None. “
“Commensal microorganisms colonize barrier surfaces BTK inhibitor price of all multicellular organisms, including those of humans. For more than 500 million years, commensal microorganisms and their hosts have coevolved and adapted to each other. As a result, the commensal microbiota affects many immune and nonimmune functions of their hosts, and de facto the two together comprise one metaorganism. The commensal microbiota communicates with the host via biologically active molecules. Recently,

it has been reported that microbial imbalance may play a critical role in the development of multiple diseases, such as cancer, autoimmune conditions, and increased susceptibility to infection. In this review, we focus on the role of the commensal microbiota in

the development, progression, and immune evasion of cancer, as well as some modulatory effects on the treatment of cancer. In particular, we discuss the mechanisms of microbiota-mediated regulation of innate and adaptive immune responses to tumors, and the consequences on cancer progression and whether tumors subsequently become resistant or susceptible to different anticancer therapeutic regiments. Eukaryotes evolved from a process of endosymbiosis between different prokaryotic cells (reviewed in [1]). The initial eukaryotes evolved surrounded by microorganisms, such as archaea, bacteria, fungi, and viruses and cross-signaling between selleck chemicals eukaryotic cells and commensal microbes mostly regulated nutrition, metabolism, and morphogenesis (reviewed in [2]). click here In our bodies, commensal microorganisms inhabit all the barrier surfaces with the largest number in the distal ileum and colon and they outnumber the human cells by a ratio of 10:1 [3]. Furthermore, the number of microbial genes is at least 100

times higher than that of human genes, although many of the microbial genes have equivalent functions [4]. Viewed from this perspective, we are symbionts or metaorganisms composed of host and microbial cells, each with their own genes (metagenome) and shared metabolic processes and products (metabolome) [5, 6]. The cohabitation of early eukaryotes with microorganisms was regulated in part by signaling through Toll/IL-1 receptor domain-containing proteins that later evolved in higher animal species into the innate Toll-like receptors (TLRs) [7]. The family of cytoplasmic NOD-like receptors developed after multicellularity was established [8]. In higher vertebrates, the innate receptor signaling played an increasingly important role in innate and adaptive immunity against pathogens while still regulating the symbiotic interaction with commensal microorganisms [9].

NK cells represent innate effectors and protect the host against foreign invaders such as viruses, parasites, bacteria, or transformed cells 6. Following stimulation, NK cells release large amounts of immunostimulatory cytokines including IFN-γ and TNF-α, and trigger target cell death through the perforin/granzyme pathway or extrinsic pathways

of apoptosis (Fas/FasLigand or TRAIL) 7. Expression of activating or inhibitory receptors on NK cells enables self and Maraviroc ic50 non-self recognition 8. The NK group family receptor (e.g. NKG2D), the killer cell immunoglobulin-like receptors (KIR, e.g. CD158a and CD158b) and the natural cytotoxicity receptors (e.g. NKp44) coordinate recognition and killing of target cells while avoiding the destruction of autologous healthy tissues 9. Depending on the balance between inhibitory and activating signals engaged by ligands expressed on tumor cells, NK cells are triggered to kill or to ignore target cells. For example, NKG2D interacts

with its ligands major histocompatibility complex (MHC) class I-related chains (MICs) A and B (MICA and MICB), contributing to the control of epithelial tumors. In cancer PKC inhibitor patients, NK cell activation can be hampered by tumor-mediated shedding of MICs 10. Recently, it has been reported that nTreg cells suppress NK cell effector functions in vitro and in vivo 11, 12. Ghiringhelli et al. have shown that Treg cell-derived TGF-β inhibits NK cell cytolytic activity and downregulates NKG2D but does not inhibit the production of IFN-γ by NK cells stimulated by IL-2Rγ-chain-dependent cytokines

11. Surprisingly, the studies focusing on the interaction of iTreg cells and before NK cells are not available, so far. In this study, we determined how tumor iTreg cells modulate NK cell function. We provide evidence that in a human in vitro system iTreg cells promote perforin and FasL-dependent cytotoxicity of non-activated NK cells, while IL-2-mediated NK cell activation was inhibited in the presence of iTreg cells. Our data provide new insights into the complex regulation of human NK cells in the tumor microenvironment. iTreg cells used here have been generated according to a protocol described earlier 13 and showed a purity of >99%. They are known to express the inhibitory cytokines IL-10 and TGF-β at high levels, but — in contrast to nTreg cells — they do not express CD25 (IL-2Rα). This phenotype is found in iTreg cells/Tr1 cells of patients with cancer or autoimmune diseases 4, 14–16 (Fig. 1A). Thus, the iTreg cells generated here — in an in vitro model mimicking the tumor microenvironment — displayed typical iTreg cell-/Tr1 cell properties. As shown in Fig. 1B, iTreg cells inhibited the proliferation of activated CD4+ T cells (from 100 to 8%) significantly.

These results suggest that both MDR1 and MRPs are involved in DC maturation under LPS and hypoxia. In fact, our results under hypoxia point to a possible downstream mechanistic pathway via hypoxia-induced

expression of HIF-1α. Interestingly, HIF-1α achieved similar values in hypoxia-DCs Selleck Bortezomib under both ABC transporter (MDR1 and MRPs) inhibitors to those under hypoxia alone. These findings are in agreement with recent studies in cancer therapy which argue for the contribution of HIF-1α in drug resistance, as HIF-1α is able to activate MDR1 [33]. Currently, it is well known that DCs are a bridge between innate and adaptative immunological responses and that LPS and hypoxia are involved in DC stimulation, but the role of ABC transporters in this context has been not explored [34]. Also, this link between hypoxia and LPS-DCs and ABC transporters Silmitasertib in vivo may be inhibited by some of the most potent immunosuppressive drugs such as cyclosporin, tacrolimus and sirolimus, and this suggests an excellent target for preventing ischaemia-derived inflammation mediated by innate immunity. As described previously, hypoxia is able to increase the release of proinflammatory cytokines and the expression of co-stimulatory molecules by murine and human DCs,

thus enhancing their potential to induce allogeneic lymphocyte proliferation [8, 26]. Hypoxia- and LPS-matured DCs induced significantly higher T cell proliferation than immature untreated DCs, achieving different degrees of T cell proliferation depending on the stimuli. Interestingly, when different subpopulations were assessed, CD8 lymphocyte proliferation was up-regulated remarkably in DCs treated with LPS, while the proliferation of B lymphocytes was higher under hypoxia. Recently it has been reported that plamacytoid DCs are able to induce B lymphocyte proliferation, which lends support to our findings [35]. DCs differentiated in the presence of MDR1 and MRP inhibitors reduced alloimmune T cell proliferation

twofold. Furthermore, ABC transporter inhibitors Dolichyl-phosphate-mannose-protein mannosyltransferase showed different profiles of lymphocyte proliferation inhibition depending on DC maturation stimuli. Thus, inhibiting ABC transporters could be an effective approach to reducing the stimulatory capacity of DC, thereby decreasing lymphocyte proliferation. DCs are usually exposed to diverse pathological and physiological conditions. In fact, LPS and hypoxia are some of the possible in-vitro stimuli that can simulate the different environments that arise in wide-ranging types of cytokines that may trigger assorted inflammatory processes. However, the effects of these stimuli on phenotype differentiation patterns of DC and of the cytokine prompt cascade remain unclear [36, 37]. In our study, we showed that lymphocytes exposed to LPS-DCs generated higher levels of proinflammatory cytokines (IL-2, IL-6, IL-10, IFN-γ and TNF-α), balanced mainly to the Th1 response.

6. X-ray results.  Post-mortem X-ray demonstrated an intense degree of peri-articular soft tissue swelling in PBS-treated rats, compared with minimal swelling in rats treated with D8 (Fig. 7). In addition, control rats showed signs of decalcification and early erosion, which was not

evident in the D8-treated animals. buy GDC-0068 In the current study, we have demonstrated for the first time the efficacy of eotaxin-2 inhibition in the prevention and treatment of AIA. Eotaxin-2, a CCR3 ligand, has been considered traditionally an important mediator in asthma [13], chronic bronchitis [2] and allergic reactions [6]. While being a major receptor for eotaxin, CCR3 also binds RANTES and MCP-4, thus acting as an important migration regulator for various inflammatory effector cells, including eosinophils, basophils [10] and mast cells [9]. Over recent years it has been become increasingly apparent that chemokines and chemokine receptors play an important role in the pathogenensis of RA [20]. Fibroblast-like synoviocytes have been shown to migrate, proliferate and produce matrix metalloproteinase under regulation of the chemokine system, which may thus Olaparib order play a direct role in the destructive process of RA [21]. This has led to increased interest in animal models of inflammatory arthritis in an attempt

to identify potential chemokine therapeutic targets. In the AIA model, CCR2 and CCR3 have been shown to be involved in initial recruitment of leucocytes to synovial tissue [16]. Inhibition of RANTES, a CCR3 agonist, reduced joint inflammation, bone destruction and cell recruitment in the AIA model [22]. Although chemokine inhibition has yet to result MRIP in the development of novel effective therapeutics in humans, this strategy is considered currently to be a promising avenue and is the subject of intense investigation [5]. The classical mode of action of eotaxin-2 involves its activity directed towards eosinophil adhesion and chemotaxis [23]. Through downregulation

of vascular cell adhesion molecule (VCAM)-1, eotaxin-2 stimulates eosinophils to detach from endothelial cells and migrate into tissue [24]. Acting through MAP-kinase, eotaxin-2 has also been shown to facilitate eosinophil recruitment at sites of allergic inflammation, by shifting their adhesion molecule usage away from VCAM-1 towards an intercellular adhesion molecule (ICAM)-1-dominated pathway [25]. Direct inhibition of the CCR3 receptor has been shown to inhibit eosinophil chemotaxis and is thus a potential therapeutic target [26]. Eotaxin-2 may also have direct inflammatory activity mediated through release of reactive oxygen species [27] and through induction of histamine and leukotriene C-4 (LTC-4) degranulation in basophils.

(1) All ammonium carbonate ‘released by this layer is transferred by forward fluid flow to the third layer. Here, the increasingly modified effluent dialysate – although by now no longer truly described as ‘dialysate’– is passed over adsorbent zirconium phosphate. This has Na+ and H+ abundant on its massive surface area. These ions exchange preferentially for adsorbed K+, Ca++, Mg++, other cations, metals and, importantly, ammonium. Thus, the ammonium created in the second layer is removed by the third in exchange for Na+ and H+. By

the end of this journey, the dialyser-emergent effluent dialysate has effectively transferred all contained click here solute removed from blood during the dialytic pass. The final column-emergent fluid is now a solution consisting of purified water, Na+, H+, HCO3- and a small quantity of acetate. One final step is required. Just as a single pass system https://www.selleckchem.com/products/LBH-589.html ‘proportions’ a chemical concentrate with R/O water to make the final dialysate, a composite dry chemical mix containing K+, Ca++ and

Mg++ re-forms the final cartridge effluent into an individualizable infusate for ‘representation’ to the dialyser. Then, again and again, the process is repeated using the same initial 6 L of tap, bottled, bore or tank water. Importantly, the cartridge also acts as a bacterial filter and an endotoxin and cytokine adsorbent.16,17 The bacterial counts of <1 cfu/mL and of detectable endotoxin at <0.3 EU/mL both approach the levels required of ultrapure water. Both components exceed AAMI dialysis-grade water standards and, while nearly achieving the European standard of 0.25 EU/mL for detectable endotoxin, European bacterial count standards are also satisfied.18 Several cartridge ‘sizes’ are available, cartridge selection determined by patient body weight and surface area and by a known or predicted pre-dialysis urea. Short hour, standard and long hour, overnight

dialysis profiles can all be supported. Earlier sorbent systems suffered from several problems: aluminium toxicity, spill-over acidosis and zirconium escape and cost non-competitiveness. The concerns about aluminium toxicity levelled at the old REDY systems are no longer an issue Mephenoxalone as the aluminium sorbent vehicle found in earlier cartridges has been removed from modern cartridge systems. Zirconium escape (or leakage) from the cartridge was also a risk in earlier systems but has not been reported in modern cartridge constructs. Spill-over acidosis is avoided if appropriate cartridge size selection is made using the specifications found in the tables that accompany the cartridges. One issue long associated with sorbent dialysis has been a slow but steady increase in the dialysate sodium during dialysis as sodium is added as an exchangeable ion from the adsorbent column to the dialysate.

Evidence from both animal models and human studies suggest that the elevated female sex hormone levels and a Th2-biased immunological state in pregnancy play a major role in promoting the expansion of autoreactive B cells. In mouse models of human SLE, both oestrogen and prolactin can exacerbate and accelerate autoimmune conditions by exerting a positive influence on the survival, proliferation, maturation and autoantibody production of the mature B cell population [28, 67-70]. Such findings from animal models strongly reflect

the evidence in human clinical studies where Venetoclax female populations have a significantly higher ratio of autoantibody-mediated autoimmune conditions (including SLE, APS, Grave’s disease, myasthenia gravis, scleroderma Cell Cycle inhibitor and Sjögren’s syndrome) than males, and these conditions are often exacerbated during pregnancy, where elevated levels of the female sex hormones occur [70]. The Th2-biased state of pregnancy, which is influenced positively by

high levels of oestrogen during pregnancy, is also well known to promote B cell proliferation, activation and antibody production in experimental animal models [70]. Evidence from animal studies and human B cell models show that the expansion and activation of autoreactive B cells can be amplified by mutual positive regulatory feedback loops between the oestrogen-receptor alpha (ER-α) pathway and other autoimmune-promoting cytokines such as interferon (IFN)-α and B cell-activating factor (BAFF) to promote survival, maturation and expansion of autoreactive B cells [71, 72]. Data from animal models, in conjunction with evidence from human studies, suggest that these co-operative signalling pathways can also promote the antibody class-switching of polyreactive natural antibody IgM to a more pathogenic IgG autoantibody production by B1 cells [13, Ribose-5-phosphate isomerase 70-74]. The positive feedback loop and the production

of IFN-α and BAFF may be activated and amplified through the innate pathways mediated by endogenous ligands and Toll-like receptors (TLRs) on B cells, monocytes and dendritic cells. Such endogenous ligands may consist of self-antigens, including lipoproteins, glycoprotein, single-stranded RNA (ssRNA) and dsDNA materials that are generated as a by-product from placental tissue-shedding during pregnancy. These endogenous ligands also provide a readily available source of autoantigens for the positive selection and activation of autoreactive B cell clones through BCR signals as well as the activation of TLR-mediated innate responses that contribute further to the exacerbation of the maternal autoimmunity and expansion of pathogenic autoantibody production. Evidence from epidemiological, clinical and experimental studies has established that autoantibodies produced by maternal B cells contribute directly to adverse pregnancy outcomes [9, 10].

Among them, SUI was the most common. Moreover, OAB symptoms in women might relate to BOO. Detailed history taking and sophisticated urodynamic studies are required for a substantial group of female patients with OAB symptoms to make the correct diagnosis and provide optimal therapy. “
“Objectives: The present study investigated selleck compound the early efficacy of naftopidil against lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Methods: Subjects comprised patients with LUTS suggestive of BPH who were followed prospectively

for 8 weeks. Inclusion criteria were: (i) international prostate symptom score (IPSS) ≥8; (ii) no previous treatment for BPH; and (iii) eligibility for naftopidil monotherapy. IPSS and quality of life index were evaluated, and uroflowmetry and residual urine volume were determined optionally. In the previous study, patients who demonstrated a decrease in total American Urological Association symptom score of 25% or more from baseline were considered responders. The ratio of onset of efficacy of naftopidil was calculated by the ratio of the number of responder in each group with the starting dose. Results: Naftopidil efficacy was analyzed for 243 patients. Significant improvement of IPSS was achieved within 1–3 days after medication. Starting dosage and average dosage were identified as factors associated with the period until onset of

naftopidil efficacy. Onset of efficacy was significantly quicker with a starting dosage of 50 mg/day as compared with 25 mg/day BMN 673 mouse (P = 0.0047). However, ratios of onset of efficacy with starting dosages of 25, 50 and 75 mg/day were 77.9, 76.7 and 85.7%, respectively, showing no significant difference between groups (P = 0.7463). Duration to onset of efficacy with naftopidil dosage ≥50 mg/day was 11.2 days, significantly early compared to dosage <50 mg/day. Incidence of adverse effect Tobramycin was 3.8%. Conclusion: Naftopidil showed early effects against LUTS suggestive of BPH within a few days. “
“Objectives: We assessed the efficacy and safety of two α1-adrenoceptor antagonists, tamsulosin and silodosin, in the treatment of male lower

urinary tract symptoms. Methods: Men aged 50 years or older who had a total International Prostate Symptom Score (IPSS) of 8 or higher were enrolled in this study. Forty-six patients were randomized into two groups. Twenty-three patients were initially prescribed tamsulosin 0.2 mg once daily for 3 months, followed by silodosin 4 mg twice daily for 3 months (group T); the other group of 23 patients were initially prescribed silodosin, followed by tamsulosin (group S). Patients then switched to the alternative treatment after a 1-month clearance period. Evaluations included clinical determination of IPSS, quality-of-life index, maximum flow rate and postvoid residual urine volume before and after treatment. Results: A total of 46 men, 23 in group T and 23 in group S, were treated and 41 (89.

The C57BL/6 mice analyzed represent the

progeny of C57BL/6J mice bred in the UAB vivarium. The ΔD-iD DH allele mutation, which had been generated in BALB/c selleckchem mice [19], was backcrossed onto C57BL/6 mice for 22 generations. Both strains of mice were maintained in a specific pathogen-free barrier facility. All experiments with live mice were approved by and performed in compliance with Institutional Animal Care and Use Committee regulations. Flow cytometric analysis and cell sorting of bone marrow mononuclear cells was performed as previously described [8, 17, 19, 28]. Developing B lineage cells were identified on the basis of the surface expression of CD19, CD43, IgM, BP-1, and/or IgD (Supporting information Fig. 1). Due to the decreased expression of CD43 on early C57BL/6 B-cell progenitors when compared to BALB/c B-cell progenitors, the scheme of Melchers was used to isolate the equivalent of Hardy fractions B (B220+ cKit+, CD25−, BP-1−) and C (B220+ Opaganib nmr cKit− CD25+ and BP-1+). The following sets of monoclonal antibodies were used: For the equivalent of Hardy fractions B and C, anti-B220 (PerCP) (BD Pharmingen, San Diego, CA, USA (, anti-BP-1 (PE) (a gift from JF Kearney), and anti-IgM (Cy5) (Jackson ImmunoResearch), West Grove, PA, USA), anti-cKit (allophycocyanin) (BD Pharmingen) and anti-CD25 (FITC) (BD Pharmingen). For Hardy fractions D, E, and F, anti-CD19 (SPRD) (Southern Biotech, Birmingham, AL, USA), anti-CD43

(FITC) (BD Pharmingen), anti-IgD (PE) (Southern Biotech), and anti-IgM (Cy-5) (Jackson ImmunoResearch). Total RNA isolation, VH7183-specific VDJCμ RT-PCR amplification, cloning, sequencing, and sequence analysis was performed as previously

described [8, 17, 19]. A listing of the 577 wild-type C57BL/6 VDJCμ unique, in-frame sequences used for analysis in this work is provided in Supporting Information Table 1. A listing of 52 VDJCμ sequences from the congenic C57BL/6 IgHa ΔD-iD mature, recirculating fraction F bone check marrow B-cell subset are provided in Supporting Information Table 2. Differences between populations were assessed where appropriate by Student’s t-test, two tailed; Fisher’s exact test, two tailed; χ2; or Levene’s test for the homogeneity of variance. Analysis was performed with JMP version 8 (SAS Institute, Cary, NC, USA), or with GraphPad Prism 5.03 (GraphPad Software, La Jolla, CA, USA). Means are accompanied by the SEM. The authors wish to thank Dr. Peter D. Burrows for his invaluable advice and support. This work was supported by NIH AI42732 (HWS), NIH AI48115 (HWS), NIH HD043327 (RLS), and by core facilities supported by NIH G20RR025858, P30 AR48311, P30AI027767, and P30 CA13148. The authors declare no financial or commercial conflict of interest. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset.

Striking differences in the CP-690550 concentration autophagy markers were observed between the hippocampus and cerebral cortex in normoxic conditions. OGD/RL induced increases both in the phagophore formation and in the autophagy flux in the first three hours in the cerebral cortex that were not observed in the hippocampus. The blocking of autophagy increased the OGD/RL-induced mortality, increased the glutamate release in both the cerebral cortex and hippocampus and abolished the OGD-induced decrease in the polyubiquitinated proteins in the cerebral cortex. We conclude that OGD induces a rapid autophagic response in the cerebral cortex that plays a neuroprotective

role. Polyubiquitination levels and control of the glutamate release appear to be involved in the

neuroprotective role of autophagy. “
“The current WHO 2007 classification divides meningiomas into a 3-grade prognostic hierarchy. Recent literature evokes two pathways to disease progression in meningiomas akin to a comparable paradigm in gliomas, but without similar prognostic connotation: de novo anaplastic meningioma (better prognosis), and transformed meningioma (worse prognosis). We present two adult cases of transformed meningiomas that display a spectrum of morphologic progression. Case 1 at presentation showed a random admixture of meningothelial, atypical and anaplastic meningioma. The tumor recurred as anaplastic meningioma. Case 2 presented as a chordoid meningioma, but ICG-001 recurred as anaplastic meningioma mainly at the invasive front in transition with residual chordoid pattern. Of interest, portions of tumor also showed papillary configuration. In accordance many with the dire prognosis for anaplastic meningioma, both patients succumbed to their disease within 2 months of recurrence.

The present study highlights two main points: First, that proper recognition of focal high-grade areas in a heterogeneous low-grade meningioma (case 1) provides critical morphologic clues to spatial histologic progression and predicts aggressive biologic behavior, as evidenced by progression to frankly anaplastic meningioma at recurrence. Second, the presence of papillary in addition to anaplastic areas, in the recurrence of a previously diagnosed chordoid meningioma supports the ostensibly heightened transforming potential of grade II meningiomas, but also reflects on the morphologic heterogeneity of high-grade meningiomas, and their potentially diverse pathways of progression. We propose that grading of meningiomas as outlined by WHO is of more critical prognostic import than histologic sub-typing, and must include a thorough survey of the tumor-brain interface.

WANG KU-CHUNG, KUO LI-CHUEH, CHEN JIN-BOR Division of Nephrology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung Introduction: The aim of study was to investigate the influences of clinical variables Roxadustat mw on the quality of life (QoL) in incident peritoneal dialysis (PD) patients. Methods: The study was a prospective, case-control, observational design. Fifty-three incident patients who received chronic PD in one PD unit were enrolled. The mean age was 48.3 ± 12.6 year-old, men to women 21:32. The observational period was two years. SF-36 health survey questionnaires

were used to measure the QoL. Comparable variables included epidemiology, social status, concomitant medical status and biochemical data. Results: The scores of SF-36 components before PD therapy were general health 58.48 ± 20.05, pain 38.64 ± 21.84, social functioning 64.62 ± 27.54, emotional well-being 48.48 ± 18.29, energy/fatigue 56.82 ± 21.59, role limitations due to emotional problems 68.69 ± 15.74, role limitations due to physical health 54.88 ± 15.19, physical functioning 65.09 ± 20.24. After six months PD therapy, unmarried subjects demonstrated higher scores in role limitations due to emotional problems (76.19 vs 47.75, p < 0.05), role

limitations due to physical health (66.07 vs 37.16, p < 0.05) than married subjects. At the end of twenty-four months PD therapy, subjects who exchanged PD fluid by GS-1101 supplier themselves showed higher scores in social functioning and physical functioning compared to those

exchanged PD fluid by assistants. Furthermore, subjects with antihypertensive demonstrated higher scores in emotional well-being than those without antihypertensive. Conclusion: PD therapy had sequential influences on the components of QoL in term of PD duration. At 6-month PD therapy, marriage status had a positive influence on QoL. In contrast, self-care and antihypertensive use had a greater contribution on QoL improvement at 24-month PD therapy. Therefore, patient-oriented PD care should be implanted into contemporary situation of PD patients. RYU HAN JAK1, HAN IN MEE1, LEE MI JUNG1, OH HYUNG JUNG1, PARK JUNG TAK1, MOON SUNG JIN3, KANG SHIN-WOOK1,2, YOO TAE-HYUN1,2 1Department of Internal Medicine, College of Medicine, Yonsei University, Seoul; 2Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea; Benzatropine 3College of Medicine, Kwandong University, Gyeonggi-do, Korea Introduction: Endothelial dysfunction is implicated in increased cardiovascular risk in non-dialyzed population. However, the prognostic impact of endothelial dysfunction on cardiovascular outcome has not been investigated in peritoneal dialysis (PD) patients. Methods: We prospectively determined endothelial function by brachial artery endothelium-dependent vasodilation (flow-mediated dilation; FMD) in 143 non-diabetic PD patients and 32 controls. Primary outcome was a composite of fatal or nonfatal cardiovascular events.