1 and 2). This relative stability

of the CD277 surface expression prompted us to further investigate the potential action of the CD277 engagement in immune cells. The role of CD277 engagement was investigated on TCR-induced cytokine production. Purified CD4+ T cells from healthy donors were cultured during 24–72 h with CD3+CD28 mAbs or CD3+CD277 mAbs or CD3 mAb+IgG1 (control condition). After 24 h of culture, IL-2 and IFN-γ production by CD4+ T cells were measured by ELISA. As expected, these two cytokines were secreted in large amounts after CD3+CD28 stimulation by comparison with the control condition (Fig. 1A: IL-2, 120 pg/mL, p=0.0079; Fig. 1B: IFN-γ, 7000 pg/mL, p=0.0317). Although the IL-2 levels produced by the CD3+CD277 co-activated CD4+ T cells were lower than the IL-2 levels obtained with CD3+CD28 NSC 683864 purchase co-stimulation, the quantity of IL-2 induced by CD3+CD277

co-activation was significantly higher than that induced with the IgG1 control (Fig. 1A: IL-2, 40 pg/mL, p=0.0159). Moreover, Ruxolitinib mouse IFN-γ secretion was strongly enhanced by CD3+CD277 co-activation (Fig. 1B: IFN-γ, 9000 pg/mL, p=0.0159) compared with the control situation, and, surprisingly, the production was even greater than that obtained after CD3+CD28 co-activation. A similar effect was obtained regarding the expression profile of the activation marker CD25 under CD3+CD277 co-stimulation (Fig. 1C). Altogether, these results suggest that the CD277 molecule acts as a T-cell co-stimulatory molecule for cytokine

production. To investigate whether similar co-stimulatory effects are obtained in NK cells, CD107 expression under P815-redirected cytotoxicity (Fig. 1D) and IFN-γ assays (Fig. 1E) were performed. The NK cells are stimulated via two different activation receptors, CD16 or NKp46, using specific mAbs, in the presence of isotypic control, CD277 mAb, anti-DNAM (positive control for a co-stimulation of the activation receptors) or anti-NKG2A (positive control for a co-inhibition of the activation receptors). The CD277 triggering Rho alone did not induce any effect on NK cell stimulation. Moreover, in contrast to DNAM (co-stimulation) or NKG2A (co-inhibition), CD277 engagement fails to modulate CD16- or NKp46-induced NK cell activation, both for degranulation as evaluated by CD107a/b staining and IFN-γ secretion. These results show that CD277 is not involved in the regulation of NK cell activation, contrary to that which was observed with T cells. The BTN3/CD277-mediated positive signals shown in T-cell cytokine production (Fig. 1A and B) are not in accordance with previous work in which another CD277 mAb clone has been used 13. To further test the robustness of our results, we investigated the capacity of CD277 triggering to regulate TCR-induced early T-cell events such as signaling pathways.

Briefly, the DE52-purified parasites were resuspended in

Balts-buffer (50 mM sodium phosphate buffer, pH 5.5) and incubation on ice for 30 min followed by a 5-min incubation at 37°C. The solution was subsequently centrifuged (1400 rpm, 7 min, 4°C) and the supernatant treated with benzonase (VWR) to remove potential DNA/RNA contamination GDC-0973 cell line (as described by the supplier). The supernatant was dialyzed against 10 mM Tris, pH 7.4, and the sVSG was purified using ion-exchange chromatography and gel filtration as described previously 79, 80. mfVSG was prepared as described previously 81. Prior to performing a size exclusion chromatography (equilibrated against 10 mM Tris, pH 7.4, containing 0.02% N-octylglucoside, Sigma-Aldrich), the mfVSG was treated with benzonase (similar as for sVSG) to remove potential nucleic acid contamination. The protein concentration of both VSGs was estimated spectrofotometrically by a detergent-compatible protein assay kit (Bio-Rad) using BSA as a standard. The purity of both sVSG and mfVSG was checked in SDS-PAGE and found to be >95%. In addition, Western blot analysis, using rabbit polyclonal anti-VSG and anti-cross-reacting determinant Abs confirmed the presence of the GPI anchor on mfVSG 82. Finally, the endotoxin levels were determined using the Limulus amebocyte lysate (LAL) test (Cambrex) according to the manufacturers’ instructions and found to be <0.5 pg/μg VSG. BM-DCs were generated as

described previously 83.

Briefly, BM-precursor cells were isolated from the hind limbs and seeded out in petri dishes (10 cm, Greiner) at 3×106 cells per dish. For microarray analysis, BM-precursor Selleck NVP-LDE225 cells were depleted of B and T cells by using anti-CD19 and anti-CD90 magnetic beads (Miltenyi Biotec), respectively. Cells were cultured in RPMI 1640 (PAA) supplemented with 10% heat-inactivated fetal calf serum (FCS, Astemizole PAA), penicillin (100 U/mL; PAA), streptomycin (100 mg/mL; PAA), L-glutamine (2 mM; PAA) and β-mercaptoethanol (50 mM; Sigma-Aldrich). Culture medium was additionally supplemented with 10% supernatant from a GM-CSF-transfected cell line 84. At d7 or d8, BM-derived DCs were harvested and replated at a density of 106 cells/mL in a 24-well plate (nontissue culture treated; Greiner). For maturation analysis of cytokine production and surface marker expression, BM-DCs were cultured for 20–24 h in the presence of TNF (500 U/mL; PeproTech), LPS (Escherichia coli 0127:B8 0.1 μg/mL; Sigma-Aldrich), sVSG or mfVSG from clone AnTat1.1 (2 μg/mL), or sVSG MiTat1.5 (2 μg/mL). For in vivo polarization assays, BM-DCs were seeded at a density of up to 5×106 cells/mL, matured for 4 h only with different maturation stimuli and additionally loaded with 40 μg/mL MOG35–55-peptide (synthesized and HPLC purified by R. Volkmer, Charité, Berlin, Germany), 10 μM OVA-peptide327–339 (Activotec) or 50–100 μg/mL OVA protein (endotoxin-free; Hyglos) as indicated.

We recommend this new technique for thenar and opposition reconstruction in patients who have severe loss of thenar muscles, injury to the median nerve, and wish to improve the appearance of thenar eminence. © 2011 Wiley-Liss, Inc. Microsurgery, 2011. “
“Autologous flaps can LGK-974 chemical structure be used in combination with prosthesis in postmastectomy breast reconstruction. The deep inferior epigastric perforator (DIEP) flap is considered the preferred choice among autologous tissue transfer techniques. However, in patients with a peculiar figure (moderately large breasts and large thighs with flat stomach), who cannot use their abdominal tissue, the transverse upper gracilis (TUG) flap with implant is investigated as a further option

for breast reconstruction. This report presents a patient who underwent the TUG flap plus implant reconstruction.

A bilateral skin-sparing mastectomy was performed removing 340 g for each breast. The volume of the TUG flaps was 225 g (left) and 250 g (right). Preoperative volumes were restored by placing under the TUG muscle a round textured implant. No complications occurred during the postoperative period both in the recipient and donor site and the outcomes of the procedure were good. In cases where the use of the DIEP flap is not possible because of past laparotomies or inadequate abdominal volume, the TUG flap plus implant may be considered as a valid alternative. © 2013 Wiley Periodicals, Inc. Microsurgery 34:149–152, 2014. see more “
“Free auricular flap transplantation is one of the treatments for nasal reconstruction. This report presents a case of nasal reconstruction where the infraorbital artery was used as a recipient vessel, and the infraorbital nerve as a recipient sensory nerve. A 75-year-old female underwent

resection of malignant melanoma of the right nasal ala. A free ear Obatoclax Mesylate (GX15-070) concha flap was used for the reconstruction. The facial artery could not be found intraoperatively; instead, the infraorbital artery was identified and anastomosed with the posterior auricular artery. The great auricular nerve was coapted with the infraorbital nerve. The results of the sensory examination were the same as those of the unaffected side. This procedure not only achieves a good aesthetic outcome, but also restores sufficient sensory function. © 2013 Wiley Periodicals, Inc. Microsurgery, 2013. “
“While modern reconstructive surgery was revolutionized with the introduction of microsurgical techniques, microsurgery itself has seen the introduction of a range of technological aids and modern techniques aiming to improve dissection times, anastomotic times, and overall outcomes. These include improved preoperative planning, anastomotic aides, and earlier detection of complications with higher salvage rates. Despite the potential for substantial impact, many of these techniques have been evaluated in a limited fashion, and the evidence for each has not been universally explored.

MND/ALS-associated SOD1, FUS and TARDBP gene mutations were excluded; however, further investigations revealed that all four Staurosporine molecular weight of the cases did show a repeat expansion of C9orf72, the recently reported cause of chromosome 9-linked MND/ALS and FTLD. We conclude

that these chromosome 9-linked MND/ALS cases represent a pathological sub-group with abundant p62 pathology in the cerebral cortex, hippocampus and cerebellum but with no significant associated cognitive decline. “
“The 2007 World Health Organization classification defined a new variant of glioblastoma (GBM) containing oligodendroglioma foci as GBM with an oligodendroglioma component (GBMO), which shows a favorable clinical outcome compared with “classic” GBM. However, all of the reported cases of GBMO have been adult cases, with no previous reports of pediatric cases. In this report, we demonstrated molecular characteristics

of a pediatric GBMO case, showing aggressive clinical behavior with 8-month overall survival. The case showed neither isocitrate dehydrogenase 1/2 genes (IDH1/2) mutation nor 1p/19q co-deletion, a hallmark of oligodendroglioal tumors. In addition, microsatellite instability, leading to the putative mechanism of temozolomide (TMZ) resistance, Roxadustat solubility dmso was frequently detected. Molecular genetic analysis may provide critical prognostic and therapeutic insights, especially for the pediatric glioma containing oligodendroglioma components. “
“We report the autopsy findings of a 63-year-old man with neurofibromatosis

type 1 (NF1), in whom widespread ischemic brain lesions caused by vasculopathy associated with the disorder were observed. The patient, who had café au lait macules, axillary freckling, and neurofibromas, was inarticulate of speech, had difficulty in maintaining a sitting position, and was hyporeactive at the age of 57 years. He then developed autonomic dysfunction, followed by consciousness disturbance and status epilepticus. Repeated MRI studies disclosed multiple, ill-defined lesions in the brain and progressive cerebral atrophy. The histopathological features of the lesions were those of ischemia that had occurred with spatiotemporal variability in the brain. Characteristically, Sclareol many arteries in the subarachnoid space manifested accumulation of cells in the intimal layer: this hyperplasia had resulted in narrowing and occlusion of the lumen. Immunoblotting demonstrated a marked decrease of neurofibromin, the NF1 product, which is known to act as a functional molecule in the normal process of vascular maintenance and repair. This case provides useful information about the pathomechanisms underlying central nervous system manifestations in patients with NF1. “
“Spatacsin (SPG11) is a major mutated gene in autosomal recessive spastic paraplegia with thin corpus callosum (ARHSP-TCC) and is responsible for juvenile Parkinsonism.

For some experiments recombinant mouse IL-10 was added to T-cell cultures (1 ng/ml; eBioscience). Proliferation was assessed by pulsing cultures overnight with 0·5 μCi/well of [3H]thymidine overnight and performing scintillation counts. Culture supernatants were harvested daily over 4 days. Expression levels of interferon-γ, IL-2, IL-4, IL-5, IL-10, IL-17 and tumour necrosis GS-1101 factor-α in supernatant samples were quantified by means of a cytofluorimetry-based ELISA system according to the manufacturer’s instructions (Flowcytomix; Bender Medsystem GmbH, Vienna, Austria). Cells were suspended in

FACS buffer (3% fetal calf serum, 5 mm EDTA in PBS). Cells were incubated with conjugated monoclonal antibodies in the presence of Fc blockers (clone 2.4G2). All data acquisition was performed on a FACSCalibur flow cytometer (Becton-Dickinson, San Jose, CA). The anti-mouse monoclonal antibodies used (Becton-Dickinson) were: CD4-FITC, CD44-phycoerythrin, CD62L-peridinin chlorophyll protein complex, CD25-allophycocyanin and Foxp3-phycoerythrin. T cells Maraviroc nmr were identified as CD3+ and either CD4+ CD8− for CD4 T cells or CD4− CD8+ for CD8+ T cells. CD44, CD62L and CD25 expression was used to assess

T-cell activation status. For FACS, regulatory T (Treg) cells were characterized as CD4+ CD44intermediate/high CD25+ cells.12 All values were expressed as the mean ± standard error of the mean (SEM). Statistical analysis was calculated by the two-tailed unpaired t-test using graphpad prism software (GraphPad Software, La Jolla, CA). A P-value < 0·05 was considered statistically significant. To confirm that the proliferation inhibition observed among ASC−/− CD3+ T cells in response to anti-CD3/CD28 stimulation9 is specifically linked to ASC deficiency and so not a consequence of a general NALP3 inflammasome dysfunction, we initially compared the proliferative response

of ASC−/− and NALP3−/− CD3+ T cells. When compared with ASC−/− CD3+ T cells, NALP3−/− CD3+ T cells did not display an impaired proliferative PD184352 (CI-1040) response to anti-CD3/CD28 stimulation (Fig. 1a), suggesting that this ASC-associated T-cell defect is NALP3 inflammasome-independent. We next investigated whether this ASC−/− T-cell phenomenon is restricted to a specific T-cell subset or if it affects T cells more globally. Therefore purified CD4+ and CD8+ T cells from ASC+/+ and ASC−/− mice were stimulated separately with plate-bound anti-CD3/CD28 and their proliferation was assessed over time. When compared with similarly stimulated WT controls, ASC−/− CD4+ (Fig. 1b) and CD8+ (Fig. 1c) T cells displayed no impairment in their proliferative response upon activation. Furthermore, no alteration in the regulation of T-cell activation markers (CD44, CD62L and CD25) was observed on ASC−/− CD4+ (Fig. 1d) and CD8+ (Fig. 1e) T cells following activation compared with WT controls.

8-fold), Hmox1 (heme oxygenase 1; 3.4-fold), Folr2 (folate receptor-2; 2.6-fold), Prdx6 (periredoxin-6; 2.5-fold), BMS-777607 concentration and Spsb4

(SPRY domain and SOCS box containing protein 4; 2.5-fold) (Fig. 5) [43-49]. If Arg1+ cells do have the potential for neuroprotection following TBI, this may be overwhelmed by Arg1− cells, which are greater in number and are less transient. Our findings demonstrate a heterogeneous macrophage response to TBI that changes over time. Expression profiling of Arg1+ and Arg1− macrophage subpopulations demonstrate that they do not exemplify previously described in vitro derived macrophage subsets [17]. They also differ from macrophages that accumulate in skin wound macrophages [50]. Skin wound macrophages, such as TBI-induced Arg1+ cells, both express Arg1 and Mrc1. However, skin macrophages additionally upregulated Clec7a, and do not express Nos2, features that distinguish them from TBI-induced Arg1+ cells. selleck products It may not be surprising that the macrophage response to TBI differs from macrophage polarization induced in vitro

or in other organs and other in vivo conditions. It is likely that macrophages can assemble their functions and products in a variety of combinations with great diversity. Our findings do demonstrate the heterogeneity of the macrophage response to TBI and they suggest that Arg1 should not in isolation be used as a marker for M2 cells. In this regard, Arg1 expression can be induced by pathways independent of IL-4/STAT6 [51]. Although we were able to identify macrophage subsets by using Arg1 as a marker in YARG mice, we could not detect robust expression of IL-12p40 by flow cytometry on days 1, 4, 7, or 14 in any macrophages or microglia by using Yet40 Reverse transcriptase mice or by gene expression profiling comparing Arg1+ and Arg1− macrophages, as assessed by gene profiling. This suggests that IL-12p40 may not be a major effector cytokine promoted by brain macrophages or microglia in TBI, and that early in TBI, IL-12p40 is not inversely proportional to Arg1 expression.

Other M1 genes are detected, however, both in Arg1+ and Arg1− cells. Thus, the use of a single marker to define M1 and M2 cells in TBI appears not to be sufficient, and the functional consequences of the Arg1+ and Arg1− cell populations on the course of TBI remain unknown. Our findings do not exclude the possibility that there are more than two subsets of responding macrophages, and this is clearly supported by the bimodal expression of MHCII in Arg1− macrophages. Also, despite the extensive differences in gene expression between these cell subsets, particularly, in the expression of chemokines, it is also possible that Arg1+ and Arg1− macrophages may have a shared lineage and/or be partially polarized and that one subtype could become or becoming the other.

Recently, a single nucleotide polymorphism associated with reduced Bcl-3 gene expression has been identified as a potential risk factor for Crohn’s disease. Here we report that in contrast to the predictions of single nucleotide polymorphism (SNP) analysis, patients with Crohn’s disease and ulcerative colitis demonstrate elevated Bcl-3

mRNA expression relative to healthy individuals. To explore further the potential role of Bcl-3 in inflammatory bowel disease (IBD), we used the dextran-sodium sulphate (DSS)-induced model of colitis in Bcl-3−/− mice. We found that this website Bcl-3−/− mice were less sensitive to DSS-induced colitis compared to wild-type controls and demonstrated no significant weight loss following treatment. Histological analysis revealed similar levels of oedema and leucocyte infiltration between DSS-treated wild-type and Bcl-3−/− mice, but showed that Bcl-3−/− SCH772984 cell line mice retained colonic tissue architecture which was absent in wild-type mice following DSS treatment. Analysis of the expression of the proinflammatory cytokines

interleukin (IL)-1β, tumour necrosis factor (TNF)-α and IL-6 revealed no significant differences between DSS-treated Bcl-3−/− and wild-type mice. Analysis of intestinal epithelial cell proliferation revealed enhanced proliferation in Bcl-3−/− mice, which correlated with preserved tissue architecture. Our results reveal that Bcl-3 has an important role in regulating intestinal epithelial cell proliferation and sensitivity to DSS-induced colitis which is distinct from its role as a negative regulator of inflammation. The nuclear factor (NF)-κB transcription factor family controls the inducible expression of more than 500 genes, including cytokines, chemokines and regulators of cell survival and proliferation [1, 2]. The dual role of NF-κB as a key regulator of inflammation and cell survival makes it a critical factor 3-oxoacyl-(acyl-carrier-protein) reductase in the pathogenesis of chronic diseases such as inflammatory bowel disease (IBD). Increased NF-κB activation is observed in the mucosa of IBD patients,

and the requirement for NF-κB for the expression of proinflammatory cytokines supports a contributory role for NF-κB in IBD [3, 4]. Indeed, in the interleukin (IL)-10−/− mouse model of colitis, increased activation of NF-κB in myeloid cells is critical for the development of disease, while mice lacking cylindromatosis tumour suppressor (CYLD) or A20, two important negative regulators of NF-κB, show increased sensitivity to dextran sodium sulphate (DSS)-induced colitis [4-7]. Moreover, the pharmacological inhibition of NF-κB by anti-sense oligonucleotides or inhibitory peptides can prevent DSS-induced colitis in mice [8]. Genetic studies have identified an equally important role for NF-κB in maintaining the homeostasis of the intestinal epithelium.

Our results showed that functional deficiency due to frameshift mutation and subsequent nonsense mutation in perA reduced BFP expression in typical EPEC strains isolated in Japan. Enteropathogenic

Escherichia coli (EPEC) causes diarrhea which represents a major health problem among infants, particularly in developing countries (1). EPEC produces localized adherence (LA) to HEp-2 cell monolayers and characteristic attaching-and-effacing (A/E) lesions on intestinal epithelial cells (2–5). The A/E phenotype is encoded by a cluster of genes including the eae gene located on the locus of enterocyte effacement (LEE), a ∼35 kb pathogenicity island in the E. coli chromosome. LA is caused primarily by type IV fimbriae known as a bundle-forming pilus (BFP) which is encoded by a cluster of 14 bfp genes located on a large virulence plasmid called the EPEC adherence factor (EAF) plasmid PD0325901 mouse (6–10). The first gene of the cluster, bfpA, encodes bundlin, the major structural subunit STA-9090 in vitro of BFP. BFP is also involved in bacteria-bacteria interaction and subsequent autoaggregation (11). In addition, the bfpF gene, which encodes a putative nucleotide-binding protein, is required for the dispersal phase of EPEC autoaggregation (12–14). N-acetyllactosamine

is presumed to be essential for the BFP receptor on epithelial cells (15). Studies on adult volunteers have demonstrated that intimin, the EAF plasmid and BFP are essential virulence determinants of EPEC (13, 16, 17). Recently EPEC strains have been classified as typical or atypical. Typical EPEC strains possess both the eae gene and EAF plasmid, whereas atypical EPEC strains do not possess the EAF plasmid (18). Recent studies have suggested that bfp-defective strains

become less virulent (19, 20) and Tennant et al. have reported that atypical EPEC expresses functional type I pili instead of BFP (21). Most of the EPEC strains isolated in Japan are atypical EPEC (22, 23). In addition to other bfp genes, the EAF plasmid contains the perA, B, and C (also called bfpT, V, and W) genes (24–26). It has been demonstrated that perA and perC are important for full expression of the bfpA and LEE genes (25). In Interleukin-3 receptor addition, perA activation is assisted by perC (27). The perC homologue (pch) is found in atypical EPEC strains (28). Though polymorphism of the perA gene (29) has been reported elsewhere, such polymorphism has not been seen in EPEC isolates in Japan. In EPEC, the type III secretion system (TTSS) mediates the delivery of a protein known as translocated intimin receptor (Tir) (30, 31). TTSS-positive strains have been shown to cause hemolysis after adhesion to sheep red blood cells (RBC) (contact hemolysis) (32), and a contact hemolysis assay is considered to be a convenient method of detecting the TTSS in E. coli. Variants of bfpA, which are clusters of 2 main clades are widely known (33).

We further demonstrate that CD4+CD25+Foxp3+ TREG cells readily inhibit these responses and mediate disease protection, which correlates with their accumulation in the draining LN and lamina propria. Moreover, TREG cells can directly suppress γδ T-cell expansion and cytokine production in vitro and in vivo, suggesting a pathogenic role of γδ T cells in intestinal inflammation. Thus, functional alterations in TREG cells provoke dysregulated CD4+ and γδ T-cell responses to commensal

antigens in the intestine. The gastrointestinal tract represents a major site where immune tolerance mechanisms assure a homeostatic Ensartinib research buy equilibrium between the mucosal immune system and commensal microorganisms 1, 2. Given the permanent co-existence of harmless and pathogenic bacteria that constantly trigger local immune responses, the intestinal mucosa must maintain tolerance in these sites. A disturbance in immune homeostasis of the human gut may provoke inflammatory bowel diseases (IBDs) like Crohn’s

disease (CD) and ulcerative colitis, both characterized by CHIR-99021 research buy an abnormal accumulation of activated lymphocytes in the gut resulting in chronic intestinal inflammation 1–5. CD4+Foxp3+ TREG cells are widely recognized as dominant mediators responsible for the control of peripheral tolerance 6–10. Functional abrogation of these cells results in over-activation and uncontrolled inflammatory responses towards tissue-derived antigens and commensal bacteria, leading to the development of various chronic inflammatory disorders 10–13. Our current understanding of the role of Foxp3+

TREG cells in the prevention of IBD development is largely derived from mouse models where intestinal inflammation is induced by adoptive transfer of CD4+ T effector (TEFF) cells into lymphocyte-deficient nude, selleck screening library SCID or RAG−/− hosts 14. Collectively, these studies show that CD4+Foxp3+ TREG cells prevent colitis development or even cure established disease by restraining pathogenic CD4+ T-cell and DC immune responses 15–18. However, other cellular targets of suppression in vivo remain ill-defined. Recently, increasing evidence points to a significant multi-faceted role for non-CD4+ lymphocytes, including γδ T cells, in the maintenance of intestinal homeostasis 19–21. More specifically, it has been shown that γδ T cells readily accumulate in inflamed tissues of IBD patients 22–25, although, in murine studies, γδ T cells have been shown to either potently reduce 26–28 or exacerbate inflammation 29–33. Some studies also identify γδ T cells as a source of rapidly activated T cells with Th17-like effector properties providing the first line of defense against pathogens 34–36.

Results: The main contributing factors of AKI were sepsis (31.1%) and ischemia (52.7%). AKI was multifactorial in 78% of patients with cancer and in 71% of patients without cancer. Hospital mortality rates were higher in patients with cancer (42.8%) than in patients without cancer (22.5%) (P = 0.014). In multivariate analyses, diabetes mellitus (DM) and cancer diagnosis were associated with hospital mortality. Cancer diagnosis was independently associated with mortality [odds ratio = 3.010 (95% confidence interval, 2.340–3.873), P = 0.001]. Kaplan-Meier analysis revealed

that subjects with DM and cancer (n = 146) had lower survival rates than subjects with DM and without cancer (n = 687) (log rank test, Navitoclax P = 0.001). Conclusion: The presence of DM and cancer were independently associated with mortality in patients both with and without

cancer. OBARA NANA1, UEDA SEIJI1, NAKAYAMA YOSUKE NAKAYAMA1, YAMAGISHI SHO-ICHI YAMAGISHI2, TAGUCHI KENSEI TAGUCHI1, ANDO RYOTARO ANDO1, YOKORO MIYUKI YOKORO1, FUKAMI KEI FUKAMI1, OKUDA SEIYA OKUDA1 1Division of Nephrology, Department of Medicine, Kurume university; 2Department of Physiology and Therapeutics of Diabetic vascular Complications, Kurume University Introduction: Injury to the renal vasculature plays important roles in the pathogenesis of acute kidney injury (AKI). However, roles of asymmetric dimethylarginine (ADMA), an endogenous inhibitor aminophylline of nitric oxide RAD001 chemical structure synthease, in AKI remain unclear. So, we investigated the kinetics and the roles of ADMA in ischemia/ reperfusion (IR)-injured mice and patients undergoing elective coronary angiography (CAG). Methods: We first examined the kinetics of ADMA, and DDAH-1, a key enzyme for ADMA degradation, levels in the kidney of IR-injured mice. Further, we examined the effects of continuous infusion of ADMA on renal IR injury, and studied whether the IR injury could be attenuated in DDAH-1 transgenic

(Tg) mice. Furthermore, we collected blood and urine samples of 52 patients before and after elective CAG at our institution. Results: After the IR injury, DDAH-1 levels were decreased and renal and plasma ADMA levels were increased in association with renal injury. Infusion of subpressor dose of ADMA exacerbated renal dysfunction, capillary loss and tubular necrosis in the kidney of IR-injured wild mice, while these IR-induced damages were attenuated in DDAH-1 Tg mice. In contrast-induced nephropathy (CIN) study, no case of obvious AKI assessed by changes in creatinine level was identified. However, levels of ADMA, high sensitivity C-reactive protein (hs-CRP), N-acetyl-β-D-glucosaminidase (NAG) and L-type fatty acid binding protein (L-FABP) were significantly increased by administration of contrast medium.