生物标志物在前列腺炎中的研究进展

前列腺炎是男性泌尿系统的常见疾病,由于前列腺炎存在病因和发病机制复杂,导致临床症状表现多种、药物治疗缺乏特异性和复发率较高等问题,因此前列腺炎的诊断、治疗和预后判断标准一直是临床关注的焦点。目前还没有诊断前列腺炎的"金标准",而生物标志物的检测有助于临床诊断、治疗和预后诊断,本文检索近年相关,对敏感性较高和特异性较好的一些前列腺炎生物标志物(细胞因子和趋化因子等)及今后研究的侧重点进行综述,从而为前列腺炎的诊断、分型治疗和预后观察提供依据。     

舒张性心力衰竭实验动物模型的研究进展

舒张性心力衰竭患者在并发高血压、糖尿病、心肌缺血和老龄化时可显著增加心衰的发病率,目前其潜在发病机制尚不完全清楚。随着我国人口老龄化的加剧,舒张性心力衰竭的患病率和死亡率明显上升,严重影响人们的生活质量和寿命。建立实验动物模型时尽量模拟临床发病诱因和特征,可以更真实地揭示疾病的发病机制或药物的作用机制。本文从舒张性心力衰竭的主要诱因重点综述构建舒张性心力衰竭实验动物模型的方法和各自的特点,为将来更多的研究舒张性心力衰竭发病机制的研究者提供依据。     

抗炎药物用于 2 型糖尿病预防与治疗的研究进展

近年来,炎症反应在2型糖尿病发病机制中的作用受到广泛关注。流行病学和实验动物研究均证明,肥胖及其诱发的慢性炎症 与2型糖尿病有密切的关系。基于诸多临床流行病学调查及大型前瞻性研究结果,目前已形成对糖尿病胰岛素耐受性的炎症发病机制的 共识。到目前为止,多种具有抗炎作用机制的活性小分子药物已经上市或进入临床研究阶段,这些药物单独治疗或与传统降糖药物联用 均取得了令人满意的效果,显示了糖尿病抗炎治疗的前景。主要综述近年来慢性炎症在2型糖尿病发生发展过程中的分子机制以及抗炎 药物用于治疗2型糖尿病的研究进展     

慢性前列腺炎病因分析及护理对策

前列腺炎是男性泌尿生殖系统常见病,约50％的男性在其一生中曾有前列腺炎的症状。其中,慢性前列腺炎（CP）更为多见,在全世界男性中的患病率为9％～14％．本病的临床表现变化多端．病因及发病机制尚未完全阐明,因此许多患者没有得到有效的治疗,严重影响息者生活质量。现对我院2003-2009年收治住院的96例慢性前列腺炎患者的资料进行总结分析如下。     

人源化鼠嵌合肝动物模型研究进展

动物模型是人类疾病研究、发病机制、药物研发的重要工具,对于困扰人类健康的肝脏疾病还没有理想的动物模型能有效地反映出人类疾病发病的机制。建立人源化鼠嵌合肝动物模型,对于研究人类肝脏疾病的发病机制、疫苗和药物的研发及疾病的诊治等方面都具有十分广阔的应用前景。     

慢性粒细胞白血病小鼠动物模型建立的研究进展*

慢性粒细胞白血病(chronic myeloid leukemia,CML)是造血干细胞(hematopoietic stem cells,HSC)恶性克隆性增殖引起的一种血液系统疾病。动物模型是研究CML发病机制及药物靶向治疗的重要载体和工具。研究表明,CML小鼠模型可以通过逆转录病毒介导、转基因和白血病细胞移植的方法建立。三种方法建立的CML小鼠模型均可用于CML发病机制及药物疗效评估研究。实验动物模型进一步通过血常规、血涂片和骨髓涂片、免疫学、分子生物学及病理学等检测手段,判断模型是否建立成功。本文就近年来CML小鼠模型的建立、鉴定及研究应用进展进行综述。     

浅谈药理研究工作中的动物实验问题

一个药物的价值如何,不仅要看它的疗效和毒性,而且要从作用机制方面进行研究和评价。如果一种新药能通过和老药不同的机制影响某种生理功能或治疗某种疾病,那么它就开辟了一个新的研究领域,能够促进人们对机体功能调节或对该种疾病的发病学和治疗学的原则产生新的理解。即使其疗效和毒性比老药并无特殊,那么此种新药也是很有价值的。药理研究工作,特别是作用机制的研究,离不开动物实验。本文拟就药理研究工作中有关动物实验问题,浅谈几点意见。一、初筛实验的质量与效率无论是合成的新药还是从生物中提取的药物,在初筛时应该采用多指标来作实验筛选,这是比较公认的     

高甘油三酯血症动物模型研究进展

高甘油三酯血症(HTG)与肥胖、代谢综合征和糖尿病密切相关,同时也是诱发急性胰腺炎(AP)和增加动脉粥样硬化性心血管疾病(ASCVD)发病风险的重要影响因素之一,是当前的研究热点。成功建立符合要求的动物模型是开展相关实验研究的关键,本文对HTG动物模型的研究现状进行了系统的总结,以期为深入研究HTG的发病机制和降脂药物的筛选提供动物模型参考。     

产后抑郁动物模型及行为学评价方法研究进展

产后抑郁症(postpartum depression,PPD)是产褥期精神综合征中最常见的一种类型。由于PPD疾病的复杂多变以及产妇分娩后所处的特殊时期,使得临床上研究该疾病存在很多局限性。因此,制备与建立临床接近PPD动物模型及行为学评价方法对研究其发病机制具有重要作用。本综述主要介绍了常用的产后抑郁症动物模型以及行为学评价方法,为深入研究PPD发病机制及药物开发提供实验方法。     

DNA微阵列技术在阿尔茨海默病及其防治药物研究中的应用

在生物技术飞速发展的今天,DNA微阵列已成为功能基因组时代大规模、高通量乃至全基因组表达和功能研究的有力工具。阿尔茨海默病,因其发病机制复杂,迄今尚无定论,因此在临床上也缺乏有效的防治药物。简要综述DNA微阵列技术应用于阿尔茨海默病发病机制、早期诊断及防治药物等方面的研究进展。     

Identification of potential causative infectious agents of chronic prostatitis

Analysis of the data on etiology and pathogenesis of inflammatory processes in prostate including acute and chronic prostatitis as well as chronic pelvic pain syndrome is presented. It has been noted that about 50% of men of fertile age had clinical signs of chronic prostatitis at least once in life and that more than 60% of admissions to urologists in outpatient practices are related with clinical signs of chronic prostatitis. An appreciable decrease in quality of life similar to that due to myocardial infarction or Crohn's disease is observed in patients with chronic prostatitis. Prostatitis often has a chronic cyclic course with exacerbation and remission phases. Not rarely the disease has primary chronic course--without an apparent beginning as acute prostatitis. This leads to late diagnostics and difficulties with identification of etiologic factor, which commonly is a conditionally pathogenic microorganisms and mixed infections. Such difficulties can be a reason for inadequate treatment and complications of chronic prostatitis such as abscess, paraprostatitis, impotence, and infertility.     

Spontaneous and prostatic steroid binding protein peptide-induced autoimmune prostatitis in the nonobese diabetic mouse

Chronic nonbacterial prostatitis is a poorly defined syndrome of putative autoimmune origin. To further understand its pathogenesis, we have analyzed autoimmune prostatitis in the NOD mouse, a strain genetically prone to develop different organ-specific autoimmune diseases. Spontaneous development of autoimmune prostatitis in the NOD male, defined by lymphomonuclear cell infiltration in the prostate gland, is well-established by approximately 20 wk of age and is stably maintained afterward. Disease development is indistinguishable in NOD and NOR mice, but is markedly delayed in IFN-gamma-deficient NOD mice. A T cell response to the prostate-specific autoantigen prostatic steroid-binding protein (PSBP) can be detected in NOD males before development of prostate infiltration, indicating lack of tolerance to this self Ag. The intraprostatic inflammatory infiltrate is characterized by Th1-type CD4(+) T cells, which are able to transfer autoimmune prostatitis into NOD.SCID recipients. We characterize here experimental autoimmune prostatitis, detected by intraprostatic infiltrate and PSBP-specific T cell responses, induced in 6- to 8-wk-old NOD males by immunization with synthetic peptides corresponding to the C1 subunit of PSBP. Three PSBP peptides induce in NOD mice vigorous T and B cell responses, paralleled by a marked lymphomononuclear cell infiltration in the prostate. Two of these peptides, PSBP(21-40) and PSBP(61-80), correspond to immunodominant self epitopes naturally processed in NOD mice after immunization with PSBP, whereas peptide PSBP(91-111) represents a cryptic epitope. These model systems address pathogenetic mechanisms in autoimmune prostatitis and will facilitate testing and mechanistic analysis of therapeutic approaches in this condition.     

Experimental autoimmune prostatitis induces chronic pelvic pain

Pain is the hallmark of patients with chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS). Despite numerous hypotheses, the etiology and pathogenesis remain unknown. To better understand CP/CPPS, we used a murine experimental autoimmune prostatitis model to examine the development, localization, and modulation of pelvic pain. Pelvic pain was detected 5 days after antigen instillation and was sustained beyond 30 days, indicating the development of chronic pain. The pain was attenuated by lidocaine treatment into the prostate, but not into the bladder or the colon, suggesting that pain originated from the prostate. Experimental autoimmune prostatitis histopathology was confined to the prostate with focal periglandular inflammatory infiltrates in the ventral, dorsolateral, and anterior lobes of the mouse prostate. Inflammation and pelvic pain were positively correlated and increased with time. Morphologically, the dorsolateral prostate alone showed significantly increased neuronal fiber distribution, as evidenced by increased protein gene product 9.5 expression. Pelvic pain was attenuated by treatment with the neuromodulator gabapentin, suggesting spinal and/or supraspinal contribution to chronic pain. These results provide the basis for identifying mechanisms that regulate pelvic pain and the testing of therapeutic agents that block pain development in CP/CPPS.     

Les prostatites chroniques: Microbiologie; Thérapeutique

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) represents an important health problem resulting in considerable morbidity and of health care expenditure. CP/CPPS is a multifactorial problem affecting men of all ages and all demographic characteristics. Over recent years, progress has been made in the epidemiology and diagnosis of CP/CPPS. A new universally accepted classification system has become the gold standard in the contemporary literature. Men with CP/CPPS have significantly higher leukocyte counts in all segmented urine samples and expressed prostatic secretion (EPS) but not in semen. In segmented cultures, the urethral culture (first 10 ml of urine), EPS and first 10 ml of urine avoided immediately after prostatic massage are the “optimal” samples to detect the microbial agent. According to the four-glass test with polymerase chain reaction testing (PCR), Chlamydia and/or Ureaplasma infection can be suspected in several cases, but their role in the pathogenesis of prostatitis remains speculative. However, testing for these infections is highly recommended in non-documented infections. Quantification, speed and specificity make real-time PCR a promising approach for the quantitative detection and identification of prostatic bacteria from CP/CPPS patients. Several antibiotics have a good correlation between pharmacokinetic/pharmacodynamic parameters and efficacy for antibiotics in the treatment of chronic prostatitis. Fluoroquinolones, cotrimoxazole and ceftriaxone have a bactericidal concentration to the main pathogens in the prostatic fluid of patients with subacute and chronic prostatitis and in prostatic tissue.     

Pathogenic consequences in semen quality of an autoimmune response against the prostate gland: from animal models to human disease

We have recently proposed an autoimmune etiology in approximately 35% of chronic nonbacterial prostatitis patients, the most frequent form of prostatitis observed, because they exhibit IFN-gamma-secreting lymphocytes specific to prostate Ags. Interestingly, this particular group of patients, but not the rest of chronic nonbacterial prostatitis patients, also presented striking abnormalities in their semen quality.In this work, we use an experimental animal model of autoimmune prostatitis on Wistar rats developed in our laboratory to investigate when, where, and how sperm cells from autoimmune prostatitis individuals are being damaged. As in patients, a marked reduction in sperm concentration, almost null sperm motility and viability, and an increased percentage of apoptotic spermatozoa were detected in samples from animals with the disease. Prostate-specific autoantibodies as well as elevated levels of NO, TNF-alpha, and IFN-gamma were also detected in their seminal plasma. In contrast, epididymal spermatozoa remain intact, indicating that sperm damage occurs at the moment of joining of prostate secretion to sperm cells during ejaculation. These results were further supported by experiments in which mixture of normal sperm cells with autoimmune seminal plasma were performed.We hypothesize that sperm damage in experimental autoimmune prostatitis can be the consequence of an inflammatory milieu, originally produced by an autoimmune response in the prostate; a diminished prostate functionality, evidenced by reduced levels of citric acid in semen or by both mechanisms simultaneously. Once more, we suggest that autoimmunity to prostate may have consequences on fertility.     

Distinction des prostatites aiguës récidivantes et chroniques

The E.A.U. (European Association of Urology) published its Guidelines on Urinary and Male Genital Tract Infections in 2001. In the chapter devoted to prostatitis, epididymitis and orchitis, the E.A.U suggests a classification distinguishing prostatitis (usual clinical picture and demonstrated infection) from chronic pelvic pain syndrome (same clinical picture without demonstrable infection). Prostatitis is divided into three categories: acute bacterial prostatitis (type I), chronic bacterial prostatitis (type II) and asymptomatic inflammatory prostatitis (histological prostatitis, type IV). Type I and II prostatitis are considered here. The E.A.U. guidelines do not mention recurrent prostatitis. The authors discuss whether or not recurrent prostatitis should be distinguished from chronic prostatitis by raising three questions: does the literature provide precise data in favour of this distinction? Does this theoretical distinction have any practical consequences? Is this distinction feasible, especially in general practice? The Stanford sesearch team (Stamey and Shortliffe) has provided documented bacteriological data demonstrating recurrence of prostatitis with different bacteria in some cases and persistence of the same pathogen in other cases. The main consequence of these two situations concern treatment (which antibiotics? for how long?) On the basis of personal unpublished data, the authors discuss the feasibility of this distinction in general practice. They show that, in the case of several recurrences of prostatitis per year, it may be difficult to distinguish recurrent prostatitis from chronic prostatitis. They also show that the duration of symptoms is not a sufficiently discriminant factor and that bacteriological findings should be considered. In conclusion, recurrent prostatitis is a particular disease which should be distinguished from chronic prostatitis. The main consequence of this distinction concerns several unresolved questions about the therapy of recurrent prostatitis. In general practice, the distinction may be difficult when only routine bacteriological tests are available. The use of Meares and Stamey’s four glass technique is unusual in this setting, making it difficult to confirm prostatic disinfection.     

Characterization of the seminal plasma proteome in men with prostatitis by mass spectrometry

Background  

Prostatitis is an inflammation of the prostate gland which affects approximately 10% of men. Despite its frequency, diagnosing prostatitis and monitoring patient response to treatment remains frustrating. As the prostate contributes a substantial percentage of proteins to seminal plasma, we hypothesized that a protein biomarker of prostatitis might be found by comparing the seminal plasma proteome of patients with and without prostatitis.     

Alpha-blockers for the treatment of prostatitis-like syndromes

Prostatitis is a common medical diagnosis. The etiology of this symptomatic syndrome can be an acute or chronic bacterial infection, a noninfectious initiator (the most common cause), or iatrogenic heat or radiation; the syndrome may coexist with benign prostatic hyperplasia. Alpha-blockers have a role in the treatment of the prostatitis syndromes. In Category I, acute bacterial prostatitis, alpha-blockers have been shown to possibly ameliorate obstructive and irritative voiding symptoms. In Category II, chronic bacterial prostatitis, alpha-blockers seem to reduce the risk of clinical and bacteriological recurrence. In Category III, chronic pelvic pain syndrome, alpha-blockers improve symptoms and quality of life. Alpha-blockers also seem to ameliorate the symptoms and reduce the risk of acute urinary retention in patients who suffer from either heat- or radiation-induced prostatic inflammation. Alpha-blockers improve lower urinary tract symptoms, including pain, in patients who are diagnosed with both prostatitis and benign prostatic hyperplasia. Evidence has proven there is definitely a role for alpha-blockers in the management of the prostatitis syndromes.     

Development and Validation of an Animal Model of Prostate Inflammation-Induced Chronic Pelvic Pain: Evaluating from Inflammation of the Prostate to Pain Behavioral Modifications

Background

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is the most common type of prostatitis. Due to the lack of a suitable animal model partly, the pathogenesis for this condition is obscure. In the current study we developed and validated an animal model for nonbacterial prostatitis and prostate inflammation-induced chronic pelvic pain in rats with the use of intraprostatic injection of λ-carrageenan.

Methods

Male Sprague-Dawley rats weighing 250–350 g were used for the experiments. After intraprostatic injection of 3% λ-carrageenan, at different time points(after 24 h, 7d, 14d and 30d of injection), radiant heat and von Frey filaments were applied to the scrotum of rats to measure the heat and mechanical thresholds respectively. Then the prostate was removed for histology, and cyclooxygenase (COX) 2 protein expression was determined by Western-blot. Evans blue(50 mg/kg) was also injected intravenously to assess for plasma protein extravasation at different time points after injection of λ-carrageenan.

Results

Compared to control group, inflamed animals showed a significant reduction in mechanical threshold (mechanical allodynia) at 24 h and 7d(p = 0.022,0.046, respectively), and a significant reduction in heat threshold (thermal hyperalgesia) at 24 h, 7d and 14d(p = 0.014, 0.018, 0.002, respectively) in the scrotal skin. Significant increase of inflammatory cell accumulation,COX2 expression and Evans blue extravasation were observed at 24 h, 7d and 14d after injection.

Conclusions

Intraprostatic λ-carrageenan injection induced neurogenic prostatitis and prostate inflammation pain, which lasted at least 2 weeks. The current model is expected to be a valuable preclinical tool to study the neurobiological mechanisms of male chronic pelvic pain.