Vascular complications of Fabry disease: enzyme replacement and other therapies

Fabry disease is an X-linked glycosphingolipid storage disorder resulting from deficiency of α-galactosidase A. Storage of globotriaosylceramide ultimately results in multiorgan pathology, including cerebrovascular, cardiovascular and renal disease. Vascular involvement is evident throughout the body but the mechanisms by which storage on a cellular level leads to end-organ pathology are unknown. Here the evidence for abnormal blood flow, vessel architecture and endothelial function will be reviewed and possible models of vascular pathology discussed. The effects of reversal of storage within vessels by enzyme replacement therapy (ERT) and the possibilities for intervention with additional agents will be considered.
Conclusion: The pathology of Fabry disease has an important vascular component, although the underlying pathophysiology is unclear. Preliminary evidence suggests that ERT may have beneficial effects on the vascular component of this multisystem disease.     

Antidepressant Befol Synthesized Via Interaction of 4-Chloro-N-(3-chloropropyl)benzamide with Morpholine

Pharmaceutical Chemistry Journal -     

糖尿病患者左心室功能的脉冲多普勒超声心动图评价

目的　评价糖尿病患者的左心室功能。方法　应用脉冲多普勒超声心动图对比观测 4 8例有、无并发症的非胰岛素依赖型糖尿病 (NIDDM)患者及 4 0例正常人的左心室功能。结果　NIDDM患者的左心室舒张及收缩功能均减退 ,早期以舒张功能减退为甚 ,继之 ,收缩功能受损。结论　高血压、冠心病、微血管病变等并发症可进一步加重舒张功能的损害     

转化生长因子β2诱导人小梁细胞凋亡的体外研究

目的　观察转化生长因子 β2 (transforminggrowthfactor β2 ,TGF β2 )是否能诱导体外培养人眼小梁细胞 (humantrabecularmeshworkcells,HTMC)发生凋亡。方法　将体外培养的第 3～ 5代人眼小梁细胞分为对照组和实验组 ,实验各组分别经 0 .32、1.0 0、3.2μg·L-1TGF β2 作用 4 8h后 ,分别用透射电镜、TUNEL法和流式细胞术检测细胞凋亡的诱导情况。结果　透射电镜观察发现凋亡细胞典型的形态学变化———核染色质凝集边集 ,凋亡小体形成等。TUNEL法检出发生DNA片段化的HTMC。经流式细胞术定量分析 ,不同浓度TGF β2 处理的HTMC凋亡细胞百分数分别为 ( 2 .79± 0 .4 4 ) %、( 4 .4 3±1.17) %、( 9.6 0± 2 .0 5 ) % ,其中 1、3.2 μg·L-1TGF β2 处理组与对照组 ( 1.4 1± 0 .34) %相比分别有显著差异和极显著差异。结论　TGF β2 能诱导体外培养HTMC发生凋亡 ,推测其可能参与了原发性开角型青光眼患者和正常人衰老过程中HTMC数目的减少。     

Chromosome aberrations in the radiation-exposed residents around Mayak Nuclear Facility in the Chelyabinsk region,Russia

Between 1949 and 1957 Mayak Nuclear Facility located in the Chelyabinsk region released some discharges of radiochemical production wastes into the Techa River and Lake Karachay which resulted in an extensive contamination of large territories with long-lived radionuclides such as ⁹⁰Sr, ¹³⁷Cs, ²³⁹Pu. Between 1994 and 1996 our research team conducted both the chromosome analysis and the electron-spin resonance (ESR) spectrometry of tooth enamel in the radiation-exposed residents of four settlements in the Techa basin. We observed significantly increased levels of chromosome aberrations in the radiation-exposed residents as compared to the controls. The ESR signal intensity and the chromosome aberration frequency in lymphocytes of the tooth donors showed a good correlation. Moreover, there was a good correlation between the level of whole-body ⁹⁰Sr activity detected by human radiation counter (HRC) and the frequency of chromosome aberrations among the radiation-exposed residents. The data showed that 15% of the inhabitants of the Muslyumovo settlement received a radiation dose exceeding 100 cGy. A large increase of chromosome damage was observed in the people born between 1949 and 1957. Therefore, the accidents at Mayak Nuclear Facility (MNF) caused the serious radionuclide contamination of the Chelyabinsk region. We suppose that radionuclides incorporated in the body, particularly, in the bone marrow are responsible for the chromosome aberrations in the inhabitants. ©1999 John Wiley & Sons, Inc. Environ Toxicol 14: 414–423, 1999     

基于UPLC-MS骨质疏松症阴虚证临床代谢标志物筛查研究

目的 筛查“肝肾阴虚证”原发性骨质疏松症患者的血清小分子差异代谢物。方法 筛选门诊符合“肝肾阴虚”证型的患者。通过纳入排除标准,筛选出肝肾阴虚组（I组）、正常组（CK组）各30例。运用UPLC-MS技术检测两组受试者血清小分子代谢物,并进行差异分析,筛选肝肾阴虚证型的差异代谢物。结果 共鉴定出小分子代谢物6 478个。初始筛选标准为OPLS-DA模型第一主成分的VIP > 1,t检验的P < 0.05。筛选I-CK组差异代谢物418个。进一步筛选标准为：①VIP > 1;②P＜0.05;③log2(FC) > 1 或者 < ?1;④Fragment score ≠ 0。共筛选出15个肝肾阴虚证差异性代谢物（氨基酸类6个：甘氨胆酸、苯丙氨酸、亮氨酸、异亮氨酸、蛋氨酸、氨基吡唑基丙酸;生物碱类2个：茶碱,骆驼蓬总碱;胆红素类2个：胆红素、(4E,15Z)-胆红素;磷脂类1个：溶血磷脂酰乙醇胺;恶唑类1个：2-甲基-4-戊氯恶唑;酚酯类1个：二苯氧苯胺;低聚肽类1个：乳基谷胱甘肽;二萜类1个：15-O DC。结论 筛选出骨质疏松症阴虚证的潜在临床代谢标志物,可用于下一步代谢通路研究。提示代谢组学技术在探索传统中医理论本质及中医药临床研究方面,具有较为广泛的应用前景。     

糖尿病患者尿微量蛋白变化与胰岛素抵抗关系的探索

目的 探讨尿微量清蛋白(mAlb),尿β2微球蛋白(β2-MG)在2型糖尿病肾病(DN)中的变化及与胰鸟素抵抗(IR)的关系.方法 检测95例2型糖尿病(T2DM)患者和25例健康体检者的尿mAlb、尿β2-MG、空腹血糖(FPG)、空腹胰岛素(F1NS),用改进稳态模型计算胰岛素抵抗指数(Homa-IR),观察各指标在不同病程中的变化,比较相同病程中各指标阳性率,分析Homa-IR与尿mAlb和β2-MG的相关性.结果 糖尿病组mAlb、β2-MG、FPG、F1NS和Homa-IR显著高于对照组;10年以上病程各指标均显著高于5年以下病程,5～10年病程的mAlb、β2-MG和FPG也显著高于5年以下病程,差异有统计学意义(P＜0.01,P＜0.05);5～10年病程和10年以上病程各指标阳性率差异无统计学意义,但5年以下病程中β2-MG阳性率显著高于mAlb、F1NS和Homa-IR的阳性率也显著高于mAlb,差异有统计学意义(P＜0.01);Homa-IR与尿mAlb和β2-MG呈正相关.结论 IR与T2DM肾损伤的尿微量蛋白有关,尿mAlb和β2-MG是早期诊断DN的灵敏指标,在DN初期,尿β2-MG灵敏度高于尿mAlb.     

DFT Modelling of Molecular Structure,Vibrational and UV-Vis Absorption Spectra of T-2 Toxin and 3-Deacetylcalonectrin

This paper discusses the applicability of optical and vibrational spectroscopies for the identification and characterization of the T-2 mycotoxin. Vibrational states and electronic structure of the T-2 toxin molecules are simulated using a density-functional quantum-mechanical approach. A numerical experiment aimed at comparing the predicted structural, vibrational and electronic properties of the T-2 toxin with analogous characteristics of the structurally similar 3-deacetylcalonectrin is performed, and the characteristic spectral features that can be used as fingerprints of the T-2 toxin are determined. It is shown that theoretical studies of the structure and spectroscopic features of trichothecene molecules facilitate the development of methods for the detection and characterization of the metabolites.     

两种方法治疗慢性分泌性中耳炎的疗效比较

目的 探讨鼻内镜下行咽鼓管置管术治疗慢性分泌性中耳炎的疗效,并观察和分析咽鼓管咽口形态与分泌性中耳炎的关系.方法 将慢性分泌性中耳炎患者73例(88耳)随机分成置管组和对照组,分别行鼻内镜下的咽鼓管置管术和传统的咽鼓管吹张术,术后随访3个月,比较两组疗效.结果 置管组38例(45耳):治愈17耳,占37.8%,好转21耳,占46.6%,总有效率84.4%;对照组35例(43耳):治愈8耳,占18.6%,好转22耳,占51.2%,总有效率69.8%.治疗后两组治愈率差异有显著性意义(P＜0.05).结论 鼻内镜下咽鼓管置管术具有微创、安全、简单、疗效好等特点,是治疗慢性分泌性中耳炎的一个良好方法;咽鼓管咽口形态可分五种类型,与分泌性中耳炎有着密切的联系.