Detection of glaucomatous damage using multifocal ERG

The first‐order kernel analysis in multifocal electroretinogram (mfERG) using low contrast stimulation is suggested as a way to detect the inner retinal responses in animal studies. In this case report, this protocol is applied to human patients with glaucoma to demonstrate the possibility of using mfERG as a tool to detect glaucomatous damage. Two patients with glaucoma were recruited and had mfERG measurements with the 103‐scaled hexagonal stimulus pattern at low (50 per cent) contrast. Their responses were analysed and compared with those from normal subjects with the mfERG measured under the same condition. In the normal subjects, there were obvious oscillatory components on the ascending and descending limbs of the first‐order kernel response to 50 per cent contrast. In the glaucomatous patients, the oscillatory component on the descending limb was obviously diminished. In addition, this component was significantly diminished in the quadrant with a glaucomatous visual field defect. This suggests that the low‐contrast stimulation condition in mERG measurement may provide a good way to detect glaucomatous damage and this may help in clinical diagnosis of glaucoma.     

Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.     

抽动障碍中医证型与血清单胺类物质的相关性研究

目的 观察抽动障碍不同中医证型患者血清多巴胺、去甲肾上腺素等单胺类神经递质的水平,并探讨各证型之间血清神经递质的水平是否存在差别.方法 采用化学荧光法测定46例抽动障碍患者(病例组)血清多巴胺、去甲肾上腺素水平,并与40例正常儿童(对照组)进行比较.结果 病例组血清多巴胺为0.449μg/ml,对照组为0.210μg/ml;病例组血清去甲肾上腺素为0.227μg/ml,对照组为0.127μg/ml,两组各均值比较,病例组血清多巴胺和去甲肾上腺素均显著高于对照组.病例组外风侵袭、肝风内动型,或兼气郁化火型,或兼脾虚痰聚型,或兼阴虚风动型血清多巴胺水平分别为0.316、0.400、0.235、0.247μg/ml,四者比较有显著性差异;病例组符证型血清去甲.肾上腺素水平分别为0.203、0.224、0.144、0.154μg/ml,四者比较差异有显著性.结论 抽动障碍患者存在多巴胺和去甲肾上腺素水平异常,且各证型血清多巴胺、去甲肾上腺素水平有明显差异,而尤其以外风侵袭、肝风内动兼气郁化火型水平最高.     

Pharmacology of the internal anal sphincter and its relevance to faecal incontinence

1 The internal anal sphincter (IAS) has a spontaneous tone and is the main contributor to the maintenance of faecal continence. The spontaneous resting tone exhibited by the sphincter can be modified by neurotransmitters from the autonomic and enteric nervous systems. 2 In this review, the influence of the sympathetic and parasympathetic nervous systems on IAS tone are discussed and the putative roles of nitric oxide, carbon monoxide, vasoactive intestinal peptide and adenosine triphosphate in non‐adrenergic non‐cholinergic transmission are considered. 3 Faecal incontinence is a common condition that places a heavy financial burden on the health service and severely affects patients’ quality of life. Resting anal pressure is reduced in patients with faecal incontinence and agents that increase sphincter tone tend to relieve symptoms. The results of clinical studies of the use of phenylephrine to treat faecal incontinence are reviewed. 4 It is concluded that the IAS is a potential target for drug development for the treatment of faecal incontinence.