Exploring the mechanisms of renoprotection against progressive glomerulosclerosis

In this review, I introduce the strategy developed by our laboratory to explore the mechanisms of renoprotection against progressive glomerulosclerosis leading to renal death. First, I describe the experimental rat model in which disturbances of vascular regeneration and glomerular hemodynamics lead to irreversible glomerulosclerosis. Second, I discuss the possible mechanisms determining the progression of glomerulosclerosis and introduce a new imaging system based on intravital confocal laser scanning microscopy. Third, I provide an in-depth review of the regulatory glomerular hemodynamics at the cellular and molecular levels while focusing on the pivotal role of Ca(2+)-dependent gap junctional intercellular communication in coordinating the behavior of mesangial cells. Last, I show that local delivery of renoprotective agents, in combination with diagnostic imaging of the renal microvasculature, allows the evaluation of the therapeutic effects of angiotensin II receptor and cyclooxygenase activity local blockade on the progression of glomerulosclerosis, which would otherwise lead to renal death.     

ANALYSIS OF AN SI EPIDEMIC MODEL WITH NONLINEAR TRANSMISSION AND STAGE STRUCTURE

A disease transmission model of SI type with stage structure is formulated. The stability of disease free equilibrium, the existence and uniqueness of an endemic equilibrium, the existence of a global attractor are investigated.     

跨界创新联盟关联信用风险传染模型研究

跨界创新联盟是企业创新过程中资源整合与共享的一种有效形式,但在带来企业创新资源共享效益的同时,联盟中复杂的关联关系也构成了联盟关联信用风险传染的新渠道。本文结合复杂网络理论与传染病模型,根据跨界创新联盟特点,在原有资产关联研究的基础上,综合考虑行业关联、资产关联和创新合作关联三种关联关系,改进了风险传播的传染病模型,并进行了数值仿真实验。结果表明:行业关联、资产关联和创新合作关联对跨界创新联盟关联信用风险传染阈值具有综合性影响,增加行业关联和创新合作关联因素,有利于提高关联信用风险传染阈值的精度。此外,资产关联度越高则感染成员密度越大;行业关联度越低,创新合作关联度越高则感染成员密度越小。     

Antioxidant activity of methimazole-copper(II) bioactive species and spectroscopic investigations on the mechanism of its interaction with Bovine Serum Albumin

Free radical-mediated oxidative stress has been implicated in numerous autoimmune disorders including Graves’ disease. Hyperthyroidism results in a marked increase in intracellular antioxidant enzymes including superoxide dismutase. The later activity is significantly increased in untreated Graves’ patients while treatment with methimazole results in normalization of the free radical and antioxidant activity indices. In this context, and considering the findings mentioned above, the aim of the present study was to evaluate unknown biological activities of methimazole and its methimazole-copper(II) complex investigating their superoxide scavenger power. Under the applied experimental conditions, methimazole did not show superoxide dismutase (SOD) activity while the copper complexes exhibited a strong superoxide radical scavenging capacity. Bearing in mind that the capacity of drugs to bind and/or interact with albumin is essential for their pharmacokinetic and pharmacodynamic properties, a complete investigation of the binding ability of both compounds by using Fourier transform infrared (FT-IR), Raman and Fluorescence spectroscopies, and UV-Vis spectrophotometry was included. Besides, in order to probe the copper ligand environment the EPR spectra of such compounds were analyzed.     

Laser secondary neutral mass spectrometry for copper detection in micro‐scale biopsies

Disease progression and clinical diagnostics of a number of hereditable metabolic diseases are determined by organ involvement in disturbed deposition of certain molecules. Current clinical imaging is unable to visualize this maldistribution with sufficient specificity and sensitivity, such as in Wilson's disease. The quest for understanding cellular Cu distribution in these patients requires element‐ and molecule‐specific images with nanometer‐scale spatial resolution. We have used a new cryo‐mass spectrometric instrument with an integrated cryosectioning chamber for preparation and analysis of frozen hydrated samples of Wilson's disease tissue. With laser post‐ionization secondary neutral mass spectrometry (laser‐SNMS), we were able to image Cu and other intrinsic elements and molecules in less than 1 mg of frozen hydrated liver tissue from a murine model of Wilson's disease. A 40–50 times higher Cu concentration was measured in the disease tissue as compared to the control mouse. Furthermore, major histomorphological changes were observed using this advanced nano‐science tool. The results showed that the combination of in‐vacuum cryosectioning and cryo‐laser‐SNMS technologies is particularly well suited for identifying specific cell structures and imaging trace element concentrations with subcellular resolution and upper‐parts‐per‐billion sensitivity in biological samples. This technology can provide a novel diagnostic tool for clinical applications in various diseases involving trace elements. Copyright © 2009 John Wiley & Sons, Ltd.     

实时三维超声联合右心声学造影评价肺源性心脏病患者右心室收缩功能的价值

目的应用实时三维超声心动图探讨肺源性心脏病患者右心室收缩功能的价值，比较右心造影对测值的影响。方法选择肺源性心脏病代偿组、失代偿组、正常对照组各20例分别进行造影前、后实时三维超声的采集成像，计算右心室舒张末容积（RVEDV）、右心室每博输出量（RVSV）和右心室射血分数（RVEF），并根据心内膜是否清晰可辨分为心内膜边界清晰者、心内膜边界欠清晰者，比较两者三维超声参数的组间差异。结果代偿组、失代偿组RVEDV较对照组均明显增加，RVEF值减低（均P＜0.01），代偿组与对照组RVSV差异无统计学意义（P＞0.05），但失代偿组RVSV与代偿组、对照组差异有统计学意义（P＜0.05）；失代偿组RVEDV较代偿组明显增大，RVEF明显减低（均P＜0.01）。心内膜边界欠清晰者造影后较造影前RVEDV、RVEF差异均有统计学意义（均P＜0.05）。结论实时三维超声能够客观地反映肺源性心脏病代偿期与失代偿期右心室收缩功能的变化，右心声学造影改善了心内膜边界的可识别性，提高了右心室收缩功能测值的可靠性。     

Enzymatic Synthesis of Fructosyl Glycerol

ABSTRACT

The enzymatic synthesis of ß2-2' and ß2-1'-D- fructopyranosyl glycerol was carried out with levansucrase from Bacillus circulans or B.subtilis, using sucrose as fructosyl donor and glycerol. The specificity and efficiency of the enzyme was modified by controlling both the water and the total substrate concentrations. The products were purified by HPLC and analyzed by ¹H, ¹³C NMR and GC-MS.     

2000 Vol.11 No.8 P.Preparation of AChE Inhibitors From Jujubogenin

A dammarane derivative dihydrojujubogenin-2-en-1-one, which possesses a skeleton and pharmacophore partially similar to those of Territrem B, a potent AChE inhibitor, was synthesized via three different paths. The anti-AChE activity of this compound and related analogue was measured.