磷酸二酯酶4抑制剂治疗特应性皮炎的研究进展

目前特应性皮炎的治疗主要是外用糖皮质激素(激素)和钙调磷酸酶抑制剂,重症患者可以联合口服免疫抑制剂和光疗。尽管糖皮质激素外用制剂的疗效显著且不良反应少,但患者的恐激素心理限制了其临床应用。临床需要一种更安全、不良反应更小的外用非激素类抗炎药物来治疗特应性皮炎。磷酸二酯酶4(phosphodiesterase 4,PDE4)抑制剂通过降解环磷酸腺苷参与调控促炎性细胞因子的释放。特应性皮炎患者炎性细胞中PDE4的活性增加,导致促炎性细胞因子和趋化因子的产生增加。靶向PDE4治疗可减少促炎症递质的产生。局部外用和口服PDE4抑制剂均已被证实安全性较好。2%crisaborole软膏,已被美国食品和药物管理局批准用于治疗2岁以上儿童和成人特应性皮炎。其他PDE4抑制剂正处于临床试验阶段,已经公布的有效性和安全性结果提示其用于特应性皮炎的治疗具有良好前景。     

小分子靶向药物在皮肤病领域的研究进展

小分子靶向药物作为新型药物,正处于治疗皮肤病临床试验研究前沿,包括Janus激酶(JAK)抑制剂,磷酸二酯酶(PDE)抑制剂和蛋白激酶C(PKC)抑制剂等。为进一步提高疗效,减少不良反应和治疗成本,阻断特异性细胞因子作用的小分子靶向药物逐步用于治疗部分难治性皮肤病。本文就小分子靶向药物在皮肤病领域中的研究进展进行综述。     

EECP联合小剂量PDE5i治疗有生育要求ED患者的临床分析

目的探讨增强型体外反搏(EECP)联合小剂量5型磷酸二酯酶抑制剂(PDE5i)治疗有生育要求勃起功能障碍(ED)患者的治疗效果。方法选取2014年6月1日至2018年5月31日山东大学附属生殖医院泌尿外科和生殖男科诊治的197例有生育要求的ED患者作为研究对象。对这197例患者进行了EECP与小剂量PDE5i的联合治疗,我们回顾性分析了他们的一般资料、精液参数、配偶妊娠结局、治疗前与治疗后的IIEF-5评分和血压。结果患者治疗后的IIEF-5评分较治疗前有显著性升高,差异具有统计学意义(P0.01),治疗后的收缩压较治疗前有显著性降低,差异具有统计学意义(P=0.013),治疗后的舒张压较治疗前的差异无统计学意义(P=0.144)。26例患者的配偶获自然妊娠,共获21个足月儿。结论 EECP联合小剂量PDE5i可显著改善ED患者的勃起功能,使部分患者配偶获得自然妊娠,为有生育要求的ED患者提供了一种无创、经济、安全和有效的治疗方法。     

十一酸睾酮+PDE5抑制剂治疗糖尿病勃起功能障碍的Meta分析

目的系统评价十一酸睾酮+PDE5(5型磷酸二酯酶)抑制剂治疗糖尿病勃起功能障碍的疗效及安全性。方法计算机检索CNKI、维普VIP、万方、Pubmed、Embase、Ovid、Cochrane等数据库,搜索建库至2020年5月发表的所有关于十一酸睾酮联合PDE5抑制剂治疗糖尿病勃起功能障碍的文献。采用Rev Man 5.3软件对数据进行Meta分析。结果总共纳入9篇符合标准的文献,其中9篇文献国际勃起功能指数(IIEF-5)评分采取随机效应模型进行分析,合并效应量MD=4.97,95%CI为4.60～5.34(P0.05);5篇文献血清睾酮采取随机效应模型进行分析,合并效应量MD=1.81,95%CI为1.54～2.09(P0.05);3篇文献男性更年期(PADAM)评分采取固定效应模型进行分析,合并效应量MD=-4.19,95%CI为-5.05～-3.32(P0.05);6篇文献报道不良反应,主要有恶心、头晕、头痛、胃部不适、面部潮红等,但所有患者不良反应程度较轻,均可耐受。结论十一酸睾酮联合PDE5抑制剂治疗糖尿病勃起功能障碍的效果较为可靠,不良反应小,值得临床上推广。     

小分子药物阿普斯特治疗甲银屑病的应用

 甲银屑病的治疗具有长期性和疗效不确定性, 尚缺乏具有证据支持为基础的治疗指南。阿普斯特是一种口服磷酸二酯酶4（PDE4）小分子抑制剂,已被美国及欧洲药监局批准用于治疗寻常型银屑病和关节型银屑病。目前已有临床试验将其用于甲银屑病的治疗。本文从阿普斯特的药理作用、临床评价、安全性等方面综述阿普斯特在甲银屑病治疗中的应用。     

外用磷酸二酯酶4抑制剂在特应性皮炎中的研究进展

特应性皮炎(AD)是一种反复发作的炎症性皮肤病,患者往往有剧烈瘙痒,严重影响生活质量。在过去,AD的治疗主要是外用糖皮质激素或钙调神经磷酸酶抑制剂。以上药物在治疗的同时常有一些显著的不良反应和局限性。因此,需开发一种更加安全有效且副作用小的药物。环核苷酸磷酸二酯酶4(phosphodiesterase 4, PDE4)是炎症细胞和免疫细胞中水解环磷腺苷(cAMP)的关键细胞内酶。AD患者白细胞中PDE4活性增加可使cAMP降解,导致促炎症因子的激活。因此,靶向抑制PDE4可以下调促炎症因子的产生,实现AD的治疗。PDE4外用制剂可以避免口服药物及传统外用药引起的不良反应,提高安全性和有效性。本文就目前已发表的相关文献对外用PDE4抑制剂治疗特应性皮炎作一综述。     

探讨中国传统性医学--从"伟哥热"引发的思考

蓝色精灵伟哥(Viagra),药学名为西地那非。在全球引起了轰动效应。在抗心绞痛的研究中无意发现有改善勃起功能的作用而使之进入临床试验。它作为首选5型PDE(5型磷酸二脂酶)抑制剂应用于临床的。男性性功能障碍原因包括心理性、器质性,西地那非被证实是有效的且不被抗高血压治疗所影响。然而,西地那非的效力随男性勃起功能障碍严重性的增加而下     

性生活质量影响因素及PDE5抑制剂治疗勃起功能障碍后性生活质量改善的多中心临床研究

目的:了解我国勃起功能障碍(ED)患者性生活质量的流行病学数据和影响性生活质量的因素,观察经PDE5-I治疗后性生活质量的改善情况。方法:从2008年6月至2009年11月,在中国的49个男科或泌尿科诊疗中心开展了一项关于对ED患者性生活质量情况(享受度、满意度及性生活次等)及PDE5-I治疗的结果的问卷调查。就诊的ED患者填写调查问卷的治疗前部分,然后根据医生的处方服用PDE5-I,4周后复诊完成问卷治疗后部分。采用软件SPSS 13.0对问卷数据进行统计分析。结果:本次调查共发放问卷5500余份,收回有效问卷4507份。ED患者平均年龄42岁,64.3%的ED患者未经过治疗,大部分ED患者的病程小于5年(74.5%)。50%的患者认为获得满意性生活重要的因素是"勃起硬度",28%的患者认为"持勃起时间"最为重要,15%的患者认为首要因素是"性高潮是否满意",另有6.7%的患者认为"获得勃起的快慢"是影响性生活满意的最重要的因素。服用PDE5-I治疗后,患者勃起硬度明显改善,95.3%的患者可以达到3、4级硬度,39.8%患者恢复正常。同时PDE5-I治疗可以显著改善ED患者性生活活质量,性生活享受度、满意度和次数明显改善(P0.001)。结论:勃起硬度和维持勃起时间是影响性生活满意的主要因素。PDE5-I治疗后可以有效的改善ED患者的勃起功能,进而明显改善患者的性生活质量,提高性生活满意度等。     

选择性酪氨酸激酶2抑制剂治疗常见皮肤病的研究进展

近年来小分子Janus激酶抑制剂被广泛用于皮肤病治疗及研究中,第一代非选择性抑制剂存在治疗指数狭窄及广泛免疫抑制相关的安全性问题。而酪氨酸激酶2作为Janus激酶家族的重要成员,参与白细胞介素6、12、23和Ⅰ型干扰素的信号传导。研究发现选择性酪氨酸激酶2抑制剂在有效治疗相关疾病的同时能够减少非选择性抑制剂潜在的不良反应,和其他Janus激酶抑制剂相比在临床上更有优势。本文对酪氨酸激酶2在相关皮肤病发病机制中的作用,以及选择性酪氨酸激酶2抑制剂用于银屑病、特应性皮炎、斑秃等皮肤病治疗的临床研究现状进行综述,为拓宽其临床应用提供更多思路。     

磷酸二酯酶-4抑制剂阿普斯特在皮肤科应用进展

阿普斯特（apremilast,商品名Otezla）是一种小分子磷酸二酯酶-4（PDE?4）抑制剂,由美国Celgene公司开发。2003年在治疗哮喘临床试验中,发现其具有抗炎作用,同时在受试者血液中检测到肿瘤坏死因子（TNF）α水平下降,故转而研究TNF?α驱动的疾病。由于银屑病发病机制与TNF?α密切相关,所以阿普斯特首先用于银屑病临床研究……     

Salvaging the oral treatment failure patient

Oral agents represent the first-line treatment for erectile dysfunction. These drugs belong to the class of phosphodiesterase type 5 inhibitors (PDE5i) and are highly effective, safe, and well tolerated. Their clinical use is characterized by an unexpectedly high dropout rate. Many patients that discontinue treatment refer to the treatment’s ineffectiveness, but they are frequently false non-responders (patients not adequately informed and counseled with respect to oral treatment). If adequately re-challenged with PDE5i, a significant number of them will be assisted. This paper summarizes key assessment points in efforts to rescue false PDE5i failures and lead them toward treatment and a satisfactory clinical response.     

There remains a role for neurologic testing of patients with erectile dysfunction

Conclusions In this era of modern medicine and phosphodiesterase-5 inhibitors (PDE5i), the range of treatment options for ED and the variety of solutions for its possible causes compel the physician to offer a more comprehensive yet targeted treatment. As clinicians, we are obligated to establish the cause of impotence. Whether it is vascular, neurologic, or psychosexual, we need to evaluate and classify the severity of the dysfunction and to select the best therapeutic option that is acceptable to the patient and addresses his pathology [6]. For example, due to poor treatment success rates with PDE5i for neurogenic ED, it would be wiser to recognize the neurologic dysfunction beforehand and be able to provide a treatment modality that would enhance success of treatment for these speci.c cases. The key factor for deciding on neurologic evaluation lies in the medical history intake, which should focus on characterizing the problem (severity, onset, and duration), but at the same time should be oriented to evaluating the need for any specialized testing. Neurologic tests are still being re.ned and improved to achieve better and more accurate results in a simpler fashion. Clinical studies are still required to de.ne the exact place of these tests in the diagnostic workup for both male and female sexual dysfunction. In this dynamic process, we must continue to use and perfect these tests in order to make them even more applicable for routine clinical use.     

Chronic dosing of phosphodiesterase type 5 inhibitors

Ten years ago, the introduction of sildenafil citrate for the treatment of erectile dysfunction fundamentally changed the field of sexual medicine. The sexual indications, along with the pharmacologic characteristics of this drug, led to its approval for on-demand use. Additional phosphodiesterase type 5 (PDE5) inhibitors were introduced for the treatment of erectile dysfunction, and each subsequent agent used the on-demand treatment paradigm. Yet, advances in laboratory investigations and accumulating clinical evidence suggest that daily dosing is feasible and may improve treatment efficacy and compliance. Recently one of these agents, tadalafil, was approved in several countries for once-daily dosing. Broad clinical experience with this treatment option is just beginning. The widespread presence of PDE5 in other vascular beds has led to additional nonsexual indications for PDE5 inhibitors.     

Nonurologic applications of phosphodiesterase type 5 inhibitors

Phosphodiesterase type 5 (PDE5) is an enzyme that catalyzes hydrolytic degradation of cyclic guanosine monophosphate, an essential intracellular second messenger that modulates diverse biologic processes in living cells. Three selective inhibitors of PDE5, sildenafil, vardenafil, and tadalafil, have been successfully used by millions of people worldwide for the treatment of male erectile dysfunction. Also, sildenafil is currently approved for the treatment of pulmonary hypertension in patients. Recent basic and clinical studies suggest potential nonurologic applications of PDE5 inhibitors, including ischemia and reperfusion injury, myocardial infarction, cardiac hypertrophy, cardiomyopathy, heart failure, stroke, neurodegenerative diseases, and other circulatory disorders. These drugs may delay or reduce the pathologic damage and also improve the overall well being and quality of life in patients. Future clinical trials on the US Food and Drug Administration-approved PDE5 inhibitors are needed, which will hopefully expedite their expanding nonurologic therapeutic use in patients.     

A practical update on bulk semen analysis

Bulk semen analysis is a highly valuable diagnostic tool used to evaluate the infertile male. Yet despite its importance, it often remains poorly understood. A basic understanding of the epidemiology of the infertile male is needed to best interpret bulk semen analysis. Its accurate interpretation allows the urologist to initiate a more efficient treatment plan. Using multiple semen parameters improves the urologist’s ability to more accurately discriminate between fertile and infertile men. We review the basic epidemiology of the infertile male and discuss the accurate interpretation of semen analysis.     

Chronic kidney disease and erectile dysfunction

Erectile dysfunction (ED) is a common condition among male chronic kidney disease (CKD) patients. Its prevalence is estimated to be approximately 80% among these patients. It has been well established that the production of nitric oxide from the cavernous nerve and vascular endothelium and the subsequent production of cyclic GMP are critically important in initiating and maintaining erection. Factors affecting these pathways can induce ED. The etiology of ED in CKD patients is multifactorial. Factors including abnormalities in gonadal-pituitary system, disturbance in autonomic nervous system, endothelial dysfunction, anemia (and erythropoietin deficiency), secondary hyperparathyroidism, drugs, zinc deficiency, and psychological problems are implicated in the occurrence of ED. An improvement of general conditions is the first step of treatment. Sufficient dialysis and adequate nutritional intake are necessary. In addition, control of anemia and secondary hyperparathyroidism is required. Changes of drugs that potentially affect erectile function may be necessary. Further, zinc supplementation may be necessary when zinc deficiency is suspected. Phosphodiesterase type 5 inhibitors (PDE5Is) are commonly used for treating ED in CKD patients, and their efficacy was confirmed by many studies. Testosterone replacement therapy in addition to PDE5Is may be useful, particularly for CKD patients with hypogonadism. Renal transplantation may restore erectile function. ED is an early marker of cardiovascular disease (CVD), which it frequently precedes; therefore, it is crucial to examine the presence of ED in CKD patients not only for the improvement of the quality of life but also for the prevention of CVD attack.     

PDE5 inhibitors and pulmonary hypertension

Phosphodiesterases (PDEs) are important components in cellular signaling in many vascular beds. Although the most recognized PDE inhibitor, sildenafil, a specific PDE5 inhibitor, is best known for its effect on the penile vascular bed resulting in erection, it also has therapeutic effects in other vascular beds, including the coronary and pulmonary vasculature. The first large, randomized, double-blind, placebo-controlled clinical trial using sildenafil in patients with pulmonary arterial hypertension was reported in 2005. As a result of this and other studies, sildenafil is now used to treat idiopathic pulmonary hypertension. Future studies are required to assess the potential use of other PDE5 antagonists and combination therapy on pulmonary hemodynamics, functional capacity, and long-term prognosis in the treatment of pulmonary arterial hypertension.     

Are phosphodiesterase type 5 inhibitors effective for the management of lower urinary symptoms suggestive of benign prostatic hyperplasia?

AIM: To review the efficacy of phosphodiesterase type 5 inhibitors(PDE5-Is) in lower urinary tract symptoms(LUTS) suggestive of benign prostate hyperplasia(LUTS/BPH). METHODS: A comprehensive research was conducted to identify all publications relating to benign prostate hyperplasia and treatment with sildenafil, vardenafil and tadalafil. To assess the efficacy, the changes in total international prostate symptom score(IPSS), IPSS subscore including voiding, storage and quality of life(Qo L), Benign prostatic hyperplasia Impact Index(BII), maximum urinary flow rate(Qmax) and the International Index of Erectile Function(IIEF) were extracted. A meta-analytical technique was used for the analysis of integrated data from the included studies to evaluate the mean difference in the results. RESULTS: Total IPSS score, IIEF and BII showed a significant improvement in trials in which LUTS/BPH with or without erectile dysfunction(ED) were compared with the placebo. For LUTS/BPH, the mean differences of total IPSS score, IIEF and BII are-2.17, 4.88 and-0.43, P 0.00001, respectively. For LUTS/BPH with comorbid ED, the mean difference are-1.97, 4.54 and-0.52, P 0.00001, respectively. PDE5-Is appear to improve IPSS storage, voiding and Qo L subscore(mean difference =-0.71,-1.23 and-0.33, P 0.00001, respectively). Although four doses of tadalafil(2.5, 5, 10 and 20 mg) failed to reach significance in Qmax(mean difference = 0.22, P = 0.10), the 5 mg dose of tadalafil significantly improved the Qmax(mean difference = 0.33, P = 0.03).CONCLUSION: PED5-Is demonstrated efficacy for improving LUTS in BPH patients with or without ED and could be considered to be the first line treatment for LUTS/BPH.     

从3例诊疗报告看精子形态学与生精细胞学检测在男科临床中的应用

近年来,精子形态学和生精细胞学检测越来越受到男科特别是生殖中心的重视,然而将未染色的精液进行形态学和细胞学分析,其对精子的畸形率及圆细胞的判断存在极大的误差。笔者通过将3例典型患者的精液染色后分析精子形态和生精细胞,做出新的病情诊断及治疗方案,从而探讨精子细胞学与生精细胞学检测在男科临床中的应用价值。     

探讨常规精液分析与计算机辅助精子分析的可比性

目的:探讨常规精液分析(SRA)与计算机辅助精子分析(CASA)的各项参数指标是否存在可比性.方法:对本院生殖医学中心自2010年2月~2011年2月期间采集的精液标本实施SRA及CASA分析.结果:本研究共计检测217例精子标本,其中检出9例(4.1%)无精子;169例(77.9%)的精子密度在(5~80)×106/mL范围内;15例(6.9%)的精子密度低于5×106/mL;24例(11.1%)的精子密度在80 x 106/mL以上.精子密度在(5~80)×106/mL范围内时,CASA与SRA两种方法测得精子活动力及平均精子密度无明显差异(P>0.05),不具有统计学意义;精子密度低于5×106/mL时,SRA方法所得平均精子密度明显低于CASA方法,差异显著(P<0.05),但两者精子活动力相比无明显差异(P>0.05),不具有统计学意义;精子密度在80×106/mL以上时,SRA方法所得平均精子密度低于CASA方法,差异显著(P<0.05),而且CASA方法测得a级精子所占百分比较高,d级精子所占百分比较低(P<0.05);经生理盐水稀释后两种检测方法所得的平均精子密度以及精子活动力相比无明显差异(P>0.05),不具有统计学意义.结论:将计算机辅助精子分析与精液常规分析相结合,能够更加客观、更加准确地判断精液的质量,进而对男性不育的临床诊治以及相关研究提供理论依据.