Therefore, peritoneal PD98059 datasheet Mφs from naive or T. cruzi-infected mice were co-cultured with naive CD90.2+ T cells purified from spleens of BALB/c mice. Antibodies specific for PD-1/PD-Ls were added to the co-cultures for 72 hr and proliferation was determined before the addition of [3H]thymidine. F4/80+ Mφs from naive mice favour Con A-stimulated naive mouse T-cell proliferation. However, F4/80+ Mφs from T. cruzi-infected mice suppress naive CD90.2+ T-cell proliferation (Fig. 2) as was shown

previously.54 T-cell proliferation was restored when anti-PD-1 or anti-PD-L1 antibodies were added. Nevertheless, PD-L2 blocking antibody treatment did not re-establish T-cell proliferation. These data suggest that T. cruzi induces a suppressive phenotype of Mφs through the up-regulation of PD-L1, which inhibits activated CD90.2+ T cells. Several studies have shown that Arg I-mediated depletion of l-arginine leads to T-cell suppression.26,27 To discover

whether Arg I is involved in the immunosuppression observed in Fig. 2, we determined Arg I expression and activity in peritoneal cells treated with PD1 and PD-L blocking antibodies and infected in vitro with T. cruzi. Arg I expression and activity were up-regulated in infected cells compared with uninfected cells. Interestingly, Arg I expression and activity were enhanced in infected cells treated with anti-PD-L2 blocking antibody compared with infected cells. However, anti-PD-1 and anti-PD-L1 blocking find more antibodies did not modify Arg I in infected cells (Fig. 3a,b). Therefore, the increase in Arg I activity and expression observed in anti-PD-L2-treated Ceramide glucosyltransferase cells might explain why anti-PD-L2 blocking antibody was not able to re-establish T-cell proliferation

(Fig. 2). Because l-arginine is the substrate for Arg I as well as for iNOS, we evaluated iNOS expression and NO production in peritoneal cells from infected mice or cells infected in vitro treated with blocking antibodies. Peritoneal cells from infected mice produce large amounts of NO compared with uninfected cells (Fig. 4a). In addition, the same effect was observed in peritoneal cells infected in vitro (Fig. 4c). Anti-PD-L2 blocking antibody treatment reduced NO production and iNOS expression in cells from infected mice (Fig. 4a,b) as well as in cells infected in vitro (Fig. 4c,d). On the other hand, we observed a slight increment in NO production in cells from infected mice treated with anti-PD-1 or anti-PD-L1. Therefore, anti-PD-L2 blocking antibody shifts the Arg I/iNOS balance towards Arg I in T. cruzi-infected cells (Figs 3 and 4). It has been demonstrated that T2-type cytokines shift l-arginine metabolism in Mφs towards Arg I, leading to polyamine biosynthesis. To investigate the influence of the PD-1/PD-Ls pathway in the cytokine profile, IL-10 and IFN-γ production were determined in infected cells treated with PD-1/PD-Ls blocking antibodies.

fumigatus conidia was compared with LPS-matured DCs (100 ng/ml for 24 hr). The percentage of DCs that have fixed FITC-A. fumigatus conidia was analysed by flow cytometry at 6 hr post-infection. Treatment with IFN-β did not alter selleckchem the capacity of DCs to internalize the pathogen whereas, as expected, LPS-matured DCs showed a reduced

capacity to uptake A. fumigatus conidia. Indeed, 55% of control and IFN-β-treated DCs phagocytosed A. fumigatus but only 35% of LPS-stimulated DCs fixed the conidia (Fig. 2b). Overall, our results indicated that IFN-β treatment did not modify the capacity of immature DCs to phagocytose A. fumigatus conidia although it strongly modulated the A. fumigatus-induced expression of co-stimulatory and maturation molecules. These results prompted us to further investigate the impact of IFN-β on the response

of DCs to A. fumigatus infection. Cytokine production critically impacts the ability of DCs to activate and prime T cells. For this reason, we assessed IFN-β capacity to modulate the profile of cytokines released by A. fumigatus-infected DCs. To this end, supernatants were harvested from DCs stimulated for 24 hr 17-AAG concentration with A. fumigatus with or without 4 hr IFN-β pre-treatment, and the release of IL-12p70, IL-23, IL-10, TNF-α and IL-6 was analysed (Fig. 3). The presence of IFN-β significantly increased the secretion of IL-12p70 and IL-6 by A. fumigatus-infected DCs but it did not modify the release of IL-10, IL-23 and TNF-α. To investigate whether Flucloronide the robust induction of IL-12p70 in IFN-β-primed DCs was determined by an increased transcription of the IL-12p35 subunit and to extend our study also to IL-27, a critical cytokine involved in regulating T cell differentiation and functions, we investigated in IFN-β-primed DC the expression of inducible subunits composing the IL-12 family members following A. fumigatus infection. Total RNA was extracted 20 hr after A. fumigatus infection with or without a 4-hr IFN-β priming and the transcripts encoding IL-12p35, IL-23p19, and IL-27p28 subunits were analysed by real-time RT-PCR (Fig. 4). The weak expression of IL-12p35 in A. fumigatus-infected

cells was increased by IFN-β pre-treatment explaining the synergistic effect on IL-12p70 secretion observed by CBA analysis (compare Figs 3 and 4). Conversely, no effect of IFN-β treatment was observed on the expression of IL-23p19, confirming the ELISA results presented in Fig. 3. Interestingly, IFN-β pre-treatment induced a robust expression of IL-27p28, which was further increased in A. fumigatus-stimulated DCs. The lack of IL-27p28 expression, in DCs stimulated with A. fumigatus alone, correlated well with the incapacity of this fungus to stimulate IFN-β gene transcription (Fig. 1) and further highlighted the type I IFN-dependent expression of IL-27, as previously demonstrated.24 All these data suggest that IFN-β can profoundly modify the response of DC to A.

However, Th-cell phenotypes can change if reorientation occurs soon after initial activation [42, 43, 56]. Similarly, the epigenetic modifications that fix a cell’s phenotype need several days to develop, NVP-AUY922 chemical structure delaying definitive adaptation of a phenotype by several days. Strikingly, the majority of Th-cell differentiation mechanisms contain one or more positive feedback loops [71, 76, 77], but hardly any negative feedback loops. Previous work has shown that negative feedback mechanisms allow cells to approach their steady states much faster than positive feedback systems do [78], that is, to differentiate faster. Th-cell phenotype

differentiation programme has these ‘slow’ feedback mechanisms hard-coded in the architecture of its signal transduction pathways, providing a window of opportunity to adjust a ‘wrong’ phenotype choice. Until recently, Th-cell phenotypes were considered to be mutually exclusive, irreversible and stable. According to this model, several days of stimulation induce epigenetic modifications that fix the pattern set out by the master transcription factors and cytokines involved in the primary response [62]. Recent work suggests that Th cells are more plastic than previously thought and that they can adopt alternative phenotypes [79,

80]. Rather than codifferentiating into dual-phenotype cells, Th cells appear to ‘add on’ a phenotype by expressing novel effector Selleck PF 2341066 cytokines, while simultaneously retaining their previous expression pattern [81]. Indeed, effective responses are associated with multifunction Th cells, that is, the production of multiple effector cytokines at the same time [82], and it has been shown that Th cells can co-express different master transcription factors after being stimulated

under the same circumstances, like a particular viral infection [83]. This evidence demonstrates that the phenotypes are certainly not exclusive and that several can be combined in single Th cells, showing that the concept of TCL dichotomous phenotypes is an oversimplification [84]. Most mathematical models for dichotomous Th differentiation can readily account for such co-expression states, however, as their presence or absence depends largely on the parameters that define the competition between the transcription factors. Thus, similar intracellular regulation can also account for ‘co-existing’ phenotypes [69, 71]. While it is now known that Th-cell phenotypes need not always be mutually exclusive, this does not prove that cells also develop into mature multiple-phenotype Th cells. It has been observed that many different master transcription factors are transiently up-regulated after Th-cell activation, and there is now evidence for stable co-expression of master transcription factors [85, 86], suggesting that these cells indeed adopt intermediate phenotypes.

Jean-Luc Cracowski is MD, PhD, professor of Clinical Pharmacology at Grenoble University, France. He

is in charge of the Clinical Pharmacology Unit at the INSERM Clinical Research Center in Grenoble, France. His main area of research is the pharmacology and physiology of human skin HM781-36B solubility dmso microcirculation. This includes the development of methods to assess skin microvascular function, their use in physiological and pathological conditions such as scleroderma and primary Raynaud’s phenomenon, and the development of new pharmacological approaches. He is coauthor of 139 publications indexed in Medline. “
“Microcirculation (2010) 17, 32–38. doi: 10.1111/j.1549-8719.2009.00004.x Objective:  Fenestrations are pores in the

liver sinusoidal endothelium that facilitate the transfer of particulate substrates between the sinusoidal lumen and hepatocytes. Fenestrations express caveolin-1 and have structural similarities to caveolae, therefore might be a form of caveolae and caveolin-1 may be integral to fenestration structure and function. Therefore, fenestrations were studied in the livers of caveolin-1 knockout mice. Methods:  Scanning, transmission and immunogold electron microscopic techniques were used to study the liver sinusoidal endothelium and other tissues in caveolin-1 knockout and wild-type mice. Results:  Comparison of fenestrations in wild-type and knockout mice did not reveal any differences on either scanning or transmission electron microscopy. The diameter Loperamide of the fenestrations was not significantly different (74 ± 13 nm knockout mice Decitabine molecular weight vs 78 ± 12 nm wild-type mice) nor was the fenestration porosity (6.5 ± 2.1 knockout vs 7.3 ± 2.4% wild-type mice). In contrast, adipocytes and blood vessels in other tissues lacked caveolae in the knockout mice. Caveolin-1 immunogold of livers of wild-type mice indicated sparse expression in sinusoidal endothelial cells. Conclusions:  The normal structure of fenestrations in the liver sinusoidal endothelium is not dependent upon

caveolin-1 and fenestrations are not a form of caveolae. “
“Please cite this paper as: Emmett, Lanati, Dunn, Stone and Bates (2011). CCR7 Mediates Directed Growth of Melanomas Towards Lymphatics. Microcirculation 18(3), 172–182. Objective:  To determine whether chemotactic-metastasis, the preferential growth of melanomas towards areas of high lymphatic density, is CCL21/CCR7 dependent in vivo. Lymphatic endothelial cells (LECs) produce the chemokine CCL21. Metastatic melanoma cells express CCR7, its receptor, and exhibit chemotactic-metastasis, whereby metastatic cells recognise and grow towards areas of higher lymphatic density. Methods:  We used two in vivo models of directional growth towards depots of LECs of melanoma cells over-expressing CCR7.

The interface between plasma and histopaque, corresponding to the PBMC fraction, was collected

and washed four times with ice-cold PBS. The cells were suspended in plain RPMI-1640 media and assessed for viability using trypan blue exclusion. They were then plated at 1·5 × 105/well in 96-well flat-bottomed tissue culture plates (Costar, Cambridge, MA, USA) and incubated at 37°C in a 5% CO2 atmosphere for 1 h to allow the macrophages to adhere. The plate was then washed three times with sterile PBS to remove non-adherent cells. All the reagents used were found to contain less than 0·01 EU/ml of endotoxin with the Limulus amoebocyte lysate (BioWhittaker Inc., Walkersville, MD, USA). To test the ability of erythrocytes PD98059 in vitro to inhibit the IC-mediated stimulation of macrophages, ICs Y-27632 order were added to 108 erythrocytes in 10% AB+ serum

to a final concentration of 35 µg/ml in 150 µl and incubated at 37°C for 30 min. A separate set of negative control cells had either RPMI-1640 medium only or were incubated with 35 µg/ml purified rabbit IgG. The erythrocytes were then added to duplicate wells of a 96-well culture plate containing attached macrophages and 10 µg/ml of polymyxin B sulphate (Sigma-Aldrich). Positive control wells contained ICs without erythrocytes or LPS (Sigma-Aldrich) at a concentration of 7 µg/ml. To test the ability of IC-loaded red cells to stimulate macrophages, red cells were incubated with ICs as above, but following incubation they were washed three times with plain RPMI-1640

and added to duplicate wells containing macrophages as above. Negative control wells contained erythrocytes that were not loaded with ICs. To block IC-mediated stimulation of macrophages, some macrophage wells were pretreated for 30 min at 37°C with 20 µg/ml of endotoxin-free purified rabbit IgG Fc fragments (Jackson Immunoresearch, West Grove, PA, USA). The plates were incubated for 8 h at 37°C in a 5% CO2 atmosphere. At the end of the incubation, the supernatants were harvested and stored at −70°C. All incubations were performed Ceramide glucosyltransferase at room temperature and all washes were performed at least three times. Immulon HB 96-well plates (Thermo Labsystems, Helsinki, Finland) were coated overnight with 6 µg/ml anti-TNF-α monoclonal antibody (Thermo Fisher Scientific). The wells were then blocked with 200 µl of blocking buffer (PBS, 1% Tween 20, 0·5% boiled casein) for 2 h and washed in wash buffer (PBS–0·05% Tween). One hundred µl of macrophage culture supernatant, diluted 1:1 in dilution buffer (0·025% Tween–0·5% boiled casein), was added to each well followed by a 2-h incubation. A standard curve was prepared by making serial dilutions of a known sample of human recombinant TNF-α (Thermo Fisher Scientific). The plates were washed again and incubated for 1 h with a 1:400 dilution of biotinylated rabbit anti-TNF-α (Thermo Fisher Scientific).

1a and b. Reference Western strain 26695 (accession number: AE000511) has a single WSS and is thus classified as the ‘A-B′-C’ type, and the reference East Asian strain F32 (accession number: AF202972) has a single ESS and is thus classified as the ‘A-B-D’ type. These references were used for a comparison of the amino acid sequence alignment in the 3′ region. Among the Philippine East Asian CagA strains, there was a conserved sequence of 58 amino acids, indicated by letters in the box (Fig. 1a), which had only a single variation in strain PHL10. The Philippine Western CagA

strains showed much more variation between the EPIYA-A and the EPIYA-B motifs, as well as between the EPIYA-B and the EPIYA-C motifs (Fig. 1b). The homology of the nucleotide and amino acid sequences was determined (data not shown). In the East Asian group, the highest degrees of homology were 97.24% and 95.89%, and the lowest were 95.97% and 93.09%, for the CH5424802 mw full nucleotide and amino acid sequences, respectively. Among the Western CagA strains, the highest degrees of homology were 99.77% and 99.41%, and the lowest were 93.55% and 90.65%, for the full nucleotide and amino acid sequences, respectively. The Japanese representative strain for East Asian type CagA, F32, and the Western representative strain, 26695, were included for comparison with the Philippine strains. The highest degrees of homology of F32 and 26695 with

the Philippine strains were 97.10% and 95.60% for the nucleotide sequences, and 96.16% and 92.96% for PJ34 HCl the amino acid sequences, respectively. The lowest degrees of homology BMN 673 order were 86.53% and 87.35% for the nucleotide sequences, and 78.40% and 77.60% for the amino acid sequences, respectively. The phylogenetic tree of the complete amino acid sequences demonstrated the genetic relationship among the 19 Philippine strains, as well as 40 references (Fig. 2).

There were two major types: an East Asian and a Western type. In addition, there was a Japanese subtype in Western CagA type (J-Western CagA subtype) (Truong et al., 2009) composed of Okinawa strains. All East Asian CagA-positive Philippine strains based on the EPIYA motif were included in the East Asian cluster. In contrast, all Western CagA-positive Philippine, Thailand, and Vietnam strains based on the EPIYA motif were included in the major Western cluster, not in the J-Western CagA subtype. CagA is considered to be a major virulence factor associated with gastric cancer. We have reported that the grades of inflammation, activity of gastritis, and atrophy are significantly higher in gastritis patients infected with the East Asian CagA-positive strain than in gastritis patients infected with the CagA-negative or the Western CagA-positive strain (Azuma et al., 2004b). The prevalence of the East Asian CagA-positive strain is associated with the mortality rate from gastric cancer in Asia (Azuma, 2004). Endemic circulation of H.

On this basis, the selective killing of M2 macrophages by RAPA is not unexpected. In fact, we previously reported that in resting human monocytes, cell activation through three different signal pathways prevents death resulting from RAPA treatment: Target Selective Inhibitor Library high throughput GM-CSF/IL-3 receptors, TLR4 and IL-1β/TNF-α/IFN-γ receptors.[28]

As levels of IL-3, IFN-γ, IL1-β and TNF-α are all significantly higher in M1 than in M2 polarization, this can explain the M1 resistance to RAPA induced apoptosis. M1-polarized macrophages mediate resistance to intracellular pathogens and tissue destruction whereas M2-polarized cells are generally oriented to tissue remodelling and repair.[42] The target of RAPA action is the inhibition of mTOR, so our findings propose that the mTOR pathway is essential

in PLX4032 cost M2 but not in M1 macrophage survival. The mTOR acts as a central sensor for nutrient/energy availability[10] and it could provide an important homeostatic mechanism for controlling the number and the function of M1 and M2 macrophages in a manner dependent upon basal nutritional status. On this basis, we can speculate that in the presence of sufficient nutrients and energy, mTOR could relay a permissive signal for M2 survival, facilitating events that drive tissue remodelling and repair. On the other hand, in conditions of limited nutrient availability, as mimicked by RAPA treatment, mTOR could preferentially ‘sacrifice’ the M2 compartment, so preserving the resistance to pathogens due to the existence of mTOR-independent pathways that regulate M1 survival at the site of inflammation. Consistent with this hypothesis is the finding that RAPA treatment impairs wound healing in patients.[43] Moreover the relevance in regulating M2 survival could add a further explanation to activity of RAPA against cancer[44] and atherosclerosis development,[45] two diseases supported also by the presence of alternative activated macrophages.[46-48] In accordance with this, Chen et al.[49] recently reported that the Carnitine palmitoyltransferase II mTOR pathway is a critical element in the regulation of monocyte differentiation

to tumour-associated macrophages and that inhibition of mTOR by RAPA reduced tumour growth both in vitro and in vivo by modulating macrophage polarization. Beyond the impact on M2 survival, RAPA induced relevant modification of macrophage phenotype and cytokine/chemokine secretion in vitro. M1 macrophages appeared more affected than M2 and, as a general trend, RAPA unbalanced the system to classic activation. In fact, in M1 macrophages, RAPA increased the expression of CD86 and CCR7 and induced a significantly higher release of IL-6, TNF-α and IL-1β (markers of classic activation) while reducing the expression of CD206 and CD209 and the release of IL-10, VEGF and CCL18 (markers of alternative activation).

An opposite pattern was observed for progression of nephropathy. The authors note that the findings of the study are consistent with CVD studies and the role that SFAs may play in insulin sensitivity and other factors affecting diabetes control. Nonetheless, the authors consider that control of BP and blood glucose and cessation of smoking should remain the therapeutic objectives for modifiable risk factors. When these objectives are obtained, other measures such as encouraging PUFA and MIFA over SFA https://www.selleckchem.com/products/AP24534.html may help prevent micro and macroalbuminuria.118 Table A5 presents a summary of the relevant studies found by the search strategy

in relation to dietary fat. With the exception of the study by Cardenas et al.118 discussed above, the studies are either of short duration and thus provide little useful evidence for the role of dietary fat in the progression of CKD. Relevant details of the studies are provided in Table A12. In summary, there are insufficient reliable studies to support a recommendation in relation to the prevention and management of CKD in people with type 2 diabetes. Intake

of protein in the usual range does not appear to be associated Cisplatin ic50 with the development of CKD. However, long-term effects of consuming >20% of energy as protein on development of CKD has not been determined. Although diets high in protein and low in carbohydrate may produce short-term weight loss and improved glycaemic control, it has not been established that weight loss is maintained in the long term. There have been few prospective controlled studies of low protein diets in people with type 2 diabetes and kidney disease. The studies that have been performed have generally been deficient in experimental design, in methods for measuring kidney function and/or in duration of follow-up. Furthermore, the level of compliance with a low protein diet has not always been assessed objectively by urinary urea

nitrogen excretion. A particular criticism is that changes in the creatinine pool PIK3C2G and creatinine intake seen in low protein diet studies render measurements of creatinine clearance or the reciprocal of serum creatinine unreliable for the assessment of GFR.119 The objective of the systematic review was to assess the effects of dietary protein restriction on the progression of diabetic nephropathy in people with diabetes (type 1 and type 2 diabetes).120 The review identified 11 studies (9 RCTs and 2 before and after trials) where diet modifications were followed for at least 4 months. Before and after trials were included as it was considered that people could act as their own controls. Of these studies 8 were of people with type 1 diabetes, one type 2 diabetes and two included both type 1 and type 2 diabetes.

One such issue is related to drug-metabolizing enzymes. Glucocorticoids are mainly metabolized via phase I reaction involving the cytochrome P-450 3A4 and may also act as a potent inducer via selleck inhibitor glucocorticoid receptor [48,49]. Although little information is available on the effect of taurine on drug metabolism, it is worth-mentioning that it can act as a positive modulator of cytochrome P-450 3A4 induction

[50]. Then, over a long term of combined treatment with both drugs, an acceleration of drug metabolism may occur, potentially leading to a reduction of the therapeutic level of steroids in the patients. This possibility is merely speculative in light of the present data and we cannot exclude that a longer treatment with both drugs would be actually required to observe a greater effect on muscle histology as well as on other parameters, such as the heart function. In fact, taurine supplementation might exert a long-term protection over prednisolone-aggravated dystrophic C646 cardiomyopathy, an effect that could be observed in older

mdx mice [23,40]. The present data provide promising early evidence about potential benefits in associating PDN with taurine to enhance muscular function in dystrophic subjects; however, longer protocols are required to better understand the therapeutic advantage over the long-term use and to rule out the occurrence of any adverse outcome. The authors wish to thank Prof Diana Conte Camerino for helpful suggestions and comments. The financial support of Italian Telethon to the project number GGP05130 is gratefully acknowledged. “
“Intravascular

large B-cell lymphoma is a rare and aggressive lymphoma with a dismal prognosis. Synchronous intravascular large B-cell lymphoma within meningioma has not previously been documented. We report a case of a 73-year-old woman of Asian descent who presented with fever of unknown origin with generalized weakness. CT scan and MRI of the head revealed a dural-based mass lesion consistent with meningioma in the left frontal cerebral convexity. Surgery was performed to remove the tumor and histopathology showed a meningioma within which was a synchronous intravascular large B-cell lymphoma. The hematology and oncology services were consulted and palliative treatment was initiated due to the patient’s poor Eastern Cooperative Oncology Group performance Levetiracetam status. The patient died within 30 days post-surgery. To the best of our knowledge, this case represents the first report of synchronous intravascular large B-cell lymphoma within a meningioma. “
“Adenohypophysis (AH) hormone producing cells represent the origin of diverse groups of pituitary adenomas (PA). Deregulation of hypothalamic hormone receptors, growth factors and cAMP signaling have been implicated in the etiology of PA. Endogenous retroviruses (ERVs) are derived from past exogenous retroviral infections and represent more than 8% of the human genome.

It is unlikely that any single treatment option will significantly alter patient outcomes, but rather incremental

gains will be achieved with an integrated, multidisciplinary approach. BVM devices have had a moderate effect on the reduction of the incidence of IDH; however, its effects are limited to an at-risk population. The expansion and integration of these technologies to create an individual patient dialysis profile may prove more successful. The role of cool temperature dialysis shows greater promise in reducing IDH; however, there is still uncertainty about the necessary reduction in temperature to achieve optimal results. With the technologies available today, BTM technology is more mature and offers a relatively simple and effective means of combating IDH in susceptible patients. The widespread use of BVM and BTM monitoring in the general HD population, not prone to IDH, cannot be supported with the evidence CT99021 mw currently available. Ultimately, these technologies will need to be trialled in combination, in a way that demonstrates a mortality and morbidity benefit, and to effectively allow the determination of an individualized HD profile that can account for the multitude of dialysis and patient factors that contribute to IDH. “
“The BLOCADE Feasibility Study aims to determine the feasibility of a large-scale randomised controlled trial with clinical endpoints comparing FK506 supplier the beta-blocking

agent carvedilol to placebo in patients receiving dialysis. The BLOCADE Feasibility Study is a randomised, double blind, placebo-controlled, parallel group feasibility study comparing the beta-blocking agent carvedilol to placebo. Patients receiving dialysis for ≥3 months and who are aged ≥50 years, or who are ≥18 years and have diabetes or cardiovascular disease, are eligible. The primary outcome is the proportion of participants who complete Aurora Kinase a 6-week Run-in phase in which all participants receive carvedilol titrated from 3.125mg twice daily to 6.25mg twice daily. Other measures include how many patients

are screened, the proportion recruited, the overall recruitment rate, the proportion of participants who remain on study drug for 12 months and the incidence of intra-dialytic hypotension while on randomised treatment. The BLOCADE Feasibility Study commenced recruiting in May 2011 and involves 11 sites in Australia and New Zealand. The BLOCADE Feasibility Study will inform the design of a larger clinical endpoint study to determine whether beta-blocking agents provide benefit to patients receiving dialysis, and define whether such a study is feasible. “
“1. Targets Patients with diabetes, hypertension Those with family history of chronic kidney disease (CKD) Individuals receiving potentially nephrotoxic drugs, herbs or substances or taking indigenous medicine Patients with past history of acute kidney injury Individuals older than 65 years 2.