Comparative pharmacokinetic study of the components of Jia‐Wei‐Kai‐Xin‐San in normal and vascular dementia rats by ultra‐fast liquid chromatography coupled with tandem mass spectrometry

A fast, sensitive, and reliable ultra‐high performance liquid chromatography coupled with tandem mass spectrometry method has been developed and validated for simultaneous quantification of geniposide, polygalaxanthone III, 3,6′‐disinapoyl sucrose, α‐asarone, β‐asarone, poricoic acid A, poricoic acid B, dehydrotumulosic acid, deoxyschizandrin, schizandrin B, and kaempferide in plasma after oral administration of extracts of Jia‐Wei‐Kai‐Xin‐San in normal and vascular dementia rats. The developed method was precise and accurate within the linearity range of the analytes. The lower limits of quantification were 1.04–2.68 ng/mL for all the analytes. Both intra‐ and inter day precision and accuracy of the analytes were all within accepted criteria. The mean extraction recoveries of the analytes and the internal standard from rat plasma were all >60.0%. The validated method had been successfully applied to compare pharmacokinetic profiles of the analytes in plasma of normal and vascular dementia rat treated with herbal extracts. Results indicated that differences existed between normal and vascular dementia model rats except dehydrotumulosic acid and kaempferide, which might be due to the pathology of vascular dementia and pharmacological effect of the analytes. These pharmacokinetic studies might benefit for the mechanism exploration and clinical use of traditional Chinese medicine formulae.     

Inbreeding depression in a zygotic algebra

We study the algebraic behavior of a three dimensional zygotic algebra in the presence of parameters 0 < s < 1 and 0 < g < 1; s for selfing and g which reflects its associated inbreeding depression. We also study the dynamics of the system for which this algebra is a model. Our methods lean towards commutative algebra and algebraic geometry and find support on the computer program Macaulay2.Our results are best understood through the geometry of a rational function of the projective plane.     

CTA成像在下肢血管闭塞病变中的应用及与血管腔内疗效的关系

本文探讨计算机体层扫描血管造影(CTA)检查在下肢血管闭塞病变中的应用价值及与血管腔内疗效的关系。选取经数字减影血管造影(DSA)确诊的93例下肢血管闭塞病变患者,采用CTA检查,分析CTA诊断病变部位结果、血管狭窄程度及与DSA诊断结果的一致性,并探讨CTA征象与患者血管腔内疗效的关系。结果显示,CTA诊断下肢血管闭塞病变部位、狭窄程度与DSA诊断结果均具有较高一致性(P<0.05);病变血管长度>1.41 cm、血管狭窄程度4级、病变血管远端CT值>62.65 Hu、钙化性斑块是下肢血管闭塞病变血管腔内治疗失败的危险因素(P<0.05)。CTA检查是诊断下肢血管闭塞病变的可靠方法,通过检查患者病变血管长度、血管狭窄程度、远端CT值及管腔内粥样斑块性质,有助于降低治疗盲目性,提高血管腔内治疗成功率。     

Review: Aptamers in microfluidic chips

This review, covering reports published from 2002 to August 2010, shows how aptamers have made significant contributions in the improvements of microfluidic chips for affinity extraction, separations and detections. Furthermore, microfluidic chip methods for studying aptamer-target interactions and performing aptamer selections have also been summarized. Accordingly, research vacancies and future development trends in these areas are discussed.     

Stability of bumps in piecewise smooth neural fields with nonlinear adaptation

We study the linear stability of stationary bumps in piecewise smooth neural fields with local negative feedback in the form of synaptic depression or spike frequency adaptation. The continuum dynamics is described in terms of a nonlocal integrodifferential equation, in which the integral kernel represents the spatial distribution of synaptic weights between populations of neurons whose mean firing rate is taken to be a Heaviside function of local activity. Discontinuities in the adaptation variable associated with a bump solution means that bump stability cannot be analyzed by constructing the Evans function for a network with a sigmoidal gain function and then taking the high-gain limit. In the case of synaptic depression, we show that linear stability can be formulated in terms of solutions to a system of pseudo-linear equations. We thus establish that sufficiently strong synaptic depression can destabilize a bump that is stable in the absence of depression. These instabilities are dominated by shift perturbations that evolve into traveling pulses. In the case of spike frequency adaptation, we show that for a wide class of perturbations the activity and adaptation variables decouple in the linear regime, thus allowing us to explicitly determine stability in terms of the spectrum of a smooth linear operator. We find that bumps are always unstable with respect to this class of perturbations, and destabilization of a bump can result in either a traveling pulse or a spatially localized breather.     

Potential role of HMG CoA reductase inhibitor on oxidative stress induced by advanced glycation endproducts in vascular smooth muscle cells of diabetic vasculopathy

Advanced glycation endproducts (AGEs)-induced vascular smooth muscle cell (VSMCs) proliferation and formation of reactive oxygen species (ROS) are emerging as one of the important mechanisms of diabetic vasculopathy but little is known about the antioxidative action of HMG CoA reductase inhibitor (statin) on AGEs. We hypothesized that statin might reduce AGEs-induced intracellular ROS of VSMCs and analyzed the possible mechanism of action of statin in AGEs-induced cellular signaling. Aortic smooth muscle cell of Sprague-Dawley rat (RASMC) culture was done using the different levels of AGEs stimulation in the presence or absence of statin. The proliferation of RASMC, ROS formation and cellular signaling was evaluated and neointimal formation after balloon injury in diabetic rats was analyzed. Increasing concentration of AGEs stimulation was associated with increased RASMC proliferation and increased ROS formation and they were decreased with statin in a dose-dependent manner. Increased NF-κB p65, phosphorylated ERK, phosphorylated p38 MAPK, cyclooxygenase-2, and c-jun by AGEs stimulation were noted and their expression was inhibited by statin. Neointimal formation after balloon injury was much thicker in diabetic rats than the sham-treated group but less neointimal growth was observed in those treated with statin after balloon injury. Increased ROS formation, subsequent activation of MAPK system and increased VSMC proliferation may be possible mechanisms of diabetic vasculopathy induced by AGEs and statin may play a key role in the treatment of AGEs-induced diabetic atherosclerosis.     

Core-shell fibrous vascular grafts with the nitric oxide releasing property

Small-diameter vascular grafts with the nitric oxide(NO) releasing property were designed and prepared.Diazeniumdiolated N,N'-dibutyl-1,6-hexanediamine(DBHD/N2O2) was first synthesized as the NO donor and doped into the biocompatible polymer poly(ε-caprolactone)(PCL).The fibrous vascular grafts were fabricated by electrospinning.Despite the reduced platelet adhesion observed on the NO releasing grafts,the cytotoxicity and burst release were apparent,especially at a higher loading level of the NO donor.In or...     

A serum-stable branched dimeric anti-VEGF peptide blocks tumor growth via anti-angiogenic activity

Angiogenesis is critical and indispensable for tumor progression. Since VEGF is known to play a central role in angiogenesis, the disruption of VEGF-VEGF receptor system is a promising target for anti-cancer therapy. Previously, we reported that a hexapeptide (RRKRRR, RK6) blocked the growth and metastasis of tumor by inhibiting VEGF binding to its receptors. In addition, dRK6, the D-form derivative of RK6, retained its biological activity with improved serum stability. In the present study, we developed a serum-stable branched dimeric peptide (MAP2-dRK6) with enhanced anti-VEGF and anti-tumor activity. MAP2-dRK6 is more effective than dRK6 in many respects: inhibition of VEGF binding to its receptors, VEGF- and tumor conditioned medium-induced proliferation and ERK signaling of endothelial cells, and VEGF-induced migration and tube formation of endothelial cells. Moreover, MAP2-dRK6 blocks in vivo growth of VEGF-secreting colorectal cancer cells by the suppression of angiogenesis and the subsequent induction of tumor cell apoptosis. Our observations suggest that MAP2-dRK6 can be a prospective therapeutic molecule or lead compound for the development of drugs for various VEGF-related angiogenic diseases.