The full-length catalase cDNA sequence as isolated from expressed sequence tags (ESTs) of Pyropia yezoensis (Ueda) M. S. Hwang et H. G. Choi (PyCAT) through rapid amplification of cDNA ends (RACE) was identified and characterized. It encoded a polypeptide of 529 amino acids, which shared 36%–44% similarity with other known catalase proteins.

Phylogenetic analysis revealed that PyCAT ALK activation was closer to the catalases from plants than from other organisms. The PyCAT mRNA expression was investigated using real-time PCR to determine life-cycle-specific expression and the expression pattern during desiccation. The mRNA expression level in gametophytes was significantly higher than in sporophytes, and the mRNA expression level of PyCAT was significantly up-regulated during the desiccation process. The recombinant PyCAT protein was purified and analyzed biochemically. The recombinant PyCAT protein exhibited high enzymatic activity (28,000 U·mg−1) with high thermal stability and a broad pH range. All these results indicate that the PyCAT is a typical member of the plant and algal catalase family and may play a significant role in minimizing the effect of oxidative damage in P. yezoensis during desiccation. “
“Coolia Meunier is an important component of benthic dinoflagellate assemblages in tropical and subtropical seas. In this study, detailed morphological observation of

Coolia species from Malaysian waters was carried out using light and electron microscopy in parallel with molecular characterization of nuclear-encoded Ulixertinib partial LSU rDNA, and internal transcribed

spacer (ITS) regions. Live specimens were collected from seaweed samples and established into clonal cultures. There are significant morphological variations between the Malaysian isolates in comparison to the type species, C. monotis Meunier. The feature that differentiates the new species is the third postcingular plate (3′′′), which is the largest hypothecal plate Meloxicam in the Malaysian isolates, whereas in C. monotis, the 3′′′ and 4′′′ plates are almost equal in size. Detailed observations of the thecal pores also revealed the presence of fine perforations within the pores of the Malaysian isolates, but these perforations are absent in C. monotis. Comparisons between Malaysian isolates and C. monotis nucleotide sequence of the ITS region showed high genetic divergence at 28%, in contrast to the 0.3%–3% divergence observed among populations of the same species. Structural comparison of the second internal transcribed spacer (ITS2) rRNA transcript between the two species showed compensatory base changes (CBCs) in the three helices of ITS2 rRNA. Based on morphological and molecular data, the Malaysian isolates are considered to represent a new species, for which the name Coolia malayensis is proposed.

Although the miRNA family constitutes only a minor fraction of the human

genome, they hold fundamental importance in diverse physiological and developmental processes due to their pleiotropic effects on the post-transcriptional regulation of many vital genes. This class of regulatory RNAs has also emerged as selleck kinase inhibitor important players in carcinogenesis; most, if not all, cancer types have abnormal miRNA expression patterns. In hepatocellular carcinoma (HCC), miRNA dysregulation plays a key role in mediating the pathogenicity of several etiologic risk factors and, more importantly, they promote a number of cancer-inducing signaling pathways. Recent studies have also demonstrated their potential values in the clinical management of HCC patients as some miRNAs may be used as prognostic or diagnostic markers. The significance of miRNAs in liver carcinogenesis emphasizes their values as therapeutic targets, while technological advances in the delivery of miRNA has shed new possibilities for their use as novel therapeutic agents against HCC. In the past few decades, genome

research has established the fundamental importance of genetic and epigenetic alterations of oncogenes and tumor suppressor genes (TSGs) in the initiation and progression of human neoplasms. The recent discovery of microRNA (miRNA) put forward an alternate regulatory element, in which the actions of miRNAs regulate cancer-inducing cellular genes post-transcriptionally. The founding member of miRNA, lin-4, was discovered in the larval development of Caenorhabditis Low-density-lipoprotein receptor kinase elegans in 1993.1 Nevertheless, the role of small RNA in gene expression regulation had to await the discovery of a second miRNA member, let-7, 7 years later.2 Pioneering studies further revealed let-7 as a negative regulator of the RAS oncogene in human tumor cells.3 This discovery soon aroused tremendous efforts into the research of cancer-related miRNAs. By now,

miRNAs have been reported in a variety of organisms, ranging from viruses to mammals. To facilitate miRNA research, a miRNA registry (miRBase) has been established and is currently maintained by the University of Manchester.4 So far, 940 human miRNAs have been reported (miRBase release 15) and the list is still expanding. The family of miRNA constitutes about 1–3% of the human genome. Most miRNA genes are situated within the intergenic regions and have their own transcription units. About a quarter are located within exons or introns of other coding genes where their transcription is controlled by the host genes. MiRNAs can be transcribed as monocistronic transcripts or in polycistronic clusters; the latter involves several miRNAs situated on a single transcript being controlled by the same promoter (Fig. 1). In the nucleus, miRNA genes are transcribed as primary-miRNAs (pri-miRNAs) by RNA polymerase II (PolII).

For the collection of conditioned media, 2 ×105 HCC cells (usually SK-Hep1 cells, whose conditioned medium contained the most activity for ERBB3 activation) were seeded with regular cultured media in 36-mm dishes overnight; after that, the media were removed from the dishes, washed three times with phosphate-buffered saline, and further cultured in serum-free media for

24 hours. Media were spun for the removal of any insoluble components for 15 minutes at 12,000g and then used to treat cells. For blockade assays, conditioned media were incubated with antibodies against NRGs (200 or 400 ng/mL) for 20 minutes at 37°C to neutralize the biological activity of NRGs and then were used to treat HCC cells. To knock down the expression of EGFR, HER2, ERBB3, or NRG1, cells were transfected with siRNAs or Atezolizumab transduced with lentivirus-based shRNAs targeting EGFR, HER2, ERBB3, or NRG1. siRNAs with randomly scrambled sequences were used as the controls. To guarantee the specificity and to avoid off-target effects, we used two clones of siRNAs or shRNAs for each gene and separately examined the silencing efficiency with respect to their target genes and their effects on the related biological results. For example, we used two clones of siRNA targeting HER2. Silencing

BVD-523 purchase of HER2 expression via both siRNA clones efficiently suppressed the phosphorylation of ERBB3 and its downstream Akt (Supporting Information Fig. 1A). Also, two clones of siRNAs targeting ERBB3 were used, and the specificity for the silencing of ERBB3 expression and for the suppression of phosphorylation

of downstream Akt was examined (Supporting Information Fig. 1B). In addition, consistent effects of both siRNA clones targeting ERBB3 and both siRNA clones targeting HER2 on cell proliferation selleck chemicals llc (Supporting Information Fig. 1C) and tumor sphere formation for HepG2, Huh7, and SK-Hep1 cells were observed (data not shown). Basically, 2 × 105 cells were seeded onto six-well plates and transfected with 5 nM siRNA with Lipofectamine as the transfectant reagent according to the manufacturer’s protocols (Lipofectamine RNAiMAX, Invitrogen). Forty-eight hours after transfection, the cells were harvested or subjected to further assays. RNA extraction, reverse transcription, and quantitative real-time polymerase chain reaction were performed as previously described. Immunoblotting analysis and immunohistochemistry assays were conducted as previously described13, 14 (see the Supporting Information). The invading activities of HCC cells were analyzed with Boyden chambers (8-μm pore size; Corning, Inc.), cell motility was assayed with wound healing assays, and cell proliferation was determined via colorimetric sodium 3′-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene sulfonic acid hydrate (XTT) assays (see the Supporting Information).

For the collection of conditioned media, 2 ×105 HCC cells (usually SK-Hep1 cells, whose conditioned medium contained the most activity for ERBB3 activation) were seeded with regular cultured media in 36-mm dishes overnight; after that, the media were removed from the dishes, washed three times with phosphate-buffered saline, and further cultured in serum-free media for

24 hours. Media were spun for the removal of any insoluble components for 15 minutes at 12,000g and then used to treat cells. For blockade assays, conditioned media were incubated with antibodies against NRGs (200 or 400 ng/mL) for 20 minutes at 37°C to neutralize the biological activity of NRGs and then were used to treat HCC cells. To knock down the expression of EGFR, HER2, ERBB3, or NRG1, cells were transfected with siRNAs or selleckchem transduced with lentivirus-based shRNAs targeting EGFR, HER2, ERBB3, or NRG1. siRNAs with randomly scrambled sequences were used as the controls. To guarantee the specificity and to avoid off-target effects, we used two clones of siRNAs or shRNAs for each gene and separately examined the silencing efficiency with respect to their target genes and their effects on the related biological results. For example, we used two clones of siRNA targeting HER2. Silencing

Selisistat cell line of HER2 expression via both siRNA clones efficiently suppressed the phosphorylation of ERBB3 and its downstream Akt (Supporting Information Fig. 1A). Also, two clones of siRNAs targeting ERBB3 were used, and the specificity for the silencing of ERBB3 expression and for the suppression of phosphorylation

of downstream Akt was examined (Supporting Information Fig. 1B). In addition, consistent effects of both siRNA clones targeting ERBB3 and both siRNA clones targeting HER2 on cell proliferation this website (Supporting Information Fig. 1C) and tumor sphere formation for HepG2, Huh7, and SK-Hep1 cells were observed (data not shown). Basically, 2 × 105 cells were seeded onto six-well plates and transfected with 5 nM siRNA with Lipofectamine as the transfectant reagent according to the manufacturer’s protocols (Lipofectamine RNAiMAX, Invitrogen). Forty-eight hours after transfection, the cells were harvested or subjected to further assays. RNA extraction, reverse transcription, and quantitative real-time polymerase chain reaction were performed as previously described. Immunoblotting analysis and immunohistochemistry assays were conducted as previously described13, 14 (see the Supporting Information). The invading activities of HCC cells were analyzed with Boyden chambers (8-μm pore size; Corning, Inc.), cell motility was assayed with wound healing assays, and cell proliferation was determined via colorimetric sodium 3′-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene sulfonic acid hydrate (XTT) assays (see the Supporting Information).

For the collection of conditioned media, 2 ×105 HCC cells (usually SK-Hep1 cells, whose conditioned medium contained the most activity for ERBB3 activation) were seeded with regular cultured media in 36-mm dishes overnight; after that, the media were removed from the dishes, washed three times with phosphate-buffered saline, and further cultured in serum-free media for

24 hours. Media were spun for the removal of any insoluble components for 15 minutes at 12,000g and then used to treat cells. For blockade assays, conditioned media were incubated with antibodies against NRGs (200 or 400 ng/mL) for 20 minutes at 37°C to neutralize the biological activity of NRGs and then were used to treat HCC cells. To knock down the expression of EGFR, HER2, ERBB3, or NRG1, cells were transfected with siRNAs or selleck chemical transduced with lentivirus-based shRNAs targeting EGFR, HER2, ERBB3, or NRG1. siRNAs with randomly scrambled sequences were used as the controls. To guarantee the specificity and to avoid off-target effects, we used two clones of siRNAs or shRNAs for each gene and separately examined the silencing efficiency with respect to their target genes and their effects on the related biological results. For example, we used two clones of siRNA targeting HER2. Silencing

Hedgehog antagonist of HER2 expression via both siRNA clones efficiently suppressed the phosphorylation of ERBB3 and its downstream Akt (Supporting Information Fig. 1A). Also, two clones of siRNAs targeting ERBB3 were used, and the specificity for the silencing of ERBB3 expression and for the suppression of phosphorylation

of downstream Akt was examined (Supporting Information Fig. 1B). In addition, consistent effects of both siRNA clones targeting ERBB3 and both siRNA clones targeting HER2 on cell proliferation this website (Supporting Information Fig. 1C) and tumor sphere formation for HepG2, Huh7, and SK-Hep1 cells were observed (data not shown). Basically, 2 × 105 cells were seeded onto six-well plates and transfected with 5 nM siRNA with Lipofectamine as the transfectant reagent according to the manufacturer’s protocols (Lipofectamine RNAiMAX, Invitrogen). Forty-eight hours after transfection, the cells were harvested or subjected to further assays. RNA extraction, reverse transcription, and quantitative real-time polymerase chain reaction were performed as previously described. Immunoblotting analysis and immunohistochemistry assays were conducted as previously described13, 14 (see the Supporting Information). The invading activities of HCC cells were analyzed with Boyden chambers (8-μm pore size; Corning, Inc.), cell motility was assayed with wound healing assays, and cell proliferation was determined via colorimetric sodium 3′-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene sulfonic acid hydrate (XTT) assays (see the Supporting Information).

GENA-01 was a prospective, randomized, actively controlled, open-label crossover multicenter on-demand trial which involved nine centres in three countries (USA, Germany and Bulgaria). It recruited 22 previously treated patients (PTPs) with severe haemophilia A (mean age 39.6 ± 14.06). Its objectives were pharmacokinetic evaluation, efficacy of on-demand treatment and surgical prophylaxis, incremental recovery of FVIII:C, immunogenicity and safety. GENA-08 was a prospective, single arm, open-label, multinational prophylaxis trial involving 11 centres in four countries

(Austria, Bulgaria, Germany and UK) which recruited 32 PTPs with severe haemophilia A (mean age 37.3 ± 13.6). The primary objective was efficacy of prophylactic treatment, treatment of breakthrough bleeding and surgical prophylaxis. The secondary objectives were incremental recovery of FVIII:C, immunogenicity

and safety. Both studies were similarly designed with regard to the A769662 inclusion/exclusion criteria, study duration and in how the data were captured and analyzed. In addition, the study populations were favourably comparable to each other with regard to age, body mass index, haemophilia joint health score (according to Hilliard et al. [8]), race and historical bleeding sites. In GENA-01, Mitomycin C molecular weight 65.1% of the bleeding episodes were spontaneous. The most common sites of bleeding were the knee (23.3%), elbow (22.8%) and ankle (15.7%). Of the bleeding, 57.4% was moderate to major and 42.2% was minor. There were 986 total bleeding episodes of which 94.4% were successfully treated (excellent or good response with excellent being abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 h after a single infusion, and good being definite pain relief and/or find more improvement in signs of bleeding within approximately 8–12 h after an infusion requiring ≤2 infusions for complete resolution). A total of 96.7% of all bleeding episodes were managed with one (90.3%) or two (6.4%) infusions. The median dose per infusion was 30 IU kg−1 (range 7–61) and

the median dose per bleeding episode was 30.9 IU kg−1 (range 8–657). The total factor consumption was 156.9 IU kg−1 month−1. In GENA-08, there was good adherence with 93.6% of prophylactic infusions given every 2 days, for a median of 3.4 infusions per week (range 2.01–3.46). The dose per infusion was 33.1 IU kg−1 (median, range 24–39.3). There were 44 breakthrough bleeding events; most (59.1%) were spontaneous and only 28 required treatment. Of the 44 haemorrhages, 28 (63.6%) were minor. There was no major or life-threatening bleeding and 50% of the patients (16/32) did not experience any bleeding episodes during the prophylactic treatment with Human-cl rhFVIII. Before study entry patients treated on demand (n = 11) had a mean monthly bleeding rate of 3.92 episodes. This was reduced to 0.04 with Human-cl rhFVIII.

GENA-01 was a prospective, randomized, actively controlled, open-label crossover multicenter on-demand trial which involved nine centres in three countries (USA, Germany and Bulgaria). It recruited 22 previously treated patients (PTPs) with severe haemophilia A (mean age 39.6 ± 14.06). Its objectives were pharmacokinetic evaluation, efficacy of on-demand treatment and surgical prophylaxis, incremental recovery of FVIII:C, immunogenicity and safety. GENA-08 was a prospective, single arm, open-label, multinational prophylaxis trial involving 11 centres in four countries

(Austria, Bulgaria, Germany and UK) which recruited 32 PTPs with severe haemophilia A (mean age 37.3 ± 13.6). The primary objective was efficacy of prophylactic treatment, treatment of breakthrough bleeding and surgical prophylaxis. The secondary objectives were incremental recovery of FVIII:C, immunogenicity

and safety. Both studies were similarly designed with regard to the Tanespimycin mouse inclusion/exclusion criteria, study duration and in how the data were captured and analyzed. In addition, the study populations were favourably comparable to each other with regard to age, body mass index, haemophilia joint health score (according to Hilliard et al. [8]), race and historical bleeding sites. In GENA-01, selleck 65.1% of the bleeding episodes were spontaneous. The most common sites of bleeding were the knee (23.3%), elbow (22.8%) and ankle (15.7%). Of the bleeding, 57.4% was moderate to major and 42.2% was minor. There were 986 total bleeding episodes of which 94.4% were successfully treated (excellent or good response with excellent being abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 h after a single infusion, and good being definite pain relief and/or selleck screening library improvement in signs of bleeding within approximately 8–12 h after an infusion requiring ≤2 infusions for complete resolution). A total of 96.7% of all bleeding episodes were managed with one (90.3%) or two (6.4%) infusions. The median dose per infusion was 30 IU kg−1 (range 7–61) and

the median dose per bleeding episode was 30.9 IU kg−1 (range 8–657). The total factor consumption was 156.9 IU kg−1 month−1. In GENA-08, there was good adherence with 93.6% of prophylactic infusions given every 2 days, for a median of 3.4 infusions per week (range 2.01–3.46). The dose per infusion was 33.1 IU kg−1 (median, range 24–39.3). There were 44 breakthrough bleeding events; most (59.1%) were spontaneous and only 28 required treatment. Of the 44 haemorrhages, 28 (63.6%) were minor. There was no major or life-threatening bleeding and 50% of the patients (16/32) did not experience any bleeding episodes during the prophylactic treatment with Human-cl rhFVIII. Before study entry patients treated on demand (n = 11) had a mean monthly bleeding rate of 3.92 episodes. This was reduced to 0.04 with Human-cl rhFVIII.

We defined persistent itch as pruritus occurring ‘frequently’ or ‘all the time’, and severe itch as persistent itch combined with PBC-40 itch score ≥10.Results: Data were available for 2705 PBC patients without a liver transplant. 1889 patients (69.8%) had experienced itch at some point in their illness. Of these, 880 (46.5%) had persistent itch and 428 (22.6%) had severe itch. Table 1 summarizes main results. Correlation between VAS and GS of itch intensity was statistically

significant (Spearman’s correlation coefficient 0.95, p<0.01). Patients Selleck Obeticholic Acid with severe itch had received the following treatments: colestyramine (217, 51%), rifampicin (70, 16.3%) and naltrexone (33,7.7%). Notably,193 (45%) patients with severe pruritus reported no anti-pruritic treatment at all.

Conclusions: Our results highlight the prevalence of pruritus in PBC. In the UK-PBC cohort, nearly a third of patients had experienced itch, of whom approximately one-half had persistent itch and one-quarter had severe itch. However, it would seem that treatment of itch was unsatisfactory as many patients with severe pruritus did not receive any anti-pruritic therapy. Our results also suggest need for improvement in the awareness among clinicians MS-275 for better management of cholestatic pruritus in PBC. Disclosures: Ulrich Beuers – Consulting: Intercept, Novartis; Grant/Research Support: Zambon; Speaking and Teaching: Falk Foundation, Gilead, Roche, Scheringh,

Zambon Richard N. Sandford – Advisory Committees or Review Panels: Otsuka; Grant/ Research Support: Intercept Stuart Kendrick – Advisory Committees or Review Panels: GlaxoSmithKline Research and Development Limited; Employment: GlaxoSmithKline Research and Development Limited; Grant/Research Support: GlaxoSmithKline Research and Development Limited David E. Jones – Consulting: Intercept The following people have nothing to disclose: Vinod S. Hegade, George F. Mells, Andreas E. Kremer, Pietro Invernizzi, Tom H. Karlsen, Gideon click here Hirschfield Autoimmune hepatitis (AIH) in humans is a severe inflammatory liver disease, characterized by interface hepatitis on histology and by the presence of circulating autoantibodies and hyper-gammaglobulinemia. There are two types of AIH, type-1 (AIH-1) and type-2 (AIH-2) characterized by distinct autoimmune serology. Patients with AIH-1 are positive for anti-smooth muscle and/or anti-nuclear (SMA/ANA) autoantibodies whereas patients with AIH-2 have anti-liver kidney microsomal type 1 (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies.

HCC development was significantly retarded in the Mdr2-KO/B6 mice versus the Mdr2-KO/FVB mice. This retardation was more prominent in males: the tumor incidence, size, and load in the Mdr2-KO/B6 males at the age of 18 months were similar to those in the Mdr2-KO/FVB males at the age of 12 months (Fig. 1). In females, the tumor incidence and load in the Mdr2-KO/B6 strain at the age of 16

months were similar to those in the Mdr2-KO/FVB strain at the age of 12 months (Fig. 1). Thus, in the Mdr2-KO/B6 mice, HCC developed approximately 6 months later in males and approximately IWR-1 in vitro 4 months later in females in comparison with the Mdr2-KO/FVB mice. To understand the mechanisms underlying the significant differences in HCC development in Mdr2-KO mutants with B6 and FVB genetic backgrounds, we followed the dynamics of chronic hepatitis in males of both strains at early stages of liver disease (1, 2, and 3 months of age; Supporting Fig. 1). At 1 month of age, the main histological parameters of chronic hepatitis and cholangitis, bile duct proliferation and portal inflammation, progressed more rapidly in the Mdr2-KO/B6 liver versus the Mdr2-KO/FVB liver. However, in the Mdr2-KO/FVB Ibrutinib molecular weight males, these parameters increased with age, whereas in the Mdr2-KO/B6 males, they peaked at 2 months and had decreased at 3 months of age. Livers of the 3-month-old

Mdr2-KO/FVB males had characteristic fibrosis with early septal formation, whereas there was no septal formation in the livers of the Mdr2-KO/B6

strain at all early ages tested (Supporting Fig. 1A). The alanine aminotransferase (ALT) and alkaline phosphatase (ALP) serum levels in the Mdr2-KO mice of both strains were increased in comparison with controls at all ages tested (Fig. 2A,B), and this was indicative of chronic hepatitis and cholangitis. However, these parameters were more profoundly increased in the Mdr2-KO/FVB mice versus the Mdr2-KO/B6 mice, especially at 2 and 3 months of age (Fig. 2A,B). Remarkably, lower levels of serum cholesterol, a well-known result of the Mdr2-KO mutation,10 were observed this website only in the Mdr2-KO/FVB mice and not in the Mdr2-KO/B6 mice (Fig. 2C). As for the control Mdr2+/− mice, serum cholesterol was significantly higher in the FVB strain versus the B6 strain at all ages tested (Fig. 2C), and this was in agreement with known differences in cholesterol and triglyceride levels between WT FVB and B6 strains.11 To understand the contribution of immune cells in this model, we followed the dynamics of the infiltration of monocytes/macrophages, neutrophils, and T cells into male Mdr2-KO livers of both strains at early stages of chronic liver disease (Fig. 3A-C and Supporting Fig. 1B). The frequency of all these cells in livers from the Mdr2-KO strains was remarkably higher than the frequency in corresponding control livers (not shown).

Vukan Cupic”, Belgrade, Serbia. “
“Most health care professionals involved in the management of people with haemophilia (PWH) believe that exercise is beneficial and its

practice is widely encouraged. This article aims to demonstrate that appropriate exercise (adapted to the special needs of the individual PWH) may be beneficial for all PWH through improved physical, psychosocial and medical status. Based on evidence gathered from the literature, many PWH, particularly those using long-term prophylaxis or exhibiting a mild/moderate bleeding phenotype, are as active as their healthy peers. PWH experience the same benefits of exercise as the general population, being physically healthier than if sedentary and enjoying a higher quality of life Omipalisib nmr (QoL) through social inclusion and higher self-esteem. PWH can also gain IWR-1 in vivo physically from increased muscle strength, joint health, balance and flexibility achieved through physiotherapy, physical activity, exercise and sport. Conversely, very little data exist on activity levels of PWH in countries with limited resources. However, regarding specific exercise recommendations in PWH, there is a lack

of randomized clinical trials, and consequently formal, evidence-based guidelines have not been produced. Based on published evidence from this review of the literature, together with the clinical experience of the authors, a series of recommendations for the safe participation of PWH

in regular physical activities, exercises and sport are now proposed. In summary, we believe that appropriately modified programmes can potentially allow all PWH to experience the physical and psychosocial benefits of being physically active which may ultimately lead to an improved QoL. “
“Summary.  Finding differences in drug utilization patterns within click here rare patient populations is challenging without access to a large sample. Our objective was to identify patient and treatment-related factors associated with differences in annual recombinant factor VIII (rFVIII) utilization in a large cohort of haemophilia A patients. This retrospective analysis utilized a large, US specialty pharmacy dispensing database from January 2006 to September 2009. Differences in median annual FVIII utilization (IU kg−1year−1) by age, severity, treatment regimen, rFVIII product type and health insurance plan were tested using non-parametric statistics and regression analysis. A total of 1011 haemophilia A patients were included in the overall analysis.