Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats

Puerarin, a major isoflavonoid derived from the Chinese medical herb Radix puerariae (kudzu root), has been reported to be useful in the treatment of various cardiovascular diseases. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of puerarin on inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. Treatment of puerarin (25 and 50 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia in rats. Administration of puerarin at 50 mg/kg, showed marked reduction in infarct size compared with that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions as well as the mRNA expression of tumor necrosis factor-α (TNF-α) in ischemic regions. These expressions were markedly inhibited by the treatment of puerarin (50 mg/kg). In addition, puerarin (10~50 μM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by formyl-Met-Leu-Phe. On the other hand, puerarin (20~500 μM) did not significantly inhibit the thiobarbituric acid-reactive substance reaction in rat brain homogenates. An electron spin resonance (ESR) method was conducted on the scavenging activity of puerarin on the free radicals formed. Puerarin (200 and 500 μM) did not reduce the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate that puerarin is a potent neuroprotective agent on MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1α and TNF-α activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression), apoptosis formation (active caspase-3), and neutrophil activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, puerarin treatment may represent a novel approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders

Superior canal dehiscence in a patient with three failed stapedectomy operations for otosclerosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>This case illustrates that superior semicircular canal dehiscence syndrome can be associated with a "pseudo"-conductive hearing loss, a symptom that overlaps with the clinical appearance of otosclerosis.</p> <p>Case presentation</p> <p>We present the case of a 48-year-old German Caucasian woman presenting with hearing loss on the left side and vertigo. She had undergone three previous stapedectomies for hearing improvement. Reformatted high-resolution computed tomographic scanning and the patient's history confirmed the diagnosis of concurrent canal dehiscence syndrome.</p> <p>Conclusion</p> <p>Failure of hearing improvement after otosclerosis surgery may indicate an alternative underlying diagnosis which should be explored by further appropriate evaluation.</p

Vortex arrays in neutral trapped Fermi gases through the BCS–BEC crossover

Vortex arrays in type-II superconductors reflect the translational symmetry of an infinite system. There are cases, however, such as ultracold trapped Fermi gases and the crust of neutron stars, where finite-size effects make it complex to account for the geometrical arrangement of vortices. Here, we self-consistently generate these arrays of vortices at zero and finite temperature through a microscopic description of the non-homogeneous superfluid based on a differential equation for the local order parameter, obtained by coarse graining the Bogoliubov–de Gennes (BdG) equations. In this way, the strength of the inter-particle interaction is varied along the BCS–BEC crossover, from largely overlapping Cooper pairs in the Bardeen–Cooper–Schrieffer (BCS) limit to dilute composite bosons in the Bose–Einstein condensed (BEC) limit. Detailed comparison with two landmark experiments on ultracold Fermi gases, aimed at revealing the presence of the superfluid phase, brings out several features that make them relevant for other systems in nature as well

Mislocalization of Visual Stimuli: Independent Effects of Static and Dynamic Attention

Shifts of visual attention cause systematic distortions of the perceived locations of visual objects around the focus of attention. In the attention repulsion effect, the perceived location of a visual target is shifted away from an attention-attracting cue when the cue is presented before the target. Recently it has been found that, if the visual cue is presented after the target, the perceived location of the target shifts toward the location of the following cue. One unanswered question is whether a single mechanism underlies both attentional repulsion and attraction effects. We presented participants with two disks at diagonal locations as visual cues and two vertical lines as targets. Participants were asked to perform a forced-choice task to judge targets' positions. The present study examined whether the magnitude of the repulsion effect and the attraction effect would differ (Experiment 1), whether the two effects would interact (Experiment 2), and whether the location or the dynamic shift of attentional focus would determine the distortions effects (Experiment 3). The results showed that the effect size of the attraction effect was slightly larger than the repulsion effect and the preceding and following cues have independent influences on the perceived positions. The repulsion effect was caused by the location of attnetion and the attraction effect was due to the dynamic shift of attentional focus, suggesting that the underlying mechanisms for the retrospective attraction effect might be different from those for the repulsion effect

ACE as a Mechanosensor to Shear Stress Influences the Control of Its Own Regulation via Phosphorylation of Cytoplasmic Ser1270

Objectives: We tested whether angiotensin converting enzyme (ACE) and phosphorylation of Ser(1270) are involved in shear-stress (SS)-induced downregulation of the enzyme. Methods and Results: Western blotting analysis showed that SS (18 h, 15 dyn/cm(2)) decreases ACE expression and phosphorylation as well as p-JNK inhibition in human primary endothelial cells (EC). CHO cells expressing wild-type ACE (wt-ACE) also displayed SS-induced decrease in ACE and p-JNK. Moreover, SS decreased ACE promoter activity in wt-ACE, but had no effect in wild type CHO or CHO expressing ACE without either the extra-or the intracellular domains, and decreased less in CHO expressing a mutated ACE at Ser(1270) compared to wt-ACE (13 vs. 40%, respectively). The JNK inhibitor (SP600125, 18 h), in absence of SS, also decreased ACE promoter activity in wt-ACE. Finally, SS-induced inhibition of ACE expression and phosphorylation in EC was counteracted by simultaneous exposure to an ACE inhibitor. Conclusions: ACE displays a key role on its own downregulation in response to SS. This response requires both the extra- and the intracellular domains and ACE Ser(1270), consistent with the idea that the extracellular domain behaves as a mechanosensor while the cytoplasmic domain elicits the downstream intracellular signaling by phosphorylation on Ser(1270).Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[01/00009-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[03/14115-2]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[06/52053-7]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)[480120/2007-2

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Hyaluronic acid as a treatment for ankle osteoarthritis

Viscosupplementation refers to the concept of synovial fluid replacement with intra-articular injections of hyaluronic acid (HA) for the relief of pain associated with osteoarthritis (OA). Intra-articular viscosupplementation was approved by the Food and Drug Administration (FDA) in 1997. It is currently indicated only for the treatment of pain associated with knee OA. However, OA can occur in several of the weight-bearing joints of the foot and ankle. Ankle OA produces chronic disability that directly impacts the quality of life. There is only limited published literature relating to the use of HA in the ankle. This paper will review the authors’ experience, indications, clinical outcomes, and complications of viscosupplementation therapy in patients with ankle OA