Regional modulation of toll-like receptor signaling pathway genes in acute epididymitis in mice.

BACKGROUND: Region-specific immune environments in the epididymis influence the immune responses to uropathogenic Escherichia coli (UPEC) infection, a relevant cause of epididymitis in men. Toll-like receptors (TLRs) are essential to orchestrate immune responses against bacterial infections. The epididymis displays region-specific inflammatory responses to bacterial-derived TLR agonists, such as lipopolysaccharide (LPS; TLR4 agonist) and lipoteichoic acid (LTA; TLR2/TLR6 agonist), suggesting that TLR-associated signaling pathways could influence the magnitude of inflammatory responses in epididymitis. OBJECTIVES: To investigate the expression and regulation of key genes associated with TLR4 and TLR2/TLR6 signaling pathways during epididymitis induced by UPEC, LPS, and LTA in mice. MATERIAL AND METHODS: Epididymitis was induced in mice using UPEC, ultrapure LPS, or LTA, injected into the interstitial space of the initial segment or the lumen of the vas deferens close to the cauda epididymidis. Samples were harvested after 1, 5, and 10 days for UPEC-treated animals and 6 and 24 h for LPS-/LTA-treated animals. Ex vivo epididymitis was induced by incubating epididymal regions from naive mice with LPS or LTA. RT-qPCR and Western blot assays were conducted. RESULTS: UPEC infection up-regulated Tlr2, Tlr4, and Tlr6 transcripts and their associated signaling molecules Cd14, Ticam1, and Traf6 in the cauda epididymidis but not in the initial segment. In these epididymal regions, LPS and LTA differentially modulated Tlr2, Tlr4, Tlr6, Cd14, Myd88, Ticam1, Traf3, and Traf6 expression levels. NFKB and AP1 activation was required for LPS- and LTA-induced up-regulation of TLR-associated signaling transcripts in the cauda epididymidis and initial segment, respectively. CONCLUSION: The dynamic modulation of TLR4 and TLR2/TLR6 signaling pathways gene expression during epididymitis indicates bacterial-derived antigens elicit an increased tissue sensitivity to combat microbial infection in a spatial manner in the epididymis. Differential activation of TLR-associated signaling pathways may contribute to fine-tuning inflammatory responses along the epididymis.

Orquiepididimitis por Salmonella spp en un lactante bajo los tres meses de edad / Salmonella spp epididymo-orchitis in a infant under three months-old

El compromiso genitourinario en una infección causada por Salmonella spp es poco frecuente, especialmente en niños. Se presenta un paciente de 40 días de vida que presentó una orquiepididimitis por Salmonella entérica serotipo Newport, con documentación microbiológica en hemocultivos, cultivo de secreción escrotal y coprocultivo. No presentó compromiso del sistema nervioso central. Un tratamiento médico y quirúrgico tempranos permitieron la evolución favorable del paciente.

Genitourinary involvement in a Salmonella spp infection is rare, especially in pediatric patients. A 40-day-old patient who presented an orchiepididymitis due to Salmonella enterica Serotype Newport is reported, with microbiological documentation in blood cultures, culture of scrotal purulent material and stool culture. There was no involvement of the central nervous system. Early medical and surgical treatment allowed the favorable evolution of the patient.

A case report: Actinobaculum suis infection associated with formation of pyogranuloma, epididymitis and azoospermia in a boar.

BACKGROUND: Actinobaculum suis is a bacterium known to cause infections of the urogenital tract of sows. Infection can occur through close contact to boars, who frequently carry the pathogen in their preputial diverticulum but do not become clinically diseased themselves. In the current case, Actinobaculum suis was isolated from pyogranuloma of inflamed epididymis in a boar with poor fertility. CASE PRESENTATION: Increased return to oestrus rate, which worsened after the purchase of a new boar, was reported in an organic farm in Switzerland. During herd examination, azoospermia of the boar was diagnosed, and slaughter, followed by examination of its urogenital tract, was carried out. Pathologically, pyogranuloma formation and epididymitis were diagnosed. Bacteriology of the pyogranulomas showed growth of Actinobaculum suis and mixed flora. After the boar was replaced, the return to oestrus rate improved tremendously. CONCLUSION: A close relative of Actinobaculum suis, namely Actinotignum schaalii, has already been associated with epididymitis in humans. Considering the present case and the parallels in human medicine, Actinobaculum suis should be included in the list of differentials of boars with poor fertility.

Epididymitis and its aetiologies in a central London sexual health clinic.

Epididymitis is a common cause of scrotal pain presentation in sexual health clinics; however, it is unclear what fraction is attributable to transmissible infections. We, therefore, reviewed the aetiologies causing epididymitis. A retrospective data analysis of all cases of epididymitis diagnosed from January 2018 to December 2018 in three sexual health clinics was conducted, collecting demographics, results, management and symptom resolution at two weeks follow up. A total of 127 cases of epididymitis (mean age 32 years, heterosexual 97, MSM 30) were included. Among them 14 cases (11%) were caused by sexual transmitted infections (<35 years n = 9; >35 years n = 5): seven cases of chlamydia, six gonorrhoea, one syphilis and one trichomonas vaginalis. There were three cases of urinary tract infection diagnosed. All cases were treated with antibiotics recommended by the British Association for Sexual Health and HIV (BASHH). At two weeks follow up post-treatment 10 (7%) were symptomatic; 91% did not attend for follow up. Sexually transmitted infections were associated with acute epididymitis in 11% of this study cohort.

Differential Immune Response to Infection and Acute Inflammation Along the Epididymis.

The epididymis is a tubular structure connecting the vas deferens to the testis. This organ consists of three main regions-caput, corpus, and cauda-that face opposing immunological tasks. A means of combating invading pathogens is required in the distally located cauda, where there is a risk of ascending bacterial infections originating from the urethra. Meanwhile, immune tolerance is necessary at the caput, where spermatozoa with immunogenic neo-antigens originate from the testis. Consistently, when challenged with live bacteria or inflammatory stimuli, the cauda elicits a much stronger immune response and inflammatory-inflicted damage than the caput. At the cellular level, a role for diverse and strategically positioned mononuclear phagocytes is emerging. At the mechanistic level, differential expression of immunoprotective and immunomodulatory mediators has been detected between the three main regions of the epididymis. In this review, we summarize the current state of knowledge about region-specific immunological characteristics and unveil possible underlying mechanisms on cellular and molecular levels. Improved understanding of the different immunological microenvironments is the basis for an improved therapy and counseling of patients with epididymal infections.

The Immune Characteristics of the Epididymis and the Immune Pathway of the Epididymitis Caused by Different Pathogens.

The epididymis is an important male accessory sex organ where sperm motility and fertilization ability develop. When spermatozoa carrying foreign antigens enter the epididymis, the epididymis shows "immune privilege" to tolerate them. It is well-known that a tolerogenic environment exists in the caput epididymis, while pro-inflammatory circumstances prefer the cauda epididymis. This meticulously regulated immune environment not only protects spermatozoa from autoimmunity but also defends spermatozoa against pathogenic damage. Epididymitis is one of the common causes of male infertility. Up to 40% of patients suffer from permanent oligospermia or azoospermia. This is related to the immune characteristics of the epididymis itself. Moreover, epididymitis induced by different pathogenic microbial infections has different characteristics. This article elaborates on the distribution and immune response characteristics of epididymis immune cells, the role of epididymis epithelial cells (EECs), and the epididymis defense against different pathogenic infections (such as uropathogenic Escherichia coli, Chlamydia trachomatis, and viruses to provide therapeutic approaches for epididymitis and its subsequent fertility problems.

Tumor of the epididymis: an uncommon presentation of disseminated coccidioidomycosis.

Coccidioidomycosis is an endemic disease of arid regions in the Western hemisphere. Its clinical presentation varies from asymptomatic nodules on chest x-rays to disseminated disease. We present the case of a 48-year-old man with a hard and heterogeneous tumor in the posterior aspect of the right testis. Color flow doppler testicular ultrasonography was performed and two nodular masses in the tail of the right epididymis were identified. An epididymectomy was performed and histopathological examination revealed coccidioidomycosis. After diagnosis, the patient was successfully treated with fluconazol.

Differential tissue-specific damage caused by bacterial epididymo-orchitis in the mouse.

Ascending bacterial urinary tract infections can cause epididymo-orchitis. In the cauda epididymidis, this frequently leads to persistent tissue damage. Less coherent data is available concerning the functional consequences of epididymo-orchitis on testis and caput epididymidis. This in vivo study addresses the functional and spatial differences in responsiveness of murine epididymis and testis to infection with uropathogenic Escherichia coli (UPEC). Whole transcriptome analysis (WTA) was performed on testis, caput, corpus and cauda epididymidis of adult C57BL/6 J wildtype mice. Following UPEC-induced epididymo-orchitis in these mice, epididymal and testicular tissue damage was evaluated histologically and semi-quantitatively at 10 days and 31 days post-inoculation. Expression of inflammatory markers and candidate antimicrobial genes were analysed by RT-qPCR. WTA revealed distinct differences in gene signatures between caput and cauda epididymidis, particularly amonst immunity-related genes. Cellular and molecular signs of testicular inflammation and disruption of spermatogenesis were noticed at day 10, but recovery was observed by day 31. In contrast to the cauda, the caput epididymidis did not reveal any signs of gross morphological damage or presence of pro-inflammatory processes despite confirmed infection. In contrast to beta-defensins, known UPEC-associated antimicrobial peptides (AMP), like Lcn2, Camp and Lypd8, were inherently highly expressed or upregulated in the caput following infection, potentially allowing an early luminal protection from UPEC. At the time points investigated, the caput epididymidis was protected from any obvious infection/inflammation-derived tissue damage. Studies addressing earlier time-points will conclude whether in the caput epididymidis a pro-inflammatory response is indeed not essential for effective protection from UPEC.

An atlas overview of characteristic features of tuberculosis that may be encountered at autopsy.

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis. Although primarily a disease of the respiratory system it may be found in any organ or tissue. Global population movements and the emergence of resistant strains are contributing to increasing numbers of cases in certain populations. Subtlety of symptoms and signs, chronicity of disease and failure to seek medical assistance may result in the diagnosis only being made at the time of autopsy. For this reason forensic pathologists need to understand the protean manifestations of the disease and the variable mechanisms by which TB may cause death. This atlas overview provides descriptions of the pathological manifestations of TB in a variety of organs with accompanying illustrations. It serves as a summary of conditions that should be checked for at autopsy in suspected or confirmed cases.

A rare case of multi-focal human TB after BCG instillation for non-muscle-invasive bladder cancer.

OBJECTIVE: To describe a left epididymitis and para-aortical involvement caused by Mycobacterium tuberculosis hominis reactivation after bacillus Calmette-Guérin instillation for non-muscle-invasive bladder cancer. PATIENT AND METHODS: A Caucasian male, aged 76 years, exposed to bacillus Calmette-Guérin for a high-grade non-muscle-invasive bladder cancer in 2015, reported painful and progressive left scrotal swelling with purulent discharge from a cutaneous fistulous track that yielded, on liquid culture, a pan-susceptible Mycobacterium tuberculosis hominis strain. Moreover, after 6 months of anti-tuberculosis treatment, an abdominal peri-aortic mass, sized 4 cm, was found and a surgical biopsy showed necrotizing granulomas; however, although smear microscopy and Xpert MTB/Rif™ performed on fresh biopsy sample were positive, liquid cultures resulted negative, indicating treatment efficacy. RESULTS: Numerous peculiar and multi-organ involvement due to BCGitis after intravesical immunotherapy have been previously described, including 17 scientific articles about epididymitis, however, no reports so far showed reactivation of Mycobacterium tuberculosis hominis after bacillus Calmette-Guérin treatment. CONCLUSION: Although BCGitis is more prevalent in patients undergoing bacillus Calmette-Guérin instillation for non-muscle-invasive bladder cancer, tuberculosis by other species of Mycobacterium tuberculosis should be always ruled out by molecular and conventional microbiology in patients with a history of Mycobacterium tuberculosis hominis exposure.

Brucellar epididymo-orchitis: a retrospective study of 25 cases.

Objective: Brucellosis is a multisystemic disease which may affect all organs. Epididymo-orchitis is the most common form of genitourinary involvement. The aim of this study was to present our eight-year experience regarding the management of patients with brucellar epididymo-orchitis (BEO).Materials and method: The medical records of male brucellosis patients treated in two centers, between 2010 and 2018 were analyzed retrospectively. The diagnosis of epididymo-orchitis was made when the patients had scrotal pain, swelling, and enlarged tender testicles and/or epididymis on clinical examination. Brucellosis was diagnosed with a positive standard tube agglutination test or a positive blood culture.Results: Brucellosis was diagnosed in 996 male patients. Of these patients, 25 had a diagnosis of BEO (2.5%). All BEO patients suffered from enlarged painful testicles, however, testicular complaints were the only presentation symptoms in three of them. All patients received medical treatment alone except one patient with testicular abscess who underwent surgical drainage besides medical treatment. All patients recovered completely and no relapses have been detected during six-month follow-up.Conclusion: Patients with epididymo-orchitis should be investigated for brucellosis especially in endemic regions. To our knowledge, BEO patients may present with isolated testicular symptoms that make a diagnostic challenge.

Brucella and non-Brucella epididymo-orchitis: comparison of ultrasound findings.

AIM: In brucellosis the male genitourinary system can be affected in a small number of patients. In this study we aimed to identify, discuss and compare the radiologic findings of 24 cases with Brucella epididymo-orchitis (BEO) and 285 cases with non-Brucella epididymis orchitis (NBEO). MATERIAL AND METHODS: The study had a retrospective design. The area of involvement, side of involvement (left, right or bilateral), presence of abscess, hydrocele and testicular involvement pattern were analyzed and compared between the BEO and NBEO cases. RESULTS: The median age of the included cases was 33 years, with a minimum of 0 and maximum of 89. Epididymo-orchitis and isolated orchitis were more frequent in BEO cases while isolated epididymis involvement was more common in patients with non-BEO (p=0.0117). Bilateral involvement was present in 20.8% and 4.6% cases in the BEO and non-BEO groups, respectively (p=0.008). The frequency of abscess was significantly higher in BEO cases (p=0.003). CONCLUSION: Although the radiological indications of BEO are similar to those of other types of epididymo-orchitis, abscess formation, bilateral involvement and testicular involvement contribute significantly to diagnosis.

Acute epididymo-orchitis from brucellosis melitensis in Australia.

Brucellosis epididymo-orchitis (BEO) is extremely rare in non-endemic areas such as Australia. While epididymo-orchitis is relatively common in adolescent men, when presented with a significant travel history, consideration should be given to rare causes such as this. Here, we present a case of BEO in a young 18-year-old man who recently migrated from Greece, with symptoms of acute scrotal pain, swelling and persistent fever. Brucella melitensis was isolated in the blood culture and confirmed with PCR. We suspect transmission was related to ingestion of unpasteurised goat dairy products. He made a full recovery after 7 days of intravenous gentamicin and 6 weeks of oral doxycycline. BEO should be considered in those who present with acute scrotal pain and fever after a recent history of travel to or from a brucellosis- endemic area.

Clinical pharmacokinetics of oral azithromycin in epididymal tissue.

OBJECTIVES: Chlamydia trachomatis is one of the major pathogens causing acute epididymitis. Azithromycin (AZM) has a good efficacy against C. trachomatis; however, the ability of AZM to penetrate into human epididymal tissue has not yet been fully elucidated. Here, we examined the appropriate dosage of oral AZM for human epididymal tissue by site-specific pharmacokinetic/pharmacodynamic (PK/PD) analysis. METHODS: Patients with prostate cancer who underwent orchiectomy were included in this study. All patients received a 1-g dose of AZM before orchiectomy. Both epididymal tissue and blood samples were collected during surgery, and the drug concentrations were measured by high-performance liquid chromatography. All concentration-time data were analyzed with a three-compartment model with first-order absorption and elimination processes to simulate AZM concentrations in serum and epididymal tissue. RESULTS: A total of 10 patients were enrolled in the current study. For the observed values, the ratio of the epididymal concentration to the serum concentration was 5.13 ± 3.71 (mean ± standard deviation). For the simulated values, the maximum concentrations were 0.64 µg/mL at 2.42 h in serum and 1.96 µg/g at 4.10 h in epididymal tissue. The 24-h concentrations were 0.239 µg/mL in serum and 0.795 µg/g in epididymal tissue. CONCLUSIONS: The penetration of oral AZM into human epididymal tissue was examined to assess the potential application of AZM for the treatment of acute epididymitis. Based on the previous reports mentioning drug-susceptibility of C. trachomatis, multiple doses of oral AZM 1 g would be recommended for epididymitis based on the site-specific PK/PD.

[Orchitis]. / Hodenentzündung.

Orchitis can be acutely symptomatic or chronically asymptomatic. Among the acute forms is the rarer isolated orchitis, which is of viral origin in most cases as well as the more frequent secondary orchitis, which is usually the result of an ascending bacterial epididymitis. In addition, sterile forms of orchitis are also seen in patients with systemic autoimmune comorbidities. Chronic asymptomatic orchitis is the term used to describe cellular immune infiltrates in the testes, which are observed in approximately 25% of cases of azoospermia during testicular biopsy. The etiopathogenesis of these infiltrates is largely unknown with postinfection and primary pathogen-independent autoimmune reactions being discussed. Animal experimental models of orchitis may be helpful to investigate the immunological mechanisms involved as well as the therapeutic possibilities.

Brucella canis infection in a young dog with epididymitis and orchitis.

INTRODUCTION: The following case report describes the clinical and diagnostic procedure for suspected brucellosis infection in a dog. A 21 month old intact male Border Collie was presented with an enlarged right testicle and epididymis. The dog was imported to Switzerland from Germany at the age of three months, but was never abroad since then. Clinical and laboratory diagnostic investigation included bacteriology and histology. An initial serological evaluation by means of rapid slide agglutination test (RSAT) was negative. Repeated examination of the same serum by a chromatographic immunoassay (ICT) revealed a positive result. Brucella canis infection was confirmed by culture. The present case is intended to underline the importance of the suspected diagnosis of 'brucellosis' in the presence of reproductive tract problems in dogs. In addition, Brucella canis has zoonotic potential and it is imperative to comply with strict hygiene management.

INTRODUCTION: Le rapport de cas suivant décrit la procédure clinique et diagnostique en cas de suspicion d'infection par la brucellose chez un chien. Un Border Collie mâle intact de 21 mois a été présenté avec un grossissement du testicule et de l'épididyme droits. Le chien avait été importé d'Allemagne en Suisse à l'âge de trois mois, mais n'avait si non jamais été à l'étranger depuis lors. Des examens diagnostiques cliniques et de laboratoire, notamment bactériologie et histologie ont été effectués. Une première évaluation sérologique au moyen du test d'agglutination rapide sur lame (RSAT) était négative. Un examen ultérieur du même sérum par une immunoanalyse chromatographique (ICT) a révélé un résultat positif. L'infection à Brucella canis a été confirmée par culture. Le présent cas souligne l'importance du diagnostic présumé de «brucellose¼ en présence de problèmes de l>appareil reproducteur chez le chien. De plus, Brucella canis a un potentiel zoonotique et il est impératif d'appliquer des mesures d'hygiène strictes.

[Mycoplasma genitalium and male urogenital diseases: An update].

Mycoplasma genitalium (MG) was first isolated by Tully from the urinary tract of the male patient with non-gonococcal urethritis (NGU) in 1981. MG is extremely difficult to be cultured and was rarely studied until the development and application of molecular biology technology. The research on MG in China is still in the primary stage. However, relevant studies abroad have found that it is an important pathogen causing human genitourinary tract infection and spreading worldwide. Male MG infection is reportedly related to NGU, prostatitis, epididymitis, balanoposthitis, male HIV infection, and male infertility. This review outlines the advances in the studies of MG in male urogenital diseases.