IGF-1 as an Important Endogenous Growth Factor for Recovery from Impaired Urethral Continence Function in Rats with Simulated Childbirth Injury.

PURPOSE: We examined the functional role of endogenous IGF-1 (insulin-like growth factor-1) in the recovery phase of stress urinary incontinence induced by simulated childbirth trauma using an IGF-1 receptor inhibitor. MATERIALS AND METHODS: Simulated birth trauma was induced by vaginal distension in female Sprague Dawley® rats. The IGF-1 receptor antagonist JB-1 (10 and 100 µg/kg per day) or vehicle was continuously delivered from 1 day before vaginal distension for 7 days using subcutaneous osmotic pumps. Seven, 14 and 21 days after vaginal distension the effect of JB-1 treatment was examined by functional analyses, including leak point and urethral baseline pressure, and urethral responses during passive increments in intravesical pressure, as well as molecular analyses in urethral tissues, including phosphorylation of Akt, apoptotic changes and peripheral nerve density using Western blot and immunohistochemistry. RESULTS: On functional analyses vehicle treated rats with vaginal distension had significantly decreased leak point and urethral baseline pressure, and urethral responses at 7 days, which recovered to the normal level 14 and 21 days after vaginal distension. In the JB-1 treated vaginal distension group leak point and urethral baseline pressure, and urethral responses were still significantly reduced 21 days after vaginal distension. On molecular analyses JB-1 treatment increased apoptotic cells, induced a significant decrease in phosphorylated Akt and prolonged the decrease of peripheral nerve density in urethral tissues. CONCLUSIONS: Suppression of endogenous IGF-1 activity delayed recovery from stress urinary incontinence induced by simulated childbirth trauma in rats. Thus, IGF-1 is likely to be an important endogenous mediator for functional recovery from childbirth related stress urinary incontinence. This suggests that IGF-1 could be an effective target for treating stress urinary incontinence in women.

Production of infectious HCV genotype 1b virus in cell culture using a novel Set of adaptive mutations.

BACKGROUND: Despite the high prevalence of genotype 1b hepatitis C virus (HCV) among patients, a cell culture system that permits entire viral life cycle of genotype 1b isolates is limited. To develop a cell-cultured hepatitis C virus (HCVcc) of genotype 1b, the proper combination of HCV genomic variants and host cells is essential. HCV genomes isolated from patients with distinctive symptoms may provide the variants required to establish an HCVcc of genotype 1b. RESULTS: We first established subgenomic replicons in Huh7 cells using HCV cDNAs isolated from two patients: one with fulminant hepatitis after liver transplantation (TPF1) and another with acute hepatitis and moderate symptoms (sAH). Replicons established from TPF1 and sAH showed mutations in NS4B and in NS3 and NS5A, respectively. Using these replication machineries, we constructed HCV genomic RNAs for each isolate. Virus infectivity was evaluated by a focus-forming assay, which is dependent on the intracellular expression of core antigen, and production of virus particles was assessed by density-gradient centrifugation. Infectious virus was only observed in the culture medium of cells transfected with TFP1 HCV RNA. A chimeric genome with the structural segment (5'-untranslated region [UTR] through NS2) from sAH and the replication machinery (NS3 through 3'-UTR) from TPF1 exhibited greater infectivity than did TFP1, despite formation of deficient virus particles in sAH, suggesting that this genomic segment potentiates virus particle formation. To identify the responsible variants, infectious virus formation was assessed in a chimeric genome carrying parts of the sAH structural segment of the TPF1 genome. A variant in NS2 (M170T) was identified that enhanced infectious virus formation. HCVcc carrying an NS2 gene encoding the M170T substitution and adaptive mutations in NS4B (referred to as TPF1-M170T) infected naïve cured Huh7 cells in a CD81-dependent manner. CONCLUSIONS: We established a novel HCVcc of genotype 1b in Huh7 cells by introducing an amino acid variant in NS2 and adaptive mutations in NS4B from HCV genomic RNA isolated from a patient with fulminant HCV after liver transplantation.

Persistent replication of a hepatitis C virus genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B in a New World monkey.

The development of effective hepatitis C virus (HCV) vaccines is essential for the prevention of further HCV dissemination, especially in developing countries. Therefore the aim of this study is to establish a feasible and immunocompetent surrogate animal model of HCV infection that will help in evaluation of the protective efficacy of newly developing HCV vaccine candidates. To circumvent the narrow host range of HCV, an HCV genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B (GBV-B), which is closely related to HCV, was generated. The chimera between HCV and GBV-B, named HCV/G, replicated more efficiently as compared with the HCV clone in primary marmoset hepatocytes. Furthermore, it was found that the chimera persistently replicated in a tamarin for more than 2 years after intrahepatic inoculation of the chimeric RNA. Although relatively low (<200 copies/mL), the viral RNA loads in plasma were detectable intermittently during the observation period. Of note, the chimeric RNA was found in the pellet fraction obtained by ultracentrifugation of the plasma at 73 weeks, indicating production of the chimeric virus. Our results will help establish a novel non-human primate model for HCV infection on the basis of the HCV/G chimera in the major framework of the HCV genome.

Chronic urinary retention could decrease the number of suburothelial myofibroblasts in the rat bladder.

AIMS: To demonstrate changes in the number of suburothelial myofibroblasts in the rat bladder due to chronic urinary retention (CUR). METHODS: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups: a CUR group and a sham-operated group. In the CUR rats, the urethra was intubated with a polyethylene catheter, and a double 4-0 silk ligature was placed around the proximal urethra, after which the catheter was removed. After 8 weeks, the cystometric findings and immunohistochemical staining of the suburothelial myofibroblasts were compared between the groups. RESULTS: The bladder weight of the control rats was 0.20 ± 0.01 g and that of CUR rats 1.6 ± 0.4 g. The bladder capacity of the control rats was 0.5 ± 0.3 ml and that of the CUR rats 12.9 ± 3.1 ml. The number of suburothelial myofibroblasts of the control rats was 417 ± 123 and that of the CUR rats 44 ± 42. The number of suburothelial myofibroblasts in the CUR rats was significantly less than that observed in the sham-operated rats (p < 0.01). CONCLUSIONS: In this study, we demonstrated that mechanical stress over a long period on the bladder wall can decrease the number of suburothelial myofibroblasts. The reduced expression of suburothelial myofibroblasts may be related to prolongation of the micturition interval by CUR.

Assessment of lower urinary tract function in children with Down syndrome.

BACKGROUND: Despite the fact that functional lower urinary tract symptoms are common among people with Down syndrome (DS), their voiding function has not been studied precisely. Our goal was to assess the lower urinary tract functions in DS. METHODS: Fifty-five DS children aged 5-15 years old and 35 age-matched control children were evaluated by ultrasonography and uroflowmetry. RESULTS: Eleven (20%) DS children had no uresiesthesia, 21 (38%) were urinated under guidance, nine (16%) urinated fewer than three times a day, two (4%) urinated more than 10 times a day, three (5%) used diapers, and 26 (47%) had urinary incontinence. Seven (13%), 15 (27%), and 10 (18%) DS children had weak, prolonged and intermittent urination, respectively, and seven (13%) had urination with straining. In contrast, none of the control subjects had urinary problems. In the uroflowmetrical analysis, 10 (18%), 20 (37%), 11 (20%) and five (9%) DS children showed "bell-shaped," "plateau," "staccato" and "interrupted" patterns, respectively; the remaining nine (16%) could not be analyzed. In contrast, 21 (60%), one (3%), four (11%), three (9%) and two (6%) control subjects showed bell-shaped, tower-shaped, plateau, staccato and interrupted patterns, respectively; the remaining four (11%) could not be analyzed. Residual urine was demonstrated in four (7%) DS children and one (3%) control child. CONCLUSIONS: Lower urinary tract symptoms and abnormal uroflowmetry findings, which can lead to further progressive renal and urinary disorders, are common in DS children. Therefore, lower urinary tract functions should be assessed at the life-long regular medical check-ups for subjects with DS.

Myostatin inhibits proliferation of human urethral rhabdosphincter satellite cells.

OBJECTIVES: Myostatin, a member of the transforming growth factor-ß superfamily, is a negative regulator of myogenesis in skeletal muscle. We examined the effect of myostatin and myostatin inhibition by an antagonistic agent, follistatin, on growth of human urethral rhabdosphincter satellite cells (muscle stem cells) to develop a new strategy for treatment of stress urinary incontinence. METHODS: Rhabdosphincter satellite cells were cultured and selected by magnetic affinity cell sorting using an anti-neural cell adhesion molecule antibody. The cells were transfected with simian virus-40 antigen to extend their lifespan. A cell proliferation assay, a cell cycle analysis and an investigation of signal transduction were carried out. The autocrine action of endogenous myostatin by western blotting, real-time reverse transcription polymerase chain reaction and immunoneutralization using an anti-myostatin antibody was also evaluated. RESULTS: Selectively cultured cells expressed markers of striated muscles and successfully differentiated into myotubes. Myostatin inhibited proliferation of these cells through Smad2 phosphorylation and cell cycle arrest. Inhibitory effects of myostatin were reversed by addition of follistatin. However, rhabdosphincter satellite cells did not appear to use autocrine secretion of myostatin to regulate their proliferation. CONCLUSIONS: Inhibition of myostatin function might be a useful pathway in the development of novel strategies for stimulating rhabdosphincter cells regeneration to treat stress urinary incontinence.

α(PS)-γ(Ge) digital anti-coincidence spectroscopy and its application to activity measurement of 225Ac.

Activity of 225Ac was measured by the digital anti-coincidence spectroscopy technique using a 4πα-γ detector configuration, composed of a sandwich type 4π plastic scintillator and Ge detectors. Ultrathin plastic scintillators were used for selective detection of α-particles emitted from 225Ac and its progenies, and the α-counting efficiencies of a 4π plastic scintillation detector for individual nuclides in the decay chain were determined as well. A list-mode multichannel analyzer was employed to record coincidence/anti-coincidence events for off-line analyses. The time difference distribution spectra revealed α-particle emission following 213Po decay without ß-particle interference from 213Bi.

Comprehensive Genome profile testing in head and neck cancer.

OBJECTIVE: Head and neck cancer (HNC) is a tumor occurring in various primary sites with limited chemotherapy options for its treatment. Recently, comprehensive genomic profiling (CGP) testing has become clinically widespread. In this study, we examined the utility of CGP in diagnosing and treating HNC. METHODS: This study included 29 patients with HNC who underwent CGP testing at the Gifu University Hospital between December 2019 and April 2022. We analyzed the types of gene mutations and tumor mutational burden (TMB) based on the CGP results. Squamous cell carcinoma accounted for 55.2%, and other cancers accounted for 44.8%. And we investigated the correlation of prognosis with gene mutations and TMB. RESULTS: Gene mutations were detected in TP53(48.3%), CDKN2A (27.6%), CDKN2B (17.2%), NOTCH1 (17.2%), PIK3CA (17.2%), ARID1A (13.8%), and NF1 (13.8%). TP53, CDKN2A and CDKN2B mutations significantly decreased survival rate in HNC. Five cases (17.2%) were TMB-high and 82.8% were TMB-low. In SCC cases treated with immune checkpoint inhibitors, TMB-high had better Overall survival than TMB-low. And all patients with TMB-high were oropharyngeal cancer. CONCLUSION: Although there were no cases in which effective treatment was actually performed based on the results of CGP, many gene mutations have been detected and several gene mutations correlated with prognosis. Furthermore, TMB can be used as a biomarker to predict the therapeutic effects of immune checkpoint inhibitors in cases of SCC.

Changes in angiotensin II type 1 receptor expression in the rat bladder by bladder outlet obstruction.

PURPOSE: To demonstrate the change in the expression of angiotensin II type 1 receptor (AT1) in the rat bladder with partial bladder outlet obstruction (P-BOO). MATERIALS AND METHODS: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups, a P-BOO group and a control group. The rats of the P-BOO group were divided into six groups: a sham-operated control group, 1 day postoperatively, 2 days postoperatively, 4 days postoperatively, 7 days postoperatively and 14 days postoperatively. The cystometric findings and immunohistochemical staining of the detrusor muscle with the AT1 antibody were compared in each group. RESULTS: AT1 localized on the cell membrane of the detrusor smooth muscle and in cytoplasm of suburothelial myofibroblasts in the control rats. The expression of AT1 disappeared in the detrusor muscle and suburothelial myofibroblasts in P-BOO, but AT1 was highly expressed in urothelial cells 1 day after surgery. The expression of AT1 in urothelial cells gradually decreased with time after surgery. AT1 completely disappeared in urothelial cells 14 days after surgery. CONCLUSIONS: The present study demonstrated that the site of AT1 expression changes in response to the mechanical stress caused by P-BOO, and finally there was no expression of AT1 in rat bladder tissue following P-BOO. These data suggest the change in AT1 expression may play a role in bladder function.

Production of infectious hepatitis C virus by using RNA polymerase I-mediated transcription.

In this study, we used an RNA polymerase I (Pol I) transcription system for development of a reverse genetics protocol to produce hepatitis C virus (HCV), which is an uncapped positive-strand RNA virus. Transfection with a plasmid harboring HCV JFH-1 full-length cDNA flanked by a Pol I promoter and Pol I terminator yielded an unspliced RNA with no additional sequences at either end, resulting in efficient RNA replication within the cytoplasm and subsequent production of infectious virions. Using this technology, we developed a simple replicon trans-packaging system, in which transient transfection of two plasmids enables examination of viral genome replication and virion assembly as two separate steps. In addition, we established a stable cell line that constitutively produces HCV with a low mutation frequency of the viral genome. The effects of inhibitors of N-linked glycosylation on HCV production were evaluated using this cell line, and the results suggest that certain step(s), such as virion assembly, intracellular trafficking, and secretion, are potentially up- and downregulated according to modifications of HCV envelope protein glycans. This Pol I-based HCV expression system will be beneficial for a high-throughput antiviral screening and vaccine discovery programs.

The long-term prognosis of nephropathy in operated reflux.

OBJECTIVE: To investigate the postoperative long-term prognosis and the factors predicting the renal function of patients with reflux nephropathy. As the serum creatinine (s-Cr) level tends to increase during infancy, the degree of reflux and renal parenchymal damage are thought to be more important factors in pediatric patients than in older patients. MATERIALS AND METHODS: This study examined s-Cr, urinary protein, and blood pressure of patients who underwent anti-reflux surgery 10 years before. It also calculated the postoperative estimated glomerular filtration rate (eGFR) and examined the correlation between the eGFR and preoperative factors (age, gender, number of urinary tract infections [UTIs], primary diagnosis, reflux grade, percentage of dimercaptosuccinic acid uptake, degree of renal parenchymal damage, s-Cr abnormality, proteinuria, and hypertension), and analyzed the factors associated with the long-term prognosis. RESULTS: The study population was 51 infants (37 boys and 14 girls). The mean age of the patients before surgery and at the follow-up examination was 3.41 ± 3.61 and 14.63 ± 3.74 years, respectively. After surgery, the s-Cr, urinary protein, and blood pressure values showed (44.7%, 26.7%, and 18.2%, respectively) were abnormal. The postoperative eGFR was a mean 90.27 ± 20.42 ml/min/1.73 m2 and primary correlated with an older age (P = 0.0361), no UTI at the primary diagnosis (P = 0.0044), reflux grade ≥8 (P = 0.0180), degree of renal parenchymal damage (group ≥2b, P < 0.0001), s-Cr abnormality (P < 0.0001), and proteinuria (P = 0.0001) at baseline. A total of 20 patients had chronic kidney disease (CKD; Fig. 1). The multiple regression analysis of these factors revealed that an older age (P = 0.0021), reflux grade ≥8 (P = 0.0134), and degree of renal parenchymal damage (group ≥2b, P < 0.0001) were significantly associated with the long-term postoperative prognosis of reflux nephropathy. Using these three factors, this study derived a multiple regression equation estimating eGFR in the 10th year after surgery (Fig. 1). DISCUSSION: In this study, severe vesico-ureteral reflux (reflux grade ≥8) and severe renal parenchymal damage (group ≥2b) were associated with a long-term decrease in the eGFR. In particular, renal parenchymal damage was closely correlated with the postoperative eGFR; thus, this was clearly a critical factor. The age at surgery showed a better correlation with the postoperative eGFR in the multiple regression analysis; thus, age was regarded as an independent prognostic factor. CONCLUSIONS: The age, reflux grade, and degree of renal parenchymal damage at baseline were factors that affected the long-term postoperative prognosis of reflux nephropathy. Patients with high-grade reflux and severe renal parenchymal damage were more likely to show a reduced CKD level at 10 years after anti-reflux surgery.

Variety of congenital urethral lesions in boys with lower urinary tract symptoms and the results of endoscopic treatment.

OBJECTIVES: We described various types of congenital urethral anomalies seen in boys with LUTS such as refractory enuresis. Their urethrograpic and endoscopic finding were reviewed and the effect of trans-urethral incision (TUI) was analyzed. PATIENTS AND METHODS: We evaluated 67 boys with lower urinary tract symptoms (LUTS, mean: 9 years old), in a period of three and a half years. A voiding cystourethrogram (VCUG) was performed in 37 patients and if we suspected a urethral abnormality, endoscopy was performed. Congenital urethral obstruction was diagnosed from VCUG and endoscopic findings and classified into Types 1, 3 and 4 posterior urethral valves (PUV) according to Douglas Stephens' description. Trans-urethral incision (TUI) was carried out for congenital urethral obstruction and the effect was judged three months later. RESULTS: On VCUG, 17 patients (45.8%) had an abnormal urethral configuration. On endoscopy, nine patients (24.3%) were diagnosed as having PUV. The effect of TUI on PUV excluding Type 3 was 80%, while that on Type 3 was 25%. DISCUSSIONS: The incidence of PUV compared to bulbar urethral narrowing was significantly different from that described in previous Japanese reports, but similar to other countries. The reason is thought to be the lack of standardized interpretations of VCUG images and endoscopic findings, resulting in the overestimation of the bulbar urethral lesion. CONCLUSION: The incidence of PUV in Japanese boys with LUTS was higher than had ever been described. The improvement rate by TUI was high in PUV excluding Type 3, but low in Type 3. The ring like strictures at the bulbar urethra may be less important than has previously been thought.

GBV-B as a pleiotropic virus: distribution of GBV-B in extrahepatic tissues in vivo.

GB virus B (GBV-B) infection of New World monkeys is considered to be a useful surrogate model for hepatitis C virus (HCV) infection. GBV-B replicates in the liver and induces acute resolving hepatitis but little is known whether the other organs could be permissive for the virus. We investigated the viral tropism of GBV-B in tamarins in the acute stage of viral infection and found that the viral genomic RNA could be detected in a variety of tissues. Notably, a GBV-B-infected tamarin with marked acute viremia scarcely showed a sign of hepatitis, due to preferential infection in lymphoid tissues such as lymph nodes and spleen. These results indicate that GBV-B as well as HCV is a pleiotropic virus in vivo.

Patient-reported postoperative pain, body image, and cosmetic satisfaction after transumbilical laparoendoscopic single-site adrenalectomy.

INTRODUCTION: Laparoendoscopic single-site surgery is a recently innovated urologic surgical procedure. Transumbilical laparoendoscopic single-site adrenalectomy (LESS-A) is technically safe and feasible in patients with benign adrenal tumors. To improve patient counseling and informed consent, we evaluated patient-reported postoperative pain, body image, and cosmetic satisfaction after transumbilical LESS-A. METHODS: We reviewed 24 patients who underwent transumbilical LESS-A and assessed their operative and esthetic outcomes and incisional pain. Incisional pain was evaluated using a 10-point visual analog scale, and the body image and cosmetic satisfaction were measured using a questionnaire that included a body image scale (range, 5-20 points) and a cosmetic scale (range, 3-24 points). RESULTS: Pure LESS-A was performed on 10 patients using a multichannel port; an additional 5-mm trocar was used in two obese patients. Supplementary to the single-incision approach, one or two 3-mm ports were used in 12 patients. The mean operative time was 203 min; the mean blood loss was 41 mL. The mean pain visual analog scale scores on postoperative days 1, 3, and 7 were 3.5, 2.2 (P = 0.012), and 1.5 points (P = 0.018), respectively. The mean body image scale and cosmetic scale scores indicating wound satisfaction 1 month after the surgery were 20 and 22 points, respectively. Although one patient had liver injury during surgery, the postoperative course during the 3-month follow-up was uneventful. CONCLUSION: Transumbilical LESS-A confers less postoperative pain and better cosmetic satisfaction than conventional laparoscopic adrenalectomy. Therefore, this procedure could potentially become a standard treatment option for benign adrenal tumors.

Natural course of voiding function in patients with human T-cell lymphotrophic virus type 1-associated myelopathy.

OBJECTIVES: Patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) frequently experience voiding dysfunction. In patients with HAM/TSP, the major symptoms are gait disturbance and voiding dysfunction. However, the detailed natural course of voiding function and the management of their urination has not previously been investigated. We examined the correlation between voiding function and clinical features and evaluated the management of urination, in the patients with HAM/TSP. PATIENTS AND METHODS: The voiding function of 47 patients (7 males, 40 females, aged 29-89 years, mean: 60.9 years) with HAM/TSP was analyzed retrospectively. All HAM/TSP patients are positive for HTLV-1. Patients were referred to a neurologist for analysis of bladder function. In the present study, we analyzed their clinical details, age at disease onset, voiding function and alterations in the management of their urination. Furthermore, we investigated the relationship between urological management and the clinical features of HAM/TSP. RESULTS: Of the 47 patients, 20 (42.5%) were able to void with or without drug therapy. Thirty-four (72.3%) experienced clean intermittent self-catheterization (CIC), with 25 of these 34 continuing CIC, 7 changing to voiding and 2 changing to management with the Foley catheter. No relationship was noted between disruption of voiding function and either age or gender. However, significant inverse correlation was observed between the age at disease onset and the time to CIC (r=-0.77, P=0.00001). CONCLUSIONS: These data suggest that the younger a patients is at HAM/TSP onset, the longer voiding function will be maintained.

The preventive effect of green tea on the gap junction intercellular communication in renal epithelial cells treated with a renal carcinogen.

OBJECTIVE: Clinical studies imply that (-)-epigallocatechin-3-gallate (EGCG), a main ingredient of green tea catechins, has a chemopreventive action against cancers and suppresses the proliferation of cancer cells. However, there is no report about its chemopreventive effect for renal cancer. We previously determined that renal carcinogens suppressed the gap junction intercellular communication (GJIC) of renal epithelial cells. In this study, we investigated the effect of EGCG on the GJIC of renal epithelial cells treated with a renal carcinogen. MATERIALS AND METHODS: Mardin-Darby canine kidney (MDCK) cells were used to determine the protective effects of EGCG on dimethylnitrosamine-induced alteration of GJIC and connexin 43 (Cx 43). The maximum concentration of EGCG was determined by the lactate dehydrogenase assay method. The scrape-loading dye transfer method was used to assess the expression and cellular localization of Cx 43. The phosphorylation status of Cx 43 was determined by Western blot analysis. RESULTS: The optimal noncytotoxic concentration of EGCG was determined to be 10 microg/ml. The levels of GJIC and Cx 43 expression were markedly decreased in MDCK cells exposed to dimethylnitrosamine. A 12-h pretreatment with EGCG greatly ameliorated the GJIC-inhibitory effects of dimethylnitrosamine. CONCLUSION: These results suggest that the preservation of GJIC may indicate the chemopreventive effect of green tea on renal epithelial cells treated with a renal carcinogen in vitro.

Upregulation of Angiotensin II Receptor and Connexin 43 in Increased Suburothelial Myofibroblasts in the Rat Inflammatory Bladder.

OBJECTIVES: Signaling pathways in suburothelial layer are involved in the bladder sensory response. The expression of angiotensin II type 1 (AT1) receptors and connexin 43 (Cx43) in suburothelial myofibroblasts was investigated in an acute bladder inflammation model. METHODS: Adult female Wistar rats underwent urethral catheterization and received 0.2 mL intravesical infusion of 0.4 M HCl to establish acute bladder inflammation model or 0.2 mL of sterile saline as control (n = 10 rats/group). Eight days after treatment, cystometry was performed. Suburothelial myofibroblasts were also collected and subjected to immunohistochemical staining to examine AT1 receptor and Cx43 expression. RESULTS: Eight days after treatment with HCl to induce acute bladder inflammation, the frequency and basal pressure of the bladder was significantly increased compared with those in control rats. The number of suburothelial myofibroblasts was significantly increased in acute bladder inflammation rats, as was the expression of AT1 receptor and Cx43. CONCLUSION: These results suggest that the increased number of suburothelial myofibroblasts, upregulation of AT1 receptor and Cx43 expression may be associated with the pathogenesis of hyperactivation of bladder sensory signaling pathways in acute inflammatory bladder.

Use of procalcitonin in patients on chronic hemodialysis: procalcitonin is not related with increased serum calcitonin.

Objectives. To investigate whether procalcitonin (PCT) could be useful for detecting bacterial infections in patients on hemodialysis (HD) and with increased calcitonin (CT). Methods. This prospective study included 42 males and 34 females on HD. The infection group consisted of 15 patients with proven bacterial infections; the other 61 patients were designated as the noninfection group. Serum C-reactive protein (CRP), interleukin (IL)-6, white blood cell (WBC) count, immature and total neutrophil (I/T) ratio, and CT were measured at the beginning of HD, and serum PCT levels at the beginning of HD and after HD. Results. The mean CT level in the both groups was apparently higher than that of nonchronic kidney disease. Significantly higher values between the infection and noninfection groups were seen for CRP, IL-6, WBC, I/T ratio, PCT, and CT. The PCT value of the area under the receiver operating characteristic curve was 0.921, which was significantly higher than the values for CRP (0.853; P < 0.01), IL-6 (0.739; P < 0.01), WBC (0.692; P < 0.01), and I/T ratio (0.584; P < 0.01). Conclusions. PCT was useful marker of bacterial infection in patients on HD and with increased CT. PCT levels should be determined before HD.

Expression of Angiotensin II Type 1 Receptor in Rat Bladder Smooth Muscle Cells in Response to a Streptzotocin Induced Diabetes Mellitus Model.

INTRODUCTION: The aim of this study was to investigate angiotensin II type 1 (AT1) receptors in rat bladder smooth muscle cells and alterations of AT1 receptors by diabetes mellitus and diuretic states. MATERIALS AND METHODS: Diabetes and diuresis were induced in adult female rats by a single intraperitoneal injection of streptozotocin and feeding 5% sucrose in water. Cystometry was performed on control, diuretic, and diabetic rats at 2 and 8 weeks after treatment. Immunohistochemical staining was used to detect expression of AT1 receptors in the bladder smooth muscle cell membrane. RESULTS AND CONCLUSIONS: In diabetic rats, expression of AT1 receptors in the bladder smooth muscle cell membrane increased at 2 weeks and further increased at 8 weeks. The local renin-angiotensin system in the rat bladder might be activated by the continuous hyperglycemia caused by intraperitoneal injection of streptozotocin administration.