Prostaglandin ethanolamides (prostamides): in vitro pharmacology and metabolism

We investigated whether prostaglandin ethanolamides (prostamides) E(2), F(2alpha), and D(2) exert some of their effects by 1) activating prostanoid receptors either per se or after conversion into the corresponding prostaglandins; 2) interacting with proteins for the inactivation of the endocannabinoid N-arachidonoylethanolamide (AEA), for example fatty acid amide hydrolase (FAAH), thereby enhancing AEA endogenous levels; or 3) activating the vanilloid receptor type-1 (TRPV1). Prostamides potently stimulated cat iris contraction with potency approaching that of the corresponding prostaglandins. However, prostamides D(2), E(2), and F(2alpha) exhibited no meaningful interaction with the cat recombinant FP receptor, nor with human recombinant DP, EP(1-4), FP, IP, and TP prostanoid receptors. Prostamide F(2alpha) was also very weak or inactive in a panel of bioassays specific for the various prostanoid receptors. None of the prostamides inhibited AEA enzymatic hydrolysis by FAAH in cell homogenates, or AEA cellular uptake in intact cells. Furthermore, less than 3% of the compounds were hydrolyzed to the corresponding prostaglandins when incubated for 4 h with homogenates of rat brain, lung, or liver, and cat iris or ciliary body. Very little temperature-dependent uptake of prostamides was observed after incubation with rat brain synaptosomes or RBL-2H3 cells. We suggest that prostamides' most prominent pharmacological actions are not due to transformation into prostaglandins, activation of prostanoid receptors, enhancement of AEA levels, or gating of TRPV1 receptors, but possibly to interaction with novel receptors that seem to be functional in the cat iris.     

螺旋CT三维成像术-SSD的应用

目的：对三维成像技术SSD的临床应用进行探讨。材料与方法：开展SSD病人20例，其中男13例，女7例，年龄24－69岁，采用西门子Balance CT机，进行容积扫功，层厚2mm-4mm，螺距1－2，三维重建图像后处理采用SSD并采取多个角度观察，分析。结果：20例SSD检查成像良好。结论：SSD是非创伤性影像检查，具有安全、简便、价廉的优点，是一种适合临床广泛应用的影像检查方法。     

Cytological findings of ROS1‐rearranged lung adenocarcinoma

ROS1‐rearranged lung adenocarcinoma has been recently identified. We report a case of ROS1‐rearranged lung adenocarcinoma with special emphasis on cytological findings. Here, we report a case of young woman with ROS1‐rearranged lung adenocarcinoma diagnosed by cytology and discuss the clinical, cytological, and molecular findings. Cytologically, the tumor consisted of small tight clusters of cells with high nuclear/cytoplasmic ratio. Nuclei were enlarged and small nucleoli were occasionally observed. Signet‐ring cells were focally identified. Neoplastic cells were positive for ROS1 immunocytochemistry. Subsequently, the translocation of ROS1 gene was confirmed in a histological specimen. In conclusion, the specific histology of adenocarcinoma on cytological materials should promote testing for ROS1 immunohistochemistry. Immunocytochemical detection of ROS1 protein helps identify patients suitable for molecular targeted therapy.     

Pharmacological characterization of a novel antiglaucoma agent,Bimatoprost (AGN 192024)

Replacement of the carboxylic acid group of prostaglandin (PG) F(2alpha) with a nonacidic moiety, such as hydroxyl, methoxy, or amido, results in compounds with unique pharmacology. Bimatoprost (AGN 192024) is also a pharmacologically novel PGF(2alpha) analog, where the carboxylic acid is replaced by a neutral ethylamide substituent. Bimatoprost potently contracted the feline lung parenchymal preparation (EC(50) value of 35-55 nM) but exhibited no meaningful activity in a variety of PG-sensitive tissue and cell preparations. Its activity seemed unrelated to FP receptor stimulation according to the following evidence. 1) Bimatoprost exhibited no meaningful activity in tissues and cells containing functional FP receptors. 2) Bimatoprost activity in the cat lung parenchyma is not species-specific because its potent activity in this preparation could not be reproduced in cells stably expressing the feline FP receptor. 3) Radioligand binding studies using feline and human recombinant FP receptors exhibited minimal competition versus [(3)H]17-phenyl PGF(2a) for Bimatoprost. 4) Bimatoprost pretreatment did not attenuate PGF(2alpha)-induced Ca(2+) signals in Swiss 3T3 cells. 5) Regional differences were apparent for Bimatoprost but not FP agonist effects in the cat lung. Bimatoprost reduced intraocular pressure in ocular normotensive and hypertensive monkeys over a 0.001 to 0.1% dose range. A single-dose and multiple-dose ocular distribution/metabolism studies using [(3)H]Bimatoprost (0.1%) were performed. Within the globe, bimatoprost concentrations were 10- to 100-fold higher in anterior segment tissues compared with the aqueous humor. Bimatoprost was overwhelmingly the predominant molecular species identified at all time points in ocular tissues, indicating that the intact molecule reduces intraocular pressure.     

螺旋CT血管造影及CT仿真内窥镜技术对主动脉夹层的诊断与评价

目的：探讨螺旋CT血管造影（SCTA）及CT仿真内镜（CTVE）技术对主动脉夹层诊断的临床应用价值。材料与方法；12例主动脉夹层行螺旋CT血管造影及二维和三维重建，二维重建包括多平面重建（MPR）及曲面重建（CRI）。三维重建包括表面遮盖成像（SSD）及最大密度投影（MIP），其中6例行主动脉CTVE成像。结果：SCTA横断面CT，MPR及CRI均显示12例主动脉夹层真腔与假腔，剥离内膜，瘤壁钙化及血栓，械断面CT显示4例内膜破裂口，MPR及CRI显示5例内膜破裂口，SSD及MIR显示12例真腔与假腔及剥离内膜，2例主动脉弓分支血管，SSD及MIP图像直观，立体感强，但均不能显示夹层动脉瘤内部结构情况及内膜破口，CTVE显示5例主动脉夹层真腔与假腔及其内壁，剥离内膜。结论：以主动脉SCTA的横断面CT图像为基础。结论其MPR，CRI，SSD，MIP及CTVE图像是诊断与评价主动脉夹层最有效无创伤性检查方法之一。     

喉癌的CT诊断

目的:进一步提高喉癌CT诊断的正确性。材料和方法:回顾分析了40例经手术病理证实的喉癌的CT表现,声门上癌13例,声门癌20例,贯声门癌7例。结果:CT清晰地显示了喉部深浅结构。包括喉旁间隙,会厌前间隙,及声门下区全貌,亦能准确显示肿瘤的大小,位置、浸润范围.软骨侵犯和颈部转移淋巴结。结论:CT诊断明显提高了喉癌T分期的准确性,为保存喉功能手术的选择提供了重要依据,但研究还表明CT诊断喉癌尚有一定的局限性。     

Criteria for choosing clinically effective glaucoma treatment: A discussion panel consensus

Abstract

Background:

In the clinical management of patients at risk for or diagnosed with primary open-angle glaucoma (POAG), the aim of medical treatment is to reduce intraocular pressure (IOP) and then maintain it over time at a level that preserves both the structure and function of the optic nerve.

Objective:

The objective of this report was to establish a consensus on the criteria that should be used to determine the characteristics of IOP-lowering medication.

Methods:

Discussion was held among a panel of 12 physicians considered to be experts in glaucoma to develop a consensus on the criteria used by them to determine the characteristics of the IOP-lowering medication chosen for initial monotherapy and adjunctive treatment of ocular hypertension (OHT) or POAG. Consensus development combined available evidence and the impressions of these physicians regarding the clinical effectiveness of IOP-lowering medication for OHT and POAG. Once the panel identified the criteria, the order of priority and the relative importance of these criteria were then established in the setting of 3 risk categories (low, medium, and high) for a patient to experience significant visual disability from glaucoma over their expected life span.

Results:

The panel identified 5 criteria to determine the characteristics of IOP-lowering medication for OHT and POAG: IOP-lowering effect, systemic adverse events (AEs), ocular tolerability, compliance/administration, and cost of treatment. IOP-lowering effect was consistently ranked as the highest priority and cost as the lowest. The priority of compliance/administration did not vary by clinical situation. Systemic AEs and ocular tolerability were ranked as higher priorities in initial monotherapy than in adjunctive treatment and ranked lower as the risk for visual disability increased. The priority given to the criteria used to determine clinical effectiveness varied both with the risk for functional vision loss from glaucoma and whether initial monotherapy or adjunctive treatment was being considered.

Conclusion:

Glaucoma treatment should be assessed with regard to the need not only to lower IOP but also to minimize systemic and ocular AEs, promote patient compliance, and minimize cost. The order of priority and relative importance given to these treatment criteria will vary as part of individualizing patient care.Key Words: consensus, criteria, intraocular pressure, glaucoma