For example, the regulator of calcineurin 1 (RCAN1) is a transcription factor that inhibits signal transduction mediated by the nuclear factor of activated T cells (NFAT) [58], and has been shown to reduce inflammatory responses in mice by stabilizing an inhibitor of nuclear factor-kappa B cells (NF-κB) [59]. Two possible causes of secondary immunodeficiency, accelerated ageing and GSK1120212 cost zinc deficiency, have been explored further. Because of the senescence associated to neurological conditions in DS such as premature Alzheimer’s disease [60] a similar ageing process in the immune system has been suggested, including mechanisms of increased apoptosis [61,62], that could be responsible for the observed lymphopenia and

immune dysfunction. The deficiency of plasma zinc levels observed in some DS subjects and the need of zinc for SOD activity have been proposed as mechanisms of immunological abnormalities. Cocchi and colleagues [25] tested

if zinc deficiency might be only transient, and check details found that plasma levels of zinc decrease over time after 5 years of age. However, observational studies examining zinc levels and immune status and clinical trials of zinc supplementation have failed to show a consistent clinical benefit [63–65]. DS children might have symptoms of chronic rhinitis and reactive airway disease, suggesting hypersensitivity to inhaled allergens. A study comparing positivity to skin prick hypersensitivity test between symptomatic DS children and age-matched controls found that 18% of cases had at least one positive allergen in the skin test, which contrasts with 54% of non-DS controls [66]. The authors conclude that allergen sensitization is not a major contributor of respiratory illnesses in DS children. Vestergen et al. [31] found only six of 44 DS

patients with elevated IgE, and none of 28 DS individuals tested had an allergen identified as a trigger for allergy symptoms. Despite the multiple immunological abnormalities outlined above, it is still unclear whether these are the major determinants Protein kinase N1 of increased risk of infections in DS children. This susceptibility to infections is probably enhanced by other co-morbidities that weaken mucosal barriers; for example, abnormal airway and ear anatomy, macroglossia, congenital heart disease and reactive airway disease or an inability to handle secretions. Anatomical abnormalities of the airways may impair clearance of secretions and facilitate infections. Bertrand et al. [67] described airway anomalies among 75% of DS children and 35% of non-DS children with recurrent respiratory symptoms who underwent fibreoptic bronchoscopy. The most common abnormality seen in both DS and non-DS groups was laryngomalacia, with 50% incidence in the DS group compared to 19% in the non-DS group. Tracheomalacia and tracheal bronchus were also observed. Evidence of pulmonary hypoplasia associated to DS has also been reported [68,69].

The mechanisms by which IL-7 maintains T-cell survival, and therefore regulate cellular fitness, have been the subject of numerous studies. Many of these have focused on the transcriptional control of key regulators of apoptosis such as anti-apoptotic factors Bcl2 and Mcl1. Evidence from knockout mice illustrates the importance played by the balance in expression of Bcl2 family members. The defects in thymopoeisis in mice lacking IL-7 or IL-7Rα R788 ic50 can be substantially rescued by over-expression of Bcl2 12, 13, or by compound deficiency with pro-apoptotic molecules such as Bax 14 or Bim 15. In vitro, it has long been

recognized that IL-7 stimulation of mutant T-cell lines or primary T cells up-regulates Bcl2 12, 13, 16–18, as well as Mcl1 19. Conversely, there have been other reports suggesting that Bcl2 expression is reduced in the absence of IL-7 signalling 3, 20–22. However, this is not observed in in vitro cultured T cells where particular care was taken to isolate viable cells 23. Therefore, find more although IL-7 can transcriptionally regulate Bcl2 expression, it remains unclear whether this accounts for the full range of IL-7 activity in vivo. While the identity of signals that regulate T-cell survival

are known, it remains unclear how such survival signals determine homeostatic fitness in order to regulate T-cell homeostasis in vivo. Are survival signals digital, permitting cell survival when intact and resulting in cell death in their absence, or do T cells indeed exhibit varying degrees of fitness depending on their current exposure to such survival signals? In this study, we report evidence for different mechanisms of IL-7 regulated T-cell survival evoked at different levels of IL-7 signalling. To examine T-cell survival in the absence of IL-7 signalling, we used a mouse model in which class I-restricted F5 TCR transgenic mice conditionally express IL-7Rα using the tetracycline regulatory system (F5 TreIL-7R rtTAhuCD2Il7r−/−, F5 TetIL-7R hereon, see Materials and Methods) 24. Induction of IL-7Rα expression, by feeding mice doxycycline (dox) throughout

life (F5 TetIL-7RON), overcomes the block in thymic development that normally occurs in Il7r−/− F5 mice and allows the generation of a normal peripheral compartment of PIK3C2G F5 T cells. In contrast to the high levels of IL-7Rα found in the thymus, peripheral T cells from dox-fed F5 TetIL-7R mice express much lower levels of IL-7Rα that are not functional in vivo 24. Nevertheless, we have previously shown that withdrawal of dox food from F5 TetIL-7R mice for three days (F5 TetIL-7ROFF) is sufficient to guarantee complete loss of residual IL-7Rα expression (referred to as IL-7R– F5 T cells hereon). Importantly, surface IL-7Rα protein is undetectable on IL-7R– F5 T cells and cells fail to phosphorylate STAT5 in response to IL-7 stimulation in vitro 2.

05) vs. media only (Fig. 1d). HKRB51

induced nonsignificantly higher DC–CD86 expression than HK2308 at both doses, respectively. By contrast, at both 1 : 10 (not shown) and 1 : 100, both live Brucella strains (RB51 and 2308) induced a significantly (P≤0.05) higher CD86 expression on infected DCs compared with media. In addition, live strain RB51-induced CD86 expression was significantly higher (P≤0.05) than both HK and IR rough and smooth strain-induced CD86 levels at the respective MOIs (Fig. 1d). At MOI 1 : 10, the live strain 2308-induced CD86 level was significantly higher (P≤0.05) than the HK2308-induced levels at MOI 1 : 10 equivalent, and at MOI 1 : 100, the live strain 2308-induced CD86 level was significantly higher (P≤0.05) than both HK and IR rough and smooth strain-induced CD86 levels with MOI 1 : 100 equivalent. Figure 1e illustrates the CD40/CD86 coexpression analyses on immature BMDCs buy Metformin treated BMN 673 solubility dmso with HK and live Brucella strains, which were similar to CD86 expression. HKRB51 induced a higher nonsignificant mean CD40/CD86 coexpression than HK2308 at both 1 : 10 (not shown) and 1 : 100. At 1 : 100, HKRB51 induced significantly higher levels

of CD40/CD86 (P≤0.05) compared with media. By comparison, strain IRRB51 induced greater DC–CD86 and CD40/CD86 expression than media at a dose of 1 : 100 (P≤0.05). However, strain IRRB51- and strain HKRB51-stimulated BMDCs were not significantly different from each other at either doses. Strain IRRB51 had lower mean values, but not statistically significant, of each costimulatory molecule expression and followed the same pattern of

CD40, CD86 and CD40/86 expression as HKRB51-stimulated DCs (Fig. 1c–e). TNF-α is an inflammatory cytokine that plays an important role in the defense against intracellular pathogens and is essential for DC maturation. IL-12 production by DCs is critical for a protective CD4 Th1 type immune response and the clearance of intracellular bacteria (Huang et al., 2001). To determine DC function based on cytokine secretion, TNF-α, IL-12p70 and IL-4 secretions from antigen-treated BMDC culture supernatants were Venetoclax analyzed using indirect ELISA. Neither HK nor IR rough strain RB51 produced significant amounts of TNF-α or IL-12 at both doses compared with media control (Fig. 2a and b). Only live strain RB51 at an MOI 1 : 100 induced BMDCs to secrete a significantly higher amount of both TNF-α and IL-12 (P≤0.05). Irrespective of the viability or the dose, strain 2308 did not induce significant levels of TNF-α or IL-12 from infected BMDCs (Fig. 2a and b). None of the strains induced detectable levels of IL-4 cytokine (data not shown). We have recently submitted another manuscript (Surendran et al., 2010) in which we determined that vaccine strain RB51 upregulated DC activation and function using our in vitro BMDC model.

53%) healthy controls. TSGA10 autoantibodies were not detected in the serum from patients with any other autoimmune disease. Autoantibodies against TSGA10 were detectable from a young age in 4/5 positive https://www.selleckchem.com/products/MLN-2238.html APS1 patients with autoantibody titres remaining relatively constant over time. Furthermore, real-time PCR confirmed TSGA10 mRNA to be most abundantly expressed in the testis and also showed moderate and low expression

levels throughout the entire body. TSGA10 should be considered as an autoantigen in a subset of APS1 patients and also in a minority of SLE patients. No recognizable clinical phenotype could be found to correlate with positive autoantibody reactivity. Autoimmune polyendocrine syndrome type 1 (APS1; alternatively known as autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy, APECED) is a rare monogenic autoimmune disease resulting from mutations in the AIRE gene. The AIRE gene plays a vital role in the removal and inhibition of self-reactive T cells in the thymus [1–3], a breakdown of which consequently leads to the development of the organ-specific autoimmune disease APS1. The disorder is characterized by the classical triad of chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure, the presence of at least two of these are traditionally required for the diagnoses. These

components begin to manifest in the first decade of life, often followed by the progressive emergence of other organ-specific autoimmune diseases including gonadal failure, see more intestinal dysfunction and insulin-dependent diabetes mellitus as well as ectodermal manifestations, all with variable penetrance. Pituitary manifestations are another lesser described component of APS1, being diagnosed in approximately 7% of all APS1 patients [4]. Patients present with single or multiple pituitary deficits, the most commonly reported deficit being isolated

growth hormone (GH) deficiency [5]. Partial adrenocorticotropin hormone deficiency, isolated hypogonadotrophic hypogonadism, central/idiopathic diabetes insipidus [5–11] and lymphocytic hypophysitis [12] have also been described. Pituitary autoantibodies in APS1 sera have been detected against both lactotrophs and eltoprazine gonadotrophs using immunohistochemistry [5, 13, 14]. APS1 patients also have autoantibodies directed towards a small number of guinea pig anterior pituitary cells, 40–50% of which are GH-producing cells [15]. In addition, a fibre-plexus staining pattern is observed in the pituitary intermediate lobe. Several of the major APS1 autoantigens previously identified are involved in monoamine and gamma-aminobutyric acid (GABA) synthesis and are expressed in pituitary tissue. APS1 patient sera target aromatic l-amino acid decarboxylase (AADC) and tyrosine hydroxylase (TH) in the anterior pituitary and glutamic acid decarboxylase 65 (GAD) in the intermediate lobe [13, 15], yet these do not account for the entire immunostaining seen.

These cells have the ability to produce and to be regulated by IL-10.30,31 Importantly, the characteristic immune functions selleck of these cells, normally identified as cytotoxic killers, are altered in the context of pregnancy where their ability to aid in angiogenesis and placental regulation is paramount. The role of uNK cells in placental growth is discussed later in this review in the context of functional studies

undertaken in our laboratory. Several human studies lend evidence to the regulation of uNK cells or monocytes by IL-10. First trimester tissue from human surgical abortions was obtained, and lymphocytes were isolated. IL-10 production was assessed in comparison to peripheral blood mononuclear cells (PBMCs). Baseline IL-10 production from uterine monocytes and uNK cells was significantly elevated above PBMC production. Furthermore stimulation with LPS of these cells enhanced production of IL-10, indicating that a pro-inflammatory click here stimulus can elicit a suppressive cytokine response in the context of the uterine milieu.18,32 Finally, primary human uterine monocytes were isolated from decidual tissues obtained post-labor, and pre-labor (cesarean), and production of IL-10 was measured via ELISPOT. IL-10 from pre-labor tissue was markedly increased above post-labor levels, and this correlated to an increase in COX-2 mRNA signal in post, but not pre, labor tissues.33

These findings highlight the necessity of inflammatory signals to induce labor that couple to mechanisms aimed at silencing the action of IL-10. Important insights into the immunological capabilities of uNK cells and decidual monocytes at the maternal–fetal interface have come from a mouse models of pregnancy established in our laboratory and others. We have studied IL-10−/− mice and their WT counterparts for pregnancy outcomes in response to exposure to inflammatory agents on gd6 or gd14, to mimic early pregnancy loss or preterm birth, respectively. Briefly, toll-like receptors (TLRs) are a group of innate immune receptors that recognize different pathogenic motifs. Injection of various

TLR agonists at find more different gestational ages mimics maternal infection and allows for assessment of adverse pregnancy outcomes because of dysregulation of decidual immunity in the presence or absence of IL-10. Studies with LPS, a TLR4 agonist, in IL-10−/− and WT mice induced fetal resorption (FR) or preterm birth on gd12 or gd17, respectively. Importantly, we found that IL-10−/− mice were highly susceptible to low doses of LPS, but WT mice required at least a 50-fold higher dose to induce adverse pregnancy outcomes. Dysregulation of innate immunity was similar in IL-10−/− and WT mice in that uNK cells became cytotoxic, produced TNF-α, and infiltrated the placental zone.19,34 Similar results were observed in response to TLR9 agonist CpG.

For all subsequent statistical analyses, IL-8, TNFα and IL-10 concentrations present in un-stimulated cultures were subtracted to give stimulus-specific cytokine levels for each

individual. The ratio of IL-10: TNFα was calculated from stimulus-specific cytokine levels. As cytokine concentrations, IL-10: TNFα ratios, smp0–3 h RP: m0–3 h RP cytokine ratios, and leucocyte percentages did not meet parametric assumptions, the Mann–Whitney U-test and Kruskal–Wallis tests were used to compare between two independent groups and K independent groups, respectively. The Wilcoxon signed-rank BVD-523 molecular weight test was used for paired comparison of periodate-treated and mock-treated WB culture cytokine production. This study comprised a total of 47 individuals from the Diokhor Tack community aged 6–53 years old, of whom 13 were not infected, 14 infected with S. mansoni only and 20 co-infected with S. mansoni and S. haematobium (Table 1). Only two participants

in the co-infected group were also positive for soil-transmitted nematode eggs. S. mansoni infection intensity did not significantly differ according to gender (F1,30: 1·433, P = 0·241), age group (F1,30: 1·397, P = 0·246) or between infected and co-infected groups (F1,30: 2·380, P = 0·133). S. haematobium infection intensity also did not significantly differ between males and females (F1, 17: 0·240, P = 0·631) check details or between age groups (F3,17: 2·501, P = 0·132) in the co-infected group. To investigate innate/early immune responses to 0–3 h RP, IL-8, TNFα and IL-10 were quantified in (-)-p-Bromotetramisole Oxalate whole-blood supernatants 24 h post-stimulation. Levels of all three cytokines were significantly higher in 0–3 h RP-stimulated cultures than in un-stimulated cultures (IL-8 Z: −5·968, P < 0·001; TNFα Z: −5·905, P < 0·001; IL-10 Z: −5·968, P < 0·001) with

all 47 participants mounting a detectable cytokine response to 0–3 h RP. Participants also produced higher levels of IL-8, TNFα and IL-10 in response to zymosan than in un-stimulated control cultures (IL-8 Z: −5·968, P < 0·001; TNFα Z: −5·841, P < 0·001; IL-10 Z: −5·905, P < 0·001). Interestingly, stimulus-specific IL-8 and IL-10 levels were higher in response to 0–3 h RP than to an equivalent concentration of zymosan in paired cultures (Wilcoxon signed-rank test, IL-8 Z: −5·661, P < 0·001 and IL-10 Z: −4·370, P < 0·001), whilst TNFα levels were higher in response to zymosan than to 0–3 h RP (Wilcoxon signed-rank test, Z: −4·529, P < 0·001). There was no significant correlation between levels of any of the 0–3 h RP-specific cytokines, and schistosome infection intensity and levels did not differ between age groups (data not shown).

An intrauterine injection of lipopolysaccharide (LPS) was administered to CD1 mice at embryonic day 16, ± CRTH2 agonist/vehicle controls. Mice were killed at 4.5 hr to assess fetal wellbeing and to harvest myometrium and pup brain for analysis of NF-κB, and T helper type 1/2 interleukins. To examine the effects of the CRTH2 agonist on LPS-induced preterm labour, mice were allowed to labour spontaneously. Direct effects of the CRTH2 agonist on uterine PD-1/PD-L1 targets contractility were examined ex vivo on contracting myometrial strips. The CRTH2 agonist increased fetal survival from 20 to 100% in LPS-treated mice,

and inhibited circular muscle contractility ex vivo. However, it augmented LPS-induced labour and significantly increased myometrial NF-κB, IL-1β, KC-GRO, interferon-γ and tumour necrosis factor-α. This suggests that the action of 15dPGJ2 is not via CRTH2 and therefore small molecule CRTH2 agonists are not likely to be beneficial for the prevention of inflammation-induced preterm labour. Preterm labour is one of the most challenging complications of human pregnancy. Its incidence in the western world remains between 6 and 15% depending on the geography and demographics of the population.[1] It

is a heterogeneous condition,[2] with the only firm causal link being that of infection.[3] Despite the increased awareness of the association between infection and inflammation and preterm labour,[4] there have been limited advances in the treatment and prevention of preterm labour. Currently, there is a drive to develop anti-inflammatory therapies to not only delay preterm labour, Sunitinib purchase but to prevent the long-term neurological damage thought to be a

result of the impact of pro-inflammatory factors on fetal inflammatory response syndrome. The transcription factor nuclear factor-κB (NF-κB), which is classically associated with inflammation, is central to regulating the biochemical pathways involved in both term labour and preterm labour.[5] The oxytocin receptor and cyclo-oxygenase-2 (COX-2) genes contain NF-κB response elements in their promoter regions.[6, 7] The oxytocin receptor mediates oxytocin-induced myometrial contractions through activation of phospholipase C and downstream calcium release from intracellular Niclosamide stores.[8] The COX-2 enzyme is the rate-limiting step for prostaglandin synthesis, which is responsible for uterine contractions and cervical dilatation. NF-κB is also involved in the transcriptional regulation of matrix metalloproteinases, including matrix metalloproteinase-9, which are required for remodelling of the extracellular matrix,[9] leading to cervical ripening and fetal membrane rupture. A positive feed-forward loop also exists from activation of NF-κB by the pro-inflammatory cytokines and subsequently their transcriptional activation, including tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β).

b. brucei infections (20). Several synthetic AMPs have also been shown to be trypanolytic. These peptides are derived from the

active sites of known AMPs and presumably operate through the same mechanisms. An exception is the shortened analogue of the cell-penetrating peptide transportan, TP10 (42), which lyses BSF T. b. brucei at micromolar concentrations. Cell-penetrating peptides permeate plasma membranes and are thought to exert their toxic effect through inhibition of GTPases (43). A truncated form of bovine myeloid antimicrobial peptide-27 (BMAP-27), BMAP-18, is active against both developmental forms of African trypanosomes and shows reduced toxicity towards mammalian cells and the tsetse INK 128 order symbiont Sodalis (again suggesting a paratransgenic control strategy) relative to native BMAP-27 (44). Small synthetic peptides derived from insect defensins have also been shown to exhibit trypanocidal activity against BSF African trypanosomes and to a lesser Fulvestrant mouse degree the PC developmental forms (21,22). The different developmental forms of African trypanosomes exhibit unique physiologies. These physiological characteristics can contribute to immune evasion, but, as illustrated by the following examples, also sensitize the parasite to killing by AMPs

from unusual sources that operate through unconventional mechanisms. The features of many AMPs (amphipathic helices with regions of cationic residues) are also exhibited by a number of neuropeptides. These similarities led Delgado and colleagues to investigate Phospholipase D1 the potential trypanocidal activity of several neuropeptides (23). A variety of neuropeptides exhibit killing activity against BSF trypanosomes at low micromolar concentrations. Trypanosomes treated with these peptides become swollen, develop large cytoplasmic vacuoles and detached flagellum. Susceptibility

of BSF trypanosomes can be attributed to their robust rate of endocytosis. Fluorescently labelled peptides accumulate in endosomes and colocalize with the lysosomal marker p67 (23) (Figure 1). Procyclic trypanosomes, which exhibit a significantly reduced rate of endocytosis, do not internalize and are thus not killed by neuropeptides (23). Dissection of the endocytic trafficking pathway indicates that neuropeptides exert their cytotoxicity in the acidified lysosome. Inhibiting endocytosis by incubating cells at 4°C or allowing uptake but blocking endosomal trafficking to the lysosome at 17°C spares BSF trypanosomes from killing by neuropeptides. Neutralizing the lysosomal lumen with NH4Cl also inhibits killing, indicating that an acidic environment is necessary (23). Release of fluorescent dextrans from the lysosome indicates that the membrane has been compromised. Subsequent cellular events are characteristic of an autophagic cell death (23).

1B) with no significant difference in spinal cord pathology (Fig. 1C). Disruption of BBB permeability is another parameter used to assess the neuroinflammatory response in EAE and susceptibility to disease. At day 10 (d10) postimmunization, we found that B6 and H3H4RKO mice had increased BBB permeability during the acute early phase of the disease compared with that of H1H2RKO mice (Fig. 1D).

These results indicate that the combined effect of disrupting H1R and H2R signaling is antipathogenic in EAE, whereas the combined effect of disrupting ABT-263 mw H3R and H4R signaling is propathogenic. HA and HRs have been shown to be important in regulating hematopoiesis [[39-41]]. We examined the frequency of different cell types in the primary and secondary lymphoid tissues of naïve B6, H1H2RKO, and H3H4RKO mice. There was no significant difference in the total number of cells in the thymus, lymph node, or spleen among the three strains (Fig. 2A). ALK inhibitor We also analyzed the frequency of CD4+, CD8+, Foxp3+

Treg, B cell (CD19+), CD11b+, CD11b+Gr1+, NKT (CD1d tetramer+), and NK (NKp46+) cells in primary and secondary lymphoid tissues and found no significant differences in the frequency of these cell types (Fig. 2B, C, D, and E), with the only exception being the lymph node B-cell frequency, which was significantly decreased in H3H4RKO compared with H1H2RKO mice (Fig. 2C). These results strongly suggest that the differences in EAE susceptibility observed between H1H2RKO and H3H4RKO mice are not due to differences in the frequency of immune cells in the primary and secondary lymphoid tissues. Although the exact pathogenic mechanisms underlying MS and EAE are not known, it is thought to be highly dependent on CD4+ T cells capable of producing IFN-γ and/or IL-17 [[2]]. HA and HRs play a role in T-cell polarization, proliferation, and cytokine production [[4]]. Therefore,

to elucidate the immune mechanisms associated with differential EAE susceptibility observed in B6, H1H2RKO, and H3H4RKO mice, we compared their MOG35–55-specific T-cell responses on d10 post immunization. In ex vivo proliferation assays, Protein kinase N1 splenocytes and draining lymph node (DLN) cells from all three strains responded equivalently in a dose-dependent fashion to MOG35–55 (Fig. 3A). Splenic and DLN cells from H1H2RKO mice restimulated ex vivo with MOG35–55 produced significantly less IFN-γ (Fig. 3B) and IL-17 (Fig. 3C) compared with restimulated cells from H3H4RKO mice. In addition, H3H4RKO mice produced significantly more IFN-γ and IL-17 compared with B6 mice. IL-4 was undetectable among the three strains. These results suggest that the differences in EAE susceptibility observed in H3H4RKO mice can, in part, be attributed to increased encephalitogenic Th1 and Th17 effector T-cell responses. Previously, we showed that H1R regulates IFN-γ and IL-4 production by activated CD4+ T cells and Th1/Th2 effector T-cell responses [[31]].

05). Conclusion: EPA improves the urinary protein in association with an increase in the EPA/AA ratio in CKD patients with dyslipidemia. EPA may have renoprotective role by reduction of proteinuria in CKD patients. The mechanisms of reduction of proteinuria by EPA would be clarified in the ongoing study. GULATI SANJEEV, KUMAR KAPIL, GUPTA UMESH, Ulixertinib in vivo KALRA VIKRAM, TIWARI S C Fortis Institute of Renal Sciences Introduction: Interstitial fibrosis &

tubular atrophy is the leading cause of graft loss in kidney transplant patient. Proliferation signal inhibitors may help in reducing calcineurin inhibitor exposure without increasing acute rejection episodes. Current study evaluated efficacy of conversion from mycophenolate to everolimus with CNI minimization in patients with biopsy proven

IFTA and deteriorating renal function. Methods: Prospective single center trial, study cohort selected from 200 live related renal transplant recipients in followup. All had received basiliximab induction and triple drug immunosupression (tacrolimus, MMF/EC-MFS, steroids). Inclusion criteria: biopsy proven IFTA, absence of significance proteinuria (<400 mg/24 hour), progressive graft dysfunction (decline of GFR > 15% see more over 1 month), eGFR > 40 ml/min/1.73 m2. All underwent conversion from mycophenolate to everolimus with CNI minimization. Results: The study group composed of 22 patients (M : F = 19:3), mean age 37 years (range 24–58). Conversion done at 24 months PRKACG (IQR: 8.5–24.5) post-transplantation and median follow-up is 22 (IQR: 5–9) months. The tacrolimus trough levels decreased from 5.1 ± 1.6 ng/ml to 3.6 ± 1.1 ng/ml (p = 0.03). The everolimus levels achieved were 6.68 ± 2.4 ng/ml and 5.7 ± 1.4 ng/ml at 1 and 3 months. The eGFR that had declined from best stable values of 59.3 ± 11.9 ml/min to 48.2 ± 9.5 ml/min at conversion stabilized and improved to 50.7 ± 11, 53.3 ± 13.1, 54.9 ± 13.9 and 57.1 ± 10.1 ml/min at 1, 3, 6 and 12 months post conversion respectively (p = 0.028 at 3 months). There were no episodes of rejection, 2 patients was withdrawn at 3 months & 24 months due to proteinuria. Conclusion: Conversion from mycophenolate to everolimus

with CNI minimization resulted in stabilization of renal function. OJIMA SAKI, IO HIROAKI, WAKABAYASHI KEIICHI, KANDA REO, YANAGAWA HIROYUKI, AOKI TATSUYA, NAKATA JUNICHIRO, YAMADA KAORI, NOHARA NAO, SHIMIZU YOSHIO, HAMADA CHIEKO, HORIKOSHI SATOSHI, TOMINO YASUHIKO Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine Introduction: Previous study reported that dialysis patients are easy to occur carnitine deficiency. Thus, they have shown the weakness of the skeletal muscle, cardiomyopathy, heart failure and renal anemia. In the randomized controlled trial of L-carnitine in dialysis patients who had dilated cardiomyopathy, the survival rate of the carnitine administrated group was significantly better than the controled group for 3 years (Rizos I.