Muscle signal alteration detected on MRI is seen in diverse pathologic conditions. We observed signal alterations within the paraspinal muscles in dogs with acute thoracolumbar intervertebral disk extrusion. The aim of this retrospective study was to describe MRI features of paraspinal muscle signal alteration in dogs with acute thoracolumbar intervertebral disk extrusion and to investigate an association of the signal alterations with neurological grade, type and location of intervertebral disk extrusion, degree of spinal cord compression, and presence of epidural hemorrhage. Medical records of dogs undergoing MRI because of thoracolumbar intervertebral disk extrusion between August 2014 and June 2016 were reviewed. MRI was evaluated for SI changes within the paravertebral musculature, their location, extension, affected muscles, contrast enhancement, and signal void in T2* sequences. Intervertebral disk herniation was categorized as acute non-compressive nucleus pulposus extrusion (ANNPE) or compressive intervertebral disk disease. In five patients, muscle biopsies of areas with signal intensity changes were taken during surgery. In total, 103 dogs were enrolled in the study. Paraspinal muscle signal alterations were visible in 37 dogs (36%) affecting the epaxial musculature (n = 17), hypaxial musculature (n = 12), or both (n = 8). All signal alterations were hyperintense on T2-weighted images and iso- or hypointense in T1-weighted images. Signal void in T2* was not observed in any dog. Postcontrast sequences were available in 30 of the 37 dogs and showed enhancement in 45%. There was neither an association with degree of compression nor epidural hemorrhage. Intervertebral disk extrusion caudal to L1 and a higher neurological grade was associated with the presence of muscle changes. Histopathology revealed mild to moderate acute muscle fiber degeneration with edema and necrosis in three of five samples. The MRI, as well as the muscle samples, show rather unspecific changes. The underlying pathomechanism might be related to ischemia or muscle spasm, but also denervation edema may explain the signal alteration.

An integrated assay system involving dual/triple-probe microdialysis techniques in rats was developed earlier for testing interactions with P-glycoprotein (P-gp) at the blood-brain barrier using quinidine/PSC-833 as a P-gp substrate/inhibitor combination. The aim of the present study was to expand our assay system to mice using microdialysis with simultaneous sampling of blood and brain and to compare the result with a primary mouse brain endothelial cell monolayer (pMBMEC) assay. Brain penetration of quinidine was dose dependent in both anesthetized and awake mice after intraperitoneal drug administration. PSC-833 pretreatment caused a 2.5-to 3.4-fold increase in quinidine levels of brain dialysate samples in anesthetized or awake animals, after single or repeated administration of PSC-833. In pMBMEC, a 2.0-to 2.5-fold efflux ratio was observed in the transcellular transport of quinidine. The P-gp-mediated vectorial transport of quinidine was eliminated by PSC-833. These results indicate that quinidine with PSC-833 is a good probe substrate-reference inhibitor combination for testing drug-drug interactions with P-gp in the in vivo and in vitro mouse systems. With increasing number of humanized transgenic mice, a test system with mouse microdialysis experimentation becomes more important to predict drug-drug interactions in humans.

No abstract

No abstract

No abstract