Development Of Prostatitis Research Articles

Preliminary study of the effect of gut microbiota on the development of prostatitis

BackgroundDysbacteriosis of intestinal tract may cause systemic inflammation, making distant anatomical locations more susceptible to illness. Recent research has demonstrated that the microbiome can affect both prostatitis and the inflammation of the prostate that is linked to prostate cancer. It is still unclear, though, whether this relationship indicates causation. We conducted a Mendelian randomization investigation on two samples to fully uncover gut microbiota’s potential genetic causal role in prostatitis.MethodProstatitis (1859 prostatitis cases and 72,799 controls) was utilized as the outcome, while SNPs highly linked with 196 microbial taxa (18 340 people) were chosen as instrumental factors. Random effects, inverse variance weighting, weighted medians, and MR-Egger were used to analyze causal effects. The Cochran’s Q test, funnel plot, leave-one-out analysis, and MR-Egger intercept test were all used in the sensitivity analysis.ResultsA causal effect in lowering the incidence of prostatitis is anticipated for five gut microorganisms (Methanobacteria, Methanobacteriaceae, Erysipelatoclostridium, Parasutterella, and Slackia; P < 0.05). Four gut bacteria, including Faecalibacterium, LachnospiraceaeUCG004, Sutterella, and Gastranaerophilales, are predicted to play a causal role in increasing the risk of prostatitis (P < 0.05). There were no discernible estimates of pleiotropy or heterogeneity.ConclusionOur investigation established the genetic links between nine gut microorganisms and prostatitis, which may offer fresh perspectives and a theoretical framework for the future prevention and management of prostatitis.

Autonomic Nervous System Dysfunction Is Related to Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common and non-lethal urological condition with painful symptoms. The complexity of CP/CPPS's pathogenesis and lack of efficient etiological diagnosis results in incomplete treatment and recurrent episodes, causing long-term mental and psychological suffering in patients. Recent findings indicate that the autonomic nervous system involves in CP/CPPS, including sensory, sympathetic, parasympathetic, and central nervous systems. Neuro-inflammation and sensitization of sensory nerves lead to persistent inflammation and pain. Sympathetic and parasympathetic alterations affect the cardiovascular and reproductive systems and the development of prostatitis. Central sensitization lowers pain thresholds and increases pelvic pain perception in chronic prostatitis. Therefore, this review summarized the detailed processes and mechanisms of the critical role of the autonomic nervous system in developing CP/CPPS. Furthermore, it describes the neurologically relevant substances and channels or receptors involved in this process, which provides new perspectives for new therapeutic approaches to CP/CPPS.

Targeting Ferroptosis Attenuates Inflammation, Fibrosis, and Mast Cell Activation in Chronic Prostatitis.

Purpose Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological disorder. Although ferroptosis is closely associated with inflammation, oxidative stress, and neuropathic pain, its role in CP/CPPS has not yet been elucidated. Therefore, we sought to explore the role and mechanism of ferroptosis in the prostatitis development. Methods The experimental autoimmune prostatitis (EAP) was established through intradermal immunization of prostate extract. Iron chelator deferoxamine (DFO) and free radical scavenger edaravone (EDA) were applied to evaluate the effects of ferroptosis inhibition on oxidative stress, ferroptosis, inflammation, fibrosis, and mast cell activation in the context of CP/CPPS. Results Increased generation of lipid peroxidation products (ROS and MDA) and decreased activities of antioxidant enzymes (SOD and CAT) suggested an aberrant oxidative stress status in EAP model. Elevated iron concentration was observed in the EAP model. Meanwhile, we discovered significant biological performances associated with ferroptosis in CP/CPPS, including the downregulation of the system Xc−/GPX4 axis and the upregulation of the ACSL4/LPCAT3 axis. EAP rats performed serious leukocyte infiltration, advanced inflammatory grade, and abnormal expression of inflammatory mediators. Abundant collagen deposition, enhanced RhoA, ROCK1, and α-SMA protein levels indicated that EAP rats were prone to suffer from stromal fibrosis compared with control group. An elevated number of degranulated mast cells and corresponding marker TPSB2 represented that mast cell-sensitized pain was amplified in the EAP model. Furthermore, reduction of NRF2/HO-1 indicated a vulnerability of EAP towards ferroptosis response. However, application of DFO and EDA had partially reversed the adverse influences mentioned above. Conclusion We first demonstrated that ferroptosis might be a crucial factor of chronic prostatitis progression. Inhibition of ferroptosis using DFO and EDA represented a promising approach for treating prostatitis by ameliorating inflammation, fibrosis, and mast cell activation.

Clinical and Immunological Rationale for the Treatment of Chronic Nonbacterial Prostatitis/chronic Pelvic Pain Syndrome (Category IIIB) Due to Herpes Virus Infection

The objective: to improve the effectiveness of treatment of patients with chronic nonbacterial prostatitis/chronic pelvic pain syndrome (category IIIB) due to herpes virus infection by evaluating the clinical and immunological features of this pathology.Materials and methods. 146 patients with chronic nonbacterial prostatitis (121 herpes virus etiology and 25 without detected viral infection) and 25 healthy young men were examined. The patients were divided into groups. Among all patients with herpesvirus etiology prostatitis, 46 patients had ejaculate DNA of herpes simplex virus 1/2 type (HSV 1/2 type), which made up the 1st comparison group, in 41 patients – DNA of cytomegalovirus (CMV) – II group comparison, and in 34 patients – the DNA of both viruses, respectively, the III comparison group. When assessing the immune status of patients, we studied the level of interferon-gamma (IFN-γ) in the blood serum and the content of secretory immunoglobulin A (sIgА) in the patients ejaculate; to assess the state of local inflammation, we studied the cytokine status of patients by examining the level of pro-inflammatory interleukin 6 (IL-6) and anti-inflammatory interleukin 10 (IL-10) in ejaculate patients. Symptoms of prostatitis were assessed by assessing the general condition by the total score (S+L) of the IPSS chronic prostatitis symptom scale. During the study, patients with prostatitis of viral etiology were treated, which were previously divided into subgroups of each of the groups that received traditional treatment according to the protocol and traditional treatment with the inclusion of Valtrovir, Overin, and Novirin, depending on the presence of the corresponding pathogen in the patients ejaculate. The above indicators of immunity and symptoms of prostatitis were compared after treatment with the corresponding indicators of patients with prostatitis of non-viral etiology (group IV control) and healthy patients (group V).Results. According to the results of the study revealed significantly higher immunosuppression rates in patients with chronic abacterial prostatitis compared with healthy patients (p&lt;0.05). When comparing the indicators of the immune and cytokine status in patients with viral and non viral prostatitis, significantly higher immunosuppression rates were identified respectively in the first, which confirms the role of herpes viruses in the development of prostatitis. After treatment (both traditional and advanced), all patients showed a positive dynamics of immunity and symptoms (p&lt;0.05).However, when comparing the levels of IFN-γ, sIgА, IL-6, IL-10, scores (S+L) after both types of treatment, the best results were found in patients after advanced treatment (p&lt;0.05).Conclusion. The role of herpes viruses in the development of chronic nonbacterial prostatitis is proved. The etiopathogenetic therapy of patients with viral prostatitis is substantiated much more effective in comparison with traditional treatment.

Increased risk of prostatitis in male patients with depression

Objectives: To investigate whether male patients with depression are at an increased risk of prostatitis.Methods: We used a universal insurance claims database in Taiwan from 2000 to 2010 to identify patients with newly diagnosed depression (n = 13,019) (depression cohort) and those without depression (n = 53,026) (comparison cohort). Both cohorts were matched by age and index year of depression incidence. Hazard ratios of prostatitis were calculated by multivariable Cox proportional hazard models.Results: The incidence of prostatitis demonstrated a 2-fold increase in the depression cohort in comparison with that observed in the non-depression cohort, with an adjusted hazard ratio of 1.70 after adjustment for age, occupation, urbanisation level, potential comorbidity and medication. Furthermore, patients with depression, relative to the non-depression cohort, were 1.85-fold more likely to develop acute prostatitis, 1.76-fold more likely to develop chronic prostatitis and 1.63-fold more likely to develop unspecific prostatitis. Major associations still existed; even those stratified by age, occupation, urbanisation level and comorbidity all showed greater increased risks of prostatitis in the depression cohort than in the non-depression cohort.Conclusions: Depression can be an independent factor associated with the increased risk of prostatitis for men. The incidence of chronic prostatitis is greater than that of acute prostatitis. Close surveillance for UTI and depression treatment and lifestyle intervention should be considered for men with high risk for prostatitis. The mechanism associated with the development of prostatitis in men with depression requires further study. In addition, the mechanism of prostatitis may need comprehensive investigation.

Microorganisms Associated with Prostatitis Using Indwelling Urinary Catheters in Okigwe, Imo State, Nigeria

Indwelling urinary catheters are standard medical devices utilized in both hospital and nursing home settings to relieve urinary retention and urinary incontinence in a prostatitis patient. The microorganisms associated with prostatitis using urinary catheters was carried out in Okigwe, Imo State using culture technique. 200 patients were examined for prostate specific antigens (PSA) using quantitative and qualitative tests and antibiotic susceptibility tests were also done. Out of 200 patients tested for PSA, 119 (59.5%) and 129 (64.5%) were positive for quantitative and qualitative respectively. 85 patients were catheterized with 80 (94.15%) having bacterial isolates while 75 (65.5%) of the 115 uncatheterized patients having bacterial growth. The organisms isolated from catheterized and uncatheterized patients were Escherichia coli 55 (3.5%), Klebsiella spp 12 (7.8%), Staphylococcus aureus 42 (27.0%), Streptococcus 20 (12.9%), Protus spp 13 (8.4%) and Pseudomanas 13 (8.4%). Higher bacterial loads were observed in the catheterized patients urine than in the uncatheterized. Streptomycin, Ceftriaxone and Augumentine were the drugs of choice in the sensitivity tests while high antimicrobial resistant rates were observed with Ampiclox, Septrin and Chlorophenicol. Generally, high prevalence rate of PSA and bacterial pathogens were reported in patients of high age (50 and above years). This calls for proper medical checks for men of 50 years and above. This check will prevent the development of prostatitis which could lead to fertility problems because of difficulty in ejaculation in prostatitis patients.

Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain.

MP44-11 GROWTH HORMONE-RELEASING HORMONE (GHRH) ANTAGONISTS REDUCE INFLAMMATION- AND TRANSFORMING GROWTH FACTOR (TGF)-?2-INDUCED PROLIFERATION OF HUMAN BPH-1 PROSTATE EPITHELIAL CELLS GROWN IN 3D CULTURE

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2016MP44-11 GROWTH HORMONE-RELEASING HORMONE (GHRH) ANTAGONISTS REDUCE INFLAMMATION- AND TRANSFORMING GROWTH FACTOR (TGF)-?2-INDUCED PROLIFERATION OF HUMAN BPH-1 PROSTATE EPITHELIAL CELLS GROWN IN 3D CULTURE Petra Popovics, Andrew V. Schally, Roberto Perez, Rhenzi Cai, and Ferenc G. Rick Petra PopovicsPetra Popovics More articles by this author , Andrew V. SchallyAndrew V. Schally More articles by this author , Roberto PerezRoberto Perez More articles by this author , Rhenzi CaiRhenzi Cai More articles by this author , and Ferenc G. RickFerenc G. Rick More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.267AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Benign prostatic hyperplasia (BPH) is frequently associated with chronic inflammation. Epithelial-to-mesenchymal transition (EMT) has been recently indicated as a major factor in the pathogenesis of BPH. Evidence also suggests that inflammatory cytokines may induce BPH. Hypothalamic neuropeptides, GHRH, luteinizing hormone-releasing hormone (LHRH) and their receptors are expressed in experimental models of BPH in which antagonists of GHRH and LHRH have been shown to suppress the levels of proinflammatory cytokines and alter the expression of genes related to EMT. These findings imply a role of GHRH/LHRH in the development of prostatitis, however, this has not been investigated to date. METHODS Human BPH-1 prostatic cell line was used to generate matrigel-embedded 3D cultures in which average sphere diameters were evaluated. Chronic inflammation was induced by treating cells with THP-1 macrophage-conditioned medium whereas EMT was triggered with TGF-ß1 or TGF-ß2 peptides. The role of secreted LHRH and GHRH in inflammation-induced proliferation was determined by using the LHRH antagonist, degarelix, and a specific GHRH antagonist developed in our lab. The presence of receptors for GHRH and LHRH was confirmed in 3D cultures by immunocytochemistry and quantitative RT-PCR. RESULTS BPH-1-derived spherical structures expressed cell membrane receptors for LHRH and GHRH. Macrophage-conditioned medium induced a 26% increase (P<0.001) in the average diameter of cells and a 2-fold elevation in the expression of the EMT markers N-cadherin (p<0.01) and Snail (p<0.001) as detected by qPCR. The expression of GHRH was also increased 2.7-fold (p<0.001), whereas mRNA levels of LHRH were slightly reduced (ns). GHRH antagonist reduced inflammation-induced increase in diameter by 64% (P<0.01), while no significant change was observed after degarelix treatment. TGF-ß2 increased average sphere diameter by 32%, but this effect was reduced by 67% by the GHRH antagonist (P<0.001). In contrast, TGF-ß1 did not significantly affect sphere diameter. CONCLUSIONS This study identifies GHRH as an important factor in inflammation-induced proliferation and TGF-ß2-triggered EMT of prostate epithelial cells and suggests the merit of further investigation to elucidate the effects of GHRH antagonists in the reduction of inflammation-induced BPH. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e602-e603 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Petra Popovics More articles by this author Andrew V. Schally More articles by this author Roberto Perez More articles by this author Rhenzi Cai More articles by this author Ferenc G. Rick More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Il‐1β‐induced post‐transition effect of NF‐kappaB provides time‐dependent wave of signals for initial phase of intrapostatic inflammation

Our previous findings have shown that systemic administration of interleukin (IL)-1 beta induces up-regulation of nuclear factor-kappa B (NF-kappaB) in mouse prostate tissue that may be responsible for leukocyte extravasation into prostate stroma. It has been hypothesized that NF-kappaB plays a role in the development of prostatitis, and that NF-kappaB activation might provide chemoattractive signals for leukocyte extravasation in the prostate. IL-1 beta was administrated intravenously, alone or with dexamethasone (Dex), to separate groups of C57BL/6J mice. Expression of NF-kappaB, chemoattractant receptors, and IL-17F in the prostates of the two groups of mice at various time periods following treatment was evaluated and compared. IL-1 beta administration up-regulated NF-kappaB/p65 activity in the mouse prostate. IL-1 beta administration promoted extravasation and accumulation of CD45+ mononuclear cells but not neutrophils in the mouse prostate stroma. IL-1 beta administration provided earlier (4 hr) CXCR1/IL-8RA receptor expression in mouse prostate as a first signal, inducing capillary homing, adhesion, and initial extravasation of mononuclear cells into the prostate tissue. IL-1 beta administration also induced relatively late (24 hr) up-regulation of VCAM1 in the endothelial cells of microvessels and of IL-17F in prostate epithelium and in stromal infiltrating leukocytes. Concomitant administration of Dex, a known NF-kappaB inhibitor, resulted in significantly down-regulated IL-1 beta-induced NF-kappaB/p65 activity, as well as reduced expression of chemokine receptors and IL-17F in mouse prostate tissue. Systemic IL-1 beta administration induces NF-kappaB-responsive genes to promote aberrant NF-kappaB/p65 activity, which may be critical in the development of prostatitis through its role in the production of chemoattractant signals that promote extravasation and stromal accumulation of mononuclear cells (mainly by CXCR1/IL-8RA), and initiation of a new wave of pro-inflammatory signals favorable to chronic inflammation (mainly by IL-17F).

Male Genital Tract Chlamydial Infection: Implications for Pathology and Infertility1

Chlamydia trachomatis infections are prevalent worldwide, but current research, screening, and treatment are focused on females, with the burden of disease and infertility sequelae considered to be a predominantly female problem. The prevalence of chlamydial infection, however, is similar in males and females. Furthermore, a role for this pathogen in the development of male urethritis, epididymitis, and orchitis is widely accepted. The role of Chlamydia in the development of prostatitis is controversial, but we suggest that Chlamydia is an etiological agent, with incidences of up to 39.5% reported in patients with prostatitis. Infection of the testis and prostate is implicated in a deterioration of sperm, possibly affecting fertility. Chlamydia infections also may affect male fertility by directly damaging the sperm, because sperm parameters, proportion of DNA fragmentation, and acrosome reaction capacity are impaired with chlamydial infection. Furthermore, the proportion of male partners of infertile couples with evidence of a Chlamydia infection is greater than that documented in the general population. An effect of male chlamydial infection on the fertility of the female partner also has been reported. Thus, the need for a vaccine to protect both males and females is proposed. The difficulty arises because the male reproductive tract is an immune-privileged site that can be disrupted, potentially affecting spermatogenesis, if inappropriate inflammatory responses are provoked. Examination of responses to infection in humans and in experimental animal models suggest that an immunoglobulin A-inducing vaccine will be able to target the male reproductive tract effectively while avoiding harmful inflammatory responses that may impair fertility.

Maternal exposure to atrazine during lactation suppresses suckling-induced prolactin release and results in prostatitis in the adult offspring.

The availability of prolactin (PRL) to the neonatal brain is known to affect the development of the tuberoinfundibular (TIDA) neurons and, as a consequence, lead to alterations in subsequent PRL regulation. Without early lactational exposure to PRL (derived from the dam's milk), TIDA neuronal growth is impaired and elevated PRL levels are present in the prepubertal male. These observations, combined with the finding that alterations in PRL secretion (i.e., hyperprolactinemia) in the adult male rat have been implicated in the development of prostatitis, led us to hypothesize that early lactational exposure to agents that suppress suckling-induced PRL release would lead to a disruption in TIDA development, altered PRL regulation, and subsequent prostatitis in the male offspring. To test this hypothesis, suckling-induced PRL release was measured in Wistar dams treated twice daily with the herbicide atrazine (ATR, by gavage, on PND 1-4 at 0, 6.25, 12.5, 25, and 50 mg/kg body weight), or twice daily with the dopamine receptor agonist bromocriptine (BROM, sc, at 0.052, 0.104, 0.208, and 0.417 mg/kg); BROM is known to suppress PRL release. Similarly, atrazine has also been reported to suppress PRL in adult females. Serum PRL was measured on PND 3 using a serial sampling technique and indwelling cardiac catheters. A significant rise in serum PRL release was noted in all control females within 10 min of the initiation of suckling. Fifty-mg/kg ATR inhibited suckling-induced PRL release in all females, whereas 25 and 12.5 mg/kg ATR inhibited this measure in some dams and had no discernible effect in others. The 6.25 mg/kg dose of ATR was without effect. BROM, used here as a positive control, also inhibited suckling-induced PRL release at doses of 0.104 to 0.417 mg/kg, with no effect at 0.052 mg/kg. To examine the effect of postnatal ATR and BROM on the incidence and severity of inflammation (INF) of the lateral prostate of the offspring, adult males were examined at 90 and 120 days. While no effect was noted at 90 days of age, at 120 days, both the incidence and severity of prostate inflammation was increased in those offspring of ATR-treated dams (25 and 50 mg/kg). The 12.5 mg/kg ATR and the two highest doses of BROM increased the incidence, but not the severity, of prostatitis. Combined treatment of ovine prolactin (oPRL) and 25 or 50 mg/kg ATR on PND 1-4 reduced the incidence of inflammation observed at 120 days, indicating that this increase in INF, seen after ATR alone, resulted from the suppression of PRL in the dam. To determine whether or not there is a critical period for these effects, dams were dosed with 25 and 50 mg/kg on PND 6-9 and PND 11-14. Inflammation was increased in those offspring from dams treated on PND 6-9, but this increase was not significant. Dosing on PND 11-14 was without effect. These data demonstrate that ATR suppresses suckling-induced PRL release and that this suppression results in lateral prostate inflammation in the offspring. The critical period for this effect is PND 1-9.

Soy of dietary source plays a preventive role against the pathogenesis of prostatitis in rats

This study examined the effects of diet on the development of prostatitis in male rats. Adult male rats were placed on either of two specially formulated diets which differed from one another by the presence or absence of soy as the protein source. A third group of rats (control) was fed standard laboratory rat chow which also includes soy as a source of protein. After 11 weeks, it was found that rats maintained on soy-free diet developed prostatitis mainly in the lateral lobe of the prostate. Increased severity and incidence of prostatitis in rats maintained on the soy-free diet coincided with a significant decrease in urinary excretion of various phytoestrogens. There was no evidence of prostatitis in rats maintained on soy-containing diets. Urinary excretion of phytoestrogens in rats maintained on soy-containing diet was also not different from controls. These results suggest that soy as a dietary source plays a protective role against the development of prostatitis in rats, and indicate that the ventral, lateral and dorsal lobes of the rat prostate have differnt sensitivities to alterations in dietary factors.