For instance, full length chimeric molecules containing the N-terminus and collagen domains of SP-D connected to the NCRD of conglutinin or human mannose binding lectin (MBL) have significantly greater neutralizing activity than wild-type SP-D [14, 15]. Furthermore full length trimers

of CL-43, or the CL-43 NCRD have strong antiviral activity [16]. Given that SP-D recognizes high mannose glycans associated with the viral hemagglutinin and the neuraminidase [6], our initial hypothesis was that the same structural adaptations were responsible for the enhanced recognition of mannose-rich oligosaccharides of mannan and IAV by CL-43 [16]. In this paper, we compare antiviral properties of NCRD preparations of SP-D and the serum collectins. We report for the first time strong antiviral activity of the bovine serum collectin

CL-46 NCRD. To further analyse the increased antiviral activity of bovine serum collectins selleck we prepared novel mutant versions of hSP-D-NCRD in which specific residues found in serum collectins replace those of wild-type SP-D. These mutants were then compared for antiviral https://www.selleckchem.com/products/Y-27632.html activity and binding to mannan. Finally, we determine interactions of functionally enhancing monoclonal antibodies raised against SP-D with bovine collectin NCRD. Virus preparations.  Influenza A virus was grown in the chorioallantoic fluid of 10-day-old chicken eggs and purified on a discontinuous sucrose gradient as previously described [17]. The virus was dialysed against PBS to remove sucrose, aliquoted and stored at −80 °C until needed. Philippines 82/H3N2 (Phil82) and Brazil78/H1N1 (Braz78) strains and their bovine serum inhibitor resistant variants, Phil82/BS and Braz78/BS, were kindly provided by Dr. E. Margot Anders (University of Melbourne, Melbourne, Australia) [18]. Post-thawing the viral stocks contained approximately 5 × 108 plaque forming units/ml. Collectin preparations.  oxyclozanide Dodecamers of wild-type recombinant human SP-D were used as control and were expressed in CHO cells and purified as described [19]. Trimeric NCRD fusion proteins, including the wild-type human and rat NCRD (hereafter, called

hSP-D-NCRD and rNCRD, respectively), mutant constructs of the hSP-D-NCRD and rNCRD, and NCRD of other collectins (apart from that of CL-46) were produced in E. coli as described [20, 21]. All fusion proteins contain an identical N-terminal His-tag that facilitates purification. An internal S-protein binding site permits detection using S-protein horseradish peroxidase (HRP), as previously described [21]. All NCRD migrated as a single major band of the appropriate size for trimers on SDS–PAGE with the expected decrease in mobility on reduction, consistent with the formation of normal intrachain disulphide bonds. All showed retention of some or all of the calcium-dependent carbohydrate binding activities of the native protein.

IL-33 may play an important downstream role in the human response to schistosome CH5424802 nmr adult worm antigen exposure. “
“Endemic regions for the pathogenic nematode Strongyloides and parasitic protist Leishmania overlap and therefore co-infections with both parasites frequently occur. As the Th2 and Th1 immune responses necessary to efficiently control Strongyloides and Leishmania infections are known to counterregulate each other, we analysed the outcome of co-infection in the murine system.

Here, we show that Leishmania major-specific Th1 responses partially suppressed the nematode-induced Th2 response in co-infected mice. Despite this modulation, successful expulsion of gut dwelling Strongyloides was not suppressed in mice with pre-existing or subsequent Leishmania infection. A pre-existing Strongyloides infection, in contrast, did not interfere with efficient type-1 responses but even increased pro-inflammatory cytokine production. Also, control of L. major infections was not affected by pre-existing nematode infection. Taken together, we provide evidence that simultaneous presence of helminth and protist parasites did not interfere with efficient host defence in

our co-infection model. The parasitic nematode Strongyloides stercoralis and the intracellular protozoan parasite Leishmania major are co-endemic in the tropics and subtropic regions (1). Leishmania/Strongyloides co-infections therefore happen frequently, and little is known about the outcome and influence on disease progression. At BVD-523 manufacturer the immunological level, helminths and protozoa induce opposite responses: while protozoa polarize towards T helper (Th) 1 immune response, helminths predominantly elicit Th2 and regulatory responses (2,3). Here, we employ the experimental infection of mice with the rodent parasites Strongyloides ratti and L. major to investigate the outcome of such co-infections in the murine system. Strongyloides spp. are gastrointestinal parasitic nematodes that

belong to the group of soil-transmitted helminths and infect a wide variety of animals and humans (4,5). It is estimated that S. stercoralis has infected 30–100 million people worldwide thereby accounting for the majority of human Strongyloides infections (1). Infective Strongyloides third-stage larvae (iL3) actively penetrate the skin of their hosts. They migrate through the MycoClean Mycoplasma Removal Kit tissues to the pharynx and are subsequently swallowed to reach the gut. There, the parasitic adults live embedded in the mucosa of the small intestine and reproduce by parthenogenesis. Eggs and hatched first-stage larvae (L1) are released with the faeces (6). Experimental S. ratti infection of mice induces a patent but transient infection that is resolved spontaneously within 30–60 days and render the mice semi-resistant to subsequent infection (7). S. ratti infection provokes a classical Th2 response that is characterized by the induction of IL-13, IL-5, IL-3 and also IL-10 alongside with high titres of S.

8–4 g, given orally or as

suppositories. One patient used antihypertensive medication (kandesartancileksetil; Atacand®ö, AstraZeneca, Södertälje, Sweden). In the patients with CD, one used sulphasalazine (Salazopyrin®, Pfizer, New York, NY, USA) (4 g) and one mesalazine (2 g) daily. A third patient with CD used nabumeton (Relifex®, Meda, Solna, Sweden) for arthrosis. All the included participants with UC (n = 10) and CD (n = 11) denied regular smoking. Prior to (day 0) and during (days 2 and 12) the intake of AndoSan™, heparinized blood collected from the included participants was, in one set of experiments, also immediately stimulated ex vivo with LPS (1 ng/ml) for 6 h at 37 °C in a 5% CO2 incubator. During this incubation, the tubes were shortly manually shaken each hour. Then, plasma was harvested and samples 3-Methyladenine stored at −70 °C until analysis for levels of cytokines. The included UC and CD patients had median disease duration of 15 (2–29) and 10 (2–29) years, respectively. The patients with UC had pancolitis (n = 3), left-sided colitis (n = 3), proctosigmoiditis https://www.selleckchem.com/products/bmn-673.html (n = 1) and proctitis (n = 3), of whom two had been treated in hospital for acute colitis. Disease location in CD was ileal (n = 1), ileocolic (n = 6) and colic (n = 4). Three patients had had ileocolic resections. To obtain baseline values of cytokine levels in healthy volunteers, equally treated plasma samples from unstimulated blood were

also analysed for this purpose. Phosphoprotein phosphatase The 15 healthy volunteers (eight men) had median age 36 (range 26–51) years and denied regular smoking and use of steady medication. Analyses.  Blood was harvested from the antecubital vein into glass tubes containing 15 IU heparin per ml or 10 mmol EDTA per ml. The EDTA blood was each time (days 0,

1, 2, 5, 8, 12) analysed for haemoglobin, haematocrite, mean cellular volume, mean cellular haemoglobin, reticulocytes, immature reticulocytes, leucocytes including a differential count of neutrophils, basophils, eosinophils, lymphocytes and monocytes, thrombocytes, C-reactive protein (CRP), urea, creatinine, bilirubin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, γ-glutamine transferase, alkaline phosphatase and pancreatic amylase. The harvested heparinized blood was immediately centrifuged (2300 g, 12 min) and plasma pipetted off and immediately stored at −70 °C till analysis for micro CRP (days 0, 2, 12) and cytokines (days 0, 2, 12). The CRP was analysed by both ordinary routine laboratory technique from EDTA blood and micro-CRP from plasma by the high sensitive Tina-quant CRP particle-enhanced immunoturbidimetric method performed using a COBAS INTEGRA 400 analyser (Roche Diagnostics, Indianapolis, IN, USA) [28]. This micro-CRP method is especially sensitive in concentrations ≤20 mg/l. Faecal calprotectin concentrations (mg/kg) (normal values <50 mg/kg) at days 0 and 12 were determined in duplicates as reported [18, 29].

29,30 Aluvihare et al.26 showed in elegant studies that murine Treg cells mediate maternal tolerance to the fetus, and their recruitment to the uterus was independent of the presence of conceptus but hormonally regulated. Furthermore, it was shown that adoptive transfer of CD4+ CD25+ Treg cells can rescue abortions in abortion-prone mice.31 While the murine studies have been concordant, human studies are limited for ethical reasons and show inconsistent results mainly regarding peripheral Treg cell changes during pregnancy. Such discrepancies might be explained by various reasons among which defining the Treg cell populations and methodological considerations like flow cytometric

gating and gestational time of sampling might play a role. Early studies24,25,27,32 reported increasing numbers of circulating Treg cells as pregnancy progresses, peaking at the second trimester and declining at the Lapatinib end of pregnancy and postpartum while others could not confirm these changes. A recent comprehensive study33 showed, on the contrary, a decrease in the number of circulating Treg cells in the second term of normal pregnancy that was probably hormonally induced. selleck chemicals llc Pathological conditions, such as recurrent abortions and infertility, have been connected to decreased numbers of circulating systemic Treg cells in the patients both during and after pregnancy.25,30 In most studies evaluating

Treg cells during human and murine pregnancy, the constitutive and high expression of CD25 was used as a

hallmark of the Treg cell subset.23,25,27 Few studies have addressed the importance of Foxp3 as a lineage marker of Treg cells Selleck Afatinib during early human pregnancy.21,33 Furthermore, to our knowledge, reports on other Foxp3+ cell populations in paired decidual and peripheral blood samples are scarce or absent. In the current study, we aimed to characterize the phenotype, cytokine mRNA profile and distribution of decidual- and peripheral blood Treg cells in paired blood and decidual samples from healthy pregnant women with emphasis on the Foxp3 expression. Our investigation confirmed that in early normal pregnancy, CD4+ CD25++ Foxp3+ and CD4+ CD25+ Foxp3+ Treg cells are locally enriched in decidua. In contrast to previous studies, the numbers of these cells in peripheral blood of women in early pregnancy did not differ from those of non-pregnant controls. Moreover, we report for the first time that a population of the recently described ‘cryptic’ CD4+ CD25− Foxp3+ cells34 is indeed present and exclusively enriched in human normal early pregnancy decidua compared with peripheral blood. In total, 29 consecutive decidual samples of which 19 were paired with peripheral blood samples from early normal pregnancy and 15 peripheral blood control samples from healthy non-pregnant women were included in the study.

Strain oxyR::CAT/oxyR−/rpoS− was produced by conjugation between strains oxyR::CAT/oxyR− (9) and rpoS− (7) with selection by chloramphenicol and tetracycline.

Strain oxyR::CAT/rpoS− was produced by conjugation DNA Damage inhibitor between strains rpoS− (7) and oxyR::CAT (9) and selection on tetracycline, chloramphenicol and trimethoprim. Strain oxyR::CAT/rpoS−/RpoS was produced by conjugation between strains rpoS− with a strain carrying the complement rpoS gene, represented as RpoS (7) and oxyR::CAT (9) and selection on tetracycline, chloramphenicol, trimethoprim, and spectinomycin. Strains katG::CAT/oxyR−, katG::CAT/rpoS− and katG::oxyR−/rpoS− were produced by conjugation between strain katG::CAT (10) and strains oxyR− (9), rpoS− (7) and oxyR−/rpoS− (above) respectively,

with selection on trimethoprim and tetracycline (katG::CAT/oxyR− and katG::CAT/rpoS) or trimethoprim, chloramphenicol and tetracycline (katG::CAT/oxyR−/rpoS−). Strains dpsA::lacZ/oxyR−, dspA::lacZ/rpoS− and dpsA::lacZ/oxyR−/rpoS− were produced by conjugation between strain dpsA::lacZ (10) and strains oxyR− (9), rpoS− (7) and oxyR−/rpoS− (above) respectively, with selection on trimethoprim and tetracycline (dpsA::lacZ/oxyR−, dpsA::lacZ−/rpoS−) or trimethoprim, chloramphenicol and tetracycline (dpsA::lacZ/oxyR−/rpoS−). Strain rpoS::lacZ/oxyR− was produced by conjugation between strain oxyR− (9) and rpoS:: lacZ (7) and selection on tetracycline and trimethoprim. After antibiotics selection, the genotypes

of all constructed mutants were confirmed by the PCR method using specific primers as previously described (7, 9). Overnight Navitoclax in vitro cultures of B. pseudomallei were subcultured (OD600∼0.1) and grown in LB at 37°C. During the mid-exponential phase cells were treated with 0.5 mM H2O2 every 10 min for 1 hr Alectinib ic50 or 0.5 mM menadione for 1 hr before harvesting during the log phase (4 hr), early stationary phase (12 hr), or late stationary phase (24, 48 and 72 hr). Cell lysates were prepared and assayed for CAT activity using acetyl-CoA and 5, 5′-dithio-bis (2-nitro-benzoic acid), or for β-galactosidase activity using O-nitrophenyl-β-D-galactoside as the substrate as previously described (11, 12). Protein concentrations were determined by the Bradford Assay (13). All cultures were assayed in triplicate, and reported values are averages from at least three independent experiments. Total RNA was extracted using the modified hot acid phenol method as described elsewhere (14). For RT-PCR experiments DNA contamination was removed by incubation with 1 U DNase I per μg RNA for 30 min at 37˚C. RT-PCR was undertaken using the Qiagen OneStep RT-PCR kit (Qiagen GmbH, Hilden, Germany) according to the manufacturer’s recommendations. The semi-quantitative RT-PCR reaction was performed in a final volume of 50 μl containing 200 ng of B. pseudomallei total RNA, 0.

004 and P = 0.001, respectively). The cell proliferation assay of CD4+ and CD8+ lymphocytes performed in stimulated samples did not show a trend from the shortest hyperoxia exposure on,

BMS-907351 nmr while we observed a decrease in proliferation with hyperoxia exposure longer than 16 h (P = 0.001, 88 h hyperoxia data compared to shorter exposures). Furthermore, we found increasing prevalence of naïve CDR45RA+CD4+ cells with duration of hyperoxia in stimulated samples (P = 0.001). The proportion of regulatory T cells (CD4+Foxp3+) in unstimulated samples did not change systematically after hyperoxia, nor did the other investigated population with regulatory properties – the NK T cells. We did not find any association between hyperoxia exposure and frequencies of CD4+ and CD8+ populations in the culture. The activation molecules (CD25, CD69, HLA-DR) and T helper (Th) 1 and Th2 chemokine receptor expressions (CXCR3, CCR4, respectively) of CD4+ T helper cells were not altered during hyperoxia. We found a decrease in prevalence of CXCR3 expressing CD4+ T (Th1) cells and increased prevalence of CCR4 expressing cells (Th2) at all time points after stimulation compared to resting cultures that was

not influenced by hyperoxia. Along with activation markers, we observed a marked increase in Foxp3 expressing CD4+ cells after stimulation in all cultures but the one with the 88-h hyperoxia exposure. Similar to proliferation assay, the escalating hyperoxia trend analysis did not show any association from the shortest hyperoxia exposure on, but we noted the very low Foxp3 expression after 88-h hyperoxia (P = 0.001, 88-h hyperoxia Afatinib data compared to shorter exposures). The prevalence of NK cells was similar in all experimental arms. In view of experimental evidence that hyperoxia may suppress autoimmunity [8–10, 13], alloreactivity [2] or modify response to infection [12], we aimed to examine the influence of hyperoxia on prevalence of naturally Adenosine occurring Tregs and basic T cell subsets important in adaptive immune response. In unstimulated cells exposed to normobaric hyperoxia of different

duration, we found no change in relative frequency of Tregs and their cellular environment including CD4+, CD8+, the Th1, Th2 populations, naïve/memory T cells or NK T cells. This finding suggests that these cell types are similarly resistant to normobaric hyperoxia while not stimulated. This in vitro finding concerning major CD4+ and CD8+ subtypes is in line with the results of other clinical studies [19, 20] which also confirmed stable numbers of circulating CD3+, CD4+, CD8+, CD25+ and HLA-DR+ expressing lymphocytes in patients undergoing repeated hyperbaric hyperoxia therapy. While some authors reported changes of circulating CD4+/CD8+ lymphocyte absolute counts and ratio [5, 6] after a single hyperbaric hyperoxia challenge, this is likely transient as 24 h after exposure they found a partial reversal to normal values.

2 ELISA S/N ratio). In both these groups we observed only short-term effects with respect to proliferative responses and IFN-γ production. AT9283 The results presented in this work indicate also that early vaccination of pigs born to immune sows with attenuated ADV vaccine leads to generation of PBMC that probably contain ADV-specific memory cells, which are characterized by a Th1-like cytokine pattern upon in vitro recall stimulation. The vaccine used in the present

study solely induced Th1-type cytokine in vitro. It was also shown that pigs vaccinated at 10 and 14 weeks of age (manufacturer’s recommendation) at the moment of first vaccination had a relatively high level of passively acquired antibodies (about 0.35 ELISA S/N ratio), but they were simultaneously able to develop an active cellular as well as humoral immunity. The duration and the intensity of the secondary proliferative responses evidenced in group 6 were even better than in group 2 (P<0.05), but weaners from this group possessed lower levels of specific antibodies from about 10 weeks of life to the end of the study. The high values of SI were also seen in pigs from group 4, but it should be noted that animals from this group had no passive protection against ADV for about 3 weeks

before vaccination. At the moment of vaccination, all weaners from this group were considered to be negative with respect to MDA, and so were in fact susceptible to infection. In practice this means that is too late to vaccinate find more at the age of 12 weeks. In the present study, besides evaluation of the influence of maternal antibodies on postvaccinal immune responses, we also wanted to estimate

the best moment for vaccination of MDA-positive pigs, taking into consideration practical and economical points of view. For example, we vaccinated the pigs once, at 8 weeks of life, to evaluate whether a single vaccination of animals at the time when they are usually introduced to the herd is enough. We also wanted to check whether earlier first vaccination (at 1 week of age) and revaccination at a later age, could be an alternative for vaccination Org 27569 of relatively big weaners (at 10 or 14 weeks of age), because it is easier for herd personnel to vaccinate 7-day-old piglets. Certainly there is still a need for further studies on the efficiency of vaccination with different protocols (challenge experiment) to confirm the protective effect. However, the present results allow us to exclude some protocols of vaccination from the challenge study (e.g. vaccination at 1 and 8 weeks, or at 8 weeks), reducing the number of sacrificed pigs, which is very important from an ethical point of view.

1A, left panels). Immature eosinophils are excluded because they express high levels of CD11b 9. After 24 h culture, 90% of the eosinophils were still alive. After incubation with LPS, the frequency of viable eosinophils was even higher (data not shown). Eosinophil activation was evidenced by increased forward scatter (FSC) and side scatter (SSC), suggesting an increase both in cell size and in the number of granules (Fig. 1B). Furthermore, the in vitro activation of eosinophils was shown by the upregulation of IL-4 mRNA and the increased secretion of IL-4 protein

(Fig. 1C). To determine whether in vitro activation of eosinophils enhances the expression DNA Damage inhibitor of plasma cell survival factors, we measured the levels of APRIL, IL-6, IL-10 and TNF-α expression (Fig. 1C and D). After incubation with medium alone, low levels of APRIL, IL-6 and TNF-α mRNA, and no expression of IL-10 mRNA were seen. Activation with LPS enhanced mRNA expression of the plasma cell survival factors and promoted the secretion of IL-6, IL-10 and TNF-α (Fig. 1C).

In addition, a significant increase in intracellular APRIL expression was observed (Fig. 1D). The upregulation of the intracellular APRIL expression was only observed when eosinophils were activated by LPS. Culture of eosinophils in medium Peptide 17 alone did not cause elevated levels of APRIL, as no significant differences in APRIL expression were seen

between freshly isolated (before) and cultured (after 24 h) eosinophils (Fig. 1D). Previously, it was shown that immunization with a T-cell-dependent antigen causes activation Fossariinae of eosinophils and potentiates the expression of plasma cell survival factors IL-6 and APRIL 8, 9. Here we asked whether induction of an immune response causes long-term changes in cytokine expression by eosinophils. BALB/c mice were immunized with alum-precipitated phOx coupled to the carrier chicken serum albumin (CSA) and at different time points after primary and secondary immunization BM eosinophils were prepared, mRNA extracted and the level of cytokine gene expression determined. We found that 6 days after primary immunization, eosinophils in the BM show an activated phenotype. Elevated levels of IL-4 mRNA were found and in addition, expression of the plasma cell survival factors APRIL and IL-6 mRNA was significantly enhanced (Fig. 2A). A long-term kinetic showed that even 60 days after primary immunization, BM eosinophils still showed a significant upregulation in the expression of the cytokines IL-4, IL-6 and APRIL when compared with BM eosinophils from normal non-immunized animals. To address the question whether the activation of eosinophils is caused by alum or whether it requires the presence of antigen, animals were injected with alum alone (Fig. 2A).

Thus, for the first time, we show how interactions between LPG and TLR-2 reduce anti-leishmanial responses via cytokine-mediated decrease of TLR-9 expression. Leishmania major, a protozoan parasite that inflicts the disease cutaneous leishmaniasis, resides and replicates in macrophages. Befitting the principle of parasitism, Leishmania infection results in the deactivation of macrophages. This deactivation can result from various processes, such as suppression of oxidative selleck chemicals burst by the Leishmania-expressed

virulence factor lipophosphoglycan (LPG) [1, 2] or by interleukin (IL)-10 [3]. IL-10 can act in an autocrine manner to inhibit macrophage activation [4]. However, whether there is a causal association between LPG and IL-10 production Roxadustat supplier is not known. Natural killer (NK) cells express Toll-like receptor-2 (TLR-2), a receptor for LPG [5]. TLR-2 is also expressed in

macrophages, implying that the observed LPG-induced deactivation of macrophages can, possibly, result from an LPG–TLR-2 interaction. However, TLR-2-deficient mice on a genetically resistant C57BL/6 background and wild-type C57BL/6 mice were comparably resistant to L. braziliensis infection [6], but the mice deficient in myeloid differentiation primary response gene 88 (MyD88) – the adaptor molecule responsible for signalling from several TLRs – on the same background were susceptible to L. braziliensis infection, suggesting that more than one TLR is involved in resistance to Leishmania infection. Another TLR that signals through MyD88 and also participates in the host-protective find more anti-leishmanial immune response is TLR-9. Host-protective anti-leishmanial immune response is elicited by using the TLR-9 ligand cytosine–phosphate–guanosine (CpG) in prophylactic mode [7-9]. As TLR-9-deficient mice on a C57BL/6 background were transiently susceptible [10], the CpG motif containing L. major DNA was suggested

to require TLR-9 for inducing a host-protective effect. TLR-9 has been shown to elicit an anti-leishmanial response through NK cells [11]. Despite discrete reports on LPG-induced macrophage deactivation and the roles for TLR-2 and TLR-9 in anti-leishmanial prophylaxis, to our knowledge neither the relationship between the Leishmania-expressed LPG, TLR-2 and TLR-9 in anti-leishmanial immune response nor the anti-leishmanial efficacy of CpG in a therapeutic mode has ever been tested. In this study, we first characterized the LPG expression levels on a virulent L. major strain and on a less virulent strain derived from the virulent strain. The virulence of the strains was expressed in terms of their ability to infect susceptible BALB/c mice and BALB/c mouse-derived peritoneal macrophages. We examined whether LPG was involved in the modulation of TLR-9 expression and function and whether TLR-2 would contribute to such modulation. We finally examined whether co-administration of CpG and anti-TLR-2 antibody could reduce infection in susceptible BALB/c mice.

Management of a patient with an elevated troponin requires an appreciation that this patient has a worse prognosis check details than someone with normal troponin followed by a clinical judgement about what further investigation is appropriate to this patient. A major difficulty for nephrologists is that the lack of evidence for specific cardiovascular therapies in patients undergoing dialysis100 makes it difficult to select a therapy that may offer a survival or other benefit. In addition, the elevated

troponin does not help determine the underlying pathology to target and some therapies such as revascularization with coronary artery bypass graft surgery carry a considerable mortality risk in patients undergoing dialysis.101 This is a major issue if troponin https://www.selleckchem.com/JAK.html is used to screen asymptomatic patients. In patients with symptoms of acute coronary syndromes, the need to investigate further is more straightforward, although evidence is still lacking. High levels of BNP suggest a myocardium under stress due to chronic volume overload, a poorly functioning ventricle or both. BNP levels can be reduced by treatment with beta-blocking

drugs in patients receiving dialysis,102,103 but the use of beta-blocking drugs is yet to be tested in an adequately powered study with clinical outcomes. Treatment with losartan reduced BNP levels in one study.104 However, results of randomized studies of renin-angiotensin system antagonists conflict in dialysis patients with some studies suggesting

benefit,105,106 and others demonstrating no benefit in the primary outcome.107 Finally, one uncontrolled study used the level of BNP to guide ultrafiltration in patients undergoing dialysis NADPH-cytochrome-c2 reductase with volume overload,108 and demonstrated that BNP and extracellular fluid volume could be lowered. However, larger controlled studies of ‘BNP-guided therapy’ are needed to determine whether this approach can reduce clinically important end-points, bearing in mind that interventions targeting an improvement in other laboratory markers in patients undergoing dialysis have not proved beneficial in randomized controlled trials.109,110 Cardiac troponin and BNP offer promise for future clinical application in patients undergoing dialysis. Although reduced kidney function may have a role in their frequent abnormal levels, their strong associations with adverse clinical outcomes in this population and the potential pathological pathways they represent provide opportunities for treatment strategies to be guided by biomarker levels. However, much remains to be done before this promise is realized, including a better understanding of day to day variability of BNP and determining a ‘reference range’ of this marker for dialysis patients with minimal cardiac pathology.