ROCK inhibitor, Y-27632, reduces FBS-induced structural alteration in organ-cultured mesenteric artery

Background Chronic treatment with fetal bovine serum (FBS) causes gradual vasoconstriction, vascular wall thickening, and contractility reduction in organ-cultured vascular tissues. We have previously demonstrated that Rho-associated kinase (ROCK) inhibitors prevent the functional alterations of small arteries in response to the FBS treatment. Here, we tested a further hypothesis that the chronic inhibition of ROCK has a protective effect on FBS-induced structural alterations. Methods To verify the new hypothesis, the rabbit mesenteric arterial rings were cultured in FBS-supplemented culture medium with or without Y-27632, a reversible ROCK inhibitor and then western blot, immunohistochemistry, apoptosis assay, and electron microscopy were performed using organ-cultured arterial rings. Results Chronic treatment with Y-27632 maintained the arterial diameter by preventing FBS-induced gradual arterial constriction during organ culture. Y-27632 also reduced the apoptosis and the loss of contractile myosin and actin filaments of smooth muscle cells. In addition, Y-27632 protected the morphological integrity between the endothelial cell layer and smooth muscle cell layer by preventing endothelial cell detachment and platelet endothelial cell adhesion molecule (PECAM) expression decrement. Conclusions Chronic ROCK inhibition provides protective effects against FBS-stimulated structural in addition to functional alterations of vascular smooth muscle cells and endothelial cells. These results strongly suggest that the RhoA/ROCK signaling is crucial for maintaining the structural and functional phenotypes of vasculature, and hence, chronic ROCK inhibition may provide protective effects on excessive growth factor-related vascular diseases including hypertension and atherosclerosis

A general algorithm for limit solutions of plane stress problems

A computational approach to limit solutions is considered most challenging for two major reasons. A limit solution is likely to be non-smooth such that certain non-differentiable functions are perfectly admissible and make physical and mathematical sense. Moreover, the possibility of non-unique solutions makes it difficult to analyze the convergence of an iterative algorithm or even to define a criterion of convergence. In this paper, we use two mathematical tools to resolve these difficulties. A duality theorem defines convergence from above and from below the exact solution. A combined smoothing and successive approximation applied to the upper bound formulation perturbs the original problem into a smooth one by a small parameter [var epsilon]. As [var epsilon] --> 0, the solution of the original problem is recovered. This general computational algorithm is robust such that from any initial trial solution, the first iteration falls into a convex hull that contains the exact solution(s) of the problem. Unlike an incremental method thut invariably renders the limit problem ill-conditioned, the algorithm is numerically stable. Limit analysis itself is a highly efficient concept which bypasses the tedium of the intermediate elastic-plastic deformation and seeks the most important information directly. With the said algorithm, we have produced many limit solutions of plane stress problems. Certain non-smooth characters of the limit solutions are shown in the examples presented. Two well-known as well as one parametric family of yield functions are used to allow comparison with some classical solutions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29642/1/0000731.pd

Sox2 and FGF20 interact to regulate organ of Corti hair cell and supporting cell development in a spatially-graded manner.

The mouse organ of Corti, housed inside the cochlea, contains hair cells and supporting cells that transduce sound into electrical signals. These cells develop in two main steps: progenitor specification followed by differentiation. Fibroblast Growth Factor (FGF) signaling is important in this developmental pathway, as deletion of FGF receptor 1 (Fgfr1) or its ligand, Fgf20, leads to the loss of hair cells and supporting cells from the organ of Corti. However, whether FGF20-FGFR1 signaling is required during specification or differentiation, and how it interacts with the transcription factor Sox2, also important for hair cell and supporting cell development, has been a topic of debate. Here, we show that while FGF20-FGFR1 signaling functions during progenitor differentiation, FGFR1 has an FGF20-independent, Sox2-dependent role in specification. We also show that a combination of reduction in Sox2 expression and Fgf20 deletion recapitulates the Fgfr1-deletion phenotype. Furthermore, we uncovered a strong genetic interaction between Sox2 and Fgf20, especially in regulating the development of hair cells and supporting cells towards the basal end and the outer compartment of the cochlea. To explain this genetic interaction and its effects on the basal end of the cochlea, we provide evidence that decreased Sox2 expression delays specification, which begins at the apex of the cochlea and progresses towards the base, while Fgf20-deletion results in premature onset of differentiation, which begins near the base of the cochlea and progresses towards the apex. Thereby, Sox2 and Fgf20 interact to ensure that specification occurs before differentiation towards the cochlear base. These findings reveal an intricate developmental program regulating organ of Corti development along the basal-apical axis of the cochlea

Giant thoracic schwannoma presenting with abrupt onset of abdominal pain: a case report

<p>Abstract</p> <p>Introduction</p> <p>Giant intradural extramedullary schwannomas of the thoracic spine are not common. Schwannomas, that is, tumors derived from neoplastic Schwann cells, and neurofibromas represent the most common intradural extramedullary spinal lesions. We report the case of a patient with a giant thoracic schwannoma presenting unusually with acute abdominal pain and with delayed neurological impairment.</p> <p>Case presentation</p> <p>A 26-year-old Hispanic man with no previous medical problems presented with acute periumbilical pain. After extensive work-up including an exploratory laparotomy for appendectomy, magnetic resonance imaging scans of the lumbar and thoracic spine revealed a giant intradural extramedullary thoracic schwannoma within the spinal canal posterior to the T9, T10, and T11 vertebral bodies. Magnetic resonance imaging signal prolongation was noted in the spinal cord both rostral and caudal to the schwannoma. The patient underwent an urgent laminectomy from T8 to L1. After sacrificing the T10 root, the tumor was removed en bloc. Postoperatively, the patient improved significantly gaining antigravity strength in both lower extremities.</p> <p>Conclusion</p> <p>The T10 dermatome is represented by the umbilical region. This referred pain may represent a mechanism by which a giant thoracic schwannoma may present as acute abdominal pain. Acute, intense abdominal pain with delayed neurologic deficit is a rare presentation of a thoracic schwannoma but should be considered as a possible cause of abdominal pain presenting without clear etiology. Although these lesions may be delayed in their diagnosis, early diagnosis and treatment may lead to an improved clinical outcome.</p