Ⅰ.The Role Of Oxidative Stress In Prostate Inflammation Pain And Effects Of N-acetylcyteine Ⅱ.Chinese Urologists' Knowledge Of And Practice Patterns For Chronic Prostatitis: Current Situation And Influencing Factors

In the 20th century, the term "prostatitis" traditionally referred to inflammation in the prostate, often attributed to infection. Prostatitis in this century usually refers to a chronic pain syndrome for which the presence of inflammation and involvement of the prostate are not always certain. Prostatitis is one of the most common entities encountered in urologic practice, and its worldwide incidence ranges from 3%to 16%. Although prostatitis is not life-threatening, it is also associated with a significant negative impact on both mental and physical domains of quality of life. In clinic, urologists always experience confusion in managing this disease; the patients are always dissatisfied with the effect of various therapies as well. It is generally acknowledged as a source of great frustration and disappointment in physicians and patients alike. Moreover, prostatitis has resulted in substantial financial costs for the patient and for society.At present, many different theories and the mechanisms of pathogenesis of prostatitis including infectious, immunological, neurological, endocrine and psychological have been proposed but precise pathophysiology remains largely unknown, which seriously blocks the development of therapy for prostatitis. In clinic, although a serious of medicine and treatment options have been developed for prostatitis according to the probable mechanisms of symptom production or propagation, the therapy is always difficult and unrewarding. The wide scope of treatment options available just reflects the lack of knowledge around prostatitis. If the underlying, primary cause of prostatitis has been demonstrated, it will bring fresh hope to the diagnosis and treatment of prostatitis.Pain is the most common and important symptom of prostatitis, and is the principal cause for office visiting and negative impact on quality of life. The mechanism of pain development in prostatitis is poorly understood. This is mainly due to the lack of a suitable and reliable preclinical animal model of prostatitis-induced pain or prostatodynia.This study was divided into three part:Part 1, An animal model for nonbacterial prostatitis and prostate inflammation pain in rats was developed with the use of intraprostatic injection ofλ-carrageenan and the reliability and validity of this model was tested by a behavior approach, histology, C0X2 protein expression and plasma protein extravasation. Part 2, The role of increased oxidative stress and oxidative damage in the occurrence, development ofλ-carrageenan-induced prostatitis and prostatodynia was explored via testing the biomarkers of oxidative damage and antioxidative system. Part 3, The analgesic and anti-inflammatory properties of N-Acetylcysteine was tested in this model. Objectives:To develop an animal model for nonbacterial prostatitis and prostate inflammation pain in rats with the use of intraprostatic injection ofλ-carrageenan, and to test the reliability and validity of this model. The final goal of this research is to provide reliable animal model for identifying the mechanisms of chronic prostatic pain (prostatodynia).Methods:In experimental groups (n=20), a sterile suspension of 3%λ-carrageenan in a volume of 50μl each was injected into both right and left ventral lobes of the prostate gland in SD rats. The nociceptive effects ofλ-carrageenan were evaluated by using a behavior approach at 24 h (n=6) or 1 wk (n=6) after injection; then the prostate was removed for histology and cyclooxygenase2 (C0X2) protein concentration measurement. Evans blue (50 mg/kg) was also injected intravenously to assess for plasma protein extravasation at 24 h (n=4) or 1 wk (n=4) after injection of X-carrageenan injection. In the control groups (n=20) the same surgical procedures were followed and 50μl of sterile normal saline, instead of X-carrageenan, was injected into both the right and left ventral prostate lobes. Results:λ-carrageenan induced modifications in pain behavior: closing of the eyes, hypolocomotion, and inflammatory changes: increase of inflammatory cell accumulation, COX2 expression, and Evans blue extravasation at 24 h after injection, but not recovered at 1 wk.Conclusions:Intraprostaticλ-carrageenan injection induced neurogenic prostatitis and prostate inflammation pain. The current model is expected to be a valuable preclinical tool to study the neurobiological mechanisms of male chronic pelvic pain. Objectives:To investigate the role of increased oxidative stress and oxidative damage in prostate inflammation pain induced by intraprostaticλ-carrageenan injection in rats, and to explore its possible mechanism.Methods:In experimental groups(n=12), a sterile suspension of 3%λ-carrageenan in a volume of 50μl each was injected into both right and left ventral lobes of the prostate gland in SD rats. The enzymatic antioxidant defense levels:the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) activities, and the nonenzymatic antioxidant defense level:glutathione (GSH) content, as well as the levels of 8-isoprostane (8-epi PGF2α), indicative of lipid peroxidation, were examined at 24 h (n=6) or 1 wk (n=6) after injection. These studies were made in prostate homogenates of rats withλ-carrageenan-induced prostatitis and of control rats treated with sterile normal saline (n=12).Results:This study revealed a significant diminution of the SOD, CAT and GSH-PX activities, and the GSH content, and a significant increase of 8-epi PGF2αlevel in experimental SD rats induced by intraprostaticλ-carrageenan injection at 24 h after injection in relation to control rat samples(P<0.05). These oxidative stress-related parameters in prostate of rats withλ-carrageenan-induced prostatitis did not recovered at 1 wk.Conclusions:The findings suggest that there exist increased oxidative stress and oxidative damage in prostate inflammation pain induced by intraprostaticλ-carrageenan injection in rats. This study implies that oxidative stress may take part in the pathophysiological processes of the occurrence, development ofλ-carrageenan-induced prostatitis and prostatodynia. Objectives:N-acetylcysteine (NAC) has, in recent years, been widely used as an antioxidant in many basic researches and clinical therapies for a range of diseases. However, the role of NAC in prostatitis and prostate inflammation pain is uncertain. The aim of the current study is to examine the possible protective effect of N-acetylcysteine on prostate inflammation pain induced by intraprostatic X-carrageenan injection.Methods:Adult SD rats of experimental groups (n=10) were treated i.p. with NAC at a dose of 300mg/kg once a day for seven days. One hour after the last NAC injection,3%λ-carrageenan was injected into the ventral prostate. Behavioral changes of animals were assessed at 24 h afterλ-carrageenan injection; then the prostate was removed for histology, C0X2 protein concentration and oxidative stress-related parameters levels (SOD, CAT, GSH-PX, GSH and 8-epi PGF2a) measurement in 6 of the 10 rats. The rest 4 rats were used for assessing the Evans blue extravasation. In the control groups (n=10) the animals were pretreated i.p. with 1.5ml sterile normal saline instead of NAC and the same surgical procedures were followed. Results:Pretreatment with both NAC significantly reduced pain behavior, inflammatory cell accumulation, C0X2 expression, and Evans blue extraction. Moreover, N-acetylcysteine pretreatment caused a decrease in 8-epi PGF2αlevels and an increase in SOD, CAT, GSH-PX and GSH levels compared to control groups.Conclusions:Systemic NAC administration produces anti-inflammatory and analgesic effects and suppresses the increased oxidative stress and oxidative damage in prostate induced by intraprostaticλ-carrageenan injection. NAC may be a promising drug for treatment of CP/CPPS. Chronic prostatitis (CP) is one of the most common entities encountered in urologic practice and represents an important international health problem. Overall,2%-10% of adult men suffer from symptoms compatible with CP at any time and approximately 15% of men suffer from symptoms of prostatitis at some point in their lives. In the USA, the cost of prostatitis is approximately USD 84,000,000 annually, exclusive of pharmaceutical spending. In cross-sectional studies, CP is associated with reductions in patients'quality of life, similar to or greater than those associated with angina, congestive heart failure, Crohn's disease and diabetes mellitus. However, CP is generally acknowledged as a source of great confusion and frustration for physicians and patients alike. Several surveys of physicians have been undertaken in order to examine the characteristics of their practice, attitude, diagnostics and treatment modalities applied in patients with CP. These surveys demonstrate that physicians show large deficits in familiarity with and knowledge of CP along with significant variability in their approaches to diagnosis and treatment. Yet, Chinese circumstances surrounding CP have not been clarified. To define the current spectrum of practice of the Chinese urologists, we initiated a comprehensive cross-sectional study to determine the current situation among the Chinese urologists on the diagnosis and treatment of patients with CP. Objective:To examine the philosophies and practices of Chinese urologists regarding the diagnosis and treatment of chronic prostatitis (CP).Methods:A sample of 656 urologists from 29 provinces (including autonomous regions and municipalities) of China were asked to complete a questionnaire that explored their practice characteristics about and attitudes towards prostatitis, and diagnosis and treatment patterns in the management of CP.Results:Of the 656 questionnaires sent,627 were included in the final analysis. Many urologists (64.6%; 394/610) considered CP to be non-bacterial in nature. For routine diagnosis assessment, the most commonly used tests were reported to be microscopic analysis of expressed prostate secretions (86.3%; 535/620) and bacterial culture (57.4%; 356/620). Most urologists (43.4%; 260/599) performed simple culture of expressed prostate secretions (EPS). More than one-third (37.7%; 225/597) of the urologists still employed the traditional classification system of chronic bacterial prostatitis, chronic nonbacterial prostatitis and prostatodynia. About two-thirds (66.6%; 412/619) of the urologists believed that CP needed to be treated. The first choice for therapy included pharmaceutical therapy (86.2%; 538/624), psychotherapy (60.7%; 379/624), prostatic massage (54.2%; 338/624) and physical therapy (44.7%; 279/624). Seventy-four percent (455/615) of the urologists chose antimicrobial agents as the first choice of therapy and these physicians tended to use fluoroquinolones (79.0%; 480/608), macrolides (45.7%; 278/608) and cephalosporins (35.2%; 214/608) for CP. Most urologists said they would prescribe antibiotics when bacterial culture was positive (64.4%; 351/545) or too many white blood cells or pyocytes (65.9%; 359/545) were present in EPS. The second most commonly used pharmaceutical therapy was alpha-blocker (60.3%; 371/615), which was prescribed to relieve the obstructive voiding symptoms by most urologists (70.3%; 395/562). The beliefs regarding the etiology affect the diagnostic and treatment strategies; meanwhile, the diagnostic practice has an influence on the selection of treatment methods.Conclusions:There is much confusion and frustration about the etiology, diagnosis and treatment of CP among Chinese urologists. Meanwhile, their practice pattern should be standardized. Moreover, it is necessary to conduct some further study on CP and constantly improve the cognitive level about CP among Chinese urologists. Objective:To determine Chinese urologists'current diagnosis and treatment of psychological problems involved in chronic prostatitis (CP).Methods:656 urologists from 29 provinces of china (including autonomous region and municipality) were surveyed by a questionnaire.Results:Forty-one percent of the urologists considered mental and psychological disorders were the causes of CP and more urologists (71.8%) believed that mental and psychological disorders were the causes but not effects of CP. Most urologists (48.5%) considered that the incidence of psychological disorders involved in CP was between 26% and 50%, and anxiety (73.6%), neurasthenia (63.5%), depression (53.7%) and hypochondriasis (41.3%) were the most common psychosomatic symptoms. About one-fifth (20.7%) of the urologists carried out psychological assessment and 60.7%performed psychotherapy routinely. The urologists who considered psychological factors were the causes of CP were more likely to carry out psychological assessment and psychotherapy, and those who carried out psychological assessment routinely were more likely to perform psychotherapy. Only 23.5% urologists applied routine methods of therapy, psychotherapy and antipsychotic to the treatment of psychological disorders in patients with CP comprehensively.Conclusions:Chinese urologists still have much confusion about the cognizance, diagnosis and treatment of psychological problems involved in CP. Moreover, it's necessary to make some further research on the methods of assessment and treatment for psychological disorders involved in CP. Objective:To identify the factors influencing practices for chronic prostatitis (CP) among Chinese urologists.Methods:A sample of 656 urologists from 29 provinces of China was asked to complete a questionnaire that explored attitudes towards CP as well as diagnosis and treatment patterns in the management of CP. Both univariate and multivariate logistic regression analysis schemes were utilized to determine the factors influencing the diagnosis and treatment of CP.Results:A total of 656 questionnaires sent. All were returned and 410 of those were included in the final univariate and multivariate analysis. Multivariate logistic regression analysis indicated that beliefs in bacterial infection in the etiology of CP (odds ratio [OR],2.544; 95% confidence interval [CI],1.650-3.923; P=0.000) was the significant factor influencing the routine performance of bacterial culture test. In the same model used, the type of hospital (OR,2.799; 95%CI,1.719-4.559; P=0.000) and the routine use of the 4-glass test or the 2-glass test (OR, 3.194; 95%CI,2.069-4.931; P=0.000) were determined to be significant factors influencing the use of the NIH new classification system. According to the same model, beliefs in bacterial infection in the etiology of CP (OR,3.415; 95%CI,2.024-5.762; P=0.000) and the routine use of bacterial culture test (OR,2.261; 95%CI,1.364-3.749; P=0.002) were important factors influencing the routine prescription of antibiotics.Conclusions:Our findings suggest that the personal beliefs, and the demographic and professional characteristics of individual urologists many influence the diagnosis and treatment of CP in China.