Signaling Pathway Blog

Ach also lowers PP2Ac phosphorylation (without affecting total PP2Ac levels) that activates the enzyme to block arginine methylation of STAT1. The reduction in STAT1 attachment to DNA finally results in diminished expression of antiviral protein, OASL, which reflects suppressed ISGs activation. In conclusion, Ach and HCV synergize to disrupt IFNa signaling by suppressing STAT1 phosphorylation

and PP2Ac-dependent induction of STAT1-PIAS1 complex formation, leading to impaired attachment of STAT1 to DNA to subsequently lower the expression of anti-viral ISG products. Thus, ethanol metabolism further http://www.selleckchem.com/products/ly2157299.html impairs anti-viral protection in the already HCV-compromised hepatocytes, thereby enhancing viral spread to neighboring non-infected alcohol-sensitized liver cells. Disclosures: The following people have nothing to disclose: Murali Ganesan, Lee K. Jaramillo, Kusum K. Kharbanda, Dean J. Tuma, Natalia A. Osna A new oral form of pentamidine, OCZ103, has been developed for the treatment of liver disease. Oral administration of OCZ103 specifically targets the liver where drug concentrations are 15- to 150-fold greater than in other organs such as the pancreas and kidney. The known anti-inflammatory effects of pentamidine,

together with the favorable hepatic bioavailability of OCZ103, suggested that OCZ103 may be effective in the treatment of liver diseases mediated by overactivation of the innate immune response. We therefore tested the hypothesis that Talazoparib solubility dmso OCZ103 would protect mice against TNF-dependent liver injury and mortality induced by galactosamine/lipopolysaccharide (GalN/LPS). Methods: C57BL/6 mice were pre-treated with vehicle control or OCZ103 IP 30 min prior to GalN/LPS administration

and evaluated for effects on liver injury and survival. Results: Liver injury from GalN/LPS was markedly reduced by OCZ103 MCE as demonstrated by statistically significant decreases in serum ALT (177 vs. 5,632 IU/ml; P<0.002) and histological grade of liver injury (1.7 vs. 3.7; P<0.001) at 6 h. As a result, hepatocyte death as detected by TUNEL staining was also significantly prevented (2.1 vs. 75.8 TUNEL positive cells/HPF; P<0.0002). Survival after GalN/ LPS administration was also markedly improved in OCZ103-treated mice. All vehicle-treated mice were dead within 8 h whereas OCZ103-treated mice had survival rates of 100% at 8 h, 67% at 12 h, and 33% at 24 and 48 h (P<0.001). Mechanistic studies revealed that OCZ103 blocked mitochondrial death pathway activation as immunoblot analysis demonstrated that cytosolic and mitochondrial levels of pro-apoptotic tBid were markedly decreased in OCZ103-treated mice. As a result, release of mitochondrial cytochrome c into the cytosol was blocked and downstream caspase 3 and 7 and PARP cleavage was prevented on Western blot analysis.

Disclosures: The following people have nothing to disclose: Nisanne Ghonem, Meena Ananthanarayanan, Carol J. Soroka, James L. Boyer ”
“The aim of this study was to clarify which or how factors could influence the

probability of sustained virological response (SVR) in 24-week telaprevir-based triple combination therapy for East Asian chronic hepatitis C patients infected with hepatitis C virus genotype 1b. Of 140 patients who were enrolled in this study, 137 received 12-week telaprevir combined with 24-week pegylated interferon alpha-2b plus ribavirin and were subjected to the analysis. Factors associated with SVR were analyzed by multiple logistic regression analysis. Of the 137 patients, 112 (82%) achieved SVR. Of 87 patients ITF2357 order with IL28B single nucleotide polymorphism rs8099917 genotype TT, 84 (97%) achieved SVR. By contrast, 28 of 50 (56%) patients with the genotype TG/GG had SVR

(P = 3.29 × 10−9). Fifty-three of 60 (88%) naïve patients and 50 of 54 (93%) prior relapsers achieved SVR. Nine of 13 (69%) prior partial responders and none of 10 (0%) prior null responders achieved SVR. Multivariable analysis identified four independent factors that were significantly associated with SVR: IL28B SNP rs8099917 genotype (P = 6.90 × 10−5), pre-existence of cirrhosis (P = 3.99 × 10−3), prior treatment response (P = 0.0126), and rapid virological response (P = 0.0239). The IL28B single nucleotide polymorphism still remained informative as a predictor Forskolin supplier of SVR to 24-week telaprevir-based triple combination therapy for East Asian patients infected with hepatitis C virus genotype 1b. Telaprevir is an

orally bioavailable peptidomimetic inhibitor of the hepatitis C virus (HCV) non-structural (NS) 3/4A serine protease.[1] Phases 2 and 3 studies conducted in the United States, Europe, and Japan have proved that this direct-acting antiviral agent (DAA) combined with pegylated interferon (peg-IFN) alpha-2a or -2b plus ribavirin (RBV) substantially increases the rate of sustained virological response (SVR) in treatment-naïve and previously treated patients infected with HCV genotype 1, albeit with higher rates of discontinuation because of adverse events, compared with peg-IFN alpha/RBV 上海皓元 combination alone.[2-10] Based on the proved efficacy and safety, the telaprevir-based triple therapy for chronic hepatitis C (CH-C) with HCV genotype 1 has been approved by each government organization.[11-13] Since November 2011, in Japan, patients have been receiving 12-week telaprevir in combination with 24-week peg-IFN alpha-2b/RBV by utilizing the government subvention. Numerous studies have reported that various host-, virus-, and treatment-related factors are associated with the outcome of peg-IFN alpha/RBV combination therapy for CH-C.

An alternative technique is to identify the supraorbital ridge by palpation. The needle is then inserted lateral to the ridge and is advanced medially MG-132 concentration into the subcutaneous tissue. After

negative aspiration, the solution is injected. Pressure should be applied to avoid periorbital hematoma. Drugs to use: lidocaine 1%-2% (10-20 mg/mL) and/or bupivacaine 0.25%-0.5% (2.5-5 mg/mL). If a combination of the 2 drugs is used, the recommended volume ratio (lidocaine/bupivacaine) is 1:1-1:3. We do not recommend the use of corticosteroids in this area, or in other trigeminal territories. Volume of injection: 0.2-1.0 mL per nerve. For patients who require repeated injections, the recommended frequency of treatments is once every 2-4 weeks, depending on the response of the individual patient. The SON is the larger of the 2 terminal branches of the frontal nerve. It courses through the supraorbital

notch or foramen and supplies palpebral filaments to the upper eyelid and conjunctiva. It then ascends on the forehead with the supraorbital artery and divides into medial and lateral branches, which supply the skin of the scalp almost as far back as the lambdoid suture. The medial branch pierces the occipitofrontalis muscle to reach the skin, while the lateral branch penetrates the epicranial aponeurosis over the forehead and scalp. Postganglionic sympathetic PD0332991 price fibers, which innervate the sweat glands of the supraorbital area, are thought to travel in the SON. The supraorbital notch or foramen lies on the superior aspect of an imaginary line coursing caudally and intersecting the pupil, the infraorbital foramen, and the mental foramen. Location of injection: above the supraorbital medchemexpress notch. Technique of injection: use a 1 mL syringe with a 30-gauge, 0.5-inch needle. Insert

the needle at the corrugator muscle, at the mid-pupillary line (Fig. 2 —). After negative aspiration, the solution may be injected at a depth of 3-4 mm. An alternative technique is to identify the supraorbital notch by palpation, at the superior margin of the orbit, mid-pupillary line. The needle is then advanced medially and inserted at a slight angle to avoid entering the foramen. The solution then may be injected at a depth of 3-4 mm, after negative aspiration. Pressure should be applied to avoid periorbital hematoma. Alternatively, after blocking the STN, redirect the needle laterally and inject. Drugs used and volume of injections are the same as for the STN block. The ATN surfaces onto the face from behind the temporomandibular joint (TMJ) within the superior surface of the parotid gland. It ascends close to the superficial temporal artery, passes over the posterior portion of the zygoma, and divides into superficial temporal branches. The cutaneous branches of the ATN supply the tragus and part of the adjacent auricle of the ear and the posterior part of the temple. The ATN also provides sensory innervation to the majority of the TMJ.

21 Obesity can also be considered a risk factor for liver tumors through activation of IL-6. Lipid accumulation induces a low-grade inflammatory response. Mice fed a high-fat diet have higher circulating levels of IL-6 and develop HCC more frequently than mice fed a low-fat diet.22 Mice lacking IL-6 display an attenuation of tumorigenesis.22 Experimental and clinical evidence show that low-grade hepatic inflammation provides a permissive environment for malignant transformation and proliferation of hepatocytes.

Currently, sophisticated molecular indices are being investigated for diagnostic and predictive value. Hoshida et al.23 describe a transcriptomic signature in tumor surrounding tissue, which predicted survival after HCC resection. This signature contained a gene set associated with inflammation and downstream targets compound screening assay of IL-6. The cause for this inflammation without overt infection might be the activation of the innate immune system by translocation of bacterial components from the gut, since gut sterilization reduced HCC in an experimental model of hepatocarcinogenesis.24 LBH589 in vivo CRP was not explicitly investigated. Investigations are needed to determine whether CRP levels reflect subclinical bacterial

translocation in cirrhosis patients and to compare the predicative value of CRP levels with other transcriptomic signatures in late HCC recurrence. Does CRP represent an inexpensive, simple prognostic marker for patients with HCC? Peck-Radosavljevic and colleagues’ current work appears to indicate that it

does, at least in the population of HCCs not amenable for surgery. In particular, CRP was a convincing outcome predictor for BCLC stages B and C, refining the prognosis of Child A and Child B patients. The testing of CRP levels as a variable in the design of trials and in the selection of patients for treatment is warranted. BCLC, Barcelona Clinic Liver Cancer; CRP, C-reactive protein; HCC, hepatocellular carcinoma; IL-6, interleukin-6; TIPS, transjugular intrahepatic portosystemic shunt ”
“Aim:  Activator protein 2α (AP-2α) belongs to the AP-2 family of transcription factors that are involved in the regulation of cell proliferation, differentiation, apoptosis and carcinogenesis and MCE公司 has been suggested to function as a tumor suppressor in many cancers. However, the physiological role of AP-2α in hepatocytes is unknown. The present study is to characterize the expression and function of AP-2α in the liver of conscience mouse. Methods:  Exogenous AP-2α was overexpressed in the mouse liver by in vivo gene delivery and changes in transcription factor expression were identified by using protein-DNA arrays and immunoblotting. Results:  Western blotting and protein/DNA arrays showed that AP-2α is expressed in the nuclei of mouse hepatocytes. Overexpression of AP-2αin vivo significantly suppressed transcription factors AP-1, CREB and c-Myc, and markedly increased CBF, c-Myb, NF-1, Pax-5, RXR, Smad3/4, TR(DR-4), USF-1 and GATA.

There were more HCV+ recipients (51.5% vs. 34.7%, p=0.03) in the DDLT group, but no differences in other demographics, rejection, graft failure or death. The prevalence of +DSA pre/post-LT (p=0.93, Table) was not different between DDLT and LDLT. There

was also no association between patient survival and the timing (pre/post), class (I vs. II), and titer of DSA between the groups. However, pre-LT DSA+ was associated with higher graft failure only in DDLT (p=0.01). Post-LT DSA+ was associated with graft failure regardless of LT type (p=0.005) but with rejection only in DDLT (p=0.0001). Biliary complications were higher in LDLT vs. DDLT (p<0.001) but independent of DSA. There was no difference in HCV recurrence or vascular complications in both ± DSA. Conclusion: Although preformed or de novo DSA have a similar prevalence

HM781-36B order in DDLT vs. LDLT, they are associated Ensartinib chemical structure with adverse graft outcomes (graft survival, rejection), mainly in DDLT. While our findings need further validation, future research should focus on mechanisms of DSA graft injury and strategies to mitigate the impact of DSA, particularly in the DDLT setting. Prevalence of Pre/Post-LT DSA (DDLT vs. LDLT) Disclosures: Josh Levitsky – Consulting: Transplant Genomics Inc; Grant/Research Support: Novartis; Speaking and Teaching: Gilead, Salix The following people have nothing to disclose: Anat R. Tambur, R Carlin Walsh, Chunfa Jie, Joseph Kang, Hugo Kaneku, Michael M. Abecassis Background: Liver resection constitutes the only curative option for intrahepatic and hilar Cholangiocarcinoma (CCA). The aim of this work was to analyze the outcome of patients undergoing liver resection for CCA, and to revisit the biological and surgical determinants of outcome, and the role of neoadjuvant and additive therapeutic 上海皓元 modalities in our single-center cohort of patients during the

last decade. Methods: Using a prospec-tively filled database of all consecutive patients undergoing surgery due to a preoperative diagnosis of hepatobiliary malignancy between December 2001 and May 2011 (n=936) at the Department of General, Visceral, and Transplant Surgery at the University of Heidelberg, demographic, anatomical, clinical, operative, surgical pathologic and follow-up data of all patients with a final diagnosis of CCA was analyzed. Results: A final surgical pathologic diagnosis of CCA was made for 236 patients. CCA was found to be intrahepatic (IHCCA, n=117, 50%), proximal extrahepatic -hilar or Klatskin’s tumor- (HCCA, n=77, 32%), or distal extrahepatic (n=42, 18%). One hundred and seventy patients (50%) underwent liver resection, including 4 patients (3.4%), who had undergone neoadjuvant chemotherapy, and 6 (5%) patients, who had undergone emboli-zation of the right portal vein. Local R0-status was achieved in 78 patients (67%). Biliary complications occurred in 31 patients (26.5%). Death within the same admission occurred in 14 cases (12%).

96, 97 In selected patients with INCPH (e.g., abdominal discomfort or hypersplenism patients), these interventions can be regarded as effective therapeutic modalities. Based on the high prevalence of thrombophilia and incidence of portal vein thrombosis in INCPH patients, several investigators

have incriminated thrombosis of small intrahepatic portal veins as an important etiological factor in the development of this disorder.6, 30 Additionally, a trend toward poor prognosis has been reported in patients with INCPH who develop portal vein thrombosis.6 As a result, anticoagulation therapy has been proposed by Selleckchem BMS 907351 several investigators to prevent disease progression and to maintain portal vein patency.6, 32, 98 However, considering the fact that gastrointestinal Trichostatin A bleeding is the main complication of INCPH and the uncertain role of thrombophilia in the pathogenesis, this treatment is still a matter of debate and cannot be generally implicated until more solid data are present. Nonetheless, we believe that anticoagulation therapy must be considered in patients

with underlying prothrombotic conditions and in patients who develop portal vein thrombosis. Generally, patients with isolated INCPH have a normal liver function and the complications of portal hypertension can be managed successfully with endoscopic therapy and shunting. However, several reports describing liver transplantation in patients with INCPH have been published. The reported indications requiring liver transplantation in these patients were medical unmanageable portal hypertension, hepatopulmonary syndrome, hepatic encephalopathy, and progressive medchemexpress hepatic failure.49, 63, 78 Recently, Karsinskas et al. described a small cohort of INCPH patients treated with liver transplantation.63 The main indication for liver transplantation was medically unmanageable severe portal hypertension; a minority was listed because of hepatic encephalopathy. Notwithstanding the fact that resistant bleeding in INCPH patients should be treated with portosystemic shunting before considering the option of

liver transplantation, only two patients underwent pretransplantation portosystemic shunting procedures (e.g., TIPS and mesocaval shunt). Presumably, the high frequency of cirrhosis misdiagnoses in these patients led to early referral for liver transplantation. To prevent unnecessary liver transplantation in these patients, early discrimination between cirrhosis and INCPH is extremely important. Based on small-sized cohorts (with limited follow-up), post-transplantation outcome in these patients is good and INCPH tends not to recur.63, 99, 100 Data on the etiology and management of INCPH are scarce, and currently applied diagnostic and therapeutic algorithms are based on personal experience or data from limited numbers of patients.

2A). Selleck Kinase Inhibitor Library Collectively, these results indicate that alterations of EZH2 directly modulate H3K27me3 and may thus affect HCC epigenome. Functionally, suppression of EZH2 expression reduced the colony-forming (Supporting Fig. 3B) and migratory abilities of HCC cells in vitro (Fig. 2B). These effects were consistently observed using two different EZH2-targeting shRNA sequences in multiple HCC cell lines, thus excluding the possibility of off-target effects and cell line-specific responses (Supporting Fig. 3C). We then explored

the functional impact of EZH2 knockdown in vivo using an orthotopic liver implantation model. MHCC97L-Luc-shEZH2 and its NTC transfectants were injected into the livers of nude mice and HCC cells were allowed to grow in an actual hepatic microenvironment. We observed a slight reduction in the ability of shEZH2 HCC cells to form tumors compared with NTC cells (Fig. 3A). However, knockdown of EZH2 markedly abolished pulmonary metastasis as evidenced

by bioluminescent imaging and histopathological analysis (Fig. 3B). Collectively, these findings suggest that EZH2 expression is crucial for HCC cell motility and metastasis. Thus far, our clinical data, click here along with our in vitro and in vivo experimental data, have provided compelling evidence that EZH2 up-regulation contributes to aggressive HCC development. Although EZH2 has already been shown to suppress several tumor and metastasis suppressors,26, 27 we hypothesized that EZH2-mediated epigenetic silencing of miRNA expression could also drive HCC metastasis. To evaluate this possibility, we compared the miRNA expression profile of cells in which EZH2 had been stably

knocked down with that of NTC transfected cells using qRT-PCR-based TaqMan miRNA expression arrays. In SMMC-7721, MHCC97L-Luc, and HepG2 cell lines, altogether 327, 342, and 366 miRNAs were detected, MCE公司 respectively. All three cell lines demonstrated altered miRNA expression patterns upon EZH2 knockdown (Fig. 4A). In SMMC-7721, MHCC97L-Luc, and HepG2 cell lines, up-regulation of 141 (43.1%), 132 (38.6%), and 133 (36.3%) miRNAs was detected upon EZH2 depletion, respectively (Fig. 4B; Supporting Table 6). This observation agrees with the consequence of removing the epigenetic suppressive function of PRC2 and indicates a widespread regulatory function of EZH2 on miRNAs expression. As for miRNAs that were down-regulated, this might be due to some unknown secondary effect of EZH2 knockdown. Although each of the three HCC cell lines had differential up-regulated miRNA species, we observed that there were 99 miRNAs being up-regulated in more than one cell line. Furthermore, there were 18 miRNAs simultaneously up-regulated in all three cell lines upon EZH2 depletion (Fig. 4C,D). The EZH2-mediated miRNA silencing in HCC was further validated in two candidate miRNAs, miR-139-5p and miR-125b.

(2011a) observed that amphipod densities on D. menziesii significantly decreased, while densities on I. cordata significantly increased at night compared to day such that the densities (per unit wet weight) on the two species were not significantly different in the dark. Overall amphipod density on P. decipiens also increased at night, but the trend was not statistically significant. However, densities of the amphipod G. antarctica, Vincristine which, as noted previously, consumes P. decipiens as fresh thallus, did significantly increase on it during the night. Aumack et al. (2011a) suggested that the amphipods were leaving their chemically defended

macroalgal refuges during the night so as to forage on diatoms, other palatable microalgae and macroalgae, and other potential food sources, while their predators were less CH5424802 order successful at foraging on them because of the darkness. We have come to describe this association between macroalgae and amphipods as a community-wide mutualism because, as detailed previously in this mini-review, chemically defended macroalgae are the dominant structural components of the community, amphipods, and to

a lesser extent also gastropods, appear to be the major second trophic level consumers in the community, and organisms at both trophic levels appear to gain substantial benefits from their association. These interactions are summarized graphically in Figure 1. Most macroalgae in the community are chemically defended from consumption, but benefit the dense assemblage of macroalgal-associated amphipods by providing an associational refuge from fish predation. The amphipods benefit the macroalgae by keeping them relatively clean of diatoms and other epiphytes. However, the dense amphipod assemblage appears to have selected for filamentous algae with an ability to grow as endophytes within medchemexpress the chemically defended macroalgae, which then provide them with a refuge from amphipod grazing. The endophytes can be pathogenic to their hosts, but evidence to date suggests that this is not always true and even when it is, the effects can be relatively mild.

This community-wide mutualism can be considered at least somewhat analogous to the relationships on tropical reefs between herbivorous fish and corals where the fish reduce macroalgal cover, benefiting the corals, and the fish benefit in turn because the increased structural complexity provided by corals increases fish recruitment (Mumby and Steneck 2008, Hughes et al. 2010). Our description of this interaction as a mutualism assumes that the macroalgae in nature are indeed benefiting from the presence of the dense associated amphipods and somewhat less abundant gastropods. Since light is considered to be the main growth-limiting environmental variable for Antarctic macroalgae (Wiencke et al. 2007, Zacher et al. 2009, Wiencke and Amsler 2012), it is reasonable to expect that the removal of light-blocking epiphytes would indeed be beneficial.

4A). HSL is minimally expressed in the liver and is undetectable in western blots of ATGLLKO or control mice (data not shown). In contrast, diacylglycerol acyltransferase-2 (DGAT2) mRNA was

markedly decreased, whereas that of DGAT1 was mildly increased. The level of microsomal triglyceride transfer protein, which is essential for VLDL synthesis, was normal (Supporting Fig. 4B). In liver slices, measures of FA oxidation were approximately one-third lower in ATGLLKO than in control tissue (Fig. 6D). On electron microscopy, ATGLLKO liver showed increased size and number of hepatocyte lipid droplets. Mitochondria appeared normal. Lipolysosomes were more abundant in ATGLLKO than in control hepatocytes (Fig. 7A-C). mRNA levels for atg5, atg7, and LC3-II were similar in ATGLLKO

mice and controls (Table 1). Western blotting revealed normal levels of the lysosomal RXDX-106 membrane protein LAMP2 (Supporting Fig. 5). Counts of lipolysosomes in ultrastructural sections of hepatocytes revealed a three-fold increase in ATGLLKO hepatocytes versus littermate controls (P < 0.001) (Fig. 7D). ATGLLKO mice have marked hepatic steatosis at all ages studied but are healthy otherwise. Gene targeting in ATGLLKO liver appears to be complete (Fig. 1) and tissue specific. In ATGLLKO mice, cardiac TG content, adipose lipolysis, fasting tolerance, white and brown adipose weights and viability until at least 1 year of BAY 80-6946 nmr age are all normal. Each of these MCE parameters is strikingly abnormal in constitutive ATGL knockout mice, which die of cardiomyopathy at approximately 4 months, the age of the youngest cohort described in this article.16, 22 During preparation of this manuscript, Ong et al.18 demonstrated that adenoviral-mediated ATGL knockdown causes detectable hepatic steatosis within 1 week. Our results support and extend these groups’ findings, providing the first description of the long-term course of

a primary hepatic steatosis. Hepatic ATGL deficiency increased liver TG content approximately three-fold at all ages studied. The levels of steatosis observed in ATGL deficiency were greater than all but the most severe, chronic forms of HFD-induced steatosis.21, 23-25 The steatosis of ATGLLKO mice is concentrated in the periportal and central zones, suggesting that ATGL exerts its greatest effect in these regions. Intriguingly, ATGLLKO cholangiocytes also accumulate excess cytoplasmic TG. This unique change was well-tolerated, with normal gamma-glutamyltransferase levels and lack of periductal inflammation or fibrosis. Of note, ATGL deficiency is expected to be present in ATGLLKO cholangiocytes and hepatocytes, because both arise from a common precursor that expresses albumin,26, 27 allowing gene excision in both cell types. These observations strongly suggest that ATGL is physiologically the main cytoplasmic TG hydrolase of both hepatocytes and cholangiocytes.

Societies and clinicians need to understand economic concepts and be able to contribute positively to economic Gefitinib order evaluations [44]. We should not allow health economists to be the sole influence on Governments on the availability of new therapy or the maintenance or introduction of treatment regimens such as prophylaxis. It is our responsibility

as a patient community to make a contribution to these vital decisions. To do this effectively, we must be able to demonstrate the efficacy of treatment or treatment regimens using outcome data. Across the developed world there is significant variation in national funding arrangements for the treatment of haemophilia and the resulting outcomes [36]. Haemophilia care in Australia is at the upper end of funding levels and effectiveness for patients. Funding of haemophilia care in Australia is supported by a unique collaborative partnership between governments, healthcare providers and people with haemophilia to deliver a highly effective model of care. Although governments provide the majority of direct and indirect health funding to support people with haemophilia, this is within a framework of shared responsibility Vismodegib cell line that recognizes the high per capita cost of this area of healthcare. In product costs alone, Australian

governments provided funding in 2013/2014 in the order of $A170 million, representing approximately 18% of the total budget for all blood 上海皓元 and blood products. This significant funding contribution is balanced by the active involvement of healthcare providers and people with haemophilia to ensure every dollar spent delivers greatest effect. This presentation outlines the Australian arrangements for supporting provision of effective care for haemophilia. In identifying the elements of these arrangements, the presentation highlights the potential benefits still to be obtained in Australia from consistent collection and recording of nationally agreed outcome measures. Australian

Funding Arrangements for the treatment of people with haemophilia consist of two main elements. The supply of product and a national framework to support improvements in clinical practice are funded under legislated National Blood Arrangements. The arrangements for delivery of care are funded by the Commonwealth and jurisdictional governments under the separate general provisions of the recently introduced National Health Reform. Under the National Blood Arrangements, the Australian Government provides 63% funding and 37% is collectively provided by state and territory governments. The National Blood Authority (NBA) is the Australian Government statutory agency that that manages the funding and represents the interests of the Australian, state and territory governments in relation to the supply of blood and blood products.