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We investigated the anorectal musclulature in normal children and anorectal malformations (ARM) to evaluate its role in bowel control mechanism. Pelves of 50 neonates died of ARM-unrelated diseases and 16 patients with anorectal malformations (8 high, 5 intermediate, and 3 low ARMs) were dissected and analyzed. Normal anorectal musculature was divided into three muscular tubes: the internal sphincter tube (IAST), longitudinal muscle tube (LMT) and transverse muscle tube (TMT). The LMT came from the outer longitudinal smooth muscle fiber of the rectum and the striated muscle fiber of the levator ani, and the TMT composed of the puborectalis and the external anal sphincter. However, in ARM, the IAST was absent and the LMT, the center of the sphincter muscle complex, was only from the levator ani and could be divided into the pelvic portion and the perineal portion. The former, from the upper rim of the puborectalis to the bulbar urethral, became narrowed and dislocated anteriorly near to the posterior urethra in high ARM and rectal pouch in intermediate ARM. The latter, below the bulbar urethra to the anal dimple, was fused to a column both in high and intermediate ARM. The columnar perineal LMT run downwards and then split, penetrated the superficial part of EAS and terminated at the deep aspect of the skin, to form the anal dimple, which represents the center of the perineal LMT from the perineal aspect. The length of the LMT was longer in high and intermediate ARM than the normal neonate. The columnar perineal LMT and narrowed pelvic LMT could be possibly identified by laparoscopic and perineal approaches retrospectively and widened to allow the passage of the rectum through. The anorectal musculature in ARM is composed of agenesic LMT and TMT and the narrowed LMT gives anatomical evidence of the center, where the neorectum should pull through.

Atherosclerosis is one of the major complications of diabetes and involves endothelial dysfunction, matrix alteration, and most importantly migration and proliferation of vascular smooth muscle cells (VSMCs). Although hyperglycemia and hyperinsulinemia are known to contribute to atherosclerosis, little is known about the specific cellular signaling pathways that mediate the detrimental hyperinsulinemic effects in VSMCs. Therefore, we investigated the cellular mechanisms of hyperinsulinemia-induced migration and proliferation of VSMCs. VSMCs were treated with insulin (100 nM) for 6 days and subjected to various physiological and molecular investigations. VSMCs subjected to hyperinsulinemia exhibited increased migration and proliferation, and this is paralleled by oxidative stress [increased NADPH oxidase activity, NADPH oxidase 1 mRNA expression, and reactive oxygen species (ROS) generation], alterations in mitochondrial physiology (membrane depolarization, decreased mitochondrial mass, and increased mitochondrial ROS), changes in mitochondrial biogenesis-related genes (mitofusin 1, mitofusin 2, dynamin-related protein 1, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, peroxisome proliferator-activated receptor gamma coactivator 1-beta, nuclear respiratory factor 1, and uncoupling protein 2), and increased Akt phosphorylation. Diphenyleneiodonium, a known NADPH oxidase inhibitor significantly inhibited migration and proliferation of VSMCs and normalized all the above physiological and molecular perturbations. This study suggests a plausible crosstalk between mitochondrial dysfunction and oxidative stress under hyperinsulinemia and emphasizes counteracting mitochondrial dysfunction and oxidative stress as a novel therapeutic strategy for atherosclerosis. � 2012 Springer Science+Business Media New York.

We have demonstrated that bladder wall tissue in spinal cord injury (SCI) rats at 10 days post-injury is more compliant and accompanied by changes in material class from orthotropic to isotropic as compared to normal tissue. The present study examined the long-term effects (3-, 6-, and 10-weeks) post-SCI on the mechanical properties of bladder wall tissues, along with quantitative changes in smooth muscle orientation and collagen and elastin content. Bladder wall compliance (defined as det(F) - 1 under an equi-biaxial stress state of 100 kPa, where F is the deformation gradient tensor) was found to be significantly greater at 3- and 6-weeks (0.873 +/- 0.092 and 0.864 +/- 0.112, respectively) when compared to the normal bladders (0.260 +/- 0.028), but at 10 weeks the compliance reduced (0.389 +/- 0.061) to near that of normal bladders. This trend in mechanical compliance closely paralleled the collagen/elastin ratio. Moreover, changes in material class, assessed using a graphical technique, correlated closely with quantitative changes in smooth muscle fiber orientation. The results of the present study provide the first evidence that, while similarities exist between acute and chronic responses of the urinary bladder wall tissue to SCI, the overall alterations are distinct, result in profound and complex time dependent changes in bladder wall structure, and will lay the basis for simulations of the bladder wall disease process.

Neither the absence of KCl from Tyrode's solution or the presence of 2·10−7 adrenalin or 1·10−5 atropine altered the response of the smooth muscle of a section of guinea pigtaeniacoli to direct electrical stimulation. The response was depressed by 26, 39, 42, 43, 63, and 86% through the action of 4·10−5 spasmolytin, 1·10−4 dimedrol, 2·10−4 promedol, 4·10−5 dibazol, 4·10−5 papaverine, and by 2.5·10−5 2,4-dinitrophenol respectively. From published reports and our own results the explanation of the spasmolytic effects of adrenalin and atropine in smooth muscle appears to be that they act by an alteration of the condition of polarization of the smooth muscle fiber membranes, whereas papaverine appears to act both on the cell membrane and on the biochemical reaction of smooth muscle.