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Background: Apalutamide, a nonsteroidal potent androgen receptor antagonist, was safe and effective in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic-CRPC (mCRPC) in global studies. In this phase 1 study, safety, pharmacokinetics (PK), and efficacy of apalutamide were evaluated in Japanese patients with mCRPC. Methods: In this open-label, multi-center study, patients received apalutamide 240 mg (once-daily, orally) for first 1 week (PK week) during which PK parameters were assessed. 1 week later (Cycle 1 Day1), after reassessing safety, continuous daily dosing (4 weeks/cycle; once-daily orally) was initiated. Endpoints evaluated were: safety, tolerability, PK and antitumour efficacy of apalutamide. Dose-limiting toxicities (DLTs) were evaluated during PK week and Cycle 1. Results: All six patients received apalutamide. The most common treatment-emergent adverse events (TEAEs) were abdominal discomfort, nasopharyngitis, dysgeusia, rash, and hot flush [2/6 patients (33.3%) each]. No death or DLTs were reported. Grade 3 TEAEs were spinal-cord compression and renal disorder (1/6 patient each). In continuous daily dosing period, PK steady-state of apalutamide was reached approximately by week 4. A significant accumulation of apalutamide was observed (mean accumulation index 3.55), based on AUC0–24. Median (range) serum prostate-specific antigen level decreased from 54.42 (8.92–310.11) ng/mL at baseline to 11.70 (0.37–47.74) ng/mL at week 12 with ≥ 50% reduction in 4/6 (66.7%) patients and 90% reduction in 2/6 (33.3%) patients. Conclusion: Apalutamide had manageable safety profile, without any DLT or any new safety signals, and favourable efficacy in Japanese mCRPC patients. Thus, it was ascertained to be an adequate dosage regimen in Japanese mCRPC patients. Trial registration: ClinicalTrials.gov identifier: NCT02162836. [ABSTRACT FROM AUTHOR]

Background: The risk of malignant neoplasms increases in kidney transplantation (KT) recipients (KTRs). However, Japanese registry studies have not been reported since 2000. Methods: We retrospectively reviewed the medical records of 346 patients who underwent KT at Gifu University Hospital, Japan since 2000. Patients were divided into two groups based on whether they developed malignancy after KT or not. The incidence, type of malignancy, risk factors, and prognosis for malignancy were examined. Results: In this study, 22 de novo malignant neoplasms were identified in 20 KTRs (7.3%), with a median follow-up period of 8.2 years. Cumulative incidence of any malignant neoplasms was 1.1% within 1 year and 4.4% within 5 years. The 5-year overall survival (OS) rates were 71.8% in KTRs with malignant neoplasms and 98.6% in KTRs without malignant neoplasms. Uni- and multivariate analysis revealed that age at KT and acute rejection (AR) episode were significant predictors for incidence of malignancy. Conclusions: The development of malignant neoplasms was associated with poor OS and graft survival. We consider that appropriate screening and investigation of symptoms are important for KTRs, particularly for older KTRs at transplantation and those with AR episode. [ABSTRACT FROM AUTHOR]

Objectives: Acute epididymitis is often associated with urethritis. Mycoplasma genitalium and Ureaplasma urealyticum have been considered as pathogens of urethritis. The aim of the present study was to determine the prevalence of these microorganisms in men with acute epididymitis. Method: A total of 56 men younger than 40 years-of-age with acute epididymitis were enrolled in the present study between January 2006 and June 2010. First-void urine specimens were subjected to culture of aerobic bacterial species, and examined for the presence of Chlamydia trachomatis, M. genitalium, M. hominis, U. parvum and U. urealyticum by polymerase chain reaction-based assays. Urethral swabs were cultured for Neisseria gonorrhoeae. Results: The number and percentage of patients positive for each microorganism were as follows: Gram-negative bacilli, 2% and 3.6%; Gram-positive cocci, 23% and 41.1%; N. gonorrhoeae, 3% and 5.4%; C. trachomatis, 28% and 50.0%; M. genitalium, 5% and 8.9%; M. hominis, 6% and 10.7%; U. parvum, 6% and 10.7%; and U. urealyticum, 5% and 8.9%. Among 25 men with non-chlamydial non-gonococcal epididymitis, who were negative for Gram-negative bacilli, M. genitalium or U. urealyticum was detected in one man each (4.0%), and M. hominis and/or U. parvum was detected in five (20.0%). Conclusion: In men younger than 40 years-of-age with acute epididymitis, C. trachomatis is a major pathogen. The prevalence of genital mycoplasmas and ureaplasmas are lower, and the role of genital mycoplasmas and ureaplasmas in the development of acute epididymitis remains to be determined. [ABSTRACT FROM AUTHOR]

The Ca2+-transport activity and intracellular localization of the translation product of cDNA for mung bean Ca2+/H+ antiporter (VCAX1) were examined. When the cDNA was expressed in Saccharomyces cerevisiae that lacked its own genes for vacuolar Ca2+-ATPase and the antiporter, VCAX1 complemented the active Ca2+ transporters, and the microsomal membranes from the transformant showed high activity of the Ca2+/H+ antiporter. Treatment of the vacuolar membranes with a cross-linking reagent resulted in a clear band of the dimer detected with antibody specific for VCAX1p. The antibody was also used for immunolocalization of the antiporter in fractions obtained by sucrose-density-gradient centrifugation of the microsomal fraction from mung bean. The immunostained band was detected in the vacuolar membrane fraction and the slightly heavy fractions that exhibited activity of the Golgi marker enzyme. A fusion protein of VCAX1p and green fluorescent protein was expressed in tobacco cells. The green fluorescence was clearly observed on the vacuolar membrane and, in some cases, in the small vesicles. The subcellular fractionation of transformed tobacco cells confirmed the vacuolar membrane localization of the fusion protein. These results confirm that VCAX1p functions in the vacuolar membrane as a Ca2+/H+ antiporter and also suggest that VCAX1p may exist in the Golgi apparatus. [ABSTRACT FROM AUTHOR]

This study was carried out to investigate the frying performance of Kizakinonatane (Brassica napus) oil during deep-fat frying of frozen French fries with/without replenishment. Commercial regular canola oil was used for comparison. The frying oils were used during intermittent frying of frozen French fries at 180, 200, and 220 ℃ for 7 h daily over four consecutive days. The Kizakinonatane oil exhibited lower levels of total polar compounds, carbonyl value, and viscosity as well as comparable color (optical density) values to that of the canola oil. The monounsaturated fatty acid/polyunsaturated fatty acid ratios were lower than that of canola oil, whereas the polyunsaturated fatty acid/saturated fatty acid ratios are higher than that of canola oil after heating. Results showed that fresh Kizakinonatane oil contains higher levels of acid value, viscosity, optical density values, tocopherols, and total phenolics contents than that of canola oil. Replenishment with fresh oil had significant effects on all chemical and physical parameters, except the acid value of the Kizakinonatane oil during frying processes. Based on the results, the Kizakinonatane oil is inherently suitable for preparing deep-fried foods at high temperatures. [ABSTRACT FROM PUBLISHER]

Thyroidization (thyroid-like appearance) in renal tissue which is made up of a colloid-like hyaline cast formation of Tamm-Horsfall glycoprotein (THP) is a common finding in chronic pyelonephritis and obstructive nephropathy. This type of pathological change is sometimes observed in renal allograft specimens. We examined allograft specimens for thyroidization and other pathological findings related to thyroidization to characterize the conditions causing such changes. One-hundred three patients who underwent renal transplantation between January 2006 and April 2008 at Gifu University Hospital (251 renal allograft biopsy specimens) were enrolled in this study. Sixteen patients had thyroidization (11 mild, 4 moderate, and 1 severe). In four patients, THP reflux on Bowman’s capsule was found, and in three patients interstitial THP deposits were observed. In four patients, tubulointerstitial nephritis was diagnosed. Fifteen of 16 patients were examined for vesicoureteral reflux (VUR) with voiding cystourethrography. Three of 15 patients had VUR. In the past medical histories of the 16 patients with thyroidization, three had low capacity bladders, two had prostate diseases, and six had previous urinary tract infections. In cases of thyroidization with additional findings, including THP reflux into Bowman’s space and interstitial THP deposits, we need to examine the patients for the presence of urinary tract diseases. In cases of thyroidization and tubulointerstitial nephritis urinary tract infections were suspected. Such subclinical urological diseases in the grafts might affect the prognosis of renal function. Therefore, appropriate management of urinary tract diseases is required. [ABSTRACT FROM AUTHOR]

Autolysosomes accumulate in tobacco cells cultured under sucrose starvation conditions in the presence of a cysteine protease inhibitor. We characterized these plant autolysosomes using fluorescent dyes and green fluorescent protein (GFP). Observation using the endocytosis markers, FM4-64 and Lucifer Yellow CH, suggested that there is a membrane flow from the plasma membrane to autolysosomes. Using these dyes as well as GFP-AtVam3p, sporamin-GFP and gamma-VM23-GFP fusion proteins as markers of the central vacuole, we found transport of components of the central vacuole to autolysosomes. Thus endocytosis and the supply from the central vacuole may contribute to the formation of autolysosomes. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the chronologic changes in renal function after laparoscopic partial (LPN) or radical nephrectomy (LRN) in patients with clinical T1 renal cell carcinoma. Methods: In this retrospective study, patients with clinical stage T1 renal cell carcinoma who underwent LPN or LRN were divided into three groups, namely, LPN‐A group including LPN patients with WIT ≤25 minutes, LPN‐B group including LPN patients with WIT >25 minutes, and LRN group. Perioperative complications that occurred within 30 days after surgery were retrieved. All patients were followed‐up every 3 months to evaluate the estimated glomerular filtration rate. The primary endpoint of this study was to assess the chronological changes in renal function after surgery. Results: A total of 153 patients were enrolled in this study. The change in estimated glomerular filtration rate between day 1 and 2 weeks after surgery was significantly lower in the LPN‐B group than in the LPN‐A group (p<0.005). Both LPN‐A and ‐B groups achieved eGFR ≥90% 2 weeks after surgery. In addition, the estimated glomerular filtration rate decline from post‐operative day 1 through 24 months in the LPN‐A group or the LPN‐B group was significantly smaller than that in the LRN group (P < 0.001, P < 0.001, respectively). Conclusion: Our results demonstrate the efficacy and safety of LPN in patients with T1 renal cell carcinoma. Although complication rates were similar in both groups, post‐operative renal function was not different between the LPN‐A and ‐B groups [ABSTRACT FROM AUTHOR]

A major membrane intrinsic protein (VM23) in vacuoles of radish (Raphanus) tap root was investigated. The cDNAs for two isoforms of VM23, γ- and δ-VM23, encode polypeptides of 253 and 248 amino acids, respectively, γ-and δ-VM23 correspond to the γ- and δ-TIP (tonoplast intrinsic protein) of Arabidopsis. The deduced amino acid sequences of the two VM23 isoforms were 60% identical. The ammo-terminal sequence of γ-VM23 showed agreement with the direct sequence of the purified VM23, suggesting that γ-VM23 is the most abundant molecule among the VM23 isoforms. When mRNAs of γ- and δ-VM23 were injected into Xenopus oocytes, the osmotic water permeability of oocytes increased 6-fold (60 to 200 μM s1) of the control oocytes. The transcripts of both isoforms were detected in a high level in growing hypocotyls and young leaves, but δ-VM23 was not detected in seedling roots. Light illumination enhanced the transcription of two genes of VM23 in cotyledons and roots but suppressed their expression in hypocotyls the growth of which was inhibited by light. These findings suggest that the expression of VM23 is tightly related to cell elongation [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the surgical and oncological outcomes and complications of laparoscopic radical cystectomy (LRC) to those of open radical cystectomy (ORC) in patients with muscle-invasive bladder cancer (MIBC). Methods: Our study focused on patients with histologically confirmed stage T2–T4a urothelial carcinoma of the bladder without distant metastases, who underwent LRC (LRC group) or ORC (ORC group). The primary endpoints in this study were the overall survival (OS) and recurrence-free survival (RFS) rates. Results: In this study, 59 patients, 17 underwent LRC and 42 underwent ORC, were enrolled. The 2-year OS rate was 100% in the LRC group and 88.0% in the ORC group (p = 0.85). The 2-year RFS rate was 63.5% in the LRC group and 69.5% in the ORC group (p = 0.321). On multivariate analysis, the histological type, positive lymph node, and positive resection margin were significantly associated with the OS rates. Conclusions: This study suggested that LRC may achieve similar oncological outcomes and fewer perioperative complications and less blood loss compared to ORC. Therefore, LRC should be considered as one of the treatment options for patients with MIBC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the association between clinical covariates or the prescribed radiation dose for the prostate and rectal hemorrhage in patients with prostate cancer (PCa) who received iodine-125 low-dose-rate brachytherapy (LDR-BT group) or the combination of LDR-BT and external beam radiation therapy (CMT group). Methods and materials: In this retrospective study, we reviewed the clinical records of 298 consecutive PCa patients with clinical stage T1c/T2 who underwent LDR-BT between August 2004 and August 2016 at a single institution. The prescribed minimum peripheral doses were 145 Gy for the LDR-BT group and 104 Gy for the CMT group. The dosimetric parameters analyzed were minimal dose received by 90% of the prostate gland, biologically effective dose, and rectal volume receiving 100% (RV100) or 150% of the prescribed dose. The endpoint of this study was the onset of any-grade clinical rectal hemorrhage after treatment. Results: The median follow-up period was 6.8 years. The 5-year overall survival rate was found to be 98.3%, and two patients (0.7%) reported biochemical recurrence during follow-up period. A total of 33 patients (11%) experienced rectal hemorrhage. However, ≥ grade 2 rectal hemorrhage occurred in eight patients (2.7%). On multivariate analysis, CMT, RV100 ≥ 0.66 mL, and hemorrhoids before treatment were identified as predictors of rectal hemorrhage after radiation therapy. Conclusions: Maximal reduction of the rectal dose seems very important to prevent serious rectal hemorrhage. In addition, we should consider the risk of rectal toxicities in patients with abnormalities in the rectal mucosa, especially hemorrhoids. [ABSTRACT FROM AUTHOR]

Objective: To investigate long-term changes in lower urinary tract symptoms in patients with prostate cancer (PCa) who underwent low-dose-rate brachytherapy with iodine-125 (LDR-BT).Patients and Methods: In this retrospective study, 313 patients with localized PCa underwent LDR-BT at Gifu University hospital between August 2004 and December 2013. The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and quality of life due to urinary symptoms (IPSS-QOL) were measured before LDR-BT; at 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after LDR-BT; and annually thereafter. Study endpoints were chronological changes in IPSS, OABSS, and IPSS-QOL compared to pretreatment values. A multivariable nonlinear regression model with robust sandwich estimator evaluated association between outcomes and time with adjustment for covariates.Results: All scores worsened immediately after LDR-BT compared to preoperative scores. However, symptoms improved with time and returned to baseline in 18-36 months. After a 5-year follow-up after LDR-BT, OABSS significantly worsened in almost all patients compared to baseline although there were gradual improvements in less than 5 years after LDR-BT.Conclusions: Our results may be of clinical importance in selecting treatment modalities for patients with localized PCa and long-term survival after definitive therapy. [ABSTRACT FROM AUTHOR]

We report the case of a 68-year-old Japanese man who presented with postrenal azotemia due to bilateral upper ureteral stenosis. The patient's right kidney was nonfunctional; therefore, right nephroureterectomy was performed for the purpose of pathologic diagnosis. Histopathologic examination revealed follicular lymphoma with diffuse change in the ureter. With chemotherapy for malignant lymphoma, the stenosis of the left ureter was alleviated, and left renal function was preserved. Primary malignant lymphoma of the ureter is extremely rare. In cases of ureteral stenosis with ureteral wall thickening for which the cause is uncertain, the possibility of malignant lymphoma of the ureter should be considered. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate predictive factors for graft loss in patients who received kidney transplantation (KT) from living kidney donors (LKDs) at a single institute in Japan. Our study focused on patients with end-stage renal disease who underwent KT from LKDs and were followed up for at least 1 year after surgery. The primary end point was graft survival (GS). GS after KT was analyzed using the Kaplan-Meier method. GS according to subgroup classification was analyzed using the log-rank test. A multivariate analysis was performed using a Cox proportional hazard model. The median follow-up period was 105.5 months after KT. The 5- and 10-year GS rates were 97.8% and 96.0% in KT recipients (KTRs) without posttransplant diabetes mellitus (PTDM) and 89.9% and 63.2% in those with PTDM, respectively. The rate of graft loss was significantly higher in KTRs with PTDM than in those without PTDM (P <. 001). Of the KTRs whose diabetes mellitus (DM) was cured after KT, those who underwent dialysis because of diabetic nephropathy had no graft loss. In the multivariate analysis, the serum creatinine level at 1 month after KT, PTDM, and human leukocyte antigen mismatches were significantly associated with graft loss after KT. In this study, the rate of graft loss in KTRs with PTDM was significantly higher than that of KTRs without PTDM. However, among KTRs whose DM was cured after KT, those who underwent dialysis because of diabetic nephropathy had no graft loss. • The rate of graft loss in kidney transplantation recipients (KTRs) with posttransplant diabetes mellitus (PTDM) was significantly higher than in those without PTDM. • Of the KTRs whose diabetes mellitus (DM) was cured after kidney transplantation (KT), those who underwent dialysis because of diabetic nephropathy had no graft loss. • The control of DM before KT may play an important role in high-risk recipients of KT who develop PTDM after KT. [ABSTRACT FROM AUTHOR]

Radical cystectomy remains the gold standard for treatment of muscle‐invasive bladder cancer. Robot‐assisted radical cystectomy has technical advantages over laparoscopic radical cystectomy and has emerged as an alternative to open radical cystectomy. Despite the advancements in robotic surgery, experience with total intracorporeal reconstruction of urinary diversion remains limited. Most surgeons have carried out the hybrid approach of robot‐assisted radical cystectomy and extracorporeal reconstruction of urinary diversion, as intracorporeal reconstruction of urinary diversion remains technically challenging. However, intracorporeal reconstruction of urinary diversion might potentially proffer additional benefits, such as decreased fluid loss, reduction in estimated blood loss and a quicker return of bowel function. The adoption of intracorporeal ileal neobladder reconstruction has hitherto been limited to high‐volume academic institutions. In the present review, we compare the totally intracorporeal robot‐assisted radical cystectomy approach with open radical cystectomy and robot‐assisted radical cystectomy + extracorporeal reconstruction of urinary diversion in muscle‐invasive bladder cancer patients. [ABSTRACT FROM AUTHOR]

We analyzed the 23S rRNA, gyrA and parC genes of Chlamydia trachomatis DNAs from men with urethritis and determined microbiological outcomes of an extended-release azithromycin (azithromycin-SR) regimen (2 g once daily for 1 day) and a sitafloxacin regimen (100 mg twice daily for 7 days) for chlamydial urethritis to clarify the macrolide and fluoroquinolone resistance status of clinical strains of C. trachomatis . We amplified the portions of 2 alleles of the 23S rRNA gene and the gyrA and parC genes from C. trachomatis DNAs in 284 first-voided urine specimens from men with chlamydial urethritis by PCR and sequenced their PCR products. We enrolled 369 men with chlamydial urethritis, comprising 314 and 55 treated with the azithromycin-SR regimen and the sitafloxacin regimen, respectively. Alleles 1 and/or 2 of the 23S rRNA gene were analyzed in 162 specimens. No mutations were found in the sequenced regions, including the central portion of domain V. The gyrA and parC genes were analyzed in 118 and 113 specimens, respectively. No amino acid changes were found within the quinolone resistance-determining region of the gyrA gene and in the sequenced region of the parC gene. The microbiological outcomes of the azithromycin-SR and sitafloxacin regimens were assessed in 176 and 30 men, respectively. The eradication rates were 96.0% (95% CI 93.1%–98.9%) for the azithromycin-SR regimen and 100% for the sitafloxacin regimen. Clinical strains of C. trachomatis with macrolide and/or fluoroquinolone resistance would be uncommon, and azithromycin or fluoroquinolone regimens could be recommended as treatments for chlamydial infections. [ABSTRACT FROM AUTHOR]

Of 73 clinical strains of Haemophilus influenzae isolated from the urethra of men with urogenital infections, we enrolled 6 strains (8.2%) with levofloxacin (LVFX) minimum inhibitory concentrations (MICs) of ≥0.03 μg/ml in this study. All the strains were isolated from non-gonococcal urethritis (NGU). We amplified the quinolone resistance-determining region of the gyrA gene and the analogous region of the parC gene from bacterial DNAs by PCR and sequenced the PCR products. Two strains with a LVFX MIC of 0.03 μg/ml had an amino acid change of Asp88 to Gly in GyrA. One with a LVFX MIC of 0.06 μg/ml had a change of Asp88 to Tyr in GyrA. Two with respective LVFX MICs of 0.12 and 0.25 μg/ml had a change of Ser84 to Leu in GyrA. One with a LVFX MIC of 1 μg/ml had changes of Ser84 to Leu in GyrA and of Ser84 to Ile in ParC. Multilocus sequence typing showed two strains with a change of Asp88 to Gly in GyrA had the same sequence type, but the others had sequence types different from each other. Single amino acid changes in GyrA alone or single changes in both GyrA and ParC could contribute to decreased susceptibility to fluoroquinolones in H. influenzae isolates from NGU. Most of the isolates with GyrA and/or ParC alterations would be multiclonal. The prevalence of such isolates would be relatively low, and they would still be susceptible to fluoroquinolones commonly prescribed for treatment of NGU. [ABSTRACT FROM AUTHOR]

We determined minimum inhibitory concentrations (MICs) of 41 antimicrobial agents for 73 clinical strains of Haemophilus influenzae isolated from the urethra of men with acute urethritis and/or epididymitis and examined the strains for the production of β-lactamase. We also compared their antimicrobial susceptibilities with those of H. influenzae strains from respiratory tract or otorhinolaryngological infections that were reported in Japan. The proportion of β-lactamase-nonproducing ampicillin-resistant strains from acute urethritis and/or epididymitis appeared to be lower, but that of β-lactamase-producing ampicillin-resistant strains appeared to be higher, compared with those from respiratory tract or otorhinolaryngological infections. However, their antimicrobial susceptibilities to a variety of other antimicrobial agents would be similar to those from respiratory tract or otorhinolaryngological infections. Almost all of the strains of H. influenzae from acute urethritis and/or epididymitis were susceptible to the agents, including ceftriaxone, quinolones, macrolides, and tetracyclines, commonly prescribed for treatment of acute urethritis based on the MIC breakpoints recommended by the Clinical and Laboratory Standards Institute. Ceftriaxone and quinolones could be effective on H. influenzae -induced urethritis. However, azithromycin treatment failures were reported in acute urethritis caused by H. influenzae strains considered susceptible to azithromycin. Further studies will be needed to determine MIC breakpoints of antimicrobial agents, which are recommended for treatment of urogenital infections, for H. influenzae strains causing these infections. Nevertheless, this study provides useful data regarding antimicrobial susceptibilities of H. influenzae strains isolated from the urogenital tract, which have rarely been studied. [ABSTRACT FROM AUTHOR]

Background: There have been few comprehensive studies on Haemophilus influenza-positive urethritis.Methods: In this retrospective study, we enrolled 68 men with H. influenzae-positive urethritis, including coinfections with Neisseria gonorrhoeae, Chlamydia trachomatis, and/or genital mycoplasmas: 2, 3, 20, and 43 treated with ceftriaxone, levofloxacin, sitafloxacin, and extended-release azithromycin (azithromycin-SR), respectively. We assessed microbiological outcomes in 54 men and clinical outcomes in 46 with H. influenzae-positive monomicrobial nongonococcal urethritis. We determined minimum inhibitory concentrations (MICs) of 6 antimicrobial agents for 59 pretreatment isolates.Results: H. influenzae was eradicated from the men treated with ceftriaxone, levofloxacin, or sitafloxacin. The eradication rate with azithromycin-SR was 85.3%. The disappearance or alleviation of urethritis symptoms and the decreases in leukocyte counts in first-voided urine were significantly associated with the eradication of H. influenzae after treatment. For the isolates, ceftriaxone, levofloxacin, sitafloxacin, azithromycin, tetracycline, and doxycycline MICs were ≤0.008-0.25, 0.008-0.5, 0.001-0.008, 0.12-1, 0.25-16, and 0.25-2 μg/mL, respectively. The azithromycin MICs for 3 of 4 strains persisting after azithromycin-SR administration were 1 μg/mL. H. influenzae with an azithromycin MIC of 1 μg/mL increased chronologically.Conclusions: H. influenzae showed good responses to the chemotherapies for urethritis. The significant associations of the clinical outcomes of the chemotherapies with their microbiological outcomes suggested that H. influenzae could play pathogenic roles in urethritis. All isolates, except for one with decreased susceptibility to tetracyclines, were susceptible to the examined agents. However, the increase in H. influenzae with an azithromycin MIC of 1 μg/mL might threaten efficacies of azithromycin regimens on H. influenzae-positive urethritis. [ABSTRACT FROM AUTHOR]

Objectives: We treated men with gonococcal urethritis with a single-dose regimen of 1 g of ceftriaxone, which is recommended as the first-line treatment for gonorrhoea in Japan, to determine its microbiological outcomes and tolerability.Methods: We enrolled 255 men with gonococcal urethritis and treated them with a single-dose regimen of 1 g of ceftriaxone. We evaluated its microbiological outcomes and tolerability. We also determined ceftriaxone MICs for pretreatment isolates of Neisseria gonorrhoeae collected from the patients.Results: The microbiological efficacy of the ceftriaxone regimen, which was determined between 5 and 9 days after treatment in 111 men based on the Japanese guideline for clinical research on antimicrobial agents in urogenital infections, was 100%. In the 194 men who returned to the clinic between 2 and 41 days after treatment, 191 (98.5%; 95% CI 96.8%-100%) were negative for N. gonorrhoeae after treatment. Ceftriaxone MICs determined for 136 pretreatment isolates obtained from these 194 men ranged from 0.001 to 0.25 mg/L. One isolate persisting after treatment exhibited a ceftriaxone MIC of 0.008 mg/L. For two isolates persisting after treatment, ceftriaxone MICs were not determined. Seven adverse events were observed in 7 (3.2%) of the 220 men treated with the ceftriaxone regimen. Four men had diarrhoea classified as grade 1. Three had urticaria during ceftriaxone administration, with one event classified as grade 1 and two events classified as grade 3.Conclusions: A single-dose regimen of 1 g of ceftriaxone was microbiologically effective against gonococcal urethritis and was safe and tolerable. [ABSTRACT FROM AUTHOR]

Objectives To detect microorganisms responsible for male acute urethritis and to define the microbiology of non-gonococcal urethritis. Methods The present study comprised 424 men with symptoms and signs compatible with acute urethritis. Their urethral swabs and first-voided urine underwent detection of the microorganisms. Demographic characteristics and clinical features of Mycoplasma genitalium-, Ureaplasma urealyticum-, Haemophilus influenza-, adenovirus- or Herpes simplex virus-positive monomicrobial non-gonococcal urethritis, or all-examined microorganism-negative urethritis in heterosexual men were compared with urethritis positive only for Chlamydia trachomatis. Results Neisseria gonorrhoeae was detected in 127 men (30.0%). In 297 men with non-gonococcal urethritis, C. trachomatis was detected in 143 (48.1%). In 154 men with non-chlamydial non-gonococcal urethritis, M. genitalium (22.7%), M. hominis (5.8%), Ureaplasma parvum (9.1%), U. urealyticum (19.5%), H. influenzae (14.3%), Neisseria meningitidis (3.9%), Trichomonas vaginalis (1.3%), human adenovirus (16.2%), and Herpes simplex virus types 1 (7.1%) and 2 (2.6%) were detected. Although some features of monomicrobial non-chlamydial non-gonococcal urethritis or all-examined microorganism-negative urethritis were significantly different from those of monomicrobial chlamydial non-gonococcal urethritis, most features were superimposed. Conclusions Predicting causative microorganisms in men with non-gonococcal urethritis based on demographic and clinical features is difficult. However, the present study provides useful information to better understand the microbiological diversity in non-gonococcal urethritis, and to manage patients with non-gonococcal urethritis appropriately. [ABSTRACT FROM AUTHOR]

We retrieved clinical data of 13 men having herpes simplex virus (HSV)-induced non-gonococcal urethritis (NGU) without visible herpetic lesions. They visited a clinic in Sendai, Japan, between April 2013 and December 2015. All the men complained of dysuria. Meatitis was observed in 9 of the 13 men. Mononuclear cells were observed in the urethral smears from 9 men. The 13 men were treated with azithromycin or sitafloxacin regimen. First-voided urine (FVU) specimens became negative for HSV in 8 of the 10 men who returned to the clinic after antibacterial treatment, and urethritis symptoms were alleviated. However, herpetic lesions were observed at the follow-up visits in 3 men, and 2 of them were still positive for HSV in their FVU. HSV could be a cause of acute urethritis without causing visible herpetic lesions. The shedding of HSV from the urethra would spontaneously cease with alleviation of urethritis symptoms in most cases of HSV-induced NGU without antiviral therapy. However, new herpetic lesions could be developed in some cases. Early antiviral therapy is beneficial for patients with HSV infections. The development of meatitis and the mononuclear cell response in the urethral smear could be helpful to diagnose HSV-induced NGU. Therefore, we should presumptively initiate anti-HSV therapy for patients with signs and symptoms suggestive of HSV-induced NGU at their first presentation. [ABSTRACT FROM AUTHOR]

We observed fluoroquinolone treatment failures in 2 men with Mycoplasma genitalium -positive non-gonococcal urethritis in Japan. A fluoroquinolone regimen of sitafloxacin 100 mg twice daily for 7 days failed to eradicate M. genitalium . In both cases, M. genitalium had fluoroquinolone resistance-associated amino acid changes both in GyrA and ParC and a macrolide resistance-associated mutation in the 23S rRNA gene. The emergence of such multi-drug resistant strains can threaten antimicrobial chemotherapy for M. genitalium infections in Japan, because we will lose the first- (azithromycin) and second-line (sitafloxacin) antimicrobial agents to treat M. genitalium infections. We prescribed an extended minocycline regimen of minocycline 100 mg twice daily for 14 days for our patients, and the regimen was successful in eradicating the M. genitalium . The extended minocycline regimen might be an option that we can try when treating multi-drug resistant M. genitalium infections in clinical practice. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis causes acute non-gonococcal urethritis, but some infected men are asymptomatic. We examined leukocytes in uncentrifuged first-voided urine (FVU) from asymptomatic men at high risk for chlamydial infection by automated urine particle analyzers to assess whether the quantification of urinary leukocytes could predict chlamydial infection in these men. We enrolled 209 asymptomatic men, whose female sexual partners had been diagnosed as having a genital chlamydial infection. Their FVU specimens were examined for quantification of leukocytes with automated urine particle analyzers and tested for Neisseria gonorrhoeae , C. trachomatis , Mycoplasma genitalium , Mycoplasma hominis , Ureaplasma parvum , and Ureaplasma urealyticum by nucleotide acid amplification tests. Eleven men positive for N. gonorrhoeae or M. genitalium were excluded from further analysis. In the remaining 198 men, 84 positive for C. trachomatis (42.4%) had 1.8–1666.9 white blood cells (WBCs)/μl (median, 43.3 WBCs/μl) in their FVU, whereas 114 negative for C. trachomatis had 0.1–1378 WBCs/μl (median, 4.8 WBCs/μl). A receiver operating characteristic (ROC) curve was constructed to examine the sensitivity and specificity of leukocytes counts for predicting chlamydial infection. A cut-off point of leukocyte counts of 12.5 WBCs/μl was determined from the ROC curve, resulting in a sensitivity of 86.9% and specificity of 88.6% for predicting chlamydial infection. Leukocyte quantification in FVU by automated urine particle analyzers showed good performance in predicting the positivity and negativity for chlamydial infection in asymptomatic men. This test could potentially develop into a relevant tool for preselecting asymptomatic men prior to C. trachomatis screening. [ABSTRACT FROM AUTHOR]

Objectives We determined the prevalence of macrolide and fluoroquinolone resistance-associated mutations in Mycoplasma genitalium DNA specimens from men with non-gonococcal urethritis (NGU) and analysed their effects on antibiotic treatments of M. genitalium infections. Methods In this retrospective study, we examined antibiotic resistance-associated mutations in the 23S rRNA, gyrA and parC genes of M. genitalium and the association of the mutations with microbiological outcomes of antibiotic treatments in men with M. genitalium-positive NGU. Results No macrolide resistance-associated mutations in the 23S rRNA gene were observed in 27 M. genitalium DNA specimens in 2011 and in 24 in 2012. However, 5 of 17 in 2013 had 23S rRNA mutations. Three of 15 in 2011, 6 of 19 in 2012 and 8 of 17 in 2013 had fluoroquinolone resistance-associated alterations in ParC. Three in 2013 had both the antibiotic resistance-associated alterations coincidentally. In two men with M. genitalium harbouring 23S rRNA mutations, the mycoplasma persisted after treatment with a regimen of 2 g of extended-release azithromycin (AZM-SR) once daily for 1 day. All nine men with mycoplasma harbouring ParC alterations were microbiologically cured with a regimen of 100 mg of sitafloxacin twice daily for 7 days. Conclusions Macrolide- or fluoroquinolone-resistant M. genitalium appears to be increasing, and the increase in fluoroquinolone-resistant mycoplasmas is especially remarkable in Japan. Mycoplasmas harbouring 23S rRNA mutations would be resistant to the AZM-SR regimen, but those harbouring ParC alterations would still be susceptible to the sitafloxacin regimen. [ABSTRACT FROM PUBLISHER]

Several microorganisms cause non-gonococcal urethritis (NGU). Failure to eradicate Mycoplasma genitalium from the urethra could be associated with persistent or recurrent urethritis; thus, the choice of antibiotics with activities potent enough to eradicate M. genitalium is crucial in the treatment of NGU. In in vitro studies, sitafloxacin has been shown to be highly active against Chlamydia trachomatis and M. genitalium. We treated 89 males with NGU, including 15 patients with persistent or recurrent NGU and 1 patient with post-gonococcal urethritis, with a 100-mg twice-daily dose regimen of sitafloxacin to assess its efficacy against NGU. We examined first-void urine samples for the presence of C. trachomatis, M. genitalium, Ureaplasma parvum, and Ureaplasma urealyticum. After treatment, we evaluated 73 patients for clinical outcomes and 44 for microbiological outcomes. Symptoms were alleviated in 62 (84.9%) patients, who were judged clinically cured. Microorganisms detected before treatment were eradicated in 42 (95.5%) patients, who were judged microbiologically cured. Regarding microbiological outcomes of specific microorganisms, eradication rates of C. trachomatis ( n = 33), M. genitalium ( n = 11), and U. urealyticum ( n = 10) were 100%, 100%, and 80.0%, respectively. In all 5 patients with M. genitalium-positive persistent or recurrent NGU who had experienced treatment failures with antibiotics, the mycoplasma was eradicated. These results suggested that the sitafloxacin regimen used, which was effective on both M. genitalium and C. trachomatis infections, could be useful as an appropriate option as first- and second-line treatment of NGU. [ABSTRACT FROM AUTHOR]

Arabidopsis TOM1 (AtTOM1) and TOM2A (AtTOM2A) are integral membrane proteins genetically identified to be necessary for efficient intracellular multiplication of tobamoviruses. AtTOM1 interacts with the helicase domain potypeptide of tobamovirus- encoded replication proteins and with AtTOM2A, suggesting that both AtTOM1 and AtTOM2A are integral components of the tobamovirus replication complex. We show here that AtTOM1 and AtTOM2A proteins tagged with green fluorescent protein (GFP) are targeted to the vacuolar membrane (tonoplast)- like structures in plant cells. In subcellular fractionation analyses, GFP-AtTOM2A, AtTOM2A and its tobacco homolog NtTOM2A were predominantly fractionated to tow-density tonoplast-rich fractions, whereas AtTOM1-GFP, AtTOM1 and its tobacco homolog NtTOM1 were distributed mainly into the tonoplast-rich fractions and partially into higher- buoyant-density fractions containing membranes from several other organelles. The tobamovirus-encoded replication proteins were co-fractionated with both NtTOM1 and viral RNA-dependent RNA polymerase activity. The replication proteins were also found in the fractions containing non-membrane-bound proteins, but neither NtTOM1 nor the polymerase activity was detected there. These observations suggest that the formation of tobamoviral RNA replication complex occurs on TOM1-containing membranes and is facilitated by TOM2A. [ABSTRACT FROM AUTHOR]

A 51-year-old HIV-positive man treated with atazanavir for 9 months presented with anuria following right flank pain. Laboratory examination indicated renal insufficiency, and abdominopelvic computed tomography scanning showed bilateral hydroureteronephrosis, but no stones were visualized. Endoscopic procedures were performed to investigate the causes of ureteral obstruction and, if possible, to insert Double-J stents in the ureters. A yellowish stone composed of pure atazanavir was found at the right ureteral orifice, and retrograde pyelography revealed a filling defect in the left ureter found to be caused by an atazanavir stone. The patient’s renal function recovered after removal of these stones. [ABSTRACT FROM AUTHOR]

Unlike urinary tract infection (UTI), asymptomatic bacteriuria (ABU) should not be treated, with some exceptions such as pregnant women and patients who will undergo traumatic urologic interventions. However, there has been no clinically available marker for their differential diagnosis. Exosomes or small extracellular vesicles carry proteins contained in cells from which they are derived, thus having the potential as a biomarker of several diseases. On the basis of the hypothesis that the molecular signature of exosomes in urine may differ between UTI and ABU patients, we examined if urinary exosomes could serve as a marker for their differential diagnosis. Exosomes were isolated by ultracentrifugation or affinity‐based method from cell culture medium of monocytic THP‐1 and uroepithelial SV‐HUC‐1 cells and human urine. Protein expression was examined by Western blot analysis, ELISA, and CLEIA. The results showed that the levels of intracellular signalling molecules Akt and ERK and transcription factor NF‐κB increased in exosomes isolated from THP‐1 and SV‐HUC‐1 cells cocultured with Escherichia coli and/or treated with lipopolysaccharide. In urinary exosomes of UTI patients, Akt significantly diminished, and an exosomal marker CD9 showed a trend to decrease after treatment with antimicrobial agents. More importantly, Akt and CD9 levels in urinary exosomes were higher in UTI patients than in ABU patients, which was also observed after correction by urine creatinine. Collectively, these results suggest that Akt and CD9 in urinary exosomes could be useful markers for differential diagnosis of UTI and ABU. [ABSTRACT FROM AUTHOR]