他达拉非治疗勃起功能障碍的安全性研究进展

勃起功能障碍(erectile dysfunction,ED)是中老年人的常见疾病。他达拉非自2002年10月开始用于治疗ED,其疗效确切,安全性高,因此越来越多的患者选择他达拉非来治疗ED。目前对他达拉非的作用机制、药代动力学、疗效、安全性等方面已经有了较多的基础及临床研究资料。本文就他达拉非治疗ED的安全性做一综述,以求该药物在临床上得到更安全的使用,为临床医生选择使用该类药物提供参考。     

Mechanism of uptake and retention of F-18 BMS-747 158-02 in cardiomyocytes: a novel PET myocardial imaging agent

Background BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02 was studied in vivo in mice. Methods and Results Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC₅₀ of 16.6±3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC₅₀ of 18.2±6.7 nmol/L, 19.8±2.6 nmol/L, and 23.1±1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers of neonatal rat cardiomyocytes (10.3%±0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91%±2%) and deguelin (89%±3%). In contrast, an inactive pyridaben analog, P-0 (IC₅₀ value>4 μmol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t_1/2) uptake was very rapid (approximately 35 seconds), and washout t_1/2 for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02 had substatial myocardial uptake (9.5%±0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver ratios of 14.1±2.5 and 8.3±0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization and demonstrated sustained myocardial uptake through 55 minutes. Conclusions F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake and slow washout. These characteristics allow fast and sustained accumulation in the heart.     

血管性勃起功能障碍动物模型的建立

目的探索建立血管性勃起功能障碍(ED)动物模型。方法雄性新西兰大白兔给予胆固醇及高脂饮食,同时用球囊导管损伤双侧髂内动脉内皮。测定术后4周、8周血脂并观察阴茎勃起情况、交配情况,同时用阴茎海绵体注射盐酸罂粟碱、阴茎血管双核素检查、髂内动脉数字减影造影(DSA)等方法研究勃起功能。结果与对照组相比,术后4周、8周模型组动物出现明显高脂血症,勃起程度明显下降,交配实验的各项观察指标均显著降低(P＜0.01),动脉造影显示双侧髂内动脉管腔直径明显缩小,双核素检查动脉显像指数(PIA)及静脉显像指数(PIV)明显降低,但第4周的模型组与对照组PIV结果没有统计学差异(P＞0.05)。结论高脂、高胆固醇饮食同时用球囊导管扩张动物髂内动脉,可以加速模型的形成,从而用于血管性ED的进一步研究。     

2型糖尿病患者的智能障碍

目的：调查没有临床神经损害体征的2型糖尿病患者早期的高级神经功能改变，方法：分别对52例2型糖尿病患者和32名健康对照者进行了韦氏智力量表的相似、数字广度、数字符号、木块图等4项分测验测定，采用二合一(相似、木块图)的方法计算简式智商，同时进行事件相关电位检查，结果：糖尿病患者组的相似、木块图分测验成绩和简式智商明显较健康对照组低下，ERP检查发现病人组N2、P3潜伏期较对照组明显延长，结论：2型糖尿病可导致高级神经功能损害。并且这种损害可能要早于周围神经损害。     

精神分裂症患者的记忆功能障碍与精神症状和疗效的关系

目的　探讨精神分裂症记忆功能与精神症状和疗效的关系。方法　对 88例精神分裂症患者分别给予奎的平、舒必利、维思通治疗。采用PANSS量表评定精神症状 ,修订韦氏成人记忆量表 (WMS -RC)测查记忆功能(治疗前用甲式 ,治疗后用乙式 )分别于治疗前、治疗后第 6周末各评一次 ,并采用Pearson相关分析和多元逐步回归进行分析。结果　治疗前记忆商数与阴性症状、一般病理性症状、PANSS总分呈显著负相关 ,与阳性症状无相关性 ;多元逐步回归分析显示治疗前记忆商数与阴性症状关系最密切 ;治疗后记忆商数增加值与阴性症状的减分值呈显著正相关 (r=0 337,P <0 0 1,88例 ) ;治疗前记忆商数与治疗第 6周末的阴性症状减分值、一般病理性症状减分值呈显著负相关 (r =- 0 2 6 5 ,P <0 0 5 ;r =- 0 2 35 ,P <0 0 5 ,88例 )。结论　本研究支持精神分裂症记忆损害与阴性症状存在相似的病理机制假说。     

Neurally Augmented Sexual Function in Human Females: A Preliminary Investigation

Objective. Neurally augmented sexual function (NASF) is the production of pleasurable genital stimulation and subsequent orgasm through the application of electrical energy to provide stimulation of the spinal cord or peripheral nerves. The purpose of this paper is to demonstrate the reproducibility of this phenomenon. Materials and Methods. Eleven otherwise healthy women, ages 32–60 years, were selected for this study. Through standard techniques, quadripolar (octopolar in the final patient) leads were placed in the epidural space percutaneuously. The lead was maneuvered initially to an L1–L2 position and then repositioned based on feedback from the patient. The patients were allowed to utilize the device ad libitum for up to 9 days. Results. Successful stimulation was achieved in 91% (10/11) of patients. These women described a greater frequency in sexual activity, increased lubrication, and overall satisfaction. A smaller subset had substantial improvement in sexual function as measured by orgasmic capacity. This subset consisted of women with secondary anorgasmia. A return of orgasmic capacity was found in 80% (4/5) of patients having secondary anorgasmia with an average intensity of ≥ 3/5 while using the device. Once the device was removed, the patients returned to their previous anorgasmic status. Conclusions. Pleasurable genital stimulation of the spinal cord is a consistently reproducible phenomenon. In a subset of the population studied, improvement in orgasmic function was noted. This was noted in the group with secondary orgasmic dysfunction.     

经尿道等离子双极电切术和TURP治疗BPH术后阴茎勃起功能障碍的比较

目的探讨经尿道等离子双极电切术(PKRP)治疗良性前列腺增生(BPH)术后对阴茎勃起功能的影响。方法PKRP、经尿道前列腺电切术(TURP)治疗BPH各95例,评价其术后1个月、3个月及1年阴茎勃起功能。结果PKRP、TURP术后1个月、3个月及1年阴茎勃起功能障碍(ED)发生率分别是3．2％、2．1％、2．1％和13．7％、10．5％、9．5％。结论PKRP术后ED发生率比TURP低,是一种对阴茎勃起功能较为安全的治疗良性前列腺增生的方法。     

多脏器功能不全综合征患者并发肠源性感染的胃肠功能保护

目的 探讨多脏器功能不全综合征(MODS)患者肠源性感染时胃肠功能管理及预后。方法对32例MODS中伴胃肠衰竭的13例患者的临床资料进行分析。结果 32例MODS患者中，伴发胃肠功能衰竭者13例，ll例成活，2例死亡，死亡率15、4％。结论 重视胃肠功能管理，加强胃肠功能保护是提高MODS患者救治率的重要因素。