口服佐洛复、万艾可或可多华治疗早泄的疗效比较

目的比较佐洛复、万艾可和可多华治疗早泄的临床效果。方法120例早泄病人随机分成4组:对照组(单纯行为疗法组)、可多华+行为疗法组、万艾可+行为疗法组和佐洛复+行为疗法组,记录病人治疗前后阴道内射精潜伏期并进行组内和组间比较,同时记录夫妻对性生活的满意程度。结果治疗前4组阴道内射精潜伏期分别为(0.8000±0.1983)min、(0.8933±0.3216)min、(0.7333±0.2397)min和(0.8500±0.2910)min,治疗后分别为(1.8200±0.5413)min、(2.6467±0.6726)min、(3.6333±0.5542)min和(4.8533±0.5710)min。从夫妻对性生活满意度来看,疗效由低到高也分别为单纯行为疗法组、可多华+行为疗法组、万艾可+行为疗法组和佐洛复+行为疗法组。结论在治疗早泄方面,佐洛复优于万艾可和可多华,可作为治疗早泄的一线用药。如病人合并勃起功能障碍,可试用万艾呵,如病人合并前列腺增生可试用可多华,但万艾可和可多华治疗早泄的临床资料不多,尚需进一步研究。     

万艾可对促排卵期子宫发育不良患者内膜容受性的影响

目的:探讨万艾可在促排卵过程中对子宫内膜过薄患者内膜厚度及血流动力学的影响。方法:122例既往促排卵周期中子宫内膜生长不良的不孕症患者随机分为两组,A组(65例):于克罗米芬(CC)/人绒毛膜促性腺激素(hCG)促排卵第8天阴道放置万艾可(100 mg/d)至排卵,B组(57例)单纯CC/hCG促排卵。检测用药前后两组患者子宫内膜厚度、内膜形态学变化、子宫动脉血流搏动指数(PI)和血流阻力指数(RI)、以及妊娠率。结果:A组子宫内膜明显增厚,子宫内膜三线征发生率明显增高(P<0.05),PI和RI值显著降低(P<0.01),妊娠率(26.2%)也显著高于B组(10.5%)(P<0.05)。结论:万艾可能促进子宫内膜生长、改善子宫内膜容受性,有助于胚胎着床,提高妊娠率。     

Ecstasy and the concomitant use of pharmaceuticals

Recent anecdotal evidence suggests that it is becoming increasingly popular among ecstasy users to attempt to negate certain side-effects or enhance the drug experience through the concomitant use of pharmaceutical drugs or supplements. This study was designed to explore the practice of deliberately using pharmaceuticals for any reason in association with ecstasy and related drug (ERD) use. A cross sectional survey was conducted with 216 adults who had used ecstasy at least once in the previous 6 months. Generally, this sample was young, well educated, and likely to be in some form of paid employment. Males were slightly overrepresented within the sample. About one quarter of the sample had deliberately taken a pharmaceutical substance for its putative effects on the euphoric effects of, or recovery from, ecstasy use. Those who reported using pharmaceuticals were significantly more likely to be male, had more 'apparent' years of use, and were more likely to have injected ERDs. As a result, there appears to be a need for harm reduction information for ecstasy users regarding the risks associated with the mixture of ERDs with pharmaceuticals and supplements. Particular attention should be paid to informing users of the potentially fatal serotonin syndrome that is likely to arise from combining serotonin-enhancing substances, such as ecstasy or SSRI and MAOI groups of antidepressants.     

Sildenafil Associated Pupil-Sparing Third Nerve Palsy

Purpose: We present, to our knowledge, the second case report of pupil-sparing third nerve palsy following the use of sildenafil citrate in a man with insulin-dependent diabetes mellitus (IDDM). Case: A 44-year-old man with IDDM for 25 years developed a pupil-sparing third nerve palsy within 12 hours after 50 mg of sildenafil intake. During this attack, HBA1c levels were elevated. Third nerve palsy recovered completely in 10 weeks following blood glucose level regulation. Conclusion: Sildenafil citrate may provoke pupil-sparing third nerve palsy in patients with systemic vascular diseases.     

蚕茸柱天胶囊联合小剂量万艾可治疗阳痿疗效观察

目的：观察蚕茸柱天胶囊联合小剂量万艾可治疗阳痿的,临床疗效。方法：60例符合诊断标准与纳入标准的阳痿患者采用区组随机观察化方法分配到实验组与对照组。其中实验组口服蚕茸柱天胶囊及小剂量万艾可;对照组单纯服用常规剂量万艾可,疗程均为8周。观察两组治疗前后国际勃起功能评分（IIEF-5）、TSS伴侣评分及中医症状积分的变化情况。结果：治疗前两组间基线特征均衡性良好（P〉0．05）;两组服药后对勃起功能改善的有效率比较,差异无显著性意义（P〉0．05）;IIEF-5评分每组治疗前后相比,差异有统计学意义（P〈0．05）;治疗后两组IIEF-5评分及TSS伴侣评分比较,差异具有显著性意义（P〈0．05）;治疗后实验组中医症状积分较治疗前明显降低（P〈0．05）,而对照组中医症状积分前后对比变化不大（P〉0．05）。结论：蚕茸柱天胶囊联合小剂量万艾可治疗阳痿不仅能够明显改善阴茎勃起状况,还可降低中医症状积分,提高患者的生活质量。     

An insight into the pharmacophores of phosphodiesterase-5 inhibitors from synthetic and crystal structural studies

Selective inhibitors of cyclic nucleotide phosphodiesterase-5 (PDE5) have been used as drugs for treatment of male erectile dysfunction and pulmonary hypertension. An insight into the pharmacophores of PDE5 inhibitors is essential for development of second generation of PDE5 inhibitors, but has not been completely illustrated. Here we report the synthesis of a new class of the sildenafil derivatives and a crystal structure of the PDE5 catalytic domain in complex with 5-(2-ethoxy-5-(sulfamoyl)-3-thienyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (12). Inhibitor 12 induces conformational change of the H-loop (residues 660-683), which is different from any of the known PDE5 structures. The pyrazolopyrimidinone groups of 12 and sildenafil are well superimposed, but their sulfonamide groups show a positional difference of as much as 1.5A. The structure-activity analysis suggests that a small hydrophobic pocket and the H-loop of PDE5 are important for the inhibitor affinity, in addition to two common elements for binding of almost all the PDE inhibitors: the stack against the phenylalanine and the hydrogen bond with the invariant glutamine. However, the PDE5-12 structure does not provide a full explanation to affinity changes of the inhibitors. Thus alternatives such as conformational change of the M-loop are open and further structural study is required.     

安特尔加枸橼酸西地那非治疗中老年勃起功能障碍的价值

目的探讨安特尔加枸橼酸西地那非治疗男性勃起功能障碍的价值.方法随机开放120名受试者在2周筛选期后进入4周的治疗期,A组安特尔加枸橼酸西地那非,安特尔120mg/d,枸橼酸西地那非4周内至少服用4次.B组单用枸橼酸西地那非.在筛选期及研究结束时填写国际勃起功能问卷(ⅡEF).研究者根据受试者记事表、ⅡEF和总评题对受试者进行疗效评价.结果增加安特尔后并不提高枸橼酸西地那非的临床总有效率,总评题及性交成功率,但明显改善了病人的性欲,提高了性满足感及性高潮的次数,两组差距有统计学意义.服药后无严重不良事件发生.结论对于性欲较低的ED患者,安特尔加枸橼酸西地那非治疗是有价值的.     

Erythropoietin in Recurrent Anterior Ischaemic Optic Neuropathy

A 44-year-old man suffered sequential episodes of anterior ischaemic optic neuropathy in first the left and then right eye. He had suffered a previous episode of anterior ischaemic optic neuropathy in the right eye. Recent studies have shown neuroprotective properties of erythropoietin. Based on our previous studies on erythropoietin in anterior ischaemic optic neuropathy, we used intravenous erythropoietin in this patient. The patient received intravenous human recombinant erythropoietin. Visual functions significantly improved following treatment. Intravenous erythropoietin, as a neuroprotective agent, may herald a new modality of treatment in anterior ischaemic optic neuropathy.     

Influence of sildenafil on lung diffusion during exposure to acute hypoxia at rest and during exercise in healthy humans

We sought to determine the influence of sildenafil on the diffusing capacity of the lungs for carbon monoxide (DL_CO) and the components of DL_CO (pulmonary capillary blood volume V _c, and alveolar–capillary membrane conductance D _M) at rest and following exercise with normoxia and hypoxia. This double-blind placebo-controlled, cross-over study included 14 healthy subjects (age = 33 ± 11 years, ht = 181 ± 8 cm, weight = 85 ± 14 kg, BMI = 26 ± 3 kg/m², peak normoxic VO₂ = 36 ± 6 ml/kg, mean ± SD). Subjects were randomized to placebo or 100 mg sildenafil 1 h prior to entering a hypoxic tent with an FiO₂ of 12.5% for 90 min. DLCO, V _c, and D _M were assessed at rest, every 3 min during exercise, at peak exercise, and 10 and 30 min post exercise. Sildenafil attenuated the elevation in PAP at rest and during recovery with exposure to hypoxia, but pulmonary arterial pressure immediately post exercise was not different between sildenafil and placebo. Systemic O₂ saturation and VO_2peak did not differ between the two conditions. DL_CO was not different between groups at any time point. V _C was higher with exercise in the placebo group, and the difference in D _M between sildenafil and placebo was significant only when corrected for changes in V _c (D _M/V _c = 0.57 ± 0.29 vs. 0.41 ± 0.16, P = 0.04). These results suggest no effect of sildenafil on DLCO, but an improvement in D _M when corrected for changes in V _c during short-term hypoxic exposure with exercise.