Leptin is upregulated in epididymitis and promotes apoptosis and IL-1ß production in epididymal epithelial cells by activating the NLRP3 inflammasome.

Epididymitis, one of the most common urological disease, is a significant cause of male infertility. Leptin is capable of modulating both reproduction and immune response. We analyzed the serum and seminal plasma levels of leptin in infertile patients with or without chronic epididymitis. Experimental epididymitis models were generated by administrating 200 µg Lipopolysaccharide (LPS) to Sprague-Dawley rats. The expression of leptin in epididymis were detected using qPCR, Western blots 6-72 h after injection, and using immunohistochemistry 72 h after injection. Besides, rat epididymal epithelial cells were isolated as an in vitro model and were treated with leptin (5-40 ng/ml, 6-48 h), LPS (1ug/ml, 6 h), and NLRP3 inflammasome inhibitor MCC950 (10 µM, 2 h). Cell Counting Kits-8 assay and Annexin V/PE assay were used to evaluate cell viability and apoptosis. Quantitive PCR and ELISA assay were used to detected inflammatory cytokines interleukin-1beta (IL-1ß) production. Western Blots were used to detect molecular related to cell apoptosis, IL-1ß maturation, and NLRP3 inflammasome. We found that patients with chronic epididymitis presented a significantly higher level of seminal plasma leptin and correlated declined sperm progressive motility. Leptin and leptin receptor expression in epididymis was significantly upregulated 24 h after LPS administration both in mRNA and protein level, and highly expressed in the epididymis epithelium 72 h after LPS administration. In epididymal epithelial cells, leptin reduced cell viability and promoted apoptosis in a concentration-dependent manner via cleavage of caspase-9, caspase-3, and PARP. Leptin enhanced the LPS-induced production of IL-1ß, which was associated with increased IL-1ß maturation and caspase-1 activation. Furthermore, NLRP3 inhibitor MCC950 attenuated the effects of leptin or co-treatment with LPS on NLRP3, ASC expression, IL-1ß maturation, and caspase-1 activation, which indicated that leptin promotes IL-1ß production via activating the NLRP3 inflammasome. These data suggested that leptin may act as a potential evaluation and treatment target for epididymitis and male subfertility.

Predictive value of haematologic parameters in diagnosis of testicular torsion: Evidence from a systematic review and meta-analysis.

To compare the difference of mean platelet volume (MPV), platelet lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), platelet (PLT) and leucocyte between testicular torsion (TT), epididymo-orchitis and healthy controls and further evaluate predictive values of these haematologic parameters in diagnosis and the differential diagnosis of TT. Databases were systematically retrieved, and reference search was also conducted manually. We applied Stata software 12.0 to perform a systematic review and meta-analysis. Ultimately, five case-control studies with 672 participants were recruited for analyses. Pooled analyses indicated that TT patients had lower NLR (WMD = -1.66, 95% CI = -3.25 to -0.06) and PLT (WMD = -27.39, 95% CI = -48.03 to -6.75) compared to epididymo-orchitis patients. In the meantime, TT patients had higher NLR and leucocyte than healthy controls (p < .05). That is to say, when a man develops TT, his NLR and leucocyte will rise up but his NLR will not reach the level of epididymo-orchitis. To sum up, NLR, PLT and leucocyte were vital factors for TT diagnosis. Leucocyte is an useful parameter for diagnosing both TT and epididymo-orchitis, but it cannot be used in differentiating the two diseases. NLR is beneficial parameter for differential diagnosis between TT and epididymo-orchitis. PLT can also be utilised in differential diagnosis among young patients.

Chronic epididymitis and leptin and their associations with semen characteristics in men with infertility.

PROBLEM: The aim of this study was to ascertain the associations between serum leptin levels and chronic epididymitis and semen parameters in patients with infertility. METHOD OF STUDY: A total of 846 patients who were diagnosed as primary infertility were enrolled and divided into four groups. The general information, blood lipids, reproductive hormones, and semen parameters were collected. Receiver operating characteristic (ROC) curves of leptin were plotted for diagnosis of the poor sperm quality. We used Student's t test and the chi-squared test to analyze their relationships and used logistic regression analysis to evaluate potential confounding factors. RESULTS: Receiver operating characteristic curve revealed that leptin had better sensitivity and specificity at the concentration of 6.02 (0.565 and 0.917). Isolated epididymitis or elevated leptin had no effect on sperm concentration and sperm membrane function, but the combination of these conditions would reduce the concentration and normal morphology rate both (P = 0.002, P = 0.005). Epididymitis or elevated leptin can affect the motility of sperms, the former presented more significance (P = 0.000), and the co-existence would further reduce the sperm motility (P = 0.001). CONCLUSION: Low sperm motility and sperm normal morphology were found to be associated with chronic epididymitis and high leptin. Simultaneously suffering from chronic epididymitis and high leptin could produce a more serious effect on sperm quality.

Comparison of inflammatory markers between brucella and non-brucella epididymo-orchitis

ABSTRACT Objectives: Brucellosis is a multi-system infectious disease that is associated with inflammation, which causes an increase in acute phase reactants. Hematological inflammatory markers of brucellosis include mean platelet volume (MPV), red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR). In this study, we aimed to evaluate the diagnostic value of hematological inflammatory markers in Brucella epididymo-orchitis (BEO), and to investigate the utility of these markers for differential diagnosis from non-Brucella epididymo-orchitis (non-BEO). Materials and Methods: We retrospectively reviewed the records of 22 BEO and 50 non-BEO patients. Hematological parameters were recorded and compared between the two groups. The main diagnostic criteria for BEO were positive clinical findings (i.e., testicular pain, tenderness and scrotal swelling), a positive Rose Bengal test result, standard tube agglutination (STA) titer ≥ 1/160, and/or a positive blood culture. Results: The most decisive factors in discriminating between BEO and non-BEO were NLR, RDW, and MPV, in decreasing order of their strength. Regardless of other factors, NLR values < 2.3 significantly increased the odds of BEO (OR=8.080, 95% CI: 1.929-33.843, p=0.004). After adjusting for other factors, RDW values >14.45% significantly increased the odds of BEO (OR=7.020, 95% CI: 1.749-28.176, p=0.006). Independent of the other factors, patients with MPV < 7.65 fL had a 6.336 times higher risk for BEO (95% CI: 1.393 - 28.822, p=0.017). Conclusion: Hematological inflammatory markers such as NLR, RDW, and MPV can aid in the differential diagnosis of BEO and non-BEO.

Comparison of inflammatory markers between brucella and non-brucella epididymo-orchitis.

OBJECTIVES: Brucellosis is a multi-system infectious disease that is associated with inflammation, which causes an increase in acute phase reactants. Hematological inflammatory markers of brucellosis include mean platelet volume (MPV), red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR). In this study, we aimed to evaluate the diagnostic value of hematological inflammatory markers in Brucella epididymo-orchitis (BEO), and to investigate the utility of these markers for differential diagnosis from non-Brucella epididymo-orchitis (non-BEO). MATERIALS AND METHODS: We retrospectively reviewed the records of 22 BEO and 50 non-BEO patients. Hematological parameters were recorded and compared between the two groups. The main diagnostic criteria for BEO were positive clinical findings (i.e., testicular pain, tenderness and scrotal swelling), a positive Rose Bengal test result, standard tube agglutination (STA) titer ≥ 1/160, and/or a positive blood culture. RESULTS: The most decisive factors in discriminating between BEO and non-BEO were NLR, RDW, and MPV, in decreasing order of their strength. Regardless of other factors, NLR values < 2.3 significantly increased the odds of BEO (OR=8.080, 95% CI: 1.929- 33.843, p=0.004). After adjusting for other factors, RDW values >14.45% significantly increased the odds of BEO (OR=7.020, 95% CI: 1.749-28.176, p=0.006). Independent of the other factors, patients with MPV < 7.65 fL had a 6.336 times higher risk for BEO (95% CI: 1.393 - 28.822, p=0.017). CONCLUSION: Hematological inflammatory markers such as NLR, RDW, and MPV can aid in the differential diagnosis of BEO and non-BEO.

Can haematologic parameters be used for differential diagnosis of testicular torsion and epididymitis?

A differential diagnosis of testicular torsion and epididymitis has serious importance for testicular health. In emergency conditions, if testicular torsion goes unnoticed and epididymo-orchitis is diagnosed, organ loss may occur. This study aimed to evaluate the usefulness of haematologic parameters for the diagnosis of both testicular torsion and epididymo-orchitis and for differential diagnosis of these two diseases. Patients were divided into three groups as those undergoing surgery for testicular torsion, those receiving medical treatment for epididymitis and a healthy control group. All patients had complete blood counts taken with determinations of mean platelet volume (MPV), platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR) and leucocyte counts. These were then compared between groups. Leucocyte, MPV and NLR values were higher in both the epididymitis and torsion groups compared to the controls (p < .001). Platelet counts and PLR were significantly higher in the epididymitis group compared to the other two groups (p < .001). Leucocyte, MPV and NLR values may be used in the diagnosis of epididymitis and testicular torsion. Platelet counts and PLR appear to be useful in differentiating epididymitis from testicular torsion. However, there is a need for prospective studies with larger numbers of patients.

[The correlation between testosterone levels and C-reactive protein in acute bacterial epididymo-orchitis]. / Korelacja stezenia testosteronu i bialka C-reaktywnego w ostrym zapaleniu jadra i najadrza.

UNLABELLED: Acute bacterial epididymo-orchitis is common urological condition that usually originates from ascending infection of lower urinary tract. It is characterized by infection of testis combined with spermatogenesis and steroidogenesis impairment. There is also a component of local and systemic inflammation. AIM: The aim of this study was to assess the effect of systemic inflammation associated with acute epididymo-orchitis on testis steroidogenesis. MATERIALS AND METHODS: 30 patients with acute bacterial epididymoorchitis treated in our ward without any oncologic involvement or other systemic inflammatory conditions were considered for the study. Total serum levels of testosterone and C-reactive protein measured within 12 hours of admission. RESULTS: Low total testosterone levels regarding to random laboratory population norms were noticed in 11 patients. Diminished serum total testosterone levels regarding to medium age levels were identified in 24 patients (80%). 29 patients had serum CRP levels elevated what gives average 22x fold. There is a statistically significant negative correlation between serum total testosterone levels and CRP serum levels were found (R - 0.75; p<0.000002 Spearman's correlation). CONCLUSIONS: There is a strong influence of ongoing systemic inflammation caused by bacterial infection on steroidogenesis in testis in acute epididymo-orchitis patients.

Clinical application of neutrophil CD64 quantification for differential diagnosis of acute scrotum.

The management of acute scrotum can be challenging, especially in infants or patients with a neurological or neurodevelopmental disorder in whom presentation, diagnosis and definitive management tends to be delayed. This leads to poor outcomes, such as loss of the affected testis. Here we present two cases of testicular torsion in patients with neurodevelopmental disorders, and a further two cases of epidydimo-orchitis in whom measurement of CD64 expression on neutrophils was helpful for differential diagnosis. These data suggest that the levels of expression of CD64 by neutrophils, known as a marker of infection, could also be useful for differentiating between testicular torsion and infection in acute scrotum.

Early diagnosis of testicular torsion in rats by measuring plasma d-dimer levels: comparative study with epididymitis.

PURPOSE: To evaluate the differential diagnosis of testicular torsion and acute epididymo-orchitis by measuring the acute increase in plasma d-dimer levels in an experimental rat model. METHODS: Thirty male Wistar rats were randomly divided into 5 groups, 1--sham operated group (acute term; 4 hours), 2--early torsion group (acute term; 4 hours), 3--late torsion group (long-term; 72 hours), 4--control of epididymitis group (vehicle injected; 0.1 ml physiologic saline injected into the left ductus deferens) (long term; 72 hours), 5--epididymitis group (0.1 ml Escherichia coli injected into the left ductus deferens), (n=6 for each group). RESULTS: Serum d-dimer levels were significantly higher compared with the sham operated group with early torsion (p=0.002). This elevation remained mildly in the late torsion group compared with the control group (p<0.001), but there was no difference between 4 and 72 hours of the testis torsions (p=0.794). On the other hand, d-dimer levels were significantly higher in the torsion groups compared to the epididymitis group (p=0.042). CONCLUSIONS: The present study demonstrated that testicular damage that occurs following testicular torsion shows a higher increase in d-dimer levels than epididymitis, suggesting that d-dimer level can be used as a diagnostic marker of testicular torsion.

Is procalcitonin valuable in the differential diagnosis of testicular torsion and epididymo-orchitis.

OBJECTIVE: To evaluate the efficacy of procalcitonin (PCT) in the differential diagnosis of testicular torsion and epididymo-orchitis. METHODS: This experimental study was performed in the research laboratory of Dicle University, School of Medicine, Diyarbakir, Turkey between March and June 2008. The study included 24 male rats randomized equally in 3 groups: sham, epididymo-orchitis, and torsion groups. Blood samples were obtained from all rats at the beginning of the study. After torsion and infection occurred in the testes, new blood samples were obtained for PCT measurement. Then, all the right testes of the rats were excised for histopathological evaluation. The Wilcoxon signed test was used for statistical evaluation. RESULTS: Pre- and post PCT levels were statically compared, and PCT levels were significantly higher in the epididymo-orchitis group. CONCLUSION: Procalcitonin could be an easy, fast, and safe marker for use in the differential diagnosis of testicular torsion and epididymo-orchitis.

Recurrent epididymo-orchitis in an 8-year-old child with Kostmann syndrome (severe congenital neutropenia).

Underlying congenital genito-urinary tract anomalies are the most common cause of recurrent epididymo-orchitis in prepubertal boys. An 8-year-old boy was admitted with recurrent pulmonary and skin infections, was diagnosed as Kostmann syndrome and developed epididymo-orchitis. This appears to be the first case of Kostmann syndrome associated with epididymo-orchitis.

[Characteristics of immunodeficiencies in patients with epididymitis].

The functional and metabolic activity of neutrophils, the expression of receptors to the Fc fragment of IgG molecules and C3 of the neutrophilic complement, and the subpopulational affiliation of peripheral lymphocytes were studied to examine immunity in patients with epididymitis. The immunological changes that occur 2-3 days earlier point to the fact that patients with epididymitis and suggest that the methods of immunological testing can be used to predict the course of an inflammatory process and the efficiency of performed treatments.

The clinical utility of serologic markers in the evaluation of the acute scrotum.

OBJECTIVE: To examine the presence of interleukin-1 (IL-1), interleukin-6 (IL-6), and creatine phosphokinase-MM (CPK-MM) in patients with acute scrotal pain and assess their clinical utility in the diagnosis of testicular torsion (TT) and epididymitis. METHODS: Twenty-five patients with acute scrotal pain were prospectively enrolled over a two-year period. History, physical examination, complete blood count, urinalysis, and scrotal ultrasound were performed. Testicular torsion was confirmed by surgical exploration. Epididymitis was diagnosed using physical examination, scrotal ultrasound, and positive urinalysis. Venous blood was assayed for IL-1, IL-6, and CPK-MM in triplicate during the routine drawing of blood in the emergency department. The data are reported as medians +/- interquartile ranges (IQRs). RESULTS: Twenty-five patients with acute scrotal pain were evaluated; 11 with TT, three with torsion of the appendix testis (TAT), ten with epididymitis, and one with varicocele. One patient had both TT and epididymitis. Interleukin-1 was not detectable in either group. The CPK-MM values between TT and epididymitis were virtually identical at 99.8 and 100 IU/L, respectively. The median value for IL-6 was 1. 03 (IQR = 0.19 to 2.86) vs 20.86 (IQR = 2.14 to 65.50) pg/mL in the torsion and epididymitis groups, respectively. The 97.5% CI for the difference of medians of 19.9 was 0.4 to 65.1, p = 0.02. Using receiver operating characteristic (ROC) curve analysis for IL-6, the area under the curve was 0.82 for torsion and 0.67 for epididymitis. Using a cutoff value of IL-6 >/= 1.41 pg/mL, the positive predictive value of IL-6 in diagnosing epididymitis was 78.6%, with a negative predictive value of 100% for TT. There were no cases of missed TT on follow-up. CONCLUSIONS: This preliminary investigation of serologic markers demonstrates that IL-6 is significantly elevated in epididymitis as compared with TT. Creatine phosphokinase-MM and IL-1 were not found to be of diagnostic utility. The small sample size of this study precludes a definitive conclusion as to the utility of these markers in the emergency department. However, IL-6 may be clinically useful as an additional element in differentiating the causes of acute scrotal pain, and further study is warranted.

Epididymitis by Brucella ovis: experimental infection in virgin ram lambs.

Ten sexually immature rams were experimentally infected with Brucella ovis, to verify the antibody kinetics and its localization in urinary and genital tracts. All animals became positive to the complement fixation test from the 2nd post infection (p.i.) week and reached the maximum titre (1:256) on the 4th p.i. week. Bacteriemia was demonstrated on 3rd, 4th and 5th p.i. weeks. Two animals, respectively slaughtered 11 and 13 weeks after the infection, showed macroscopic and microscopic genital lesions and the etiologic agent was cultured from their urine and genital organs.

Tissue penetration of sparfloxacin in a rat model of experimental Escherichia coli epididymitis.

The epididymal, testicular, and prostatic tissue penetration of sparfloxacin, a new quinolone, was assessed in a rat model of acute epididymitis. Seventy-two hours after injection of 0.1 ml (10(6) cfu/ml) of an Escherichia coli suspension into the right epididymis via the right ductus deferens, a single oral dose of sparfloxacin 50 mg/kg body weight was administered. One, 2, 4, 8, 12, and 24 h after administration the animals were sacrificed and the sparfloxacin concentrations and "areas under the curve" (AUC0-24) in both epididymides, both testes, the prostate gland and in the serum were measured by bioassay. The highest mean AUC0-24 was found in the prostate gland, followed by left epididymis, right epididymis, serum, right testis, and left testis (190, 79, 60, 28, 12, and 9 mg/kg x h, respectively). Though there was no statistically significant difference in the sparfloxacin concentration of both epididymides (p = 0.09), the mean AUC0-24 was significantly higher in the non-infected left epididymis (p < 0.0001). The AUC0-24 and sparfloxacin concentrations of the right infected epididymis were significantly higher than those observed in the serum (p < 0.0001). In both testes, the AUC0-24 and sparfloxacin concentrations were lower than in the serum (p < 0.0001), however, the concentration exceeded the MIC tenfold for approximately 20 h. It is concluded that the pharmacokinetic properties of sparfloxacin (good in vitro activity, high penetration into the prostate gland, testes, infected and non-infected epididymides) make this drug a recommendable choice for the initial treatment of acute epididymitis caused by E. coli.

[Sexual function after the surgical treatment of acute epididymitis]. / Polovaia funktsiia posle operativnogo lecheniia ostrogo épididimita.

Operative management of acute epididymitis performed in 150 patients aged 18-67 produced better therapeutic results compared to 150 patients treated conservatively (9.1 patient day versus 13.3 days). Follow-up for 2-4 years showed marked intergroup differences as regards anatomic changes in the epididymis revealed by palpation and ultrasound scanning. Echographic pattern was altered in 25 operated on and 92 patients treated conservatively. Copulative function was diminished in few cases in those operated on and much more frequently after conservative treatment, libido and erection in particular. Reproductive function was impaired more profoundly after conservative treatment as well. These patients demonstrated lower levels of testosterone and estradiol but higher content of LH and FSH. The latter hormones did not vary with age among the groups. Better effect of scrotal drainage in acute nonspecific epididymitides is attributed to the influence of inflammation-affected epididymis on the contralateral testicle more intensive under conditions of closed (nondrained) inflammation.

[Serum sialic acid levels in patients with acute prostatitis or acute epididymitis].

The serum sialic acid concentration in 17 male healthy adults, 11 patients with acute prostatitis and 12 patients with acute epididymitis was measured with a specific enzymatic assaykit. The concentration was studied in relation to erythrocyte sedimentation rate, total serum protein and its fraction, C-reactive protein, and white blood cell count. Blood samples were obtained from the patients immediately before antimicrobial chemotherapy and the subsequent 3, 5, 7, 14, and 28 days. The pretreatment sialic acid concentration in the patients was significantly greater than that in the control subjects (P greater than 0.001). The mean serum sialic acid concentration in the patients reached a maximum level 3 days after the beginning of the treatment, and then gradually decreased. There was a significant correlation between the daily change of the serum sialic acid level and those of the erythocyte sedimentation rate, alpha2-globulin, and alpha1-globulin. Serum sialic acid proved to be a useful biochemical marker in acute prostatitis and acute epididymitis.