Fever of unknown origin revealing testicular nocardiosis: a case report and literature review.

BACKGROUND: Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis. CASE PRESENTATION: We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient's condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis. CONCLUSIONS: To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.

Evaluating ChatGPT ability to answer urinary tract Infection-Related questions.

INTRODUCTION: For the first time, the accuracy and proficiency of ChatGPT answers on urogenital tract infection (UTIs) were evaluated. METHODS: The study aimed to create two lists of questions: frequently asked questions (FAQs, public-based inquiries) on relevant topics, and questions based on guideline information (guideline-based inquiries). ChatGPT responses to FAQs and scientific questions were scored by two urologists and an infectious disease specialist. Quality and reliability of all ChatGPT answers were checked using the Global Quality Score (GQS). The reproducibility of ChatGPT answers was analyzed by asking each question twice. RESULTS: All in all, 96.2 % of FAQs (75/78 inquiries) related to UTIs were correctly and adequately answered by ChatGPT, and scored GQS 5. None of the ChatGPT answers were classified as GQS 2 and GQS 1. Moreover, FAQs about cystitis, urethritis, and epididymo-orchitis were answered by ChatGPT with 100 % accuracy (GQS 5). ChatGPT answers for EAU urological infections guidelines showed that 61 (89.7 %), 5 (7.4 %), and 2 (2.9 %) ChatGPT responses were scored GQS 5, GQS 4, and GQS 3, respectively. None of the ChatGPT responses for EAU urological infections guidelines were categorized as GQS 2 and GQS 1. Comparison of mean GQS values of ChatGPT answers for FAQs and EAU urological guideline questions showed that ChatGPT was similarly able to respond to both question groups (p = 0.168). The ChatGPT response reproducibility rate was highest for the FAQ subgroups of cystitis, urethritis, and epididymo-orchitis (100 % for each subgroup). CONCLUSION: The present study showed that ChatGPT gave accurate and satisfactory answers for both public-based inquiries, and EAU urological infection guideline-based questions. Reproducibility of ChatGPT answers exceeded 90% for both FAQs and scientific questions.

Antimicrobial peptide MPX attenuates LPS-induced inflammatory response and blood-testis barrier dysfunction in Sertoli cells.

Orchitis accounts for a high proportion of male animal reproductive disorders. Hence, it is urgent to identify drugs for the prevention and treatment of orchitis. Antimicrobial peptides (AMPs) are currently recognized as one of the most promising alternatives to antibiotics. However, the protective effects of AMPs on lipopolysaccharide (LPS)-induced orchitis have not been reported. In this study, we developed an LPS-induced orchitis model in which primary bovine Sertoli cells were used as model cells. MPX was indicated to effectively reduce the inflammatory response of Sertoli cells. MPX attenuated the gene expression of the proinflammatory cytokines TNF-α, IL-6 and IL-1ß by suppressing the MAPK pathway, especially the phosphorylation of p38 and ERK. MPX also decreased the oxidative stress response caused by LPS and upregulated Occludin and Claudin-1 expression, thereby maintaining the integrity of the blood-testis barrier. Moreover, we found that MPX inhibited apoptosis in Sertoli cells. In a mouse model, we found that MPX significantly inhibited the disruptive effects of LPS, reducing seminiferous epithelium damage, vacuolations, hyperplasia, and apoptosis in spermatogenic cells and rescuing spermatogenesis. In addition, the expression of inflammatory factors such as IL-1ß, IL-18, IL-6 and TNF-α was decreased after MPX treatment in the mouse testes. MPX had no effect on other organs in mice, indicating its safety. This study was undertaken to investigate how MPX regulates the inflammatory response in Sertoli cells and provide a reference for the clinical prevention and treatment of male animal orchitis.

Effects of Rosmarinus officinalis on orchitis following spermatic cord torsion-detorsion in male mice with emphasis on anti- inflammatory and antioxidant properties.

Orchitis as inflammation of testis occurs following traumatic injuries such as testicular torsion leading to high levels of oxidative stress and inflammation. Rosmarinus officinalis is a herb with anti-inflammatory and antioxidant properties. This study assessed therapeutic effects of rosemary following testicular torsion. A total of 36 male mice were categorised; control, torsion, rosemary (100 and 200 mg/kg) and torsion+rosemary groups. Torsion was induced surgically, and rosemary was gavaged. Total antioxidant capacity of extract was approved by Ferric Reducing Ability of Plasma. Malondialdehyde and Griess protocols were hired to assess oxidative stress. Finally, sperm parameters and testosterone levels were analysed. Immunofluorescent (of Tumour Necrosis Factor Alpha), hematoxylin and eosin stainings and expression of inflammatory genes (Interleukin-1α, Interleukin-1ß, Interferon-γ) were also assessed. Data were analysed using SPSS (v. 19), and graphs were drawn by GraphPad Prism (v. 9). Significantly (p < .05), oxidative stress indices and inflammatory genes expression were increased in torsion group, and total antioxidant capacity was increased in rosemary groups. In torsion+rosemary groups, total antioxidant capacity, sperm parameters and testosterone levels were increased, and inflammatory gene expression decreased significantly (p < .05). Rosemary with anti-inflammatory and antioxidant properties accelerates testicular healing in torsion cases, especially in therapeutic dose of 200 mg/kg.

Surgical management of tuberculous epididymo-orchitis: a retrospective study of 81 cases with long-term follow-up.

BACKGROUND: Nowadays, most studies of tuberculous epididymo-orchitis (TBEO) are case reports or small sample cohort series. Our study is aimed to present the largest series of TBEO with our management experiences and long-term follow-up outcomes. METHODS: Patients diagnosed with TBEO after surgical procedures at Department of Urology, West China Hospital from 2008 to 2019 were included. All clinical features, auxiliary examination results, treatment and histopathological findings were extracted if available. RESULTS: Eighty-one patients (mean age 50.77 ± 16.1 years) were included. Scrotal swelling (N = 47, 58.0%) and pain (N = 29, 35.8%) were the most common presenting complaint. Pyuria and microscopic hematuria were observed in twenty-two (27.2%) and eight patients (9.9%), respectively. Urine acid fast bacilli cultures were available in 16 patients and all were negative. The mean duration between the onset of symptoms and the definite diagnosis was 6.42 ± 7.0 months. TBEO was considered in 30 (37.0%), tumors in 28 (34.6%) and nonspecific bacterial epididymo-orchitis in 23 (28.4%) patients. All patients received triple therapy of chemotherapy-surgery-pharmacotherapy and definite diagnosis was confirmed through histopathology of surgical specimens. Fifty-five patients were followed up regularly (mean follow-up 82.35 ± 36.6 months). One patient (1.2%) died from liver cirrhosis and no recurrence was observed. Postoperative complications included erectile dysfunction in 4 patients (4.9%), premature ejaculation in 5 patients (6.2%) and sterility in 7 patients (8.6%). CONCLUSIONS: We recommend patients with advanced TBEO to receive triple therapy of chemotherapy-surgery-pharmacotherapy. Physicians should pay more attention to patients' sexual function and fertility during follow up after treatment completed.

Hard bilateral syphilitic testes with vasculitis: a case report and literature review.

BACKGROUND: We report the case of a patient with syphilitic testicular gumma and vasculitis with adrenal failure due to chronic steroid use. CASE PRESENTATION: A 63-year-old male presented with hard right eye swelling and very firm bilateral testes on palpation, which he had for 2 years. Testicular tumor markers were negative; syphilis test was positive. Radiological examination suggested aortitis and bilateral testicular malignancy. The patient received ampicillin for the infection and prednisolone for vasculitis. Left orchidectomy was performed to confirm the presence of testicular tumor; histological examinations revealed granulomatous orchitis. The prednisolone doses were adjusted because of relapses and adverse effects of steroid use. Unfortunately, the patient died in the intensive care unit because of uncontrolled blood pressure and pneumonia. CONCLUSIONS: This is a rare case of syphilis with testicular involvement and vasculitis. This report shows the importance of broadening the differential diagnoses of testicular firmness.

Methane Ameliorates Lipopolysaccharide-Induced Acute Orchitis by Anti-inflammatory, Antioxidative, and Antiapoptotic Effects via Regulation of the PK2/PKR1 Pathway.

OBJECTIVE: The present study is aimed at investigating the anti-inflammatory, antioxidative, and antiapoptotic effects of methane on lipopolysaccharide- (LPS-) induced acute orchitis and its potential mechanisms. METHODS: Adult male rats were intraperitoneally (i.p.) injected with methane-rich saline (MS, 20 mL/kg) following LPS (5 mg/kg, i.p.). The survival rate was assessed every 12 h until 72 h after LPS induction, and surviving rats were sacrificed for further detection. The wet/dry (W/D) ratio was determined, and testicular damage was histologically assessed. Inflammatory cytokines in the testes and serum, including interleukin-1ß (IL-1ß), IL-6, IL-10, and tumor necrosis factor-α (TNF-α), were measured using ELISA and RT-qPCR. Oxidative stress was evaluated by the level of superoxide dismutase (SOD) and malondialdehyde (MDA). Testicular apoptosis was detected via TUNEL staining. The expression of prokineticin 2 (PK2)/prokineticin receptor 1 (PKR1) was also analyzed using RT-qPCR, western blotting, and immunohistochemistry. RESULTS: It was found that methane significantly prolonged rat survival, decreased the W/D ratio, alleviated LPS-induced histological changes, and reduced apoptotic cells in the testes. Additionally, methane suppressed and promoted the production of pro- and anti-inflammatory cytokines, respectively. Furthermore, methane significantly increased SOD levels, decreased MDA levels, and decreased testicular expression of PK2 and PKR1. Therefore, methane exerts therapeutic effects on acute orchitis and might be a new and convenient strategy for the treatment of inflammation-related testicular diseases.

Protective effect of Alpha-Linolenic acid on Lipopolysaccharide-Induced Orchitis in mice.

Previous studies have demonstrated that polyunsaturated fatty acids (PUFAs) have anti-inflammatory effects. One specific PUFA, alpha-linolenic acid (ALA), shows both anti-inflammatory and antioxidant properties. In the testes, inflammatory mediators are known to increase when orchitis is induced by bacterial lipopolysaccharide (LPS). This study aimed to determine whether the anti-inflammatory properties of ALA could have a protective effect against LPS-induced orchitis in mice. The mice were divided into untreated control, orchitis and ALA-treated orchitis groups. Orchitis was induced by intraperitoneal injection of LPS. The ALA-treated group was administered ALA by gavage three days before intraperitoneal LPS injection. Cyclooxygenase-2 (COX-2), cytosolic phospholipase A2 (cPLA2), inducible nitric oxide synthase (iNOS) enzymes and nuclear factor kappa-B (NF-κB) in the testes, as well as serum interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-α), were analysed using enzyme-linked immunosorbent assay (ELISA) tests. LPS administration increased the expression of several inflammatory mediators, including IL-6, TNF-α and NF-κB, as well as the COX-2, cPLA2 and iNOS enzymes. ALA administration significantly prevented the LPS-induced increases in these inflammatory mediators and enzymes (p < .05). The anti-inflammatory and antioxidant effects of ALA may make it a useful candidate for the treatment of orchitis caused by bacterial LPS.

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.

Severe Epididymo-Orchitis and Encephalitis Complicating Anti-PD-1 Therapy.

BACKGROUND: Immune checkpoint inhibitors such as pembrolizumab and nivolumab have emerged as active treatment options for patients with many cancers, including metastatic melanoma, but can also cause symptomatic or life-threatening immune-related adverse events, including encephalitis. Epididymitis and orchitis are rare complications of these therapies. CASE PRESENTATION: We describe herein a patient with metastatic melanoma who developed epididymo-orchitis followed by encephalitis while receiving pembrolizumab. The patient developed testicular pain and fever after his third dose of pembrolizumab; ultrasound evaluation demonstrated bilateral epididymo-orchitis. He then developed headaches, fever, and altered mental status over the next week and was admitted to the hospital. Lumbar puncture revealed inflammatory changes consistent with meningoencephalitis; he did not improve with broad-spectrum antibiotics, and an extensive workup for infectious etiologies, including cerebrospinal fluid testing using a clinical metagenomic next-generation sequencing assay, was negative. He received high-dose steroids for suspected autoimmune encephalitis, and both his orchitis and meningoencephalitis improved rapidly after one dose. He fully recovered after a 5-week taper of oral steroids. DISCUSSION: Here, we report a case of epididymo-orchitis complicating immune checkpoint inhibitor therapy. This patient subsequently developed severe encephalitis but rapidly improved with steroids. Clinicians should be aware of rare complications of these agents. KEY POINTS: Epididymo-orchitis is a rare and potentially life-threatening complication of anti-programmed death protein 1 (anti-PD-1) therapy.For patients on anti-PD-1 therapy who develop either epididymo-orchitis or epididymitis without clear infectious cause, immune-related adverse events should be considered in the differential diagnosis.If severe, epididymo-orchitis related to anti-PD-1 therapy may be treated with high-dose corticosteroids.

Atypical testicular pain.

Testicular tuberculosis (TB) is rare, and, because of this, the lack of pathognomonic clinical features and its tendency to mimic other commoner conditions, the diagnosis is frequently delayed or may be missed. In this case, the initial clinical presentation was typical for bacterial epididymo-orchitis in a 38-year-old man. When the patient failed to improve with standard treatment including broadening of antibiotics, the diagnosis was re-considered because some unusual signs suggested testicular malignancy or lymphoma. Further, history-taking and subsequent cross-sectional imaging with CT/MRI identified co-existent pulmonary nodularity, thoracic and abdominal lymphadenopathy and bony changes that, together, raised the suspicion of TB. Mycobacterium tuberculosis was confirmed on DNA-based testing of the hydrocele fluid, although standard acid-fast bacilli culture was negative. This case prompted a review of the literature to explore the optimal steps in the investigation and diagnosis of this rare disease.

Positron emission tomography and reframing vasculitis as a spectrum of disease when investigating a patient with a fever of unknown origin.

A retired businessman presented to the infectious diseases department with a history of ongoing fevers and myalgia and raised inflammatory markers. This continued despite adequate antibiotic treatment of an epididymo-orchitis. Extensive investigations, including bone marrow and liver biopsies and a positron emission tomography, did not reveal a cause but showed reactive change in the bone marrow. Later, he developed a vasculitic rash and vision loss due to non-arteritic anterior ischaemic optic neuropathy. High-dose steroids were immediately initiated. A temporal artery biopsy was performed, which confirmed a healing large vessel vasculitis, possibly giant cell arteritis. He has responded very well to therapy. We must better appreciate the limitations of positron emission tomography in investigating a fever of unknown origin. The case also encourages awareness of autoimmune disorders as the leading category of causative diseases for this in older age groups.

Testicular plasmacytoma misdiagnosed as orchitis.

Testicular plasmacytomas are rare, accounting for only 1.3% of all extramedullary plasmacytomas. The infrequency in which it is encountered, coupled with its non-specific clinical and sonographic presentation, makes its diagnosis a challenge. We present a case of a 70-year-old man with multiple myeloma, which was systemically responding to chemotherapy, who developed testicular swelling, erythema and pain. Ultrasound findings were concerning for infection, although urine and serum testing were unremarkable. The patient did not improve after several rounds of antibiotics prompting further evaluation. The patient underwent radical orchiectomy which revealed testicular plasmacytoma. Fluorescent in situ hybridisation (FISH) of the testicular tissue noted mutations which had not been present in the FISH analysis of bone marrow. Positron emission tomography scan later revealed new retroperitoneal plasmacytomas involving the new clone and his chemotherapy regimen needed to be adjusted for treatment.

Fatal Powassan Encephalitis (Deer Tick Virus, Lineage II) in a Patient With Fever and Orchitis Receiving Rituximab.

Importance: Powassan virus is a rare but increasingly recognized cause of severe neurological disease. Objective: To highlight the diagnostic challenges and neuropathological findings in a fatal case of Powassan encephalitis caused by deer tick virus (lineage II) in a patient with follicular lymphoma receiving rituximab, with nonspecific anti-GAD65 antibodies, who was initially seen with fever and orchiepididymitis. Design, Setting, and Participants: Comparison of clinical, radiological, histological, and laboratory findings, including immunohistochemistry, real-time polymerase chain reaction, antibody detection, and unbiased sequencing assays, in a single case report (first seen in December 2016) at an academic medical center. Exposure: Infection with Powassan virus. Main Outcomes and Measures: Results of individual assays compared retrospectively. Results: In a 63-year-old man with fatal Powassan encephalitis, serum and cerebrospinal fluid IgM antibodies were not detected via standard methods, likely because of rituximab exposure. Neuropathological findings were extensive, including diffuse leptomeningeal and parenchymal lymphohistiocytic infiltration, microglial proliferation, marked neuronal loss, and white matter microinfarctions most severely involving the cerebellum, thalamus, and basal ganglia. Diagnosis was made after death by 3 independent methods, including demonstration of Powassan virus antigen in brain biopsy and autopsy tissue, detection of viral RNA in serum and cerebrospinal fluid by targeted real-time polymerase chain reaction, and detection of viral RNA in cerebrospinal fluid by unbiased sequencing. Extensive testing for other etiologies yielded negative results, including mumps virus owing to prodromal orchiepididymitis. Low-titer anti-GAD65 antibodies identified in serum, suggestive of limbic encephalitis, were not detected in cerebrospinal fluid. Conclusions and Relevance: Owing to the rarity of Powassan encephalitis, a high degree of suspicion is required to make the diagnosis, particularly in an immunocompromised patient, in whom antibody-based assays may be falsely negative. Unbiased sequencing assays have the potential to detect uncommon infectious agents and may prove useful in similar scenarios.

[Current Aspects of Epididymo-Orchitis]. / Aktuelle Aspekte der Epididymo-Orchitis.

BACKGROUND: Acute epididymitis is an inflammation of the epididymis. It mostly occurs unilaterally and may spread to the testis ('epididymo-orchitis') if untreated. Increasing technological advances allow for an even more detailed examination of concurrent symptoms such as ejaculate changes and the whole spectrum of pathogenic agents, which ranges from sexually transmitted pathogens such as Chlamydia and gonococci to enterobacteria and, rarely, viruses. This review summarises major aspects of the disease including the latest scientific findings. METHODS: A selective literature search including the last 40 years was performed via Medline. RESULTS: With about 400 cases a year in 100 000 men, acute epididymitis is the most common urogenital infection in men. It occurs across all age groups including children. Despite the fact that bacterial ascension is aetiologically of utmost relevance, only one out of three men reports signs of dysuria or urethritis. In young, sexually active men, sexually transmitted pathogens are regularly found in addition to the characteristic enterobacteriae, even if these men have an unremarkable sexual history. 88% of epididymal abscess formations can be successfully treated without surgery. Patients with indwelling urethral catheters are at a high risk of multiple drug resistance and should be treated empirically with both a fluoroquinolone and a third-generation cephalosporin until antimicrobial susceptibility testing has been completed. About 40 out of 100 patients develop post-inflammatory sub-fertility. Here, virulence factors like haemolysin A produced by uropathogenic E. coli have a negative impact on semen parameters compared to those patients suffering from epididymitis induced by haemolysin A negative strains. With adequate antibiotic treatment there is no evidence for testicular atrophy. Only one out of 10 men relapses. These cases should be examined thoroughly for subvesical obstruction. Some of them may benefit from prophylactic vasectomy. CONCLUSIONS: This review presents key aspects of acute epididymitis, which are increasingly adopted in updated guidelines.

Lymphotropic administration of photosensitizer as a model of target therapy of testicle inflammation: Experimental and clinical data.

BACKGROUND: The existence of zones of humoral skin-subskin tissue linkage with internal organs as well as the possibility of targeted administration of preparation into the affected organs were studied. METHODS: An experimental study of preparation and distribution in the bodies of mice was held by both intravenous and lymphotropic methods of administration. By means of detection with a photosensitizer (as a marker), the study was conducted on healthy mice and mice with testicle inflammation. Based on the experimental results, the study has been implemented into the clinical practice of treatment of acute inflammatory diseases of testicle and its epididymis. Patients were administered antibiotics either by the lymphotropic method, or by traditional methods. RESULTS: The concentration of the preparation, administered by the lymphotropic method, maintained in target organs (testicles) at a high level for a longer time, while the intravenous injections provided fast achievement of high concentrations. Moreover there was a lower level of accumulation of the photosensitizer in parenchymal organs after subcutaneous (lymphotropic) administration. CONCLUSIONS: The presence of humoral connection of certain areas of skin and subcutaneous tissue with testicles and their epididymis was proved. It was found that the lymphotropic administration leads to earlier clinical improvement and normalization of laboratory indices, and, thus, to significant reduction in hospital stay. Such results open the possibility of targeted drug delivery to the diseased organs. In perspective, the method may be used in treating patients not only in urology, but also in surgery, as well as for many acute, chronic or cancer diseases.

Targeting high mobility group box protein 1 ameliorates testicular inflammation in experimental autoimmune orchitis.

STUDY QUESTION: Does high mobility group box protein 1 (HMGB1) regulate inflammatory reactions in a rat model of experimental autoimmune orchitis (EAO)? SUMMARY ANSWER: HMGB1 appears to be involved in regulating inflammatory reactions in testes, as HMGB1 is translocated from testicular cells during the course of EAO and blocking its action by ethyl pyruvate (EP) reduces disease progression and spermatogenic damage. WHAT IS KNOWN ALREADY: Despite its immune privileged status, the human testis is prone to inflammatory lesions associated with male factor infertility. Accumulating evidence shows that HMGB1 plays an important role in onset and progression of autoimmune diseases. STUDY DESIGN, SIZE, DURATION: This is a cross sectional and longitudinal study involving Wistar male rats immunized with testicular homogenates to induce EAO 50 (EAO50; n = 10) and 80 (EAO80; n = 10) days after first immunization. Control adjuvant animals received saline instead of testicular homogenate (n = 16). Untreated animals (n = 10) were also studied. An interventional study was performed to block the action of HMGB1 starting 20 days after first immunization in EAO animals and respective controls (n = 17). Rats were treated i.p. with EP and the effect of EP treatment on testicular pathogenesis was evaluated 30 days later. Moreover, human testicular biopsies from infertile men with focal lymphocytic infiltrates (n = 7) and sections with intact spermatogenesis (n = 6) were probed with antibodies against HMGB1. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testicular RNA and protein extracts from EAO animals, EAO animals treated with EP and relevant controls were used for analysis of cytokine expression by real-time RT-PCR and enzyme-linked immunosorbent assay. HMGB1 was co-localized on rat testicular cross sections with antibodies against testicular macrophages (TM), peritubular cells (PTC) and Sertoli cells (SC). Interaction of HMGB1 and its receptors (RAGE, TLR4) as well signaling pathways after HMGB1 stimulation were studied in isolated TM, PTC and SC by proximity ligation assay and western blot, respectively. Furthermore, HMGB1 immunofluorescence on human testicular biopsies was performed. MAIN RESULTS AND THE ROLE OF CHANCE: HMGB1 was translocated from the nuclei in EAO testes and testes of infertile men with impaired spermatogenesis and lymphocytic infiltrates. Elevated HMGB1 levels were observed during late phase of EAO. In testicular somatic cells HMGB1 receptors Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) were differentially expressed: HMGB1-TLR4 binding was predominant in TM, while HMGB1-RAGE interaction was prevalent in SC and PTC. In support, HMGB1 triggered extracellular signal regulated kinase (ERK)1/2 and cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) activation in SC and PTC, while TM responded to HMGB1 stimulation with p38 mitogen-activated protein kinase (MAPK) and p65 nuclear factor Kappa B (NF-ĸB) phosphorylation followed by increased tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) mRNA levels. In vivo treatment of EAO animals with EP 20 days after induction of disease revealed beneficial effects, as documented by reduced disease progression and spermatogenic damage, lower macrophage numbers, as well as decreased concentrations of HMGB1 and IL-6 in the testis compared with EAO controls. LIMITATIONS, REASONS FOR CAUTION: The ability of HMGB1 to bind to a wide range of receptors makes it difficult to prevent its action by blockade of a specific receptor; therefore we applied EP, a drug preventing HMGB1 release from cells. Due to its mode of action EP decreases also the secretion of some other pro-inflammatory cytokines. Using isolated primary cells imposes limitations for cell transfection studies. As a compromise between purity and yield primary cells need to be isolated from animals of different age, which has to be considered when comparing their responses. WIDER IMPLICATIONS OF THE FINDINGS: HMGB1 could be a promising target in attenuating testicular damage caused by inflammatory reactions.

Effect of P/E-selectin blockage on antisperm antibody development and histopathological alterations in experimental orchitis.

AIM: This study aimed to evaluate the effect of P/E-selectin blockage on antisperm antibody (ASA) development and histopathological alterations in experimental orchitis. MATERIALS AND METHODS: Thirty-six Wistar albino-type male rats weighing 100-150 g were included in the study. Rats were allocated into six groups (n = 6) including control (CG), sham (SG), orchitis (OG), antimicrobial treatment (AG), P/E-selectin blockage (PESG), and both antimicrobial and P/E-selectin treatment (TG) groups. In CG, serum samples were taken from the tail vein prior to the procedure and followed by extraction of both testes. In SG, 1 ml of saline solution was injected in testicular parenchyma. OG was obtained by injecting 0.1 ml 106 cfu/ml Escherichia coli (0:6 strain) and 1 ml saline solution into the right testes. AG received ciprofloxacin (50 mg/kg/day) twice a day through gastrogavage 24 hours after generating orchitis. In PESG, P/E-selectin antibody (100 µg) was administered intravenously via the tail vein 24 hours after the induction of orchitis. Finally, both ciprofloxacin and P/E-selectin antibody were administered in TG 24 hours after the induction of orchitis for 14 days. At the end of treatment, 1 ml of serum sample was obtained to evaluate the ASA, P-selectin and E-selectin levels. In order to evaluate spermatogenesis (Johnsen score) and testicular injury (Cosentino score), both testes were extracted at the end of the 14th day. RESULTS: In orchitis-induced groups (OG, ATG, PSEG, TG), ASA levels were significantly increased at the 14th day when compared to SG (p < 0.05). In TG, ASA levels were decreased when compared to AG. However, similar alteration in ASA levels was not detected in PSEG (p > 0.05). In OG and AG, P-selectin levels were decreased at the 14th day when compared to levels observed on 0 day (p < 0.05). E-selectin levels on 0 day showed that each group had higher levels of E-selectin when compared to CG (p > 0.05). There was no significant difference regarding E-selectin when compared to CG (p > 0.05). No significant differences regarding E-selectin levels were detected on the 0th and 14th days between AG and CG (p > 0.05). When the Cosentino and Johnsen scores were compared among groups, TG and PSEG has decreased scores of Cosentino than OG on the right testicle (p < 0.05). In contrast, an increased Johnsen score was detected in TG and PSEG when compared to OG (p < 0/05). No significant difference was detected for both Cosentino and Johnsen scores on the left testicle (p > 0.05). There was no difference with regard to the right and left testicular injury in TG. In P/E-blocked groups, decreased histopathological alterations were observed in the contralateral testis. CONCLUSION: P/E-selectin blockage may reduce ASA production after orchitis when combined with antimicrobial treatment. P/E-selectin blockage not only has a protective effect on blood-testis barrier but also decreases the histopathological alterations in both the affected and contralateral testis. Histopathological parameters of spermatogenesis may also be prevented by P/E-selectin blockage in experimental orchitis.

Testicular and kidney masses in a HIV-infected man.

A 37-year-old Caucasian male presented with what appeared clinically and diagnostically as testicular and kindey tomour's. However, syphilis serology and histology confirm that the lesions were gumma's. Without routine syphilis serology, the correct diagnosis may have been missed.

The great mimic: syphilis mimicking testicular tumour. Conservative management using antibiotics alone with testicular sparing.

We present the case of a 47-year-old man who attended a genitourinary (GU) medicine clinic with posthitis and a painless testicular mass on examination. Initial ultrasound revealed a 2-cm well-defined hypoechoic mass within the right testis and he was referred to urology on suspicion of malignancy. Subsequent syphilis serology was positive and the penile lesion and testicular mass were felt to be consistent with syphilis. After liaising with the urology department, and in view of negative tumour markers (lactate dehydrogenase, alfa-fetoprotein and human chorionic gonadotrophin) and known penicillin allergy, he was managed conservatively with four weeks of oral doxycycline. Follow-up ultrasound scans revealed adequate response of the testicular mass, with the last scan, performed at 10 months post-treatment, showing complete resolution. This is the first documented case of conservative management of a testicular syphilitic lesion using antibiotics alone with testicular sparing.