We analyzed the effect of IQGAP1 knockdown on actin and MT of confluent EC. The results indicate that IQGAP1 knockdown in EC monolayers decreases MT captured at the interendothelial junctions and decreases lymphocyte diapedesis. Further, drug-induced MT depolymerization decreases paracellular lymphocyte diapedesis. These results indicate that endothelial IQGAP1 tethers MT to interendothelial junctions and participates in junction remodeling during lymphocyte TEM. IQGAP1 has been shown to colocalize with AJ cadherin complex and regulate cadherin-mediated cell–cell

adhesion 24, 26, 27. In EC, we observed IQGAP1 enrichment at the interendothelial junctions (Fig. 1B). To study the role of EC IQGAP1 in lymphocyte TEM, endothelial IQGAP1 expression was inhibited by RNAi. IQGAP1 siRNA transfection of HUVEC consistently reduced IQGAP1 protein expression more than 80% (Fig. 1A–C). However, confluent Tanespimycin solubility dmso IQGAP1-knockdown EC monolayers developed normal AJ, reflected by β-catenin (Fig. 1E) and VE-cadherin (Fig. 2D) localization at the junctions, similar to the control monolayers (Figs. 1D and 2C). Further, analysis of cell surface expression of VE-cadherin and PECAM-1 by flow cytometry identified no change in IQGAP1-knockdown versus control cells (data not shown). Functionally,

electrical impedance across an IQGAP1-knockdown versus the control monolayer was unchanged (data not shown). Dorsomorphin Taken together, these data indicate that IQGAP1 is not required for the surface expression or assembly of endothelial junction components. Next, we sought to characterize the effect of IQGAP1 knockdown on EC cytoskeletal

components since IQGAP1 regulates dynamic filamentous-actin (F-actin) polymerization 23, 35, 36 and MT capture at the cell cortex 21–23. Biochemical analysis of free and polymerized tubulin within EC determined IQGAP1 knockdown decreased the ratio of polymerized tubulin to free tubulin levels in the cytosolic extracts Resveratrol (Fig. 2A and B). Further, measurements of MT density underlying junctions by immunofluorescent double-staining of VE-cadherin and tubulin indicated that tubulin fluorescence intensity per μm2 area adjacent to the VE-cadherin band among IQGAP1 knockdown EC (Fig. 2D and C) decreased by ∼40% (Fig. 2E). These data indicate that IQGAP1 knockdown induced loss of polymerized MT at the interendothelial junctions. To evaluate the effect of IQGAP1 knockdown on the actin cytoskeleton of confluent EC, the population of F-actin and globular-actin (G-actin) in cells was measured. Quantification of results by densitometry did not show any effect in F-actin content by IQGAP1 knockdown (Fig. 2F). Consistent with the biochemical assay, F-actin distribution did not change between IQGAP1 knockdown cells versus control cells by immunofluorescence microscopy (Fig. 2G and H).

Our findings constitute a novel demonstration of the extreme sensitivity of the TCR to minor alterations selleck screening library in peptide conformation. “
“Department of Obstetrics and Gynecology, Universite de Montreal, Sainte-Justine Hospital Research Centre, Montreal, QC, Canada Inflammation during pregnancy has devastating consequences for the placenta and fetus. These events are incompletely understood, thereby hampering screening and treatment. The inflammatory profile of villous tissue was studied in pregnancies at high-risk of placental dysfunction and compared to uncomplicated pregnancies. The systemic inflammatory profile was

assessed in matched maternal serum samples in cases of reduced fetal movements (RFM). Placentas from RFM pregnancies had a unique inflammatory profile characterized by increased interleukin (IL)-1 receptor antagonist and decreased IL-10 expression, concomitant with increased numbers of placental macrophages. This aberrant cytokine profile was evident in maternal serum in RFM, as were increased levels of alarmins (uric acid,

HMGB1, cell-free fetal DNA). This distinct inflammatory profile at the maternal-fetal interface, mirrored in maternal serum, could represent biomarkers of placental inflammation and could offer novel therapeutic options JQ1 supplier to protect the placenta and fetus from an adverse maternal environment. “
“Severely burned mice are susceptible to sepsis stemming from Enterococcus faecalis translocation due to the impaired generation of M1 macrophages (M1Mϕs) in local translocation sites. In our previous studies, CCL2 has been characterized as a major effector molecule on the burn-associated generation of M2Mϕs, an inhibitor cell type for resident Mϕ conversion into M1Mϕs. In this study, we tried to protect burned mice orally infected with E. faecalis utilizing CCL2 antisense oligodeoxynucleotides (ODNs). We show that M2Mϕs in mesenteric lymph nodes (MLNs) were not demonstrated in burned mice treated with CCL2 antisense ODNs. M1Mϕs were not induced by heat-killed E. faecalis from resident Mϕs transwell-cultured with mesenteric lymph

node macrophages Methane monooxygenase (MLN-Mϕs) from burned mice, while M1Mϕs were induced by the same antigen from resident Mϕs transwell-cultured with Mϕs which were isolated from burned mice treated with CCL2 antisense ODNs. Bacterial growth in MLNs was shown in burned mice orally infected with a lethal dose of E. faecalis. However, after the same infection, sepsis did not develop in burned mice treated with CCL2 antisense ODNs. These results indicate that bacterial translocation and subsequent sepsis are controlled in burned mice orally infected with a lethal dose of E. faecalis by gene therapy utilizing CCL2 antisense ODNs. Infectious complications are responsible for a high mortality rate of thermally injured patients.

By this account, multitalker variability might be only one of many types of variability that could yield this same effect. Variability in noncontrastive cues (as is prevalent in infant-directed speech) has been thought to be helpful for word and language

learning in young infants, although relatively few reports indicate that this is indeed supportive of learning, as opposed to merely preferred by infants. Singh (2008) is a notable exception. She familiarized 7.5-month-olds to words using both high- and low-affect productions, and found that infants only segmented the words in the presence of high affective variability, that is, high prosodic variability. Similarly, infants segment words from infant-directed speech but not adult-directed speech in novel speech strings containing statistical cues to word boundaries (Theissen, Hill, & AG-014699 order Saffran, 2005). This raises the possibility that highly variable prosody alone may be sufficient to support word learning in this task, as well. These results suggest that the established view that infants use the statistical structure of contrastive cues to learn phonological categories (Kuhl et al., 2007; Maye et al., 2002, 2008; McMurray et al., 2009; Vallabha et al., 2007) may be incomplete. We suggest that by 14 months, even though infants appear to discriminate tokens within a dimension, they might not

be fully committed to VOT as a relevant dimension for distinguishing words that vary in voicing, and must determine which dimensions are relevant by examining relative variability. Of course, the behavioral experiments reported here and in Rost and Decitabine cell line McMurray (2009) do not offer definitive proof of our dimensional weighting account. Further empirical and computational work will be necessary to fully establish this account. However, as we argue in the subsequent sections, the dimensional weighting account is consistent with both the task demands framework for explaining the switch task and with broader exemplar models of speech (e.g., Pierrehumbert, 2003). Moreover, the use of relative Palbociclib chemical structure variability as a mechanism of weighting crops up in numerous domains of learning and may represent a general principle of learning. Thus, when the

present behavioral data are coupled with the seeming universality of such mechanisms and strong computational models (Apfelbaum & McMurray, 2010; Toscano & McMurray, 2010a), this seems to be quite a reasonable explanation. In the task demands framework (Werker & Curtin, 2005; Werker & Fennell, 2006), attentional demands on the infant create an apparent U-shaped developmental trend where infants’ speech perception abilities are intact and preserved, but infants are unable to access them in a difficult task, as they struggle to balance perceptual, phonological, and lexical representations. There is no doubt that the switch task is particularly hard. Infants fail at the switch-task test but succeed at the easier looking-preference test (Yoshida et al., 2009).

Tfh cells can enter the follicle and secrete cytokines and other molecules to help the formation of germinal centre (GC), high-affinity long-living plasma cells and memory B cells [15, 16]. A previous study has shown a higher frequency of Tfh cells and increased levels of anti-CCP antibodies in patients with new-onset RA [17]. However,

how Tfh cells are associated with different stages of differentiated B cells in the pathogenesis of RA is not fully understood. In addition, how these immunocompetent cells respond to the commonly used therapies of disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) and Tripterygium wilfordii PF-02341066 molecular weight in RA patients has not been clarified. T. wilfordii, a Chinese herb, has potent immunosuppressive activity and has been used for the treatment of RA in the clinic for some time [18, 19]. In the current study, we characterized the frequency of Tfh and different stages of differentiated B cells in 25 patients with new-onset RA and 1 month after therapies

with T. wilfordii and DMARDs as well as 15 gender- and age-matched healthy controls. Our findings suggest that activated B and Tfh cells may contribute to the pathogenesis RO4929097 cell line of RA and the frequency of activated B and Tfh cells may be used as a biomarker for evaluating the therapeutic responses of individual patients with RA. A total of 25 patients with new-onset RA (<6 months of disease duration) were recruited sequentially at the in-patient service of the First Hospital and China–Japan Union Hospital of Jilin ZD1839 University from February 2013 to May 2013. Another 15 gender-, age- and ethnicity-matched HC were recruited during the same period and they had no history of any chronic inflammatory disease. Individual patients with RA were diagnosed according to the diagnosis criteria established by the American College of Rheumatology [20] and the disease severity of individual

patients was evaluated using the disease activity score 28 (DAS28) [21]. Individual RA patients were excluded if she/he received treatment with DMARDs, corticosteroids or immunosuppressive for any reason during the past 6 months or had other chronic inflammatory and autoimmune diseases, such as diabetes, multiple sclerosis, inflammatory bowel disease, metabolic syndrome, hypertension, cardiovascular diseases, cancer or recent infection. Written informed consent was obtained from individual subjects and the experimental protocol was approved by the Ethical Committee of the First Hospital of Jilin University. Demographic and clinical characteristics, including age and gender, were recoded by physicians and are shown in Table 1.

There is some experimental evidence supporting this contention. Earlier studies described that antigens of A. suum potentiate ‘reaginic’ response to ovalbumin (95,96). Also, Ascaris pseudocoelomic body fluid and the purified allergen ABA-1 prolonged the response to ovalbumin as third-party allergen, but they did not enhance the IgE

levels to this allergen (97). In another investigation, co-administration of hen egg lysozyme with the excretory/secretory products of N. brasiliensis results in the generation of egg-lysozyme-specific lymphocyte proliferation, IL-4 release and IgG1 antibody responses, supporting the role of some nematode products as adjuvants for third-party antigens (98). Furthermore, it has been shown that unidentified components in the body fluid

of Ascaris promote a Th2 response and are adjuvants for specific Quizartinib IgE synthesis to some parasitic allergens like ABA-1 (57). Because, in addition to this allergen, A. lumbricoides extract has at least 11 human-IgE-binding components, the BAY 73-4506 research buy adjuvant effect may be more generalized (24), and because of co-exposure, this could happen for cross-reactive and non-cross-reactive mite allergens, a process that may have roots in the co-evolutionary relationship between worms and vertebrates (99). Based on their findings from early epidemiological studies, Lynch et al. (100,101) suggested that the prevalence of allergies may be lower in individuals with high parasite burdens of geohelminths compared with those with low burdens. This idea is now widely accepted and has been related to the acute and chronic clinical phenotypes observed in helminth-infected humans (102). In addition, intermittent mass de-worming programmes in preschool and school-aged 4��8C children (103) reduce parasite burdens and boost the immune response to the parasites, because reinfections may elicit immune responses different in nature from the original primary infections (102). Therefore, it is theoretically possible that, in the presence of

intermittent infections with low worm burdens, exposure to A. lumbricoides promotes allergic sensitization and asthmatic symptoms by increasing the synthesis of parasite-specific, mite-specific and mite–parasite cross-reacting IgE antibodies. The clinical impact may be particularly important in urban zones of underdeveloped countries, because in rural areas, the infections are usually more intense and associated with higher degrees of immunosuppression. Also, differences in mite fauna and levels of mite allergen exposure may influence the type of sensitization and, in consequence, the relevance of cross-reactivity. Cross-reactivity is a frequent feature of the adaptive immune response, involving antibodies or T lymphocyte receptors directed to diverse molecules (antigens or allergens) and resulting in diverse biological or clinical effects.

18G AUTOMATED NEEDLES   J Mai, A Aravindan, H Dickson, J Yong, M Suranyi, J Wong   228 URINARY TRACT INFECTIONS AT LIVERPOOL HOSPITAL   Z Hasan, M Maley, M Surany, J Wong   229 THE INFLUENCE OF DIETARY VITAMIN D INTAKE ON VITAMIN D STATUS IN CHRONIC KIDNEY DISEASE PATIENTS   E Murray, K Campbell, L Orazio, N Isbel, W Petchey   230 AGE AND SERUM CALCIUM ARE ASSOCIATED WITH INFRA-RENAL AORTIC CALCIFICATION IN PATIENTS WITH CHRONIC KIDNEY DISEASE   R Dua, B Nguyen, K Sangla, J Golledge   231 VITAMIN D INSUFFICIENCY AND CHRONIC KIDNEY DISEASE IN AUSTRALIA: THE AUSDIAB STUDY   M Damasiewicz, D Magliano, R Daly, C Gagnon, Z Lu, P Ebeling,

S Chadban, R Atkins, P Kerr, J Shaw, K Polkinghorne 1300–1400 LUNCH & TRADE EXHIBITION  

Hall G 1400 ASM CONCLUDES “
“Aims:  The aims of this study is to correlate colour duplex ultrasonography (US) with contrast fistulography for the detection of functional stenoses in the check details autogenous AVF (arterio-venous fistula) circuit. Methodology:  Colour duplex US scans of 93 dialysis patients with dysfunctional CT99021 mw AVF were compared with fistulograms performed within 6 weeks of the US. The AVF circuit was divided into six zones: inflow artery; anastomosis; distal vein; mid vein; proximal vein; and central vein. Colour duplex US and fistulogram images/reports were independently re-reported for stenoses in each fistula zone by two trained clinicians blinded to the outcomes. For each fistula, only zones examined by both modalities were included in the study. Kappa analysis of the results was performed to assess the accuracy of colour duplex US in the dysfunctional AVF circuit. Results:  Most AVF studied were radio-cephalic (59%) or brachio-cephalic (22%). Stenoses identified within the AV circuit in order

of frequency were: distal vein (41), mid vein (23), arterial (12), proximal vein (7) and anastomosis (3). The interval between US and fistulogram studies was 33 ± 29 days. Congruence of results between US and fistulograms ranged from 85% to 96%, depending on the zone examined. Kappa analysis of this US versus fistulogram data was also moderate to good, ranging from 0.72 and 0.91. Conclusions:  Colour duplex US provides an accurate Celastrol diagnostic assessment of a dysfunctional autogneous AVF, and is an important planning tool for subsequent open or endovascular intervention. It is particularly accurate in the peri-anastomotic area of the fistula which harbours the majority of fistula problems. “
“Aim:  3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may have an adjunctive effect on chronic inflammation and nutrition status in renal dialysis patients. Therefore, we performed a systematic review of randomized controlled trials to assess the effect of statins on chronic inflammation and nutrition status in dialysis patients.

melitensis. In this work, we use as a clumping strain a B. melitensis 16M strain overexpressing aiiD (an AHL-acylase that destroys the QS signal molecules) called MG210. The characterization of the clumps produced by this strain allowed us to demonstrate the presence of exopolysaccharide(s), DNA and OMVs, three classical components of extracellular matrices. https://www.selleckchem.com/products/bmn-673.html Moreover, here, we provide the first structural information on the complex exopolysaccharide produced by B. melitensis 16M since we found that its molecular weight is about 16 kDa and that it is composed of glucosamine, glucose and mostly mannose. In addition, we found the presence of 2- and/or 6- substituted

mannosyl residues, which provides the first insights into the linkages involved in this polymer. We demonstrate that the MG210 strain displays increased adherence properties both on polystyrene and on HeLa cell surfaces. Taken together, our data reinforce the evidences that B. melitensis could form biofilms in its lifecycle. All the strains

and plasmids used in this study are listed in Table 1. Brucella strains were grown with shaking at 37 °C in 2YT medium (10% yeast extract, 10 g L−1 tryptone, 5 g L−1 NaCl) containing appropriate antibiotics from an initial OD600 nm of 0.05. The Escherichia coli DH10B (Gibco BRL) and S17-1 strains were grown in Luria–Bertani medium with appropriate Tamoxifen molecular weight antibiotics. Chloramphanicol and nalidixic acid were used at 20 and 25 μg mL−1, respectively. For exopolysaccharide purifications, Brucella were grown in RPMI 1640 medium supplemented with 10 g L−1 of d-xylose and appropriate antibiotics. DNA manipulations were performed according to standard techniques (Ausubel et al., 1991). Restriction enzymes were purchased from Roche, and primers were purchased from Invitrogen. Derivatives of the replicative plasmids pRH001 and pRH002 Axenfeld syndrome (Hallez et al., 2007) harboring aiiDsuis or aiiDmelitensis were constructed using the Gateway technique (Invitrogen). The destination

vectors pRH001 and pRH002 harbor a chloramphenicol resistance (cat) marker and the toxic cassette ccdB. This group of genes is flanked by attR1 and attR2 recombination sites. The wild-type allele corresponding to the total AiiD protein of Brucella suis (amino acids 1–761) was amplified with primers AiiD-B1 (5′-ATGAACGTCGCGAGTGCC-3′) and AiiD-B2 (5′-AAGATGGCTGCATAATC-3′). The wild-type allele corresponding to the total AiiD protein of B. melitensis (amino acids 1–782) was amplified with primers AiiD-B3 (5′-ATGAACGTCGCGAGTGCC-3′) and AiiD-B4 (5′-AAGATGCCTGCATAATCAGG-3′). Brucella melitensis 16M genomic DNA was used as the template for all amplifications. The resulting PCR products (aiiDsuis and aiiDmelitensis, respectively) were cloned into pDONR201 (Invitrogen Life Technologies) by the BP reaction as described previously (Dricot et al., 2004).

Colony formation was investigated by crystal violet staining. Strong expression of TLR7 was detected in the normal prostate epithelia of Wild-type (WT) mice, but not in TLR7-deficient mice. In contrast, TLR7 expression was weak in transgenic adenocarcinoma of mouse prostate (TRAMP)-C2 cells, as compared with murine bone marrow-derived macrophages (BMDMs). Moreover, TLR7 mRNA was markedly expressed in RWPE-1 cells (non-cancerous prostate epithelial cells), but not in PC3 and DU145 (prostate cancer cells). Immunohistochemically, TLR7 expression Venetoclax cell line gradually

decreased in TRAMP mice depending on the pathologic grade of the prostate cells. TLR7 agonists increased both the gene and protein expression of TLR7 and promoted production of proinflammatory cytokines/chemokines and IFN-β gene expression in prostate cancer cell lines. Moreover, loxoribine inhibited

the growth and colony formation of TRAMP-C2 cells dependent of TLR7. These findings suggest that TLR7 may participate in tumour suppression in the prostate cells. “
“Quantitative PCR is becoming widespread for diagnosing and monitoring post-transplantation diseases associated with EBV and CMV. These assays need to be standardized to manage patients in different facilities. Five independent laboratories in Japan compared home-brew assays and a prototype assay system to establish a standard quantitative procedure for measuring EBV and CMV. Reference standards and a total of 816 (642 EBV and 174 CMV) whole blood samples from post-transplantation recipients were used for this multicenter evaluation. The for prototype reference standard for EBV was compared to a panel of samples, with a theoretical expected value XL765 datasheet made using EBV-positive cells containing two virus genome copies per cell. The mean ratio of the reference standard at each site to the standard of the prototype assay was ≤4.15 for EBV among three different sites and ≤3.0 for CMV between two laboratories. The mean of the theoretical expected number of the EBV genome: prototype reference

was close to 1.0. The correlation coefficients between the viral copy numbers determined using the prototype assay and those using each home-brew assay were high (EBV, 0.73–0.83, median = 0.78; CMV, 0.54–0.60, median = 0.57). The dynamics of the EBV and CMV loads in transplant recipients were similar between the assay types. There was an inter-laboratory difference among the quantification results, indicating that a unified protocol and kit are favorable for standardizing the quantification of EBV and CMV. Such standardization will help to standardize the diagnosis and monitoring of diseases associated with EBV and CMV. Herpes viruses are widespread pathogens in the human population and often become reactivated in latently infected immunocompromised patients. These viruses thus frequently occur after hematopoietic stem cell and solid organ transplantation, and occasionally result in symptomatically severe disease (1, 2).

Over the next 3 years she suffered from recurrent sinusitis, otitis media, chest infections (sputum cultures positive

for Moraxella catarrhalis and Haemophilus species) and viral warts. She has a sister with features of DBA – low haemoglobin at 10·4 g/dl, raised mean corpuscular volume (MCV), lymphopenia, elevated fetal haemoglobin (HbF) (3%), high erythrocyte adenosine deaminase (eADA) levels, mildly reduced T cell numbers and slight reduction in proliferative responses to standard mitogens. The sister’s immunoglobulin levels, including functional antibody levels, are normal and she has not required any specific therapy for her anaemia. Investigations in infancy showed a normocytic Enzalutamide anaemia, normal serum immunoglobulins [IgG 7·3 g/l (normal range 3·0–10·5), IgA 0·28 g/l (0·1–1·2), IgM 1·07 g/l (0·3–1·5)] and good vaccine responses to conjugated Haemophilus influenzae type b and unconjugated pneumococcal polysaccharide vaccines. By the age of 9, serum IgG levels had dropped to 4·94 g/l (normal range 6·0–13·0). Lymphocyte proliferation responses to phytohaemagglutinin, pokeweed mitogen, OKT3, tetanus, varicella JQ1 order and herpes antigens were reduced. Intravenous immunoglobulin (IVIG) replacement therapy was commenced, and stopped after 8 years for reassessment of immune function. Four years later, she had persistent anaemia (Hb 10·0 g/dl, MCV 95·6fl) and low IgG (3·37 g/l), IgA (0·96 g/l) and IgM (0·79 g/l). Bone marrow cytogenetic

studies

were normal, excluding microdeletions in 19q13 and 5q- syndrome. Specific antibody tests showed absent antibodies against measles and reduced tetanus and pneumococcal antibody levels. She was diagnosed to have common variable immunodeficiency as no other causes of low IgG and low levels of specific antibodies were identified. High resolution CT scan chest showed evidence of right middle lobe bronchiectasis and bilateral lower lobe bronchiectasis worse on the left. Intravenous immunoglobulin therapy was recommenced at this stage. Lymphocyte subset analysis showed lymphopenia at 833 × 106/µl (normal range 1500–3500), CD3+ T cells 536 (800–2700), helper CD4+ T cells 291 (400–1700), cytotoxic CD8+ T cells 191 (300–1200), CD19+ B cells 158 (100–600) and CD16+CD56+ Methane monooxygenase natural killer cells 32 (90–600). B cell studies showed a reduced class-switched memory B cell subset at 2·5%. Lymphocyte proliferation responses to OKT3, phytohaemagglutinin and pokeweed mitogen remained reduced (see Table 1). Peripheral blood eADA level performed recently was high at 594 (normal range 40–100 u/l), consistent with the diagnosis of DBA. She has remained well on home therapy with weekly subcutaneous immunoglobulin infusions over the last 3 years. Polymerase chain reaction (PCR)-based methods for mutation detection.  Genomic DNA was extracted from the patient’s leucocytes with a commercial DNA purification kit, as per the manufacturer’s instructions.

Clotting in the dialysis circuit is triggered by both the extrinsic and the intrinsic pathways at the same time but to different degrees depending on the composition of the dialysis membrane and design and composition of the lines. Once the blood flow is initiated, plasma proteins deposit on the dialyser surface, and factor XII and high-molecular-weight kallikrein accumulate and act as initiating factors for contact coagulation

selleck inhibitor – the Intrinsic Pathway. Peripheral blood leucocytes and monocytes, which contact the dialyser membrane, become adherent or activated and release blebs of surface membrane rich in tissue factor – activating the Extrinsic pathway. Platelets become activated by contact and in response to turbulent flow and high shear stress. The surface of platelets provides an enhancing environment promoting the interaction of coagulation cascade components. These triggers activate the clotting cascade, platelet aggregation, activation and degranulation, cytokine release and activation of circulating white cells, all of which can contribute in differing degrees to the triggering of or progressive activation www.selleckchem.com/products/apo866-fk866.html of the clotting cascade leading to thrombosis in the dialysis circuit. Anticoagulation is routinely required to prevent clotting of the dialysis lines

and dialyser membranes, in both Parvulin acute intermittent haemodialysis and

continuous renal replacement therapies.5 As the field of anticoagulation is constantly evolving it is important to regularly review advances in knowledge and changing practices in this area.6 The responsibility for prescribing and delivering anticoagulant for haemodialysis is shared between the dialysis doctors and nurses. Dialysis is a medical therapy, which must be prescribed by an appropriately trained doctor. The prescribing doctor usually determines which anticoagulant agent will be used and the dosage range. The doctor’s prescription may include broad instructions such as ‘no heparin’, ‘low heparin’ or ‘normal heparin’. In a mature dialysis unit the dose and delivery of anticoagulant is, however, the responsibility of professional and experienced dialysis nurses, who have latitude within parameters determined by detailed written policies or standing orders. Dosing regimens, while generally safe and effective, are somewhat unscientific. In terms of monitoring, most units do not practise routine monitoring, although the anticoagulant effect of unfractionated heparin (UF heparin) can be monitored with some accuracy by the APTT or the activated clotting time tests where indicated. The dialysis nurses know there is too much anticoagulation if the needle sites continue to ooze excessively for a prolonged period (e.g. more than 15 min) after dialysis.