肾小球疾病时微量元素代谢的变化

用发射光谱法测定了55倒广州地区居民患肾小球疾病时血清和头发申锌、铜、铁、钴、铬、锰含量，观察对象包括肾病综合征组17例，肾炎组17例，尿毒症组21例．对照组为30例健康人。其年龄、性别构成比、地区与观察组无显著性差异．结果经统计学检验发现肾病综合征组病人血清锌、铜、钴及头发锌、钴含量均明显下降，头发铜无明显变化，肾炎组血清钴、头发钴明显下降，血清锌、铜及头发锌、铜无明显变化。尿毒症组病人血清锌、头发锌、钴显著下降，血清钴、铜及头发铜无明显变化．肾炎组、肾病综合征组及尿毒症组病人血清及头发申铁、铬、锰均无明显变化。     

Effect of Notoginsenoside- Rg1 on the Expression of Several Proteins in the Striatum of Rat Models with Parkinson''s Disease

After establishing hemi-Parkinsonian rat models, the relationships between neuron death and the expression of several proteins, such as c-Fos, GFAP, GDNF, NF-κB and some cytokines were determined. Therapeutics experiments with notoginsenoside-Rg1 were carried out. The research results show that the expressions of GFAP, NF-κB and c-Fos will obviously increase in the lesion side of the striatum and the expression of GDNF will decrease, which implies that the signal transduction pathway may participate in the apoptosis in neurons. The levels of some cytokines such as TNF-α, IL-1β in the striatum of PD rat models increased compared to those of normal rats. The results of the therapeutics experiments show that notoginsenoside-Rg1 may repress the immune inflammation response and regulate the immune function through the neuro-immune molecular network. Therefore, notoginsenoside-Rg1 can be used as an effective drug for anti-oxidation and anti-inflammation, and can be used in the therapy of Parkinson's disease(PD).     

光学成像在疾病诊断中的应用

当前，医生们利用各种成像技术与疾病进行斗争，其中光学成像技术是获得高分辨率图像的新方法，其原理是每种生物介质具有各自特有的光谱特性，可赖以区分病变组织和正常组织，或对潜在问题准确定位。而光学相干层析则是最精确的光学成像技术，可提供１０～２０μｍ量级的高分辨率及比迄今为止任何其他技术都高的灵敏度。本文着重讨论光学相干层析术的基本原理及目前发展状况     

Sensitivity and significance of disease outcome measures in inflammatory bowel disease

In inflammatory bowel disease (IBD), proxy measures of clinical outcome are often collected into summary indices of qualitative self-rated disease markers, clinical observations, and quantitative biochemical analyses. In Crohn's disease (CD), a frequently used index is the Crohn's disease activity index (DCAI). This index consists of six qualitative variables and two quantitative variables. The aim of this presentation is to illustrate the use of this index to calculate its range, to estimate errors in the index, its sensitivity, and the number of significant steps in the index. The measure of sensitivity of the summary index was analyzed for the signal-to-noise ratio (SNR), the reference change value (RCV) and the confidence interval (CI). If identical errors were assumed in patient self-rated health and clinically judged disease manifestations, such as tumours and fistulas, the majority of the variance of the index was caused by the self-rated experience of health, the number of days over which the individual variable was rated, and the prognostic multiplier of each variable.The range of the index has no upper limit, but can be estimated to 403 units, of which patient self-rating of well-being account for up to one-third of the summary index maximal score range. The median signal noise measure of index sensitivity was 18 SDs. The two disease classification limits of 150 units for moderate disease and 450 for severe disease on average cover an interval of limit ±41.5 units vs. ±60.5 units. In judgments on change in clinical outcome the RCV interval of steps of 121 units are valid. Conclusion: Both variance and range of the CDAI summary score are primarily decided by the self-rated experience of well-being. Variables on disease signs have a minor impact on the index. Rating of the two important outcome parameters: Self-experienced health and medical outcome would favourably be given in two individual scores.Presented at the 10th Conference Quality in the Spotlight, March 2005, Antwerp, Belgium.     

Folding of the Tau Protein on Microtubules

Microtubules are regulated by microtubule‐associated proteins. However, little is known about the structure of microtubule‐associated proteins in complex with microtubules. Herein we show that the microtubule‐associated protein Tau, which is intrinsically disordered in solution, locally folds into a stable structure upon binding to microtubules. While Tau is highly flexible in solution and adopts a β‐sheet structure in amyloid fibrils, in complex with microtubules the conserved hexapeptides at the beginning of the Tau repeats two and three convert into a hairpin conformation. Thus, binding to microtubules stabilizes a unique conformation in Tau.     

A Hot‐Segment‐Based Approach for the Design of Cross‐Amyloid Interaction Surface Mimics as Inhibitors of Amyloid Self‐Assembly

The design of inhibitors of protein–protein interactions mediating amyloid self‐assembly is a major challenge mainly due to the dynamic nature of the involved structures and interfaces. Interactions of amyloidogenic polypeptides with other proteins are important modulators of self‐assembly. Here we present a hot‐segment‐linking approach to design a series of mimics of the IAPP cross‐amyloid interaction surface with Aβ (ISMs) as nanomolar inhibitors of amyloidogenesis and cytotoxicity of Aβ, IAPP, or both polypeptides. The nature of the linker determines ISM structure and inhibitory function including both potency and target selectivity. Importantly, ISMs effectively suppress both self‐ and cross‐seeded IAPP self‐assembly. Our results provide a novel class of highly potent peptide leads for targeting protein aggregation in Alzheimer’s disease, type 2 diabetes, or both diseases and a chemical approach to inhibit amyloid self‐assembly and pathogenic interactions of other proteins as well.     

Determination of four acidic nonsteroidal anti‐inflammatory drugs in wastewater samples by dispersive liquid–liquid microextraction based on solidification of floating organic droplet and high‐performance liquid chromatography

A simple, environmentally friendly, and sensitive dispersive liquid–liquid microextraction based on solidification of floating organic droplet for the extraction of four acidic nonsteroidal anti‐inflammatory drugs (ketoprofen, naproxen, ibuprofen, and diclofenac) from wastewater samples subsequent by high‐performance liquid chromatography analysis was developed. The influence of extraction parameters such as pH, the effect of solution ionic strength, type of extraction solvent, disperser solvent, and extraction solvent volume were studied. High enrichment factors (283–302) were obtained through the developed method. The method provides good linearity (r > 0.999) in a concentration range of 1–100 μg/L, good intra‐ and inter‐day precision (relative standard deviation < 7%) and low limits of quantification. The relative recoveries of the selected compounds were situated over 80% both in synthetic and real water samples. The developed method has been successfully applied for the analysis of the selected compounds in wastewater samples.     

A reversed‐phase compatible thin‐layer chromatography autography for the detection of acetylcholinesterase inhibitors

A dual readout autographic assay to detect acetylcholinesterase inhibitors present in complex matrices adsorbed on reversed‐phase or normal‐phase thin‐layer chromatography plates is described. Enzyme gel entrapment with an amphiphilic copolymer was used for assay development. The effects of substrate and enzyme concentrations, pH, incubation time, and incubation temperature on the sensitivity and the detection limit of the assay were evaluated. Experimental design and response surface methodology were used to optimize conditions with a minimum number of experiments. The assay allowed the detection of 0.01% w/w of physostigmine in both a spiked Sonchus oleraceus L. extract chromatographed on normal phase and a spiked Pimenta racemosa (Mill.) J.W. Moore leaf essential oil chromatographed on reversed phase. Finally, the reversed‐phase thin‐layer chromatography assay was applied to reveal the presence of an inhibitor in the Cymbopogon citratus (DC.) Stapf essential oil. The developed assay is able to detect acetylcholinesterase inhibitors present in complex matrixes that were chromatographed in normal phase or reversed‐phase thin‐layer chromatography. The detection limit for physostigmine on both normal and reversed phase was of 1×10^?4 μg. The results can be read by a change in color and/or a change in fluorescence.     

Peptide-derived from Seahorse Exerts a Protective Effect against Cholinergic Neuronal Death in in vitro Model of Alzheimer's Disease

Hippocampus trimaculatus are highly valued and the most heavily traded seahorse species for traditional medicine purposes in many Asian countries. One of the main interesting features in H.trimaculatus is their richness in protein which can be hydrolyzed into bioactive peptides. In the previous study, H. trimaculatus was hydrolyzed using commercial enzymes, the peptides responsible for neuroprotective activity was identified as HTP-1. In the present study, in vitro co-culture system of neuronal (PC12) cells and Aβ₄₂ oligomer-stimulated murine microglia cells (BV2 cells) were used to test neuroprotective effects of HTP-1. The co-culture system showed that HTP-1 protected PC12 cells from BV2 neurotoxic responses. In addition, the activation of PI3K/Akt signaling pathway by HTP-1 were confirmed. The PI3K/Akt activation was found to be mediated through transforming growth factor-β (TGF-β) induction by HTP-1. Furthermore, this signaling pathway was found to up-regulate the expression of pro survival protein expression in PC12 cells. Collectively, HTP-1 has potent protective effect against neuronal cells death in in vitro model of Alzheimer's disease.