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1.
Prostate ; 80(12): 917-925, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32569423

RESUMO

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an intractable problem of the urogenital system. The aetiopathogenesis and effective treatments for CP/CPPS are needed to be untangled. Pirfenidone is a molecule that exhibits anti-inflammatory, antifibrotic, and antioxidative stress capacities in a variety of animal experiments and clinical trials. This study was aimed to investigate the therapeutic effect of pirfenidone on CP/CPPS and to identify the mechanism responsible for it. METHODS: A CP/CPPS model was induced in rats by intraprostatic injection of complete Freund's adjuvant (CFA). Blood and prostatic tissues were harvested for assessment after the administration of pirfenidone or vehicle for 4 weeks. RESULTS: The findings revealed that pirfenidone significantly ameliorated chronic pelvic pain and inhibited prostatic inflammation and fibrosis. Further study found that pirfenidone suppressed the expression of proinflammatory mediators, including tumor necrosis factor-α, interleukin-1ß (IL-1ß), IL-6, IL-8. Pirfenidone exhibited a potent antioxidant capacity through improving the activities of glutathione, catalase, total superoxide dismutase, and reducing the production of malondialdehyde. Furthermore, pirfenidone also facilitated the polarization of M2 macrophages and suppressed the activation of the nuclear factor-κB (NF-κB) signaling pathway. CONCLUSIONS: Pirfenidone can exert a beneficial effect against CFA-induced CP/CPPS by anti-inflammatory, antioxidative, antifibrotic properties, and the function is mediated at least partly through the M2 polarization of macrophages and the inhibition of NF-κB signaling pathway. These findings suggest that pirfenidone holds promise as a potential therapeutic for the treatment of CP/CPPS.


Assuntos
Dor Crônica/tratamento farmacológico , Dor Pélvica/tratamento farmacológico , Prostatite/tratamento farmacológico , Piridonas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Polaridade Celular/efeitos dos fármacos , Doença Crônica/tratamento farmacológico , Dor Crônica/metabolismo , Dor Crônica/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , NF-kappa B/metabolismo , Dor Pélvica/metabolismo , Dor Pélvica/patologia , Fosforilação/efeitos dos fármacos , Prostatite/metabolismo , Prostatite/patologia , Ratos , Síndrome
2.
Prostate ; 80(12): 1006-1011, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32572997

RESUMO

BACKGROUND: Fungal prostatitis is exceedingly rare with mostly case reports. METHODS: Electronic medical records at three medical centers were searched for cases of fungal prostatitis due to endemic mycoses and Cryptococcus over the preceding 10 years. RESULTS: Seven cases were identified from 105 600 prostate biopsies within the Southern California Permanente Medical Group for an incidence of 0.0066%. An additional eight cases were identified from two other health care systems. Excluding four patients without available clinical data, 11 patients were reviewed, most of whom underwent biopsy due to elevated prostate-specific antigen. Four were asymptomatic and the remainder had nonspecific signs or symptoms. All biopsies revealed granulomatous inflammation and fungal organisms. Seven patients had coccidioidomycosis, three patients had cryptococcosis (confirmed in two cases and suspected by organism morphology in the other), and one patient had likely histoplasmosis based on organism morphology. Prolonged antifungal treatment was standard; outcomes were favorable. CONCLUSION: Fungal prostatitis due to endemic mycoses and Cryptococcus is uncommon and associated with favorable outcomes but generally involves prolonged therapy.


Assuntos
Criptococose/patologia , Cryptococcus/isolamento & purificação , Prostatite/microbiologia , Adulto , Idoso , Biópsia , Criptococose/epidemiologia , Criptococose/microbiologia , Doenças Endêmicas , Humanos , Masculino , Pessoa de Meia-Idade , Prostatite/epidemiologia , Prostatite/patologia , Estados Unidos/epidemiologia
3.
Prostate ; 80(11): 895-905, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32506665

RESUMO

BACKGROUND: Intraprostatic inflammation is an emerging prostate cancer risk factor. Estrogens are pro-inflammatory while androgens are anti-inflammatory. Thus, we investigated whether serum sex steroid hormone concentrations are associated with intraprostatic inflammation to inform mechanistic links among hormones, inflammation, and prostate cancer. METHODS: We conducted a cross-sectional study among 247 men in the placebo arm of the Prostate Cancer Prevention Trial who had a negative end-of-study biopsy, most (92.7%) performed without clinical indication per trial protocol. Serum estradiol, estrone, and testosterone were previously measured by immunoassay in pooled baseline and Year 3 serum. Free estradiol and free testosterone were calculated. Inflammation was visually assessed (median of three prostate biopsy cores per man). Polytomous or logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of some or all cores inflamed (both vs none) or any core inflamed (vs none) by hormone tertile, adjusting for age, race, and family history. We evaluated effect modification by waist circumference and body mass index (BMI). RESULTS: In all, 51.4% had some and 26.3% had all cores inflamed. Free (P-trend = .11) but not total estradiol was suggestively inversely associated with all cores inflamed. In men with waist circumference greater than or equal to 102 cm (P-trend = .021) and BMI ≥ 27.09 kg/m2 (P-trend = .0037) free estradiol was inversely associated with any core inflamed. Estrone was inversely associated with all cores inflamed (T3: OR = 0.36, 95% CI 0.14-0.95, P-trend = .036). Total (T3: OR = 1.91, 95% CI 0.91-4.02, P-trend = .11) and free (T3: OR = 2.19, 95% CI 1.01-4.74, P-trend = .05) testosterone were positively associated with any core inflamed, especially free testosterone in men with waist circumference less than 102 cm (T3: OR = 3.51, 95% CI 1.03-12.11, P-trend = .05). CONCLUSIONS: In this first study in men without prostate cancer and irrespective of clinical indication for biopsy, contrary to the hypothesis, circulating estrogens appeared to be inversely associated, especially in heavy men, whereas androgens appeared to be positively associated with intraprostatic inflammation.


Assuntos
Hormônios Esteroides Gonadais/sangue , Prostatite/sangue , Idoso , Biópsia , Peso Corporal , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Neoplasias da Próstata/prevenção & controle , Prostatite/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Clin Lab ; 66(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32013341

RESUMO

BACKGROUND: This study was performed to explore the total prostate-specific antigen (tPSA) concentration, free PSA (fPSA) concentration, free-to-total PSA ratio (% fPSA), tPSA density (tPSAD), and neutrophil-to-lymphocyte ratio (NLR) in blood in patients with concurrent benign prostatic hyperplasia (BPH) and histologic prostatitis, and to provide new ideas for the diagnosis of prostatitis. METHODS: Patients who underwent transurethral bipolar plasmakinetic prostatectomy from June 2017 to June 2018 were retrospectively divided into two groups according to the degree of pathological inflammation of the resected prostate tissue: group A (BPH with histologic acute and chronic inflammation), group B (BPH with histologic chronic inflammation). The preoperative PSA-related indexes and NLR in blood were respectively compared between two groups. RESULTS: Groups A and B comprised 59 and 41 cases, respectively. The values of tPSA, tPSAD, and NLR were all significantly higher in group A than B, and the value of % fPSA was significantly lower in group A than B (p < 0.05). There was no significant difference for the value of fPSA between the two groups (p > 0.05). CONCLUSIONS: Histologic acute prostatitis can cause changes of PSA-related indexes and NLR in blood, which has important clinical significance in diagnosis of prostatitis.


Assuntos
Linfócitos/citologia , Neutrófilos/citologia , Antígeno Prostático Específico/sangue , Hiperplasia Prostática , Prostatite , Idoso , Idoso de 80 Anos ou mais , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/patologia , Prostatite/sangue , Prostatite/epidemiologia , Prostatite/patologia , Estudos Retrospectivos
5.
Prostate ; 80(1): 28-37, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573117

RESUMO

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a disorder that is characterized by persistent pelvic pain in men of any age. Although several studies suggest that the transient receptor potential vanilloid 1 (TRPV1) channel is involved in various pathways of chronic pain, the TRPV1 channel has not been implicated in chronic pelvic pain associated with CP/CPPS. METHODS: Male C57BL/6J (B6) and TRPV1 knockout (TRPV1 KO) mice (5-7 weeks old) were used to study the development of pelvic allodynia in a murine model of CP/CPPS called experimental autoimmune prostatitis (EAP). The prostate lobes, dorsal root ganglia (DRG), and spinal cord were excised at day 20. The prostate lobes were assessed for inflammation, TRPV1 expression, and mast cell activity. DRG and spinal cord, between the L6-S4 regions, were analyzed to determine the levels of phosphorylated ERK1/2 (p-ERK 1/2). To examine the therapeutic potential of TRPV1, B6 mice with EAP received intraurethral infusion of a TRPV1 antagonist at day 20 (repeated every 2 days) and pelvic pain was evaluated at days 20, 25, 30, and 35. RESULTS: Our data showed that B6 mice with EAP developed pelvic tactile allodynia at days 7, 14, and 20. In contrast, TRPV1 KO mice with EAP do not develop pelvic tactile allodynia at any time point. Although we observed no change in the levels of TRPV1 protein expression in the prostate from B6 mice with EAP, there was evidence of significant inflammation and elevated mast cell activation. Interestingly, the prostate from TRPV1 KO mice with EAP showed a lack of mast cell activation despite evidence of prostate inflammation. Next, we observed a significant increase of p-ERK1/2 in the DRG and spinal cord from B6 mice with EAP; however, p-ERK1/2 expression was unaltered in TRPV1 KO mice with EAP. Finally, we confirmed that intraurethral administration of a TRPV1 antagonist peptide reduced pelvic tactile allodynia in B6 mice with EAP after day 20. CONCLUSIONS: We demonstrated that in a murine model of CP/CPPS, the TRPV1 channel is key to persistent pelvic tactile allodynia and blocking TRPV1 in the prostate may be a promising strategy to quell chronic pelvic pain.


Assuntos
Doenças Autoimunes/metabolismo , Prostatite/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Gânglios Espinais/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/imunologia , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oligopeptídeos/farmacologia , Dor Pélvica/tratamento farmacológico , Dor Pélvica/imunologia , Dor Pélvica/metabolismo , Dor Pélvica/patologia , Fosforilação , Prostatite/tratamento farmacológico , Prostatite/imunologia , Prostatite/patologia , Medula Espinal/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/deficiência
6.
Fundam Clin Pharmacol ; 34(2): 160-172, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31642541

RESUMO

Prostate cancer and prostatitis are both significant health concerns. A large number of studies have established that the occurrence of the two is closely related. However, the most common prostatitis, type III chronic prostatitis/chronic pelvic pain syndromes (CP/CPPS), is reported to not correlate with the occurrence of prostate cancer. Although the etiology of CP/CPPS is unknown, it may be related to the autoimmune mechanism favored by most studies. Manipulating the immune system and targeting tumor microenvironment are promising new methods for the treatment of prostate cancer. Therefore, this review focuses on the immune cells and cytokines of CP/CPPS and prostate cancer from the perspective of biological immunology and immune microenvironment. We discuss T-regulatory (Treg) and T helper 17 (Th17) cells dysfunction, the abnormal regulation of T helper 1(Th1) and T helper 2 (Th2) cells, macrophages, and their related cytokines as key activators in CP/CPPS. In addition, we discuss the roles of Treg and Th17 cells, Th1 and Th2 cells, and related cytokines in modulating prostate cancer progression. This review highlights the concept that immune cells and cytokines provide a research strategy for the etiology of CP/CPPS and offer potentially promising targets for the treatment of prostate cancer.


Assuntos
Citocinas/imunologia , Neoplasias da Próstata/patologia , Prostatite/patologia , Animais , Doença Crônica , Progressão da Doença , Humanos , Masculino , Neoplasias da Próstata/imunologia , Prostatite/imunologia , Microambiente Tumoral/imunologia
7.
Pan Afr Med J ; 37: 290, 2020.
Artigo em Francês | MEDLINE | ID: mdl-33654514

RESUMO

Introduction: acute prostatitis is a common urological condition. The purpose of this study was to analyze the epidemioclinical features and therapy of acute prostatitis associated with noncancerous prostate at the Lubumbashi University Clinics. Methods: we conducted a descriptive cross-sectional and retrospective study of a series of 25 patients with documented acute prostatitis and treated at the Lubumbashi University Clinics over a period of four years, from 2015 to 2018. All patients with prostate cancer were excluded from our study. Data were collected via a survey form based on different study parameters divided into 3 categories, namely epidemiological data including age, study period, residence, clinical data with subjective signs, objective signs, general status, findings on rectal examination as well as paramedical data divided into laboratory and imaging tests. Results: acute prostatitis associated with noncancerous prostate accounted for 1.27% of all surgical diseases and 7.66% in urology. The most affected age group was 19-37 years (64% of cases), mean age was 33.16±2.4 years. Seventeen patients (68%) were followed up in outpatient clinics and 8 (32%) in hospital. Clinically, fever above 38.5°C was found in 15 patients (60%), dysuria in 11 patients (44%), acute urinary retention in 3 patients (12%), burning during urination in 8 patients (32%), pain syndrome in 21 patients (84%), tender prostate on rectal examination in 18 patients (72%). Ultrasound was the only examination performed in 16 patients (64%). Biologically, assessment of inflammation was performed almost systematically in all patients (100%) including complete blood count (CBC), sedimentation rate (SR), C reactive protein (CRP) levels; blood culture was performed in 4 patients (16%), three of whom had positive blood culture. All patients underwent cytobacteriological examination of the urine or prostatic secretions collected by prostate massage. Urine culture was sterile in 6 patients (24%) and positive in 19 patients (76%). Escherichia coli was the most common germ in 16 out of a total of 19 patients (84.21%). All patients received rectal anti-inflammatory drugs. Fluoroquinolones were the most used antibiotics in 18 patients (64%), twelve of whom received antibiotics as monotherapy. Six out of 25 (24%) cases were associated with orchiepididymitis. The lenght of treatment ranged from 2 to 4 weeks, with either sterilization in secretions or urine or disappearance of leukocyturia as the criteria for treatment discontinuation. Thus, out of 19 patients with positive culture on admission, 14 underwent a second culture (73.68%) at 2 weeks of treatment, three of whom (12%) still had positive test and had to undergo a third culture 4 weeks after they had started treatment. Patient's course was good in 22 cases (88%) with complete clinical and biological remission; three patients (12%) persisted in symptoms which became chronic; no patients had prostatic abscess. Conclusion: acute prostatitis associated with noncancerous prostate is a really worrying urological, nosologic condition whose management must be rigorous, especially in people at risk, namely those with intense sexual behaviour. Endorectal ultrasound and prostate massage should be integrated into patient care at the Lubumbashi University Clinics.


Assuntos
Anti-Inflamatórios/administração & dosagem , Infecções Bacterianas/diagnóstico , Próstata/patologia , Prostatite/diagnóstico , Doença Aguda , Adolescente , Adulto , Antibacterianos/administração & dosagem , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Estudos Transversais , República Democrática do Congo , Epididimite/complicações , Epididimite/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Orquite/complicações , Orquite/diagnóstico , Prostatite/tratamento farmacológico , Prostatite/patologia , Estudos Retrospectivos , Adulto Jovem
8.
Sci Rep ; 9(1): 19233, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848441

RESUMO

Environmental and nutritional factors, including fatty acids (FA), are associated with prostatitis, benign prostate hyperplasia and prostate cancer. We hypothesized that different FA in normolipidic diets (7%) affect prostate physiology, increasing the susceptibility to prostate disorders. Thus, we fed male C57/BL6 mice with normolipidic diets based on linseed oil, soybean oil or lard (varying saturated and unsaturated FA contents and ω-3/ω-6 ratios) for 12 or 32 weeks after weaning and examined structural and functional parameters of the ventral prostate (VP) in the systemic metabolic context. Mongolian gerbils were included because they present a metabolic detour for low water consumption (i.e., oxidize FA to produce metabolic water). A linseed oil-based diet (LO, 67.4% PUFAs, ω-3/ω-6 = 3.70) resulted in a thermogenic profile, while a soybean oil-based diet (SO, 52.7% PUFAs, ω-3/ω-6 = 0.11) increased body growth and adiposity. Mice fed lard (PF, 13.1% PUFA, ω-3/ω-6 = 0.07) depicted a biphasic growth, resulting in decreased adiposity in adulthood. SO and PF resulted in hepatic steatosis and steatohepatitis, respectively. PF and SO increased prostate epithelial volume, and lard resulted in epithelial hyperplasia. Animals in the LO group had smaller prostates with predominant atrophic epithelia and inflammatory loci. Inflammatory cells were frequent in the VP of PF mice (predominantly stromal) and LO mice (predominantly luminal). RNAseq after 12 weeks revealed good predictors of a later-onset inflammation. The transcriptome unveiled ontologies related to ER stress after 32 weeks on PF diets. In conclusion, different FA qualities result in different metabolic phenotypes and differentially impact prostate size, epithelial volume, inflammation and gene expression.


Assuntos
Gorduras na Dieta/efeitos adversos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ácidos Graxos/efeitos adversos , Lesões Pré-Cancerosas/metabolismo , Hiperplasia Prostática/metabolismo , Prostatite/metabolismo , Transcriptoma/efeitos dos fármacos , Animais , Gorduras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Masculino , Camundongos , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Prostatite/induzido quimicamente , Prostatite/patologia
9.
Urologiia ; (5): 14-21, 2019 Dec.
Artigo em Russo | MEDLINE | ID: mdl-31808626

RESUMO

BACKGROUND: According to the literature, bacterial count of uropathogens isolated from expressed prostate secretion and urine which is sufficient for a diagnosis of bacterial prostatitis I and II categories, remains contradictory. Undoubtedly, the identification of microorganisms from affected organ in high titers indicates the presence of a relevant infectious-inflammatory process. In turn, there is no consensus on the development of bacterial prostatitis at lower titers of uropathogens. Thus, the aim of our study was to identify and compare the potential features of the development and occurrence of an infectious inflammatory process in the prostate during the reproduction of bacterial prostatitis in an animal model using a low titer of causative uropathogens. MATERIALS AND METHODS: A total of 16 "New Zealand" mature male rabbits aged 24+/-2 weeks old with weight of 3.5+/-0.3 kg were examined. Inoculation was performed via transurethral route, according to the developed experimental technique. E. coli was used as bacterial agent with a count of 1 x 103 CFU/ml, 1 x 105 CFU/ml and 1 x 107 CFU/ml. All animals were randomized into 4 groups of 4 individuals depending on the titer of the inoculated microorganisms (groups 1-3, respectively), group 4 - control (with inoculation by Sol. NaCl 0.9%). Sacrification and vivisection were performed on days 1, 3, 7 and 14 of the control days. Biopsy specimens from the lower urinary tract and internal genital organs of laboratory animals (bladder, urethra, prostatic complex - 6 biopsies #1A-1D, 2A, 2B) were evaluated morphologically and bacteriologically. Analytical evaluation of the experimental data was presented using descriptive statistical methods. RESULTS: In experimental groups (Groups 1-3), bacteriological examination of prostatic complex biopsies showed growth of microflora in all samples in titers of 101-107 CFU / ml. In group 1, the maximum concentration of uropathogen was observed on day 7, compared to day 1 in both groups 2 and 3. In all observed cases, the highest degree of bacterial contamination was noted in the biopsy specimens from paraprostatic tissues and distal part of the prostate, which was 4.0+/-1.7 lg CFU/ml and 3.5+/-1.9 lg CFU/ml, respectively, and the smallest in proximal prostatic loci (1C) and bladder neck (2B) - 3.0+/-1.2 lg COE / ml and 3.0+/-1.7 lg COE / ml, respectively. According to the morphological study, a relevant progression of the suppurative and destructive inflammation (with foci of colliquation necrosis) was identified in group 1 in the biopsies from the prostate with a maximum degree of changes on day 7 with subsequent formation of loose connective tissue proliferation areas by 14 days. This indicates the conversion of the inflammatory process to the chronic stage. These changes corresponded with the results of histopathological studies in groups 2 and 3 where higher titers of bacterial agent were used. In group 4 (control) the commensal flora was bacteriologically determined in the biopsies, but there were no signs of inflammation, according to the results of the morphological study. CONCLUSION: In experimental model, we found that E. coli 103 CFU / ml induces the development of a phasic inflammatory process in the structures of the prostatic complex. These processes resulted in the formation of irreversible proliferative changes. As a consequence, it shold be recommended to consider these signs of contamination when evaluating the results of bacteriological examination of expressed prostate secretion/urine samples during planning treatment strategy.


Assuntos
Infecções Bacterianas , Prostatite , Animais , Progressão da Doença , Escherichia coli , Humanos , Masculino , Prostatite/patologia , Coelhos , Distribuição Aleatória
10.
S Afr J Surg ; 57(4): 43, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31773934

RESUMO

SUMMARY: Tuberculous (TB) prostatitis is rare; usually occurring in immunocompromised men. It can mimic benign prostatic hyperplasia (BPH), chronic prostatitis or prostate cancer. This report in an immunocompetent 72-year-old man adds to the clinical spectrum of the five prior reported cases. A low threshold for prostatic biopsy led to a histological evaluation and subsequent microbiological confirmation of TB. This attests to the value of such an approach in arriving at the correct diagnosis and the institution of appropriate anti-tuberculous therapy even amongst immune-competent men.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Prostatite/tratamento farmacológico , Prostatite/microbiologia , Tuberculose dos Genitais Masculinos/patologia , Idoso , Biópsia por Agulha , Diagnóstico Diferencial , Seguimentos , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/etiologia , Imagem por Ressonância Magnética/métodos , Masculino , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/etiologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/etiologia , Prostatite/patologia , Doenças Raras , Medição de Risco , África do Sul , Resultado do Tratamento , Tuberculose dos Genitais Masculinos/diagnóstico , Tuberculose dos Genitais Masculinos/tratamento farmacológico
11.
Andrologia ; 51(11): e13435, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31613015

RESUMO

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common clinical syndrome with unknown aetiology. In this study, we used the T2 peptide in C57BL/6 (B6) mice and Sprague Dawley (SD) rats model during different stages. We sought to understand the role of CD4+ T cells and macrophages in CP/CPPS. A total of 16 B6 mice and 18 SD rats were divided into five groups: B6-naïve (n = 6), B6 model (n = 10), SD-naïve (n = 6), SD-45-day model (n = 6) and SD-56-day model (n = 6). The B6 model group was subcutaneously injected with 0.2 ml of (225µg/ml) T2 peptide on 0 and 14th day and was finally sacrificed on 28th day. The SD-45- and SD-56-day model groups were subcutaneously injected with 1ml of (50 µg/ml) T2 peptide on 0 and 14th day and were finally sacrificed on 45th and 56th day respectively. An equivalent volume of normal saline (NS) solution was injected to the naïve groups and analysed the pain and voiding behaviour. We have calculated the prostate index, H&E staining and immunofluorescence of CD4+ T cells and macrophages (CD68) in each group. T2 peptide immunization in B6 mice and SD rats caused severe prostatitis and cell infiltration, mainly composed of CD4+ T cells and macrophages. The SD-56-day model group showed more severe inflammatory cells infiltration than SD-45-day model group. Moreover, inflammatory cells infiltration and red secretions in B6 model were less than SD model. Expression of CD4+ T cells and macrophages was also consistent with H&E results. These results indicated that different stages of CP/CPPS, inflammatory response, and the inflammation of the rat were stronger than the mouse. Our study suggests that CD4+ T cells and macrophages are key factors in the development of CP/CPPS.


Assuntos
Prostatite/imunologia , Animais , Comportamento Animal , Linfócitos T CD4-Positivos/fisiologia , Modelos Animais de Doenças , Macrófagos/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Próstata/imunologia , Próstata/patologia , Prostatite/metabolismo , Prostatite/patologia , Prostatite/psicologia , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
12.
J Neuroinflammation ; 16(1): 189, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653262

RESUMO

BACKGROUND: Prostatodynia is the main symptom of chronic prostatitis and the main reason that patients go to the hospital for treatment. Although a variety of factors, including inflammatory immune response, nervous system sensitization, and psychological factors, have been shown to play important roles in the induction and development of chronic pain in prostatitis, the underlying cause of chronic prostatodynia maintenance in prostatitis patients remains unclear. METHODS: A mouse model of chronic prostatitis induced by carrageenan injection was used. The von Frey test was used to measure pain behavior. The microglial and astrocyte activations were immunohistochemically demonstrated with antibodies against Iba1 and GFAP. The expression of cytokine or signaling pathway was detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting. RESULTS: In this study, we provide several lines of evidence to demonstrate that activated spinal astrocytes contribute to the later phase (5 weeks after carrageenan injection) of carrageenan-induced prostatitis pain. First, activation of spinal astrocytes but not microglia was found in the spinal cord dorsal horn at 5 weeks. Second, intrathecal injection of the astroglial toxin L-2-Aminoadipate acid (L-AA) but not microglial inhibitor minocycline reduced mechanical allodynia at 5 weeks. Third, chronic prostatitis induced a profound and persistent upregulation of connexin-43 hemichannels in spinal astrocytes, and spinal injection of the connexin-43 inhibitor carbenoxolone (CBX) effectively reduced pain symptoms. Fourth, increased expression and release of chemokine C-X-C motif ligand 1 (CXCL1) in the spinal dorsal horn and intrathecal injection of a CXCL1 neutralizing antibody or the CXCR2 (a major receptor of CXCL1) antagonist SB225002 significantly reduced mechanical allodynia at 5 weeks. CONCLUSIONS: In this study, we found that a novel mechanism of activated spinal astrocytes plays a crucial role in maintaining chronic prostatitis-induced persistent pain via connexin-43-regulated CXCL1 production and secretion.


Assuntos
Astrócitos/patologia , Carragenina/toxicidade , Dor/patologia , Prostatite/patologia , Medula Espinal/patologia , Animais , Astrócitos/efeitos dos fármacos , Masculino , Camundongos , Dor/induzido quimicamente , Prostatite/induzido quimicamente , Medula Espinal/efeitos dos fármacos
13.
Investig Clin Urol ; 60(5): 388-395, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501802

RESUMO

Purpose: To investigate if inflammation as a potential cause of false-positive lesions from recent UroNav magnetic resonance imaging (MRI) fusion prostate biopsy patients. Materials and Methods: We retrospectively identified 43 men with 61 MRI lesions noted on prostate MRI before MRI ultrasound-guided fusion prostate biopsy. Men underwent MRI with 3T Siemens TIM Trio MRI system (Siemens AG, Germany), and lesions were identified and marked in DynaCAD system (Invivo Corporation, USA) with subsequent biopsy with MRI fusion with UroNav. We obtained targeted and standard 12-core needle biopsies. We retrospectively reviewed pathology reports for inflammation. Results: We noted a total of 43 (70.5%) false-positive lesions with 28 having no cancer on any cores, and 15 lesions with cancer noted on systematic biopsy but not in the target region. Of the men with cancer, 6 of the false positive lesions had inflammation in the location of the targeted region of interest (40.0%, 6/15). However, when we examine the 21/28 lesions with an identified lesion on MRI with no cancer in all cores, 54.5% had inflammation on prostate biopsy pathology (12/22, p=0.024). We noted the highest proportion of inflammation. Conclusions: Inflammation can confound the interpretation of MRI by mimicking prostate cancer. We suggested focused efforts to differentiate inflammation and cancer on prostate MRI.


Assuntos
Biópsia Guiada por Imagem , Imagem por Ressonância Magnética Intervencionista , Imagem por Ressonância Magnética , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Prostatite/diagnóstico por imagem , Prostatite/patologia , Ultrassonografia de Intervenção , Idoso , Sistemas de Dados , Reações Falso-Positivas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Int J Mol Sci ; 20(15)2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31390729

RESUMO

Inflammation is inherent in prostatic diseases and it is now accepted that it may facilitate cellular proliferation in both benign and malignant conditions. The strong relationship between prostatic inflammation and pathogenesis of benign prostatic hyperplasia (BPH) is supported by epidemiologic, histopathologic and molecular evidence. Contrariwise, the role of inflammation in prostate carcinogenesis is still controversial, although current data indicate that the inflammatory microenvironment can regulate prostate cancer (PCa) growth and progression. Knowledge of the complex molecular landscape associated with chronic inflammation in the context of PCa may lead to the introduction and optimization of novel targeted therapies. In this perspective, evaluation of the inflammatory component in prostate specimens could be included in routine pathology reports.


Assuntos
Suscetibilidade a Doenças , Neoplasias da Próstata/etiologia , Prostatite/complicações , Animais , Biomarcadores , Transformação Celular Neoplásica , Progressão da Doença , Humanos , Mediadores da Inflamação , Masculino , Prevalência , Neoplasias da Próstata/epidemiologia , Prostatite/epidemiologia , Prostatite/metabolismo , Prostatite/patologia
15.
Prostate ; 79(13): 1498-1504, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31376214

RESUMO

BACKGROUND: This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism. METHODS: RWPE-2 cells were randomly divided into three groups: (a) RWPE-2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE-2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague-Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 ß-estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA. RESULTS: ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX-2) through inhibiting TLR4-NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2-COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate. CONCLUSIONS: ESWT improved CP/CPPS and reduced inflammation by degrading COX-2 in microenvironment through TLR4-NFκB-inhibiting pathway. TRAF2 regulator in ERK1/2-COX-2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Tratamento por Ondas de Choque Extracorpóreas , NF-kappa B/metabolismo , Prostatite/terapia , Receptor 4 Toll-Like/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular , Doença Crônica , Regulação para Baixo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , NF-kappa B/antagonistas & inibidores , Dor Pélvica/metabolismo , Dor Pélvica/patologia , Dor Pélvica/terapia , Prostatite/metabolismo , Prostatite/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator 2 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/biossíntese
16.
Urol Int ; 103(4): 415-422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31466070

RESUMO

INTRODUCTION: To assess the association of prostate volume index (PVI), defined as the ratio of the central transition zone volume to the peripheral zone volume, and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA) risk in patients presenting with normal digital rectal exam and prostate-specific antigen (PSA) ≤10 ng/mL at baseline random biopsies. METHODS: We evaluated patients with a negative digital rectal examination (DRE) and a PSA ≤10 ng/mL who underwent initial baseline prostate biopsy from 2010 to 2017. Parameters evaluated included age, PSA, total prostate volume (TPV), PSA density (PSAD), PVI and PCI. All patients underwent 14 core trans-perineal standard biopsies. The association of factors with the risk of PCA was evaluated by logistic regression analysis, utilizing 2 multivariate models: model I included age, TPV, PVI and PCI; model II included age, PSAD, PVI and PC. RESULTS: Overall, 564 Caucasian patients were included. PCA and PCI were detected in 242 (42.9%) and 129 (22.9%) cases respectively. In patients with PCA, the median PVI was 0.83 (interquartile range [IQR] 0.62-1.04). In patients with PCI, the median PVI was 1.12 (IQR 0.81-1.47). In model I, age (OR 1.080) TPV (OR 0.961), PVI (OR 0.517) and PCI (OR 0.249) were associated with PCA risk. In model II, the age (OR 1.074), PSAD (OR 3.080), PVI (OR 0.361) and PCI (OR 0.221) were associated with PCA risk. CONCLUSIONS: Higher PVI and PCI predicted decreased PCA risk in patients presenting with normal DRE, and a PSA ≤10ng/mL at baseline random biopsy. In this subset of patients, PVI is able to differentiate patients with PCI or PCA.


Assuntos
Calicreínas/sangue , Antígeno Prostático Específico/sangue , Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Prostatite/sangue , Prostatite/patologia , Idoso , Biópsia , Doença Crônica , Diagnóstico Diferencial , Exame Retal Digital , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Retrospectivos
17.
Cancer Epidemiol Biomarkers Prev ; 28(10): 1594-1603, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31337640

RESUMO

BACKGROUND: Previous meta-analyses have estimated summary positive associations between clinical prostatitis and prostate cancer. However, none have accounted for detection bias, the possibility for increased prostate cancer screening and detection in men with clinical prostatitis, in their pooled estimates. METHODS: We searched for studies that investigated the relation between clinical prostatitis and prostate cancer through November 2018. Random effects meta-analysis was used to calculate summary odds ratios (OR) among all studies and in strata defined by methods used to reduce detection bias.Results: Although an increased odds of prostate cancer was seen among men with a history of clinical prostatitis in all 38 eligible studies combined [OR, 2.05; 95% confidence interval (CI), 1.64-2.57], this estimate attenuated to null among studies that performed the most rigorous analyses to limit detection bias (OR, 1.16; 95% CI, 0.77-1.74). CONCLUSIONS: Our findings indicate that previously reported positive associations between clinical prostatitis and prostate cancer are likely due to detection bias. IMPACT: Studies using rigorous detection bias methods are warranted to replicate these findings, as well as to examine the possible relation between prostate inflammation and prostate cancer directly, rather than indirectly through the diagnosis of "prostatitis," which includes a large proportion of men without evidence of prostate inflammation.


Assuntos
Neoplasias da Próstata/epidemiologia , Prostatite/epidemiologia , Viés , Detecção Precoce de Câncer/métodos , Humanos , Calicreínas/sangue , Masculino , Modelos Estatísticos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Prostatite/sangue , Prostatite/patologia
18.
Arch Ital Urol Androl ; 91(2)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266275

RESUMO

INTRODUCTION/AIM: Although prostatic calculi/calcifications are encountered frequently in the urological practice, little is known about the incidence of such lesions, their mechanism of formation, their relationship to other prostate conditions and their clinical significance. The purpose of this study is to describe the characteristics and to investigate the clinical significance of prostatic calcifications (PCs) in patients with chronic bacterial prostatitis (CBP). MATERIALS AND METHODS: This study was conducted between 01/02/2013 and 20/02/2018. The patient population for this study included subjects with or without PCs and a confirmed diagnosis of NIH category II Chronic Bacterial Prostatitis (CBP). Demographics and clinical history of each assessed patient were reviewed. Eligible patients underwent prostatic ultrasound with post-void residual measurement, and the Meares-Stamey "4-glass" test. Symptom severity was measured using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostatic Symptoms Score (IPSS). Antimicrobials were administered to confirmed cases of CBP according to the results of susceptibility tests. After four weeks off-therapy, the NIH-CPSI and IPSS tests were repeated. Variables were compared between patients with and without prostatic calcifications. RESULTS: Ninety-five CBP patients were included in the study. According to the presence of PCs detected by ultrasound examination, patients were divided into two groups: 41 had PCs (group 1) and 54 didn't (group 2). No significant between-group baseline differences were found regarding age, marital status, prostate volume, the proportion of common CBP pathogens. Concerning highrisk sexual behavior, a significantly higher number of men with PCs practiced anal penetration. Moreover, a significantly higher number of men with PCs had a history of chronic prostatitis relapsing episodes. Microbiological eradication and the complete resolution of clinical symptoms occurred in similar proportions between the two groups. However, intergroup analysis resulted in significantly higher scores of the NIH-CPSI test in group 1, both at the pre-therapy and at the post-therapy time points. Conversely, no IPSS score differences between groups 1 and 2 were found at both pre- and post-therapy time points. CONCLUSIONS: Prostatic calcifications do not seem to influence the microbiological outcome of antibacterial treatment. However, the CBP symptoms appear to be more severe in carriers of prostatic calcifications, either before or after antibacterial therapy.


Assuntos
Infecções Bacterianas/patologia , Calcinose/diagnóstico , Doenças Prostáticas/diagnóstico , Prostatite/patologia , Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Calcinose/patologia , Doença Crônica , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Doenças Prostáticas/patologia , Prostatite/tratamento farmacológico , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
19.
Arch Ital Urol Androl ; 91(2)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266276

RESUMO

The aim of the present case-series analysis was to assess the safety and efficacy of pollen extract in association with vitamins in order to reduce the chronic prostatic inflammation in patients with class IV chronic prostatitis (CP). Nineteen non-consecutive patients performed a prostate biopsy for a suspect of prostate cancer. The biopsy histopathological examination showed a class IV CP, in presence of mild/moderate/high degree of inflammation, in association with an extensive (multiple biopsy sites, i.e., ≥ 3) high-grade prostatic intraepithelial neoplasia PIN (HGPIN) and/or atypical small acinar proliferation (ASAP). According to EAU Prostate Cancer Guidelines prostate biopsy was repeated after 6 months, because of the presence of extensive HGPIN or ASAP. Oral administration of pollen extract in association with vitamins (two capsules every 24 h) was prescribed until the repeat biopsy. Repeat biopsy histopathological examination showed, in 13 patients (68.4%), a lower degree of inflammation (absent/mild/moderate).


Assuntos
Extratos Vegetais/administração & dosagem , Pólen/química , Prostatite/terapia , Vitaminas/administração & dosagem , Idoso , Biópsia , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Prostática Intraepitelial/diagnóstico , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Prostatite/patologia , Resultado do Tratamento
20.
Prostate ; 79(12): 1439-1449, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31233226

RESUMO

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent disease of the urogenital system. Alcohol has been reported to be closely related to CP/CPPS. Thus, we intended to verify the role of alcohol in CP/CPPS and determine the underlying mechanism. METHODS: We induced experimental autoimmune prostatitis (EAP) mouse model by intradermally injecting a mixture of prostate antigens (PAgs) and complete Freund's adjuvant on days 0 and 28. Mice were treated with alcohol (control-alcohol and EAP-alcohol groups) or vehicle (control-vehicle, and EAP-vehicle groups) from day 32 to 42. Forty-two days after PAg injection, the pathological appearance of the prostate tissues was evaluated, and histological analyses of the prostate were performed. Chronic pelvic pain was assessed by applying von Frey filaments to the lower abdomen. Proinflammatory cytokines were detected by enzyme-linked immunosorbent assay tests. Then, we explored the effects of the NLRP3 inhibitor MCC950 on chronic pelvic pain and prostatic inflammation in this model. RESULTS: Histological analyses showed diffuse inflammation in the stromal tissues that were characterized by severe infiltration of neutrophils and mononuclear cells in mice in the EAP-alcohol group compared with EAP-vehicle group. Chronic pain tests showed that the response frequency was significantly increased using a von Frey filament at forces of 0.4, 1.0, and 4.0 g in EAP-alcohol group compared with EAP-vehicle (P < .05). The levels of proinflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17, and IL-1ß were all significantly elevated in EAP-alcohol group compared with the EAP-vehicle group (P < .05). However, between the control-alcohol and control-vehicle groups, chronic pain tests, histological assays, and cytokine determinations showed no differences. Furthermore, our results demonstrated that MCC950 could decrease the expression level of NLRP3 inflammasome-related proteins including NLRP3, ASC, and caspase-1. The chronic pain tests, histological assays, and cytokine determinations showed that MCC950 could attenuate the chronic pain and prostatic inflammation through the inhibition of the NLRP3 inflammasome. CONCLUSIONS: This study indicated that alcohol could aggravate the severity of prostatic inflammation in EAP model though activating the NLRP3 inflammasome. Furthermore, the role of MCC950 in inhibiting NLRP3 inflammasome and decreasing IL-1ß secretion to alleviate EAP severity may show that it is a promising therapeutic agent for CP/CPPS.


Assuntos
Doenças Autoimunes/imunologia , Etanol/farmacologia , Dor Pélvica/imunologia , Próstata/imunologia , Prostatite/imunologia , Álcoois/farmacologia , Animais , Doenças Autoimunes/patologia , Dor Crônica/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Furanos/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis , Inflamassomos/imunologia , Inflamação/imunologia , Masculino , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Próstata/efeitos dos fármacos , Próstata/patologia , Prostatite/patologia , Ratos , Ratos Wistar , Sulfonamidas/farmacologia , Sulfonas
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