Expansion of Myeloid-Derived Suppressor Cells Correlates with Renal Progression in Type 2 Diabetic Nephropathy

Type 2 diabetic nephropathy (T2DN) progresses with an increasingly inflammatory milieu, wherein various immune cells are relevant. Herein, we investigated the levels of myeloid-derived suppressor cells (MDSCs) and their clinical implication in patients with T2DN. A total of 91 subjects (T2DN, n=80; healthy, n=11) were recruited and their PBMCs were used for flow cytometric analysis of polymorphonuclear (PMN-) and monocytic (M-) MDSCs, in addition to other immune cell subsets. The risk of renal progression was evaluated according to the quartiles of MDSC levels using the Cox model. The proportion of MDSCs in T2DN patients was higher than in healthy individuals (median, 6.7% vs. 2.5%). PMN-MDSCs accounted for 96% of MDSCs, and 78% of PMN-MDSCs expressed Lox-1. The expansion of PMN-MDSCs was not related to the stage of T2DN or other kidney disease parameters such as glomerular filtration rate and proteinuria. The production of ROS in PMN-MDSCs of patients was higher than in neutrophils of patients or in immune cells of healthy individuals, and this production was augmented under hyperglycemic conditions. The 4th quartile group of PMN-MDSCs had a higher risk of renal progression than the 1st quartile group, irrespective of adjusting for multiple clinical and laboratory variables. In conclusion, PMN-MDSCs are expanded in patients with T2DN, and may represent as an immunological biomarker of renal progression.

Effect of the Sodium-Glucose Cotransporter 2 Inhibitor, Dapagliflozin, on Genitourinary Infection in an Animal Model of Type 2 Diabetes / 대한배뇨장애요실금학회지

Purpose@#To investigate the effect of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, on inflammatory cytokines of urogenital tissue in a rat model of type 2 diabetes (T2DM) to infer pharmaceutical influence of dapagliflozin on genitourinary infection or inflammation. @*Methods@#Study animals were divided into the following 4 groups of 10 animals each: (1) the Otsuka Long-Evans Tokushima Fatty (OLETF)-DA group treated with dapagliflozin at 1.0 mg/kg/day, (2) the OLETF-VO group treated with voglibose at 0.6 mg/kg/day, (3) the control group (OLETF-CO) given water, and (4) the Long-Evans Tokushima Otsuka (LETO) rats were included as nondiabetic control group. Changes in blood glucose, 24-hour urine volume, and urine glucose were measured. The interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels in the bladder and the urethra were quantified, respectively. @*Results@#The urine glucose level and the 24-hour urine volume at 12 weeks of treatment were significantly higher in the OLETF-DA group than that in any other group (P<0.05). The cytokine analysis of the bladder and urethra showed higher IL18 and IL-1β in the OLETF-DA and the OLETF-CO groups than that in the OLETF-VO and LETO groups (P<0.05). The cytokine levels did not differ between the OLETF-DA and the OLETF-CO groups, and the level of IL-18 in the OLETF-DA group was higher in the urethra than in the bladder. @*Conclusions@#This study revealed that dapagliflozin increased the urine glucose concentration, resulting in an inflammatory response remain in the urogenital tract as the untreated diabetic rats. Therefore, when treating patients with T2DM with dapagliflozin, careful attention should be paid to genitourinary infection or inflammation.

In vivo validation of metastasis-regulating microRNA-766 in human triple-negative breast cancer cells / 한국실험동물학회지

Breast cancer is the second most common cancer and the most frequent cancer in women worldwide. Recent improvements in early detection and effective adjuvant chemotherapies have improved the survival of breast cancer patients. Even with initial disease remission, one-third of all breast cancer patients will relapse with distant metastasis. Breast cancer metastasis is largely an incurable disease and the main cause of death among breast cancer patients. Cancer metastasis is comprised of complex processes that are usually not controllable by intervention of a single molecular target. As a single microRNA (miRNA) can affect the aggressiveness of breast cancer cells by concurrently modulating multiple pathway effectors, a metastasis-regulating miRNA would represent a good disease target candidate. In this study, we evaluated the functional capacity of a newly defined human metastasis-related miRNA, miR-766, which was previously identified by comparing a patient-derived xenograft primary tumor model and a metastasis model. Compared to vector-transfected control cells, miR-766-overexpressed triple-negative breast cancer cells exhibited similar primary tumor growth in the orthotopic xenograft model. In contrast, tumor sphere formation and Matrigel invasion were significantly decreased in miR-766-overexpressed breast cancer cells compared with control cancer cells. In addition, lung metastasis was dramatically reduced in miR-766-overexpressed breast cancer cells compared with control cells. Thus, miR-766 affected the distant metastasis process to a greater extent than cancer cell proliferation and primary tumor growth, and may represent a future therapeutic target to effectively control fatal breast cancer metastasis.

Murine Sca1+Lin- bone marrow contains an endodermal precursor population that differentiates into hepatocytes

The direct differentiation of hepatocytes from bone marrow cells remains controversial. Several mechanisms, including transdifferentiation and cell fusion, have been proposed for this phenomenon, although direct visualization of the process and the underlying mechanisms have not been reported. In this study, we established an efficient in vitro culture method for differentiation of functioning hepatocytes from murine lineage-negative bone marrow cells. These cells reduced liver damage and incorporated into hepatic parenchyma in two independent hepatic injury models. Our simple and efficient in vitro protocol for endodermal precursor cell survival and expansion enabled us to identify these cells as existing in Sca1+ subpopulations of lineage-negative bone marrow cells. The endodermal precursor cells followed a sequential developmental pathway that included endodermal cells and hepatocyte precursor cells, which indicates that lineage-negative bone marrow cells contain more diverse multipotent stem cells than considered previously. The presence of equivalent endodermal precursor populations in human bone marrow would facilitate the development of these cells into an effective treatment modality for chronic liver diseases.

Tissue transglutaminase-interleukin-6 axis facilitates peritoneal tumor spreading and metastasis of human ovarian cancer cells / 한국실험동물학회지

Inflammation has recently been implicated in cancer formation and progression. As tissue transglutaminase (TG2) has been associated with both inflammatory signaling and tumor cell behavior, we propose that TG2 may be an important link inducing interleukin-6 (IL-6)-mediated cancer cell aggressiveness, including cancer stem cell-like characteristics and distant hematogenous metastasis. We evaluated the effect of differential TG2 and IL-6 expression on in vivo distant metastasis of human ovarian cancer cells. IL-6 production in human ovarian cancer cells was dependent on their TG2 expression levels. The size and efficiency of tumor sphere formation were correlated with TG2 expression levels and were dependent on TG2-mediated IL-6 secretion in human ovarian cancer cells. Primary tumor growth and propagation in the peritoneum and distant hematogenous metastasis into the liver and lung were also dependent on TG2 and downstream IL-6 expression levels in human ovarian cancer cells. In this report, we provide evidence that TG2 is an important link in IL-6-mediated tumor cell aggressiveness, and that TG2 and downstream IL-6 could be important mediators of distant hematogenous metastasis of human ovarian cancer cells. Intervention specific to TG2 and/or downstream IL-6 in ovarian cancer cells could provide a promising means to control tumor metastasis.

Osteopontin Potentiates Pulmonary Inflammation and Fibrosis by Modulating IL-17/IFN-gamma-secreting T-cell Ratios in Bleomycin-treated Mice

Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPN-deficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of CD4+ alphabeta T cells and IL-17-producing gammadelta T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of CD4+ alphabeta T cells and the percentage of IFN-gamma-producing gammadelta T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in CD4+ T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-gamma T cells.

Kinetics of IFN-gamma and IL-17 Production by CD4 and CD8 T Cells during Acute Graft-versus-Host Disease

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-gamma and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 --> BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 --> BALB.B GVHD model, we showed that the production of IFN-gamma and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-gamma and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

Microbiological Characteristics of Acute Prostatitis After Transrectal Prostate Biopsy

PURPOSE: We aimed to identify microbiological characteristics in patients with acute prostatitis after transrectal prostate biopsy to provide guidance in the review of prevention and treatment protocols. MATERIALS AND METHODS: A retrospective analysis of medical records was performed in 1,814 cases who underwent prostate biopsy at Seoul St. Mary's Hospital and St. Vincent's Hospital over a 5 year period from 2006 to 2011. Cases in which acute prostatitis occurred within 7 days after the biopsy were investigated. Before starting treatment with antibiotics, sample collections were done for culture of urine and blood. Culture and drug susceptibility was identified by use of a method established by the Clinical and Laboratory Standards Institute. RESULTS: A total of 1,814 biopsy procedures were performed in 1,541 patients. For 1,246 patients, the procedure was the first biopsy, whereas for 295 patients it was a repeat biopsy. Twenty-one patients (1.36%) were identified as having acute bacterial prostatitis after the biopsy. Fifteen patients (1.2%) had acute prostatitis after the first biopsy, and 6 patients (2.03%) experienced acute prostatitis after a repeat biopsy. Even though the incidence of acute bacterial prostatitis was higher after repeat biopsy than that after the first biopsy, there was no statistically significant intergroup difference in terms of incidence (chi2=1.223, p=0.269). When the collected urine and blood samples were cultured, Escherichia coli was found in samples from 15 patients (71.4%), Klebsiella pneumoniae in 3 patients (14.3%), Enterobacter intermedius in 1 patient (4.8%), E. aerogenes in 1 patient (4.8%), and Pseudomonas aeruginosa in 1 patient (4.8%). A fluoroquinolone-resistant strain was confirmed in 5 cases (23.8%) in total. Three cases of E. coli and 1 case of Klebsiella had extended-spectrum beta-lactamase activity. CONCLUSIONS: Empirical treatment of acute prostatitis should be done with consideration of geographical prevalence and drug resistance. This study will provide meaningful information for the management of acute prostatitis after transrectal prostate biopsy.

CP-690550 Treatment Ameliorates Established Disease and Provides Long-Term Therapeutic Effects in an SKG Arthritis Model

Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-gamma, and IL-6 and increased level of immunoregulatory IL-10.

Establishment of High Throughput Screening System Using Human Umbilical Cord-derived Mesenchymal Stem Cells

The use of high throughput screening (HTS) in drug development is principally for the selection new drug candidates or screening of chemical toxicants. This system minimizes the experimental environment and allows for the screening of candidates at the same time. Umbilical cordderived stem cells have some of the characteristics of fetal stem cell and have several advantages such as the ease with which they can be obtained and lack of ethical issues. To establish a HTS system, optimized conditions that mimic typical cell culture conditions in a minimal space such as 96 well plates are needed for stem cell growth. We have thus established a novel HTS system using human umbilical cord derived-mesenchymal stem cells (hUC-MSCs). To determine the optimal cell number, hUC-MSCs were serially diluted and seeded at 750, 500, 200 and 100 cells per well on 96 well plates. The maintenance efficiencies of these dilutions were compared for 3, 7, 9, and 14 days. The fetal bovine serum (FBS) concentration (20, 10, 5 and 1%) and the cell numbers (750, 500 and 200 cells/well) were compared for 3, 5 and 7 days. In addition, we evaluated the optimal conditions for cell cycle block. These four independent optimization experiments were conducted using an MTT assay. In the results, the optimal conditions for a HTS system using hUC-MSCs were determined to be 300 cell/well cultured for 8 days with 1 or 5% FBS. In addition, we demonstrated that the optimal conditions for a cell cycle block in this culture system are 48 hours in the absence of FBS. In addition, we selected four types of novel small molecule candidates using our HTS system which demonstrates the feasibility if using hUC-MSCs for this type of screen. Moreover, the four candidate compounds can be tested for stem cell research application.

Safety and Efficacy of Bearxat(R)XL Tablet (alfuzosin 10 mg) in Patients with Benign Prostatic Hyperplasia: A Prospective Multicenter Study of Primary Care Clinics / 대한남성과학회지

PURPOSE: A prospective multi-center study was conducted to evaluate the safety and efficacy of alfuzosin (10 mg), for male lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in primary care clinics. MATERIALS AND METHODS: Three hundred twenty-four patients with complaints of LUTS associated with BPH were enrolled from 17 clinics. Patients received a 12-week course of 10 mg alfuzosin (Bearxat(R)XL Tablet) once daily, and underwent follow-up at 2~4 and 12 weeks post-treatment. The maximum flow rate (Qmax) and residual urine volume (RUV) were measured at each visit. The International Prostate Symptom Score (IPSS), Quality of Life (QoL), and International Index of Erectile Function (IIEF-5) were evaluated at baseline and post-treatment. During the study period, the presence of orthostatic hypotension was evaluated by blood pressure measurement before and after a postural change. Any adverse effects of alfuzosin including retrograde ejaculation were assessed. RESULTS: Of the 324 enrolled patients, 62 (19.1%) patients dropped out and a total of 262 patients were evaluated. Each value of Qmax, RUV, IPSS, QoL, and IIEF-5 was significantly improved from 14.19+/-8.85 ml/sec, 41.10+/-81.44 ml, 18.04+/-7.36, 3.81+/-0.86, and 11.75+/-6.91, respectively, at baseline, to 15.68+/-6.25 ml/sec, 24.29+/-29.46 ml, 12.19+/-5.59, 2.54+/-0.91, and 12.33+/-7.55, respectively, at end-point. Retrograde ejaculation was found in 2 patients (2/255, 0.78%) at 2~4 weeks and 1 patient (1/152, 0.66%) at 12 weeks. The frequency of orthostatic hypotension was 13.27% (30/226) at baseline, 13.11% (27/206, p=0.8658) at 2~4 weeks, and 14.29% (19/133, p=0.8348) at end-point. The number of patients with adverse events was 36 where the number of adverse events was 60. Among those 60 adverse events, 8 events were related to treatment, which consisted of headache (2), dizziness (2), palpitation (1), voiding difficulty (1), erectile dysfunction (1), and arthralgia (1). CONCLUSIONS: Treatment with alfuzosin (10 mg) once daily led to significant improvements in LUTS associated with BPH and QoL in primary care clinic patients. alfuzosin (10 mg) use resulted in few hypotensive events, no deleterious effect on sexual function, and no drug related SAEs during the study. The study findings suggest that alfuzosin (10 mg) can be safely prescribed in primary care clinics for male LUTS with efficacy.

Preliminary Report about the Efficacy of Prototype Pressure Sensor for the Real-Time Intravesical Pressure Monitoring in the Rabbit / 대한남성과학회지

PURPOSE: To maintain physiologic intravesical pressure is important in preventing secondary renal functional impairment in patients with voiding problems like neurogenic bladder or severe bladder outlet obstruction. Therefore, if real-time monitoring of the intravesical pressure were possible, physicians could not only monitor voiding status more precisely but also manage patients with voiding problems appropriately to protect renal function. In this study, we evaluate the validity of the prototype intravesical pressure sensor in a rabbit model. MATERIALS AND METHODS: The manufactured prototype intravesical pressure sensor was placed into the intravesical space of each of 3 rabbits. Conventional cystometry was performed and the intravesical pressure was measured by the prototype intravesical pressure sensor at the same time in all of the animals. The measured intravesical pressure by the prototype intravesical pressure sensor was compared with the measured value by conventional cystometry. The reliability between the two methods was determined using cross-table analysis. RESULTS: In each of the 3 animals, the index of coincidence was observed as 0.70, 0.79, and 0.77, respectively. This result meant that the intravesical pressure monitoring by the prototype intravesical pressure sensor showed good reproducibility with respect to the continuous intravesical pressure monitoring by conventional cystometry. CONCLUSIONS: In this study, we demonstrated the reliability of the prototype intravesical pressure sensor to monitor intravesical pressure change compared with the conventional cystometric result. Further investigations to overcome the limitations of the prototype intravesical pressure sensor will be necessary for real clinical application.

The Prevalence and Clinical Significance of Urethritis and Cervicitis in Asymptomatic People by Use of Multiplex Polymerase Chain Reaction

PURPOSE: Our purpose was to conduct a screening test for urethritis or cervicitis as a sexually transmitted disease (STD) by using multiplex polymerase chain reaction(PCR) and to determine the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis in asymptomatic people. MATERIALS AND METHODS: From July 2010 to December 2010, 709 persons who came to the hospital for a general checkup were tested. Multiplex PCR assays were done with first voided urine samples or endocervical swabs by use of the Seeplex(R) STD6 ACE Detection kit. RESULTS: The mean age in this study was 45.4+/-8.1 years. Among the 709 persons, 229 (32.3%) had a positive result for at least one microorganism, 48 (6.8%) had two different species, 6 (0.8%) had three different species, and 1 person had four different species. The overall prevalence of asymptomatic STDs such as urethritis or cervicitis was 7.1% (50/709). The prevalence rates of chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis infection in asymptomatic persons were 5.6% (40/709), 0.4% (3/709), 0.3% (2/709), 22.1% (157/709), 11.6% (82/709), and 1.1% (8/709), respectively. CONCLUSIONS: With only a single sample, we could identify the prevalence rates of six microorganisms and the overall proportion of urethritis or cervicitis in asymptomatic people. This proportion cannot be neglected; therefore, screening tests for sexually transmitted diseases such as urethritis or ervicitis should be recommended to asymptomatic people.

Maturation-Resistant Dendritic Cells Ameliorate Experimental Autoimmune Uveoretinitis

BACKGROUND: Endogenous uveitis is a chronic inflammatory eye disease of human, which frequently leads to blindness. Experimental autoimmune uveoretinitis (EAU) is an animal disease model of human endogenous uveitis and can be induced in susceptible animals by immunization with retinal antigens. EAU resembles the key immunological characteristics of human disease in that both are CD4+ T-cell mediated diseases. Dendritic cells (DCs) are specialized antigen-presenting cells that are uniquely capable of activating naive T cells. Regulation of immune responses through modulation of DCs has thus been tried extensively. Recently our group reported that donor strain-derived immature DC pretreatment successfully controlled the adverse immune response during allogeneic transplantation. METHODS: EAU was induced by immunization with human interphotoreceptor retinoid-binding protein (IRBP) peptide(1-20). Dendritic cells were differentiated from bone marrow in the presence of recombinant GM-CSF. RESULTS: In this study, we used paraformaldehyde-fixed bone marrow-derived DCs to maintain them in an immature state. Pretreatment with fixed immature DCs, but not fixed mature DCs, ameliorated the disease progression of EAU by inhibiting uveitogenic CD4+ T cell activation and differentiation. CONCLUSION: Application of iBMDC prepared according to the protocol of this study would provide an important treatment modality for the autoimmune diseases and transplantation rejection.

Intratumoral Administration of Secondary Lymphoid Chemokine and Unmethylated Cytosine-phosphorothioate-guanine Oligodeoxynucleotide Synergistically Inhibits Tumor Growth in Vivo

Secondary lymphoid tissue chemokine (SLC), which is expressed in T cell zones of secondary lymphoid organs, including the spleen and lymph nodes, strongly recruits both T lymphocytes and mature dendritic cells. As appropriate interaction of tumor-specific T cells and mature dendritic cells, equipped with tumor antigens, is a prerequisite for effective T cell immunity against established tumors, we mobilized lymphocytes and dendritic cells to tumor sites by intratumoral injection of secondary lymphoid tissue chemokine-Fc (SLC-Fc) fusion protein using the B16F10 murine melanoma model. Activation of dendritic cells, another prerequisite for the effective activation of naive tumor-specific T cells, was achieved by the addition of immunostimulatory cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG-ODN) into the tumor site. Intratumoral administration of SLC-Fc or CpG-ODN revealed antitumor effects against B16F10 murine melanoma grown in the subcutaneous space. Co-treatment of SLC-Fc and CpG-ODN displayed synergistic effects in reducing the tumor size. The synergistic antitumor effect in co-treatment group was correlated with the synergistic/additive increase in the infiltration of CD4+ T cells and CD11c+ dendritic cells in the tumor mass compared to the single treatment groups. These results suggest that the combined use of chemokines and adjuvant molecules may be a possible strategy in clinical tumor immunotherapy.

Measurement of Bladder Volume Using an Implantable Volume Sensor in Rats / 대한남성과학회지

PURPOSE: Real-time monitoring of urinary bladder volume can not only provide information on urinary bladder function more precisely in laboratories and in the setting of intravesical pressure monitoring, but can also help areflexic neurogenic bladder patients have notice of the timing for optimal urination to prevent secondary complications. Thus we introduce a new implantable bladder volume monitoring device and its usefulness. MATERIALS AND METHODS: Ten male Sprague-Dawley rats were used under intraperitoneal anesthesia. Two microelectrodes produced by a micro-electrical-mechanical systems (MEMS) process were stitched onto each side wall of the urinary bladder and 25 G needles were inserted through the bladder dome. The distances between two microelectrodes converted from capacitances recorded by LCR meter were monitored in real-time during cystometry. Urinary bladder volume was estimated with its shape approximated as a sphere. RESULTS: Estimated bladder volume correlated well statistically with infused volume in (p0.05, repeated measures ANOVA). CONCLUSIONS: In our animal model, an implantable volume-monitoring device produced reliable data. Therefore, we expect that it should be an excellent tool for detecting urinary bladder volume and producing more accurate and useful information during urodynamic laboratory studies with small animals. Furthermore, we expect that this study will be the foundation of research for the clinical application of bladder volume monitoring devices to areflexic neurogenic bladder patients.

Biocompatibility of Parylene-C as a Coating Material of Implantable Bladder Volume Sensor / 대한남성과학회지

PURPOSE: Development of an implantable bladder volume sensor that could reduce complications and improve the quality of life for neurogenic bladder patients is assignment task that falls in the field of urology. Nevertheless, there is lack of research on whether biomaterials are biocompatible to the urinary bladder or not. Polyethylene glycol (PEG), polydimethylsiloxane (PDMS) and parylene-C are well known biocompatible materials in other fields of medicine. Because PEG is biodegradable and PDMS has a relatively low affinity to substrate with less durability than parylene-C, we evaluated the biocompatibility of parylene-C to the urinary bladde,r comparing of it to PEG and PDMS. MATERIALS AND METHODS: Nine rabbits were classified into three groups. Coin shaped aluminum substrates were affixed onto the external wall of the urinary bladder in each rabbit. At this point, the three rabbits which had substrates coated with PEG were assigned to group 1, those with PDMS were assigned to group 2 and those with parylene-C were assigned to group 3. In each group, one rabbit was sacrificed at one week, another rabbit was sacrificed at two weeks and the other rabbit was sacrificed at four weeks. At each time microscopic evaluation was done. To detect macrophages, we used fluorescence microscopy and applied MAC 387 staining. RESULTS: At one week, macrophage accumulation was observed on the external surface of the urinary bladder adjacent to the device no matter which material was used as a coating, but it had almost disappeared by four weeks. In addition, the inflammatory reaction was limited at the external surface of the urinary bladder, and did not expand into the muscular layer. CONCLUSIONS: With respect to biocompatibility, there was no difference among the three biomaterials. With its characteristics of durability and easy affinity regardless of the type of substrate, parylene-C would make an excellent coating material for a bio-device implantable into the urinary bladder.

Prevalence and Risk Factors for Extended Spectrum Beta-Lactamase-Producing Uropathogens in Patients with Urinary Tract Infection

PURPOSE: The aim of this study was to determine the prevalence and risk factors of extended spectrum beta-lactamase (ESBL)-producing microorganisms in urinary tract infection. MATERIALS AND METHODS: total of 2,312 patients older than 25 years and diagnosed from January 2007 to December 2009 as having urinary tract infection were studied. The prevalence of ESBL-producing microorganisms including Escherichia coli and the antimicrobial susceptibility of E. coli were examined. Univariate analyses were performed with gender, age, inpatient status, previous hospitalization, recent history of urinary catheterization, recent exposure to specific antibiotics, and past history of urogenital organ operation as risk factors for the emergence of ESBL-producing microorganisms. Then, multivariate analysis was performed with all significant variables. RESULTS: In outpatient urinary tract infection, the antimicrobial susceptibility of E. coli to each of the third-generation cephalosporins, cefotaxime, ceftazidime, and ceftriaxone, was 87.6%, 93.4%, and 87.7%, respectively, and the prevalence of ESBL-producing E. coli was 12.1%. In inpatient urinary tract infection, the susceptibility of E. coli was 78%, 84.5%, and 76.9%, respectively, and the prevalence was 23.1%. CONCLUSIONS: The overall prevalence of ESBL-producing microorganism was 12.6% and the risk appeared to be increased in cases with a previous hospitalization, a recent history of urinary catheterization, inpatient status, cefaclor medication, cefminox administration, and female gender.

Prevalence and Risk Factors for Extended Spectrum Beta-Lactamase-Producing Uropathogens in Patients with Urinary Tract Infection

PURPOSE: The aim of this study was to determine the prevalence and risk factors of extended spectrum beta-lactamase (ESBL)-producing microorganisms in urinary tract infection. MATERIALS AND METHODS: total of 2,312 patients older than 25 years and diagnosed from January 2007 to December 2009 as having urinary tract infection were studied. The prevalence of ESBL-producing microorganisms including Escherichia coli and the antimicrobial susceptibility of E. coli were examined. Univariate analyses were performed with gender, age, inpatient status, previous hospitalization, recent history of urinary catheterization, recent exposure to specific antibiotics, and past history of urogenital organ operation as risk factors for the emergence of ESBL-producing microorganisms. Then, multivariate analysis was performed with all significant variables. RESULTS: In outpatient urinary tract infection, the antimicrobial susceptibility of E. coli to each of the third-generation cephalosporins, cefotaxime, ceftazidime, and ceftriaxone, was 87.6%, 93.4%, and 87.7%, respectively, and the prevalence of ESBL-producing E. coli was 12.1%. In inpatient urinary tract infection, the susceptibility of E. coli was 78%, 84.5%, and 76.9%, respectively, and the prevalence was 23.1%. CONCLUSIONS: The overall prevalence of ESBL-producing microorganism was 12.6% and the risk appeared to be increased in cases with a previous hospitalization, a recent history of urinary catheterization, inpatient status, cefaclor medication, cefminox administration, and female gender.

The Changes of the Erectile Function and Histology of the Corpus Cavernosum in a Rat Model of Metabolic Syndrome / 대한남성과학회지

PURPOSE: We evaluated the changes of the erectile function and histology of the corpus cavernosum in a rat model of metabolic syndrome. MATERIALS AND METHODS: We used male spontaneous hypertensive rats (SHRs) as an experimental group (n=6) and Wistar-Kyoto rats as a control group (n=6). The SHRs were fed with a high fat diet, but the Wistar-Kyoto rats were fed with a normal fat diet for 12 weeks. All the groups were then checked for body weight and various biochemiclal parameters. To investigate penile erection, the intracavernosal pressure (ICP), mean arterial pressure (MAP) and cGMP level of the corpus cavernosum were recorded for all the groups. Serial sections of the penis were used to perform Masson's trichrome staining and immunohistochemistry for determining the TGF-beta 1 expression. RESULTS: We confirmed that metabolic syndrome was induced in the experimental group by the significant difference of the various biochemical parameters. (ED note: For the results of erectile function? This wasn't clear.)As a result of erectile function, the ICP/MAP ratios were checked as 51.0+/-7.5% and 31.0+/-5.5%, respectively, for the control and experimental groups. So the ICP/MAP ratio of the latter was markedly decreased compared with the former and the cGMP level of the corpus cavernosum was the same for both groups. On Masson's trichrome staining, the number of smooth muscle cell was decreased and the collagen fibers with an irregular, distorted arrangement were increased in the experimental group. The immunoreactivity for TGF-beta 1 tended to increase in the experimental group. These histological findings revealed that fibrosis of the corpus cavernosum occurred in the experimental group. CONCLUSIONS: Our results demonstrate that metabolic syndrome is harmful to erectile function and it leads to histological changes of the corpus cavernosum according to a rat model of metabolic syndrome.