta1, TbetaRI, and the receptor kinase activity of TbetaRII by inducing tyrosine phosphorylation on key amino residue of TbetaRII in renal distal tubule cells. These combinational effects might contribute to the pathogenesis of renal fibrosis.