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1.
Mol Oncol ; 17(3): 445-468, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36321189

RESUMO

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has a high prevalence of up to 15% and accounts for 90-95% of prostatitis diagnoses, and yet its etiopathogenesis and link to prostate cancer (PCa) are still unclear. Here, we investigated microRNAs in exosomes isolated from blood and post-prostatic-massage urine of CP/CPPS type IIIb patients and healthy men. THP-1 monocytes (human leukemia monocytic cell line) were treated with exosomes and subjected to mRNA arrays "Cancer Inflammation and Immunity Crosstalk" and "Transcription Factors." Using The Cancer Genome Atlas, the expression of CP/CPPS-associated microRNAs was analyzed in PCa and normal prostate tissue. In silico functional studies were carried out to explore the disease ontology of CP/CPPS. In CP/CPPS, urine exosomes exhibited significant upregulation of eight PCa-specific microRNAs (e.g., hsa-miR-501, hsa-miR-20a, and hsa-miR-106), whose target genes were significantly enriched for GO terms, hallmark gene sets, and pathways specific for carcinogenesis. In THP-1 monocytes, CP/CPPS-derived urine exosomes induced upregulation of PCa-associated proinflammatory genes (e.g., CCR2 and TLR2) and proto-oncogene transcription factors (e.g., MYB and JUNB). In contrast, CP/CPPS-derived blood exosomes exhibited molecular properties similar to those of healthy men. Thus, CP/CPPS exhibits molecular changes that constitute a risk for PCa and should be considered in the development of PCa biomarkers and cancer screening programs.


Assuntos
Exossomos , MicroRNAs , Neoplasias da Próstata , Prostatite , Masculino , Humanos , Prostatite/genética , Prostatite/diagnóstico , Doença Crônica , Próstata , Exossomos/genética , Dor Pélvica/genética , Neoplasias da Próstata/genética , MicroRNAs/genética , Proto-Oncogenes , Massagem
2.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34360623

RESUMO

Investigations in male patients with fertility disorders revealed a greater risk of osteoporosis. The rodent model of experimental autoimmune-orchitis (EAO) was established to analyze the underlying mechanisms of male infertility and causes of reduced testosterone concentration. Hence, we investigated the impact of testicular dysfunction in EAO on bone status. Male mice were immunized with testicular homogenate in adjuvant to induce EAO (n = 5). Age-matched mice were treated with adjuvant alone (adjuvant, n = 6) or remained untreated (control, n = 7). Fifty days after the first immunization specimens were harvested. Real-time reverse transcription-PCR indicated decreased bone metabolism by alkaline phosphatase and Cathepsin K as well as remodeling of cell-contacts by Connexin-43. Micro computed tomography demonstrated a loss of bone mass and mineralization. These findings were supported by histomorphometric results. Additionally, biomechanical properties of femora in a three-point bending test were significantly altered. In summary, the present study illustrates the induction of osteoporosis in the investigated mouse model. However, results suggest that the major effects on bone status were mainly caused by the complete Freund's adjuvant rather than the autoimmune-orchitis itself. Therefore, the benefit of the EAO model to transfer laboratory findings regarding bone metabolism in context with orchitis into a clinical application is limited.


Assuntos
Doenças Autoimunes/complicações , Osso e Ossos/metabolismo , Orquite/complicações , Osteoporose/imunologia , Animais , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Doenças Autoimunes/fisiopatologia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Orquite/metabolismo , Orquite/patologia , Orquite/fisiopatologia , Osteoporose/diagnóstico por imagem , Microtomografia por Raio-X
3.
J Urol ; 205(3): 653-663, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33026903

RESUMO

PURPOSE: We identify which nonantibiotic strategies could reduce the risk of infectious complications following prostate biopsy. MATERIALS AND METHODS: We performed a literature search on MEDLINE®, Embase® and the Cochrane Database for randomized controlled trials (inception to May 2020) assessing nonantibiotic interventions in prostate biopsy. Primary outcome was pooled infectious complications (fever, sepsis and symptomatic urinary tract infection) and secondary outcome was hospitalization. Cochrane risk of bias tool and GRADE approach were used to assess the bias and the certainty of evidence. The study protocol was registered with PROSPERO (CRD42015026354). RESULTS: A total of 90 randomized controlled trials (16,941 participants) were included in the analysis, with 83 trials being categorized into one of 10 different interventions. Transperineal biopsy was associated with significantly reduced infectious complications as compared to transrectal biopsy (RR 0.55, 95% CI 0.33-0.92, p=0.02, I2=0%, 1,330 participants, 7 studies). Rectal preparation with povidone-iodine was also shown to reduce infectious complications (RR 0.50, 95% CI 0.38-0.65, p <0.000001, I2=27%, 1,686 participants, 8 studies) as well as hospitalization (RR 0.38, 95% CI 0.21-0.69, p=0.002, I2=0%, 620 participants, 4 studies). We found no difference in infectious complications/hospitalization for 6 other interventions, ie number of biopsy cores, periprostatic nerve block, number of injections for periprostatic nerve block, needle guide type, needle type and rectal preparation with enema. In 2 interventions (needle diameter, rectal preparation with chlorhexidine) meta-analysis was not possible. Finally, 7 studies had unique interventions. The certainty of evidence was rated as low/very low for all interventions. CONCLUSIONS: Transperineal biopsy significantly reduces infectious complications compared to transrectal biopsy and should therefore be preferred. If transrectal biopsy is performed, rectal preparation with povidone-iodine is highly recommended. The other investigated nonantibiotic strategies did not significantly influence infection and hospitalization after prostate biopsy.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Infecções Bacterianas/prevenção & controle , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/prevenção & controle , Povidona-Iodo/uso terapêutico , Próstata/patologia , Infecções Urinárias/prevenção & controle , Biópsia/efeitos adversos , Biópsia/métodos , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
World J Urol ; 38(1): 17-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31183524

RESUMO

BACKGROUND: A 68-year-old man died of cerebral arterial embolism 6 days after transrectal prostate biopsy with a single p.o. dose of trimethoprim sulfamethoxazole (TMP-SMX) as prophylaxis. The case precipitated analysis of local antibiotic resistance and complication rates. MATERIALS AND METHODS: Data on E. coli resistance from Oslo University Hospital and national data on hospitalizations and mortality after biopsy were retrieved from local microbiology files and the Norwegian Patient Registry (NPR) 2011-2017. RESULTS: Urine E. coli resistance against TMP-SMX increased from 35% in 2013 to more than 60% in 2015. For ciprofloxacin, the resistance increased from 15% in 2013 to about 45% in 2016. The highest annual E. coli resistance in blood cultures for TMP-SMX and ciprofloxacin was 37% and 28%, respectively. 10% of patients were hospitalized with a diagnosis of infection within the first 60 days after biopsy and there was a relative increase in mortality rate of 261% within the first 30 days. Due to the severity of the figures, the story and the NPR data were published in Norway's leading newspaper and were succeeded by a series of chronicles and commentaries. CONCLUSIONS: Several critical points of the biopsy procedure were not performed according to current standards. We believe that the patient might have died of septic embolism after biopsy. As a result of the findings and the debate, local practice was changed from transrectal to transperineal prostate biopsies.


Assuntos
Antibioticoprofilaxia/métodos , Biópsia/efeitos adversos , Ciprofloxacina/uso terapêutico , Resistência Microbiana a Medicamentos , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Próstata/patologia , Idoso , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/etiologia , Infecções por Escherichia coli/microbiologia , Evolução Fatal , Humanos , Masculino
5.
Hum Reprod ; 34(7): 1195-1205, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31211847

RESUMO

STUDY QUESTION: Can dexamethasone improve infertility-related cauda epididymidal tissue damage caused by bacterial epididymitis? SUMMARY ANSWER: Dexamethasone in addition to anti-microbial treatment effectively reduces long-term deleterious epididymal tissue damage by dampening the host's adaptive immune response. WHAT IS KNOWN ALREADY: Despite effective anti-microbial treatment, ~40% of patients with epididymitis experience subsequent sub- or infertility. An epididymitis mouse model has shown that the host immune response is mainly responsible for the magnitude of epididymal tissue damage that is fundamentally causative of the subsequent fertility issues. STUDY DESIGN, SIZE, DURATION: Bacterial epididymitis was induced in male mice by using uropathogenic Escherichia coli (UPEC). From Day 3 after infection onwards, mice were treated with daily doses of levofloxacin (20 mg/kg, total n = 12 mice), dexamethasone (0.5 mg/kg, total n = 9) or both in combination (total n = 11) for seven consecutive days. Control animals were left untreated, i.e. given no interventional treatment following UPEC infection (total n = 11). Half of the animals from each group were killed either at 10 or 31 days post-infection. PARTICIPANTS/MATERIALS, SETTING, METHODS: A mouse model of induced bacterial epididymitis was applied to adult male C57BL/6J mice. At the respective endpoints (10 or 31 days post-infection), epididymides were collected. Effectiveness of antibiotic treatment was assessed by plating of epididymal homogenates onto lysogeny broth agar plates. Overall tissue morphology and the degree and nature of tissue damage were assessed histologically. Quantitative RT-PCR was used to assess local cytokine transcript levels. Blood was drawn and serum analysed for systemic IgG and IgM levels by ELISA. In addition, correlation analyses of clinical data and serum-analyses of IgG and IgM levels in patients with epididymitis were performed. MAIN RESULTS AND THE ROLE OF CHANCE: The addition of dexamethasone to the standard anti-microbial treatment did not further worsen epididymal tissue integrity. In fact, an obviously dampened immune response and reduced tissue reaction/damage was observed at both 10 and 31 days post-infection following combined treatment. More specifically, epididymal duct continuity was preserved, enabling sperm transit. In contrast, in untreated or antibiotic-treated animals, damage of the epididymal duct and duct constrictions were observed, associated with a lack of cauda spermatozoa. In line with the bacteriostatic/bactericidal effect of levofloxacin (alone as well as in combination), local cytokine transcript levels were significantly and similarly reduced in animals treated with levofloxacin alone (P < 0.01) or in combination with dexamethasone (P < 0.05) compared to UPEC-infected untreated animals. Interestingly, the addition of dexamethasone to the anti-microbial treatment induced a unique dampening effect on adaptive immunity, since systemic IgG and IgM levels as well as the pan-T cell marker CD3 were reduced at both 10 and 31 days post-infection. LIMITATIONS, REASONS FOR CAUTION: Breeding studies to address the fertility-protecting effect of the combined treatment were not possible in the experimental animals because the vas deferens was ligated (model specific). WIDER IMPLICATIONS OF THE FINDINGS: Whereas innate immunity is necessary and involved in acute bacterial clearance, adaptive immunity seems to be responsible for long-term, subclinical immunological activities that may negatively affect the pathogenesis of bacterial epididymitis even after effective bacterial eradication. These effects can be reduced in mice by the additional treatment with dexamethasone. This immunological characteristic of bacterial epididymitis shows similarities to the Jarisch-Herxheimer reaction known from other types of bacterial infection. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by grants from the Deutsche Forschungsgemeinschaft, Monash University and the Medical Faculty of Justus-Liebig University to the International Research Training Group on 'Molecular pathogenesis of male reproductive disorders' (GRK 1871). R.W., K.L.L. and M.P.H. were supported by grants from the National Health and Medical Research Council of Australia (ID1079646, ID1081987, ID1020269 and ID1063843) and by the Victorian Government's Operational Infrastructure Support Program. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: No clinical trial involved.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Epididimo/efeitos dos fármacos , Epididimite/tratamento farmacológico , Infertilidade Masculina/tratamento farmacológico , Imunidade Adaptativa/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/farmacologia , Carga Bacteriana , Citocinas/metabolismo , Dexametasona/farmacologia , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Epididimo/metabolismo , Epididimo/patologia , Epididimite/complicações , Epididimite/metabolismo , Epididimite/patologia , Transição Epitelial-Mesenquimal , Fibrose , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Infertilidade Masculina/etiologia , Levofloxacino/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL
6.
J Chemother ; 31(1): 15-22, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30508403

RESUMO

Transurethral resection of the prostate (TURP) is one of the most common urological procedures. With the increasing rate of multiresistant infections including urosepsis, it is essential for all surgeons to adhere to the relevant international guidelines to prevent infectious complications. The aim of this prospective, multinational, multicentre study was to evaluate compliance with recommended infection control measures regarding TURP procedures. The study was performed as a side questionnaire to the annual Global Prevalence Study of Infections in Urology (GPIU) between 2006 and 2009. Patients that had undergone TURP were eligible. Baseline data about hospitals and patients were collected. The questionnaire contained questions regarding preoperative microbiological investigations, catheter care and performance of perioperative antibiotic prophylaxis. A total of 825 men were included from 138 participating centres from Africa, Asia, Europe and South America. Only 50.1% of the patients received perioperative antibiotic prophylaxis with a median duration of 3 days (interquartile range [IQR] = 1-7 days). Preoperative urine culture was taken in 59.2%. The catheter was replaced in 1 week prior to the surgery only in 38.3% of cases. Compliance with the recommended infection control measures regarding TURP were only moderate, despite high grade recommendations in relevant international Guidelines. Stronger guideline adherence is necessary to improve patient care decrease antibiotic consumption in line with antibiotic stewardship in surgical practices.


Assuntos
Antibioticoprofilaxia/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Complicações Pós-Operatórias/prevenção & controle , Ressecção Transuretral da Próstata/métodos , Adulto , Idoso , Antibioticoprofilaxia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Ressecção Transuretral da Próstata/efeitos adversos
7.
Eur Urol Focus ; 5(1): 20-28, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30503175

RESUMO

CONTEXT: Prostate biopsy is one of the most performed procedures in urology. As a diagnostic procedure it should be of low risk. However, morbidity following prostate biopsy is common due to infectious complications. OBJECTIVE: To describe how to reduce infectious complications following prostate biopsy. We report on antibiotic and technical interventions to reduce infectious complications. EVIDENCE ACQUISITION: The data presented are based on a narrative review. Search in PubMed and Medline was performed until May 2018 with a focus on randomised controlled trials and meta-analyses. Articles were reviewed for data on symptomatic infections, hospitalisation, and adverse events. EVIDENCE SYNTHESIS: Antibiotic prophylaxis is the standard of care. However, the duration of antibiotic preemptive treatment is still under debate. The use of augmented antibiotic prophylaxis as well as targeted antibiotic prophylaxis might be of potential value, but evidence is currently limited. Moreover, no antibiotic class was shown to be clearly superior to another. The evaluation of the technical aspects during prostate biopsy reveals that rectal preparation with povidone-iodine is clearly effective to reduce infectious complications. Transperineal biopsy has a potential benefit to reduce infectious complications, but powerful randomised controlled studies are missing. Finally, the number of biopsy cores, the application of periprostatic nerve block, or the use of a cleansing enema has no impact on prostate biopsy in terms of infectious complications. CONCLUSIONS: The available data only suggest that rectal preparation with povidone-iodine as well as antibiotic prophylaxis is of significant advantage to reduce infectious complications following prostate biopsy. The augmented and targeted antibiotic prophylaxis shows some potential, but need further validation. PATIENT SUMMARY: In this review we evaluate the best management strategy to prevent infectious complications following prostate biopsy. We show that antibiotic prophylaxis is essential for prostate biopsy and that rectal preparation with povidone-iodine is mandatory.


Assuntos
Infecções Bacterianas/prevenção & controle , Biópsia/efeitos adversos , Povidona-Iodo/administração & dosagem , Próstata/microbiologia , Administração Retal , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Metanálise como Assunto , Povidona-Iodo/uso terapêutico , Próstata/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Urol Clin North Am ; 38(3): 285-92, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21798390

RESUMO

Prostatitis syndrome is a frequent condition in men. It is not known in most patients if the prostate is the only organ involved. Therefore, the disease is characterized as chronic prostatitis-chronic pelvic pain syndrome (CP-CPPS). Although many studies have been performed in patients with CP-CPPS, current trial evidence is conflicting and therapeutic options are controversial. Given the need for long-term treatment in CP-CPPS patients, phytotherapeutics, such as pollen extract, are an option due to few side effects. Preclinical studies on pollen extract have shown effects on smooth muscles of the bladder and urethra, strong antiinflammatory effects, and antiproliferative effects.


Assuntos
Fitoterapia , Extratos Vegetais/uso terapêutico , Pólen , Prostatite/tratamento farmacológico , Humanos , Masculino , Extratos Vegetais/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
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