Identification of ginkgolide targets in brain by photoaffinity labeling

Ginkgolides are terpene trilactones in Ginkgo biloba, a popular medicinal herb for memory disorders. Although ginkgolides are known for various neurobiological effects, their macromolecular target in brain is unknown. In this work, we employed benzophenone derivatives of ginkgolides to identify their binding target in brain. Photolabeling of bovine hippocampus homogenates identified a series of α‐tubulin isotypes. Selective photolabeling of α‐tubulin over β‐tubulin, which is equally abundant in brain, suggested that ginkgolides might modulate microtubule biology differently than typical microtubule‐binding agents, such as taxol. In fact, ginkgolide A did not affect microtubule polymerization or cell proliferation; instead, it inhibited detyrosination of α‐tubulin and reorientation of microtubule‐organizing centers. Taken together, the current findings indicate that ginkgolides constitute a new class of microtubule‐binding agents with distinct effects on α‐tubulin biology.     

In situ saphenous vein bypass grafts: angiographic evaluation and interventional repair of complications

In situ saphenous vein grafts are being used with increasing frequency for bypass procedures involving the femoral and popliteal arteries. Complications of these procedures include anastomotic stenoses and persistent arteriovenous fistulae that may result in failure of the graft. Balloon angioplasty and embolotherapy with detachable balloons were employed successfully in three or four recent cases of patients with complications from in situ grafts. Tailored angiography is essential for evaluating in situ grafts, and interventional techniques are extremely useful for managing complications.     

激素治疗增加绝经后健康妇女尿失禁的发病率和严重程度

问题：在绝经后健康妇女中，激素治疗（hormone therapy，HT）对尿失禁（urinary incontinence，UI）的效果如何？     

重复胃镜检查的原因分析

0　引言　胃镜检查是上消化道疾病诊断的重要方法之一 .了解重复胃镜检查的原因及结果 ,有利于探讨疾病发生发展的基本规律 ,有利于发现诊断和治疗中存在的问题 ,从而提高对消化疾病的诊治水平 .1　材料和方法1.1　材料　随机抽检 1996 / 1998胃镜检查资料为调查对象7812例 ,其中行 2次以上胃镜检查者 937例 .调查内容包括性别、年龄、职业、主要症状和体征、病程、初步诊断、内镜检查时间、次数、内镜诊断、病理诊断、确诊时间 .1.2　方法　回顾性调查上述材料的临床特征 .列表统计研究对象一般情况的分布状况 ,计算各年龄段比例构成 ,各病…     

Interaction of Nucleoside Analogues with the Sodium–Nucleoside Transport System in Brush Border Membrane Vesicles from Human Kidney

The therapeutic efficacy of nucleosides and nucleoside analogues as antitumor, antiviral, antiparasitic, and antiarrhythmic agents has been well documented. Pharmacokinetic studies suggest that many of these compounds are actively transported in the kidney. The goal of this study was to determine if therapeutically relevant nucleosides or analogues interact with the recently characterized Na⁺-driven nucleoside transport system of the brush border membrane of the human kidney. Brush border membrane vesicles (BBMV) were prepared from human kidney by divalent cation precipitation and differential centrifugation. The initial Na⁺-driven ³H-uridine uptake into vesicles was determined by rapid filtration. The effect of several naturally occurring nucleosides (cytidine, thymidine, adenosine), a pyrimidine base (uracil), a nucleotide (UMP), and several synthetic nucleoside analogues [zidovudine (AZT), cytarabine (Ara-C), and dideoxycytidine (ddC)] on Na⁺–uridine transport was determined. At a concentration of 100 µM the naturally occurring nucleosides, uracil, and UMP significantly inhibited Na+-uridine transport, whereas the three synthetic nucleoside analogues did not. Adenosine competitively inhibited Na+-uridine uptake with a K _i of 26.4 µM (determined by constructing a Dixon plot). These data suggest that naturally occurring nucleosides are substrates of the Na⁺–nucleoside transport system in the renal brush border membrane, whereas synthetic nucleoside analogues with modifications on the ribose ring are not. The K _i of adenosine is higher than clinically observed concentrations and suggests that the system may play a physiologic role in the disposition of this nucleoside.     

Physical properties and stability of two emulsion formulations of propofol

We have compared the physical properties of two commercial emulsion formulations of the intravenous anaesthetic propofol, (Diprivan, AstraZeneca, and Propofol Intravenous Emulsion, Gensia Sicor Pharmaceuticals) which appear to differ primarily in the additive content and formulation pH. Diprivan contains disodium edetate and has a pH of 7-8.5, while the Gensia product contains sodium metabisulphite and is formulated to a pH of 4.5-6.4. The average zeta potential of Diprivan at pH 8 was -50 mV while that of the Gensia product at pH 4-5 was -40 mV. This information suggests that the physical stability of Propofol Intravenous Emulsion should be lower than that of Diprivan. Three random batches of both products were subjected to a range of stability tests, including shaking, thermal cycling, and freeze-thaw cycling, and the emulsion droplet size distribution was then assessed by dynamic light scattering, light diffraction, and electrical and optical zone sensing. Both emulsions initially showed narrow submicrometre particle size distributions. An increased level of droplets larger than 5 microm could be detected in Propofol Intravenous Emulsion after as little as 4 h shaking (300 strokes/min at room temperature) and visible free oil could be detected after 8-12 h shaking. In contrast, Diprivan showed no increase in the large droplet count after shaking for times up to 16 h. A similar difference in the emulsions was found after one freeze-thaw cycle, with Propofol Intravenous Emulsion exhibiting extensive coalescence, while that of Diprivan was at the limits of detection. We conclude that these two products have different physical stability characteristics, and that this may in part be due to the reduced zeta potential in Propofol Intravenous Emulsion compared to that of Diprivan.     

Irregularly shaped small shadows on chest radiographs, dust exposure, and lung function in coalworkers' pneumoconiosis.

The predominant shapes of small opacities on the chest radiographs of 895 British coalminers have been studied. The aims were to determine whether irregular (as distinct from rounded) small opacities can be identified reproducibly, whether their occurrence is related to dust exposure, and whether they are associated with excess prevalence of respiratory symptoms or impairments of lung function. Six of the doctors responsible for regular radiological surveys of all British coalminers each classified all 895 radiographs twice and independently, using the International Labour Organisation's 1980 classification system. The majority view was that 39 films showed predominantly irregular small opacities, 131 showed predominantly small rounded opacities, and 587 showed no small opacities. Readers' opinions varied about the presence and shapes of shadows on the other 138 films. In general, consistency between readers (and within readers on repeated viewings) was satisfactory. The occurrence and profusion of irregular shadows were related significantly both to the men's ages and additionally to their cumulative exposure to respirable coalmine dust as determined from 15 years' dust monitoring close to where the miners had worked. For any given level of exposure, the average level of profusion of the small irregular opacities was less than the corresponding profusion of small rounded opacities. The prevalence rates of chronic cough and phlegm, and of breathlessness, were higher in those with small irregular opacities than in those with no small opacities (category 0/0), but the differences were not statistically significant after adjustment for other factors including smoking habits. The presence of irregular (but not rounded) small shadows was associated with an impairment in respiratory function averaging about 190 ml deficits in both FEV1 and FVC. These deficits were not explicable in terms of the men's ages, body sizes, and smoking habits and they were in addition to the lung function losses attributable to the miners' dust exposure as such. It is concluded that the presence and profusion of small irregular opacities should be taken into consideration when assessing the severity of coalworkers' simple pneumoconiosis.     

Anaplastic renal cell carcinoma following neuroblastoma

Renal cell carcinoma is unusual in children. We report a case of anaplastic renal cell carcinoma arising in a 7-year-old girl following treatment for Stage III neuroblastoma. The renal cell carcinoma has unusual histologic and ultrastructural features, which are discussed. The case is further unusual in that few children with advanced stage neuroblastoma survive long enough to develop second malignant neoplasms. © 1995 Wiley-Liss, Inc.     

New Considerations in the Use of Vaginal Mesh for Prolapse Repair

The proliferation of mesh-based transvaginal prolapse surgical repair methods and products has generated increased scrutiny of the evidence-based foundation in support of these techniques. Recent developments in this arena include the publication of the Society of Gynecologic Surgeons Systematic Review Group, which concluded that supportive evidence for transvaginal mesh is limited, and a Public Health Notification from the Food and Drug Administration (FDA), regarding “serious complications associated with transvaginal placement of surgical mesh in repair of pelvic organ prolapse and stress urinary incontinence.” This article reviews available literature regarding transvaginal mesh use, specifically regarding material, technique, and patient characteristics that may influence the rates of iatrogenic complications of transvaginal mesh prolapse repairs. Compliance with the FDA Public Health Notification is encouraged, and additional clinical practice guidelines are provided.