Tracking extended mucociliary transport activity of individual deposited particles: longitudinal synchrotron X‐ray imaging in live mice

To assess potential therapies for respiratory diseases in which mucociliary transit (MCT) is impaired, such as cystic fibrosis and primary ciliary dyskinesia, a novel and non‐invasive MCT quantification method has been developed in which the transit rate and behaviour of individual micrometre‐sized deposited particles are measured in live mice using synchrotron phase‐contrast X‐ray imaging. Particle clearance by MCT is known to be a two‐phase process that occurs over a period of minutes to days. Previous studies have assessed MCT in the fast‐clearance phase, ～20 min after marker particle dosing. The aim of this study was to non‐invasively image changes in particle presence and MCT during the slow‐clearance phase, and simultaneously determine whether repeat synchrotron X‐ray imaging of mice was feasible over periods of 3, 9 and 25 h. All mice tolerated the repeat imaging procedure with no adverse effects. Quantitative image analysis revealed that the particle MCT rate and the number of particles present in the airway both decreased with time. This study successfully demonstrated for the first time that longitudinal synchrotron X‐ray imaging studies are possible in live small animals, provided appropriate animal handling techniques are used and care is taken to reduce the delivered radiation dose.     

Procyanidins are potent inhibitors of LOX-1: a new player in the French Paradox

Lectin-like oxidized LDL receptor-1 (LOX-1) is an endothelial receptor for oxidized LDL (oxLDL) and plays multiple roles in the development of cardiovascular diseases. We screened more than 400 foodstuff extracts for identifying materials that inhibit oxLDL binding to LOX-1. Results showed that 52 extracts inhibited LOX-1 by more than 70% in cell-free assays. Subsequent cell-based assays revealed that a variety of foodstuffs known to be rich in procyanidins such as grape seed extracts and apple polyphenols, potently inhibited oxLDL uptake in Chinese hamster ovary (CHO) cells expressing LOX-1. Indeed, purified procyanidins significantly inhibited oxLDL binding to LOX-1 while other ingredients of apple polyphenols did not. Moreover, chronic administration of oligomeric procyanidins suppressed lipid accumulation in vascular wall in hypertensive rats fed with high fat diet. These results suggest that procyanidins are LOX-1 inhibitors and LOX-1 inhibition might be a possible underlying mechanism of the well-known vascular protective effects of red wine, the French Paradox.     

氧自由基与心血管疾病

随着氧自由基（ＯＦＲ）在疾病中的研究日趋深入,大量的资料证实氧自由基与充血性心力衰竭,动脉粥样硬化、心肌缺血、心律失常及淋巴细胞与心力衰竭的关系诸方面的发生,发匀有密切关系。     

The role of TLC in the screening of inherited metabolic diseases

Summary Thin-layer chromatography (TLC) is a rapid, reliable and inexpensive screening technique for diagnosis of inherited metabolic diseases (IMD). Our screening program encompasses five main situations where the use of TLC is considered to be vindicated: (i) analysis of amino acids; (ii) screening for sugar defects; (iii) detection of pathological oligosaccharidurias; (iv) screening for organic acid disorders; and (v) detection of abnormalities in tryptophan metabolism. Examples are presented of chromatograms obtained from pathological samples. Presented at the 21^st ISC held in Stuttgart, Germany, 15^th–20^th September, 1996     

包头市青山区8～10岁儿童碘缺乏病甲状腺肿大率及尿碘监测分析

调查了内蒙古青山区８～１０岁儿童碘缺乏病甲状腺肿大率，结果表明，甲状腺肿大率为１９．６％，且以城乡结合部居住儿童为高，监测了其尿碘，尿碘水平１００μｇ／Ｌ以下者为１１．２％，其中５０μｇ／Ｌ者了有发现，据此情况，今后仍要强化防治工作。     

血液病与微量元素关系的研究

研究了血液病与微量元素的关系,发现再生障碍性贫血患者治疗前血清Ｃｕ升高（Ｐ〈０．０５）,缓解后Ｃｕ恢复正常。骨髓增生异常综合征（ＭＤＳ）中ＲＡ＋ＲＡＳ组Ｃｕ及Ｃｕ／Ｚｎ比值高,Ｚｎ值降低不明显;ＲＡＥＢ＋ＲＡＥＢ－Ｔ组Ｃｕ及Ｃｕ／Ｚｎ高,Ｚｎ值明显降低（Ｐ〈０．０５）。急性白血病、淋巴瘤、多发性骨髓瘤及慢粒患者血清Ｃｕ、Ｚｎ及Ｃｕ／Ｚｎ比值与对照组比较均呈显著差异（Ｐ〈０．０５￣０．０１）,而缓解     

Molecular dynamics and pharmacophore modelling studies of different subtype (ALK and EGFR (T790M)) inhibitors in NSCLC

Extensively validated 3D pharmacophore models for ALK (anaplastic lymphoma kinase) and EGFR (T790M) (epithelial growth factor receptor with acquired secondary mutation) were developed. The pharmacophore model for ALK (r² = 0.96, q² = 0.692) suggested that two hydrogen bond acceptors and three hydrophobic groups arranged in 3-D space are essential for the binding affinity of ALK inhibitors. Similarly, the pharmacophore model for EGFR (T790M) (r² = 0.92, q² = 0.72) suggested that the presence of a hydrogen bond acceptor, two hydrogen bond donors and a hydrophobic group plays vital role in binding of an inhibitor of EGFR (T790M). These pharmacophore models allowed searches for novel ALK and EGFR (T790M) dual inhibitors from multiconformer 3D databases (Asinex, Chembridge and Maybridge). Finally, the eight best hits were selected for molecular dynamics simulation, to study the stability of their complexes with both proteins and final binding orientations of these molecules. After molecular dynamics simulations, one hit has been predicted to possess good binding affinity for both ALK and EGFR (T790M), which can be further investigated for its experimental in-vitro/in-vivo activities.