4b). Nuclear factor (NF)-κB signalling is also involved in TNF-α-mediated MMP-9 production, but interestingly, this pathway was not affected by atorvastatin (Fig. 4c). To determine whether the

MEK/ERK signalling pathway mediates TNF-α-induced MMP-9 production by MOVAS cells, cultures were co-incubated with a MEK inhibitor, U0126 and MMP-9 message levels assayed by quantitative RT–PCR. U0126 effectively inhibited MMP-9 production in a dose-dependent manner (Fig. 4d), indicating that the signalling via the MEK/ERK pathway is necessary for TNF-α-mediated MMP-9 production by MOVAS cells. We have identified previously three key steps in the development of coronary artery damage in a disease model of KD [30]. These pathogenic steps include T cell activation and proliferation, production

of TNF-α and TNF-α-mediated Alvelestat price MMP-9 production. In the mouse model of KD, T cell activation triggers a massive inflammatory response characterized by marked lymphocyte proliferation and cytokine production. Local inflammation and production of TNF-α at the coronary arteries stimulates the production of MMP-9 by SMC, resulting in elastin breakdown and aneurysm formation. https://www.selleckchem.com/products/PF-2341066.html All three steps in concert lead to coronary artery damage and aneurysm formation in the animal model of KD. Atorvastatin inhibited lymphocyte proliferation in response to superantigen stimulation in a dose-dependent manner. This inhibition was also observed for production of soluble mediators of inflammation including IL-2 and TNF-α. The inhibitory effect on both proliferation and cytokine production was rescued completely by mevalonic acid, confirming that the mechanism responsible for this inhibitory activity on immune activation was at HMG-CoA reductase, a similar mechanism of action in inhibiting cholesterol metabolism. Similarly, TNF-α-induced MMP-9 production was reduced in a dose-dependent

manner in response to atorvastatin. Inhibition of ERK phosphorylation appears to be the mechanism responsible for inhibition of MMP-9 production. The ability of atorvastatin to modulate these key pathogenic steps stems from its ability to inhibit the conversion of HMG-CoA to l-mevalonate. Consistent with previous findings, our data confirm that the inhibition of T cell proliferation is dependent selleck on the mevalonate pathway, as the addition of mevalonic acid to statin-treated cells rescued the inhibitory effect observed [31]. The inhibition of the mevalonate pathway by statins leads to the loss of isoprenoid intermediates, such as geranyl pyrophosphate and farnesyl pyrophosphate. These isoprenoid intermediates act as essential lipid attachments for the post-translational modification of several small GTP-binding proteins, one of which is Ras [32]. The Ras/Raf/Mek/Erk pathway has been demonstrated previously to be a key element involved in T cell activation, as it is involved in production of the activator protein 1 (AP1) transcription factor.

80 Various approaches have been used to clarify the discrepancies and possible underlying mechanisms, including generation of MDDC or the analysis of peripheral blood DCs in patients with chronic HCV, by studying the effectiveness of recombinant HCV proteins or cell-culture-adapted strains of HCV on DC in vitro. Some researchers also reported that HCV-infected cells trigger a robust IFN response in PDC by a mechanism that requires active viral replication, direct cell–cell contact, and Toll-like receptor 7 (TLR7) signalling, and showed that the activated PDC supernatant inhibits HCV infection in an IFN receptor-dependent manner.81 As there is clearly controversy regarding MDC’s ability to activate

T cells, it is unclear whether on a per cell basis MDCs from HCV-infected individuals are able

to prime naive T cells. Additionally, reduced numbers of peripheral blood MDC have been observed in HCV-infected individuals and may play buy Ixazomib a role in the defective response to vaccine. Canaday et al.82 specifically focused on analysis of peptide–MHC complex formation and presentation, the culmination of uptake, degradation and trafficking of antigen. They Obeticholic Acid found that this specific antigen-presenting cell function is preserved in the setting of chronic HCV infection. As the liver is the primary site for HCV replication, DC changes in peripheral blood may or may not reflect what is happening locally at the site of infection. Several studies demonstrated enrichment Lepirudin of DC in the liver compartment compared with peripheral blood.80 Galle et al.83 employed electron microscopy, immunohistochemistry and immunofluorescence to show that DC are indeed enriched in the livers of HCV-infected individuals. Wertheimer et al.84 also showed a clear enrichment of DC in the intrahepatic compartment

compared with the peripheral circulation. To investigate the contribution of intrahepatic PDC and MDC to local immune responses during HCV infection, Lai et al.85,86 developed methods to isolate and characterize MDC and PDC from human liver. The MDC from HCV-infected liver demonstrated greater expression of MHC class II, CD86 and CD123, that were more efficient stimulators of allogeneic T cells and secreted less IL-10. In contrast, PDC were present at lower frequencies in HCV-infected liver and expressed higher levels of the regulatory receptor BDCA-2. In HCV-infected liver, the combination of enhanced MDC function and a reduced number of PDC might contribute to viral persistence in the face of persistent inflammation. Nattermann et al.87 demonstrated that chronic HCV infection, associated with intrahepatic DC enrichment, migration of DC is markedly affected by interaction of HCV E2 with CD81. A two-photon confocal microscopic analysis revealed that DC and T lymphocytes were rapidly recruited within human liver slices undergoing an ex vivo HCV infection.

faecalis infection, whereas all of the SCIDbgMN mice inoculated with Mϕs from burned WT mice died after the same infection.

Also, burned CCL2-knockout mice treated with rCCL2 were shown to be susceptible to E. faecalis infection, and M2Mϕs were isolated from these mice 25. In the present study, we tried to protect thermally injured mice orally infected with a lethal dose of E. faecalis by gene therapy utilizing phosphorothioate-CCL2 antisense oligodeoxynucleotides (ODNs). Antisense ODNs, ribozymes and small-interfering RNA have been used for cytokine knockdown therapy 26, 27. As compared with alternative technologies for blockage of CCL2, antisense ODNs have a higher specificity and probability of success 28. The advantage of antisense ODNs designed as phosphorothioates specifically to heterogeneous nuclear RNA or mature mRNA sequences is resistance to degradation by RNases GSK3235025 solubility dmso 26. Therefore, for the blockage of CCL2 in severely burned mice orally infected with E. faecalis, Gemcitabine mw phosphorothioate-CCL2 antisense ODNs were utilized in this study. In our previous studies 23, 24, CCL2 produced in response to burn injury was shown to play a

major role on the M2Mϕ predominance in severely burned mice. Therefore, for the elimination of M2Mϕs; we tried to reduce serum CCL2 levels of severely burned mice by treatment with CCL2 antisense ODNs. Various concentrations of CCL2 antisense ODNs were administered

to mice 2 and 12 h after burn injury. Sera, obtained from these mice 24 h after burn injury, were assayed for CCL2 by ELISA. Serum specimens obtained from normal mice treated with saline and severely burned mice treated with scrambled ODNs were utilized as controls. CCL2 was not detected in the sera of normal mice, whereas the sera of severely burned mice treated with scrambled ODNs contained 1.3 ng/mL of CCL2. However, 77–100% of CCL2 was eliminated from the sera of severely burned mice after treatment with 1 μg/mouse (Fig. 1A) or more (10 and 100 μg/mouse, Fig. 1B) of CCL2 antisense ODNs. These results indicate that the gene therapy utilizing CCL2 antisense ODNs is feasible to decrease CCL2 levels in severely burned mice. The disappearance of MLN-M2Mϕs in severely burned mice treated Dapagliflozin with CCL2 antisense ODNs was examined. Severely burned mice were treated twice with 10 μg/mouse of CCL2 antisense ODNs 2 and 12 h after burn injury. Mϕs isolated from mesenteric lymph nodes (MLN-Mϕs) of these mice 1–8 days after burn injury were cultured for 24 h without any stimulation. Culture fluids harvested were assayed for CCL17 as a biomarker of M2Mϕs. The amounts of CCL17 detected in the culture fluids were compared with those of CCL17 that were produced by the same MLN-Mϕs derived from controls (burned mice treated with scrambled ODNs).

Each board member not only has to be passionate in this mission but also should be capable of transmitting our mission to his/her country as an ambassador.

Based on discussions in the last consecutive meetings, the International Advisory Council reached a conclusion that it was time to move forward for a real action plan to improve the situation. In order to start a real action, we launched four work groups (Table 2). The first work group is for validation of eGFR equations and creatinine standardization. Two different GFR equations are currently used in Japan and China, and the ethnic coefficients for the US Modification of Diet in Renal Disease equation are also different between these countries. Because these

Asian eGFR equations were not created by a GFR reference method, the work group will compare two methods: inulin clearance Ulixertinib and diethylene triamine pentaacetic acid plasma clearance. The second objective of this work group is to support countries in validating these Asian equations for their own ethnicity. The validation of the Japanese equation is currently under operation in Taiwan and Korea. The third objective is to standardize creatinine measurements. As the first step, the work group will compare the results of mTOR inhibitor the isotope dilution mass spectrometry (ISDM)-traceable creatinine method for standard creatinine solution among different countries. If a systemic error exists, a plasma sample will be shipped to the central laboratory for calibration. The second work group is for the Pan-Asian CKD registry and risk analysis. This work group will collect existing registry data and analyze

the methodology in each registry. As the second step, the work group will establish a common methodology, which enables us to compare the data among different countries and areas. The third work group is for publishing a CKD guideline for Asia–Pacific people. Despite the availability of all the existing guidelines (e.g. KDIGO, CARI, EBPG, K/DOQI), the members all agreed that PRKACG there was a need for the development of the guideline under the AFCKDI for the people in Asia–Pacific region. The work group will study existing guidelines for CKD by other organizations and reference them. The work group will make recommendations taking into consideration the available evidences and local implementation factors including socioeconomic ones. The work group will produce statements/guidelines/practice points on areas of screening, evaluation and treatment in different stages of CKD. The last work group is for launching and managing a new portal website for the CKD initiative in the Asia–Pacific region by the AFCKDI.

The effect of perioperative transfusion of old RBCs on postoperative complications after free muscle sparing transverse rectus abdominis myocutaneous (TRAM) flap surgery was retrospectively

investigated. Two hundred sixty-one patients undergoing breast reconstruction were assigned to two groups: no transfusion and transfusion groups. Transfused patients were further divided according to the RBC storage duration (fresh, ≤14 days; old, >14 days). Postoperative complications such as vascular www.selleckchem.com/btk.html thrombosis, hematoma, and flap congestion were noted. Patients who received old blood (n = 34), compared with those received fresh blood (n = 40) or no transfusion (n = 187), had a higher incidence of postoperative complications (44.1% vs. 20.0% or 12.8%, P < 0.05). Perioperative transfusion of old RBCs can be associated with an increase in postoperative complications after free muscle sparing TRAM flap surgery. © 2014 Wiley Periodicals, Inc. Microsurgery 34:434–438, 2014. "
“Lower abdominal, perineal, and Epigenetics Compound Library cell line groin (LAPG) reconstruction may be performed in a single stage. Anterolateral thigh (ALT) flaps are preferred here and taken as fasciocutaneous (ALT-FC), myocutaneous (ALT-MC), or vastus lateralis myocutaneous (VL-MC) flaps. We aim to present the results of reconstruction from a series of patients and guide flap selection with an algorithmic approach

to LAPG reconstruction that optimizes outcomes and minimizes morbidity. Lower abdomen, groin, perineum, vulva, vagina, scrotum,

and bladder wounds reconstructed in 22 patients using ALT flaps between 2000 and 2013 were retrospectively studied. Five ALT-FC, eight ALT-MC, and nine VL-MC flaps were performed. All flaps survived. Venous congestion occurred in three VL-MC flaps from mechanical cause. Wound infection occurred in six cases. Urinary leak occurred in three cases of bladder reconstruction. One patient died from congestive heart failure. The ALT flap is time tested and dependably addresses most LAPG defects; flap variations are suited for niche defects. We propose a novel algorithm to guide reconstructive decision-making. pheromone © 2014 Wiley Periodicals, Inc. Microsurgery, 2014. “
“Introduction. As peripheral nerve specialists can have a wide variety of training backgrounds, few standards of care exist with respect to necessary incision length, amount of dissection, and operative technique for common nerve decompressions. Methods. Approaches for the following 12 common peripheral nerve surgeries were minimized using shorter incisions and a simple lighted retractor: zygomatico-temporal and auriculotemporal, greater occipital, brachial plexus, ulnar, radial, median, lateral femoral cutaneous nerve of the thigh, peroneal at the groin, fibular neck and lateral calf, and tibial and inner ankle. The new “minimal” incision length was recorded as was that of the “classical” approach as taught to the senior author and frequently represented in atlases.

Act1−/− mice and has no or minor influence on disease development. Thus, not surprisingly we found that T cells are necessary for IgG, but not IgM, autoantibody production and IgG antibody-related symptoms in lupus-like disease in B6.Act1−/− mice. Although the absolute number of T3 B cells was less in TKO mice than in B6.Act1−/− mice, the ratio of T3:T1 was

similarly elevated in both strains as compared with WT mice, suggesting that this step in B-cell differentiation is T-cell independent. In fact, the absence of T cells alone (in TCRβ/δ−/− mice) led to elevated levels of T2 and T3 B cells and elevated ratios of T2:T1 and T3:T1. Serum BAFF levels were https://www.selleckchem.com/products/PLX-4720.html significantly higher in T-cell-deficient mice (13 ng/mL versus 10 ng/mL in WT and B6.Act1−/− mice) and could possibly be the mechanism driving this differentiation, however levels did not reach those seen in BAFF-Tg mice (>35 ng/mL, [21]), making further studies

needed to firmly make such conclusion. T3 B cells have been shown to consist of primarily anergic B cells highly enriched for autoreactivity and may represent a population of cells specifically enriched during autoimmunity [32]. It has been suggested that the strength of BCR signaling during T1 B-cell stimulation decides whether the cells will differentiate along the T2-FM/MZ pathway (strong signal) or become anergic T3 B cells (attenuated signal). As increased BAFF signaling has been associated with increased survival of www.selleckchem.com/products/VX-809.html immature B cells with lower antigen-binding affinity (including

potentially autoreactive B cells) [33], it is not surprising that many T1 B cells in Act1-deficient mice differentiate into anergic T3 B cells. Interestingly, our data imply that in TKO mice, when BAFF levels are increased at the same time as the response to BAFF is elevated, T3 cells are partially rescued shifting the balance toward the T2 and eventually MZ/FM B-cell subsets. This is consistent with data from BAFF-Tg mice, Vitamin B12 where the very high levels of BAFF (>35 ng/mL) favors accumulation of T2 B cells rather than T3 B cells [33]. Thus, the absolute level of serum BAFF and/or responsiveness to BAFF may be instrumental in driving immature B-cell differentiation, resulting in (i) controlled T2/T3 differentiation at normal BAFF levels, (ii) increased T3 B-cell differentiation at intermediate BAFF levels hereby preventing autoimmunity by anergizing potentially autoreactive B cells, and (iii) complete T2/FM/MZ differentiation at very high BAFF levels resulting in T-cell-independent autoimmunity as seen in BAFF-Tg mice. MZ B cells are known to differentiate from T2 B cells in an NF-κB-dependent (p65 and c-Rel) manner [34], although the initiating signals inducing differentiation remain to be identified.

Recently we have developed a novel method to induce IL-17 production and generate Th17 cells using exclusively microbial stimulation [18], a method that

mimics much more closely the in vivo conditions during infection. Although we can confirm defective Th17 generation and IL-17 production by cells isolated EPZ-6438 molecular weight from patients with HIES [9–11], several important aspects are now apparent when using this improved methodology. First, defective IL-17 induction differs between stimulation with S. aureus or C. albicans. When Th17 responses were assessed both these microorganisms, which are the most important in HIES patients, were equally defective in generating CD4+ IL-17+ cells. Surprisingly, however, C. albicans

was still capable of stimulating approximately 20–30% of normal IL-17 production, while S. aureus was completely defective as an IL-17 stimulus in HIES patients (Fig. 1c). This finding is important as it may explain why it is mainly mucosal; nailbed infection is the most common Candida complication in HIES patients (83% in one large study), while systemic candidiasis is relatively rare [3]. Notably, patients with chronic mucocutaneous candidiasis who have the same clinical spectrum of Candida infection [19] have also been reported to have a specific defect in Candida-induced selleck screening library IL-17 production [20]. This supports the conclusion that IL-17 is important in mucosal anti-Candida host defence and that the lower IL-17 found in our patients is indeed clinically relevant. Secondly, an important observation of our study is represented by

crotamiton indistinguishable immunological responses in patients with the ‘classical’ clinical form of HIES, independent of the presence or absence of STAT3 mutations. All the patients who had a strong phenotype of the disease displayed similar defects in IL-17 production and Th17 generation. Our data are supported by the report of one HIES patient without STAT3 mutation and defective Th17 responses [21], and suggests strongly that in patients with the ‘classical’ presentation of HIES, but in which no STAT3 mutation is found, defects in the same immunological pathways are the most probable cause of the disease. This may also imply that defective Th17 responses are a more sensitive diagnostic tool for HIES. Thirdly, one of the most interesting findings of our study is the description of a clear association of a milder phenotype of the disease in a Dutch family with a less severe defect in IL-17 production, due probably to the linker domain triplet that did not lead to a frameshift [13]. Patients from this family suffer from skin infections with S. aureus, candidiasis of the nailbeds (but not of the mucosae), dermatitis, hyper-IgE and eosinophilia, but they lack any respiratory infections (either with S. aureus or other pathogens).

Then, the cells were cultured in 30 wells of 96-well round-bottomed plates (Corning Inc., Corning, NY) at a density of 2 × 105 cells per well in 150 μl of complete RPMI-1640 medium supplemented with 2 mm l-glutamine, 20 μm 2-mercaptoethanol,

sodium pyruvate, non-essential amino acids, 100 IU/ml penicillin and 100 μg/ml streptomycin, 10 mm HEPES (all from Lonza, Verviers, Belgium), and 5% inactivated human AB serum (Sigma-Aldrich, St Louis, MO) together with p143–160 of Equ c 1 (10 μg/ml) at + 37°C. On day 5, 50 μl of fresh medium was added together with recombinant human IL-2 (rIL-2, final concentration 10 IU/ml; Miltenyi Biotec, Bergisch Gladbach, selleck inhibitor Germany). On day 10, the cells were restimulated with p143–160 along with 1·5 × 105 γ-irradiated (3000 rads) autologous PBMCs as selleck kinase inhibitor antigen-presenting

cells (APCs) and rIL-2 (10 IU/ml) in a total volume of 150 μl. On day 15, 50 μl of fresh medium was added together with rIL-2 (final concentration 10 IU/ml). Finally, on day 20, the wells were split to create two replicate plates by transferring 50 μl of cell suspension per well to new 96-well daughter plates. Cultures in one of the daughter plates were stimulated with Equ c 1143–160 (10 μg/ml) and the other served as a control plate. Proliferation was measured, as described below. Positive cultures (stimulation index > 2) were transferred onto a 48-well plate and restimulated with Equ c 1143–160 (10 μg/ml) and rIL-2 (25 IU/ml) in the presence of 106 γ-irradiated autologous PBMCs as APCs. The cell lines were incubated for 14 days and supplemented with fresh medium and rIL-2 (25 IU/ml) every

2–3 days before analyses. The T-cell proliferation assays were set up in triplicates on 96-well round-bottomed plates with 2·5 × 104 T cells and 5 × 104 autologous PBMCs together with the Equ c 1 peptide p143–160 (10 μg/ml) and rEqu c 1 (100 μg/ml). The plates were then incubated for 3 days at Etofibrate +37°C, after which the cells were pulsed for 16 hr with 1·0 μCi of [3H]thymidine (GE Healthcare, Little Chalfont, UK) per well and harvested onto glass-fibre filters (Wallac, Turku, Finland). Thymidine incorporation was then measured by scintillation counting (MicroBeta Trilux 1450, Wallac), and the results were displayed as mean counts per minute (CPM) or as stimulation indices (SI; CPM of a stimulated culture divided by CPM of an unstimulated culture). The HLA restriction of the p143–160-specific TCLs was studied by inhibiting the proliferative response to p143–160 with monoclonal antibodies (1 μg/ml) to HLA-DR (clone L243) and HLA-DQ (clone SPVL3), as described previously.[14] A response with at least a 50% inhibition to p143–160 was considered significant. In addition, allogeneic, partially HLA-matched PBMCs from a person expressing only one shared allele with the subject from whom the TCL was derived were used in proliferation assays.

Definitive evidence that IFN was escaping the uterus was provided by Oliveira et al.75 who demonstrated a 500–1000-fold increase in antiviral activity in the uterine vein compared to the uterine artery or jugular blood of early pregnant ewes. These results provided strong support for the early evidence showing low, but detectable levels of IFN-τ7 and antiviral activity8 in the blood. Work from this same group later demonstrated that the antiviral activity was indeed caused by release of IFN-τ.76

These important studies were the first to definitively selleck screening library demonstrate that IFN-τ had a direct systemic effect, and that this effect could increase CL lifespan. Interestingly, Tuo et al.78 had previously shown

that exogenous IFN-τ had dramatic effects on immune cell recirculation and redistribution in lambs by reducing CD4+, CD5+ and gamma delta + T cells in the peripheral circulation without changing numbers of CD8+ T cells. This effect occurred within 6–12 hr of treatment and peripheral immune cell populations returned to pre-treatment control values by 48 hr. Furthermore, IFN-τ was shown to cause a dose-dependent reduction in lymphocyte proliferation79 and to suppress lymphocyte blastogenesis80in vitro. In contrast, IFN-τ stimulated NK Selleck GSI-IX cell activity in sheep PBMC.81 Taken together, these experiments provide evidence that, while ruminants and humans possess different mechanisms for supporting CL function during early pregnancy, there exists the distinct possibility that they may share functions as a result of the fact that they are both present in the peripheral circulation during the very earliest stages of pregnancy recognition signaling and both can apparently bind and alter function of circulating immune cells. Support for this hypothesis is currently limited owing to few of studies examining the effects of either hCG or IFN-τ on circulating immune cell function. However, work carried out in eltoprazine later pregnancy

in cattle clearly supports similarities between humans and cattle in alterations in peripheral and endometrial immune cell populations.12 For example, in cattle there was an increase in peripheral cells exhibiting the T regulatory phenotype (CD4+ CD25+) as well as recruitment of these cells to the endometrium. T regulatory cells secrete IL-4 and can induce tolerance to paternal alloantigens and inhibition of T regulatory function is associated with compromised pregnancy.12 We recently conducted a transcriptional profiling experiment to identify genes regulated in PBL by pregnancy and progesterone in cattle82 (Ott and Gifford unpublished). Results from these studies clearly indicated that a large number of known interferon-stimulated genes increase in PBL of early pregnant cows. In addition, some genes not previously thought to be IFN responsive were also increased.

The urinary NGF levels of OAB, IC/PBS and controls from previous studies were used for comparison. NGF levels were compared among subgroups and between urinary tract diseases with or without associated OAB symptoms. The urinary NGF levels

Silmitasertib clinical trial were also compared among natural filling, after normal saline filling and after potassium chloride test in a group of OAB and IC/PBS patients. Results: Patients with acute bacterial cystitis, urinary tract stones or urothelial cell carcinoma had elevated NGF levels that were not associated with the presence of OAB symptoms. Symptomatic cystitis patients who had resolved OAB symptoms after antibiotic treatment had a significant decrease in urinary NGF levels. The urinary NGF levels decreased significantly in OAB patients with effective antimuscarinic treatment for 6 months, but remained stationary and higher than the controls for up to 12 months after treatment. Conclusion: Urinary NGF is not produced solely in patients with OAB or IC/PBS. Acute bacterial cystitis, urinary tract stones and urothelial cell carcinoma can have high selleck urinary NGF production. “
“Overactive bladder syndrome (OAB), characterized by urinary frequency, nocturia and urgency with or without incontinence, is a widespread medical condition

with significant impact on quality of life. Three main factors have been proposed regarding the cause of OAB: myogenic, neurogenic and urotheliogenic. Disturbance of any of the three factors or a combination of these factors can attribute to OAB. Metabolic derangement, bladder outlet obstruction and inflammation can increase the excitability of nerve, detrusor muscle and alter the sensory Calpain and barrier functions of the urothelium. The detection of proteins in the urine such as NGF, PGE2, and proinflammatory chemokines may advance our understanding of the pathophysiology of OAB and offer novel

diagnostic biomarkers of OAB. Overactive bladder syndrome (OAB) is a common medical condition with significant impact on quality of life across the world. It is characterized by urinary frequency, nocturia and urgency with or without incontinence.1 It has been estimated that the prevalence of OAB was 10.7% in the worldwide population in 2008, and will increase to 20.1% in 2018.2 It occurs more frequently in women than in men, and its incidence increases with age.3 Although many basic and clinical studies have been performed, the cause of OAB remains to be established.4 The mainstay of current pharmacological treatment involves the use of muscarinic antagonists, but their therapeutic effectiveness is limited by a combination of limited efficacy and troublesome side-effects.5,6 Therefore, finding the etiology of OAB is important for developing effective treatments. Here we review recent research in the pathophysiology of OAB and focus on bladder outlet obstruction (BOO), metabolic syndrome and inflammation (Fig.