Role of calcifying nanoparticles in the development of testicular microlithiasis in vivo.

BACKGROUND: Calcifying nanoparticles (NPs) have been proven to be associated with a variety of pathological calcification and previously detected in semen samples from patients with testicular microlithiasis (TM). The present study was designed to test the hypothesis if human-derived NPs could invade the seminiferous tubules and induce TM phenotype. METHODS: The animals were divided into three groups. Normal saline (0.2 mL) was injected into the proximal right ductus deferens in group A as a control group. The experimental groups, B and C received Escherichia coli (106 cfu/mL, 0.2 mL) and human-derived NPs suspension (0.2 mL), respectively. Rats were euthanized in 2 batches at 2 and 4 weeks. Testicular pathology, ultrastructure and inflammatory mediators were assessed. RESULTS: Chronic inflammatory changes were observed at 2 weeks in both groups B and C. Moreover, the innermost layer of sperm cells were structurally impaired and a zone of concentrically layered collagen fibers around the human NPs body was formed in the lumen of the seminiferous tubule in group C only, in which TM phenotype of remarkable calcification surrounded by cellular debris within the seminiferous tubules was built at 4 weeks. CONCLUSIONS: The results obtained from our study suggested a potential pathogenic effect of NPs in the development of calcification within the seminiferous tubules, which should be addressed in the future studies.

Melatonin improves bladder symptoms and may ameliorate bladder damage via increasing HO-1 in rats.

This study aims to investigate the efficacy and possible mechanisms of melatonin in treating interstitial cystitis (IC), as melatonin is involved in anti-inflammatory and immunomodulatory effects and plays an important role in neuroprotection. IC was induced by intraperitoneal injection of cyclophosphamide (CP) with melatonin pretreatment or vehicle pretreatment. On day 7, the voiding behaviors were observed. Bladders were harvested for histologic examination, analysis of the expressions of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) by Western blotting, and also processed for immunohistochemical staining of substance P (SP). Proinflammatory cytokines were measured by ELISA immunoassays. L6-S1 spinal cords were harvested for measurement of SP by radioimmunoassay. CP injection resulted in severe cystitis with increase in voiding behaviors, histological damage, mast cell proliferation, SP, and proinflammatory cytokine expression, which were significantly downregulated by melatonin pretreatment. Pretreatment with melatonin further enhanced the expression of HO-1 and significantly reduced iNOS expression. Melatonin significantly improved bladder symptoms and histological damages in rats with CP-induced cystitis by diminishing bladder oxidative stress, blocking iNOS, upregulation of HO-1, and downregulating the expression of SP.

Resection of a giant renal angiomyolipoma in a solitary kidney with preoperative arterial embolization.

Renal angiomyolipoma is a type of benign tumor that occurs sporadically in addition to being associated with tuberous sclerosis. Preoperative embolization of large tumors is important to avoid excessive blood loss during surgery. We reported a patient with a 5505-g giant renal angiomyolipoma in a solitary kidney. The patient was treated with preoperative embolization and radical nephrectomy without complications. This type of treatment for an enormous angiomyolipoma can reduce the risk of uncontrolled hemorrhage caused by rupture of the tumor during the operation and should be considered for the treatment of similar tumors.

Caveolin-1 may participate in the pathogenesis of bladder pain syndrome/ interstitial cystitis.

OBJECTIVES: To determine whether caveolin-1 expression is associated with bladder pain syndrome/interstitial cystitis (BPS/IC) and to better understand the pathogenesis of BPS/IC. METHODS: The study population was composed of 19 women with BPS/IC and 7 healthy women as controls. Midstream urine specimens were collected before cystoscopy and cold cup bladder biopsies were obtained from the trigone of the bladder. Caveolin-1 protein expression was determined by indirect immunofluorescence and Western blot analysis in cases and controls, using a rabbit polyclonal antibody against caveolin-1. χ(2) test and Student's t test were used in the statistical analysis. RESULTS: A statistical difference of caveolin-1 protein expression was observed between BPS/IC and healthy controls (p < 0.05, χ(2) test). Western blot analysis showed that the mean relative integrated density value of caveolin-1 in (BPS/IC) patients was significantly higher than that in the control group (p < 0.001, Student's t test). CONCLUSIONS: The results of our study demonstrate that there is a relationship between the raised levels of caveolin-1 expression and BPS/IC. This preliminary study may provide a basis for further investigation of the role of caveolin-1 in the pathogenesis of BPS/IC.

Nanobacteria may be linked to testicular microlithiasis in infertility.

Testicular microlithiasis (TM) in infertility is an uncommon pathologic condition of unclear etiology that is characterized by calcium deposits within the seminiferous tubules. Nanobacteria (NB), as novel microorganisms mediating tissue calcification, have been discovered in some diseases. In this study, we hypothesized that NB may participate in the pathogenesis of TM, particularly in infertility. Seventeen infertility patients with TM detected by scrotal color Doppler ultrasonography and 17 infertility patients without TM as controls were enrolled in the study. The NB were isolated and cultured from semen samples and urine samples. After 3 to 6 weeks of culture, 10 of 17 (58.8%) semen samples and 2 urine samples from infertile patients with TM showed the growth of white granular microbes that firmly attached to the bottom of the culture flask and were visible to the naked eye. In the control group, only 1 of 17 (5.9%) semen samples from infertile patients without TM showed the growth of white granular microbes. The cultured microbes were identified by indirect immunofluorescent staining (IIFS), transmission electron microscopy (TEM), and 16s rRNA gene expression. IIFS and TEM revealed NB to be coccoid and 100 to 500 nm in diameter. The BLAST result revealed that the 16s rRNA gene sequence from the cultured microbes was 97% the same as that of the known NB. Our results showed that NB may be linked to the development of TM, which may provide a potential target for the diagnosis and treatment of infertility with TM.

Decreased nanobacteria levels and symptoms of nanobacteria-associated interstitial cystitis/painful bladder syndrome after tetracycline treatment.

INTRODUCTION AND HYPOTHESIS: This study was designed to detect whether nanobacteria (NB) reside in urine and bladder tissue samples of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) and whether antibiotic therapy targeting these organisms is effective in reducing NB levels and IC/PBS symptoms. METHODS: Twenty-seven IC/PBS patients underwent cystoscopy. Bladder biopsies and urine samples were obtained and cultured for NB, which were identified by indirect immunofluorescent staining and transmission electron microscopy. RESULTS: Eleven bladder samples showed growth of microbes that were identified to be similar to NB. Homologous study of the 16S ribosomal RNA gene suggested that the NB could be the pathogen. For enrolled 11 patients, NB levels decreased dramatically after tetracycline treatment, and they reported significant reduction in the severity of IC/PBS symptoms. CONCLUSIONS: A high prevalence of NB was observed in female IC/PBS, and anti-NB treatment effectively improved the symptoms, which suggest that NB may cause some cases of IC/PBS.

FASLG polymorphism is associated with cancer risk.

Many studies have reported the association between the FASLG -844T/C polymorphism and cancer risk, but the data are remaining controversial. A pooled analysis was performed to assess this relationship comprehensively. Medline, PubMed, Embase and Web of Science were searched, and data were extracted and cross-checked independently by three authors. A total of 18 published studies including 22389 subjects were involved in this analysis. Overall, the -844C allele was associated with a significantly increased cancer risk (for CC versus TT: OR=1.23, 95% confidence interval (CI)=1.04-1.45; for CC+TC versus TT: OR=1.15, 95% CI=1.01-1.30; for CC versus TT+TC: OR=1.20, 95% CI=1.05-1.38). In the subgroup analysis by ethnicity, significantly elevated risks were found among Asians (for CC versus TT: OR=1.61, 95% CI=1.37-1.89; for CC+TC versus TT: OR=1.36, 95% CI=1.16-1.60; for CC versus TT+TC: OR=1.44, 95% CI=1.22-1.70). In the subgroup analysis by study design, significantly increased risks were found among population-based case-control studies (for CC versus TT: OR=1.40, 95% CI=1.06-1.84; for CC+TC versus TT: OR=1.25, 95% CI=1.01-1.55; for CC versus TT+TC: OR=1.31, 95% CI=1.06-1.61). These findings indicate that the FASLG -844C allele is emerging as a low-penetrant cancer susceptibility allele for cancer development. However, more comprehensive understanding of the association would certainly have an immense prospect in the promising field of individualised preventive care.

[Correlation between activation of L5-S2 spinal cord astrocytes and effect of substance P in chronic prostatitis pain].

OBJECTIVE: To observe the expressions of the substance P (SP) mRNA and neurokinin-1 receptor (NK-1R) in the posterior horn of the L5 - S2 spinal cord in the rat model of chronic prostatitis pain, and to investigate the changes in the activation of astrocytes and influence of SP on this activation in rat spinal cord astrocytes cultured in vitro. METHODS: The rat model of chronic prostatitis pain was established by injection of complete Freund's adjuvant (CFA) and assessed by the tail flick threshold test, the control rats injected with sodium chloride and all observed at 0, 14 and 28 days. Changes in the expressions of SP mRNA, NK-1R, glial fibrillary acidic protein (GFAP), tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) in the posterior horn of the L5 - S2 spinal cord were detected by RT-PCR and Western blot. Rat spinal cord astrocytes were cultured in vitro and divided into a control group, cultured with ITS cell culture fluid, and two experiment groups, with Group 1 stimulated with SP at the concentration of 10(-9) - 10(-6) mol/L for 12 hours followed by determination of the expressions of TNF-alpha, IL-1beta, NO and NOS by ELISA and nitrate reductase and colorimetric methods, and Group 2 at 10(-7) mol/L for 0, 24, 48 and 72 hours followed by detection of the GFAP expression by Western blot. RESULTS: The expressions of SP mRNA, NK-1 R, GFAP, TNF-alpha and iNOS in the posterior horn of the L5 - S2 spinal cord were obviously higher in the rat prostatitis pain models than in the controls, successively higher at 28 than at 14 and 0 d (P < 0.01), and so was the expression of GFAP at 28 than at 14 d in the experiment groups (P < 0.05). SP induced a gradual increase at 10(-7) mol/L in the expression of GFAP in the spinal cord astrocytes at 0 -72 h, significantly different from that of the control group (P < 0.01), and it promoted the excretion of TNF-alpha and IL-1beta and the activity of NO and NOS at 10(-9) - 10(-6) mol/L at 12 h in a concentration-dependent manner, with marked differences between the experiment and control groups (P < 0.01, P < 0.05). But a decreased excretion of IL-1 beta was observed in the 10(-6) mol/L group, though with no significant difference from the control (P > 0.05). CONCLUSION: Chronic prostatitis pain could upregulate the expressions of the excitatory transmitter SP and receptor in the L5 - S2 spinal cord, and result in the activation of astrocytes and increased excretion of proinflammatory cytokines, which may be associated with the persistence and generalization of prostatitis pain.

Intrathecal administration of resiniferatoxin produces analgesia against prostatodynia in rats.

BACKGROUND: Prostatodynia remains a difficult clinical problem. Resiniferatoxin (RTX), an ultrapotent vanilloid, can produce a selective and long-lasting desensitization of nociception via C-fiber sensory neurons. Substance P (SP) and calcitonin gene-related peptide (CGRP) released from C-fibers are key neurotransmitters in visceral pain. In this study, we evaluated the analgesic effect of intrathecal RTX on rat prostatodynia. METHODS: Male Sprague-Dawley rats were divided into 3 groups for different treatment. In group A, sham operation was preformed. In group B, 100 microl complete Freund's adjuvant (CFA) was injected into the rat's bilateral ventral prostate to induce chronic inflammation. In group C, after prostatitis formed, 50 microl 10 nmol/L RTX was injected into the rat's lumbosacral (L5-S2) vertebral canal. SP and CGRP contents in the spinal cord were investigated by immunohistochemistry and radioimmunoassay (RIA). Their transcriptional levels in dorsal root ganglion (DRG) were determined by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, pelvic nerve afferent discharge was recorded to explore the neuro-electrophysiological mechanisms underlying RTX-induced effect. RESULTS: SP and CGRP released in the spinal cord and their synthesis in DRG were increased significantly in response to CFA-induced chronic prostatitis, whereas this increase was effectively inhibited by intrathecal RTX. Meanwhile, pelvic nerve afferent electrical activity was enhanced significantly in rats with chronic prostatitis, but it was attenuated markedly in RTX-treated rats paralleled by the change of neuropeptides. CONCLUSIONS: Intrathecal RTX administration could produce an analgesic effect on rat prostatodynia. Suppression of pelvic nerve afferent electrical activity may be a crucial mechanism underlying RTX-induced analgesia. RTX intrathecal application may present a novel analgesic strategy of prostatodynia.

Loss of ryanodine receptor calcium-release channel expression associated with overactive urinary bladder smooth muscle contractions in a detrusor instability model.

OBJECTIVE: To investigate the changes in spontaneous bladder smooth muscle contractions that occur during detrusor instability (DI), and to test the possibility that altered function or expression of ryanodine receptors (RyRs) could account for the increased bladder contractions. MATERIALS AND METHODS: After 8 weeks of partial bladder outlet obstruction, DI was confirmed in female experimental rats by filling cystometry. Muscle strips were dissected from freshly isolated bladders, and isometric tension recorded in strips from DI and normal bladders. The contractions were recorded during electrical stimulation or exposure to various agents. Western blot analysis was used to determine RyR expression in DI and normal bladder muscle. RESULTS: In DI bladder muscle, spontaneous contractile activity persisted in the presence of blockers for known neurotransmitter receptors in the bladder wall. The RyR blocker ryanodine significantly increased the spontaneous contractile frequency in normal bladder strips, but failed to affect spontaneous contractions in DI muscle. Caffeine inhibited spontaneous contractile activity in both the DI and normal strips. After administering the l-type Ca(2+) channel antagonist nimodipine, the myogenic contractile activity was abolished in normal strips; in contrast, in DI strips, the amplitude of contractions was reduced but the frequency of contractions was unchanged. Western blot analysis showed that RyR expression was lower in DI muscle than in normal bladder muscle. CONCLUSION: These results provide the first characterization of a loss of regulation of spontaneous contractile activity by RyRs in DI muscle associated with a significant decrease in RyR expression. RyRs in normal detrusor muscle act as negative-feedback regulators of spontaneous contractile activity, presumably by releasing Ca(2+) that activates Ca(2+)-dependent K(+) channels to decrease contractility. This mechanism might be weakened in DI muscle, resulting in spontaneous contractile overactivity.

[Characteristics on diagnosis and treatment of renal tuberculosis].

OBJECTIVE: To study the new characteristics on diagnosis and treatment of renal tuberculosis (RT). METHODS: Eighty-seven patients with renal tuberculosis were retrospectively reviewed; their diagnosis was established by standard microbiological and histological techniques. RESULTS: Atypical RT was diagnosed by various examinations, including urinary analysis, polymerase chain reaction of tuberculosis (PCR-TB), ultrasonography, intravenous urography (i.v.U), and computerized tomography (CT). Treatment consisted of antituberculous chemotherapy in all patients, in combination with nephrectomy (62.5%) or enterocystoplasty (4.6%). CONCLUSIONS: The differential diagnosis of RT should be emphasized, especially for atypical RT, provided a much more specific diagnosis in clinical suspicion of RT. i.v.U can not be regarded as a specific examination for RT. Computerised tomography (CT) can be used for early diagnosis of RT. Surgery for RT is still ablative.

[Ultrastructural observation of detrusor in BPH patients].

OBJECTIVES: To observe the detrusor ultrastructure in BPH patients and to investigate the relationship between detrusor instability and ultrastructure. METHODS: The patients were divided into groups of detrusor instability(DI) and detrusor stability(DS) according to urodynamics examination. The structure of the detrusor were observed by light microscopy and transmission electron microscopy(TEM). RESULTS: The intercellular intermediate junctions and cytoplasmic process junctions in DS were 11.34 +/- 3.23 and 4.26 +/- 1.78 respectively. The intercellular intermediate junctions decreased obviously (3.12 +/- 1.47, P < 0.01) instead of a large amount of cytoplasmic process junctions (26.37 +/- 7.14, P < 0.01) in DI. CONCLUSIONS: There is a close relevance between intercellular junctions and DI. The observation of the ultrastructure of the detrusor is helpful for the diagnosis of BPH with DI and for the clinical treatment.