These findings of COX-2 and iNOS were further validated with Western blot analysis. As seen in Figure 4c, 0.1 to 1 mM SAC did inhibit TNF-α-induced COX-2 and iNOS expressions, while 10–20 μM SAC could not inhibit TNF-α-induced COX-2 and iNOS. Since these inflammatory mediators relevant to NSAID administration are transcribed through either selleck chemicals llc cytosolic phospholipase A2 (cPLA2) activation or NF-κB activation, we compared the changes of cPLA2, IκBα, and NF-κB p50/p65. As seen in Figure 4d, TNF-α administration

instead of NSAID significantly increased activation of cPLA2, as well as activation of NF-κB p50/NF-κB p65 through increased phosphorylation of IκBα. SAC in 1–5 μM significantly decreased cPLA2 as well as IκBα phosphorylation, leading to RAD001 in vivo significant attenuation of NF-κB p65. These findings were further validated with IKKβ kinase assay (Fig. 4e), showing 1–5 μM SAC significantly decreased IKKβ activity. Host can react against oxidative change through direct anti-oxidative enzyme, and phase 2 anti-oxidative response through Nrf2 transcriptional activation and heme oxygenase-1 (HO-1) activation. As shown in Figure 5a, SAC increased SOD-1 and GPX-2. Also, SAC significantly increased either HO-1mRNA or HO-1 expressions. Among phase 2 enzyme response, GST-π was significantly increased

with SAC in a dose-dependent manner. Nrf2 was significantly decreased after TNF-α administration, while SAC, N-acetyl cysteine (NAC as professional anti-oxidant) or trichostatin A (TCA as

professional HDAC inhibitor) all significantly MCE increased Nrf2 even under TNF-α challenge (Fig. 5b). In contrary to HO-1 and GST-π, SAC was weak at inducing γ-GCS and NQO-1, while NAC and TCA induced these enzymes. Regulation of histone deaceylator (HDAC) has been known to be associated with transcription of inflammatory mediators, after which HDAC inhibitor can enforce anti-inflammatory mediators. Therefore, HDAC inhibiting activity can be a basis for global anti-inflammation. We compared the HDAC inhibitory activity among SAC, NAC, TCA, L-cysteine (LC), diallyl trisulfide (DATS), and sulforaphane. As seen in Figure 5c, except LC, all compounds showed significant HDAC inhibitory activities. However, SAC and TCA showed the highest inhibitory activities among these compounds (P < 0.01). Lastly, what kinds of signal transduction pathway were implicated in these inhibitions through HDAC inhibition was investigated. As seen in Figure 5d, ERK1/2 and p38 was significantly attenuated with SAC, while JNK was not changed. Using the inhibitor of ERK1/2 and p38, these engagements of ERK1/2 and p38 were further confirmed.

Post–polymerase

chain reaction allelic discrimination was carried out through the measurement of allele-specific fluorescence on the Opticon 2 detection system (MJ Research, Waltham, MA). Random samples were confirmed by direct genotyping, which provided concordant results in all cases; controls were included in all analyzed batches, and quality controls were used to verify the reproducibility of the results. Valid genotypic data were obtained Selleckchem Sirolimus for more than 99% of the analyzed subjects.27 Results are expressed as means and SDs. Mean values were compared by analysis of variance or Wilcoxon testing as appropriate, and frequencies were compared by Fisher’s exact test for trends. The association between the I148M PNPLA3 SNP, steatosis severity, NASH, and fibrosis was evaluated by multivariate logistic regression analysis. Analyses were carried out with JMP 6.0 statistical analysis software (SAS Institute, Inc., Cary, NC). We previously showed that overtransmission of the rs738409 G allele affected patients in a subset of 71 family Linsitinib trios of patients included in this study, and this indicated that the rs738409 G allele is a genetic factor

predisposing people to NAFLD development.31 In the present study, the frequency distribution of the rs738409 SNP was in Hardy-Weinberg equilibrium in the 149 patients with NAFLD. Heterozygosity for the at-risk G allele was observed in 41% of patients, and homozygosity was observed in 15% (Table 1). As reported in adults, the rs738409 genotype and the presence of the rs738409 G allele were not significantly associated with the body mass, adiposity, lipid levels, or insulin resistance (Table 2). Furthermore, the rs738409 genotype and the G allele were not associated with basal insulin levels

or insulin and glucose levels 30, 60, 90, and 120 minutes after oral glucose tolerance testing or with the quantitative insulin sensitivity check index, insulin sensitivity index, AST levels, and liver function tests [including the prothrombin time and albumin, pseudocholinesterase, and 上海皓元医药股份有限公司 platelet levels (not shown in detail)]. In contrast to what was observed in adults, the rs738409 genotype was not associated with ALT levels in this series of pediatric patients. The relationship between the rs738409 genotype and the severity of liver steatosis (grades 1-3) is shown in Fig. 1. The rs738409 G allele was strongly associated with the severity of steatosis (P < 0.0001) in a dose-dependent manner. In particular, the prevalence of grade 2 steatosis was higher in patients with the GG genotype versus those with the CG genotype, and the prevalence of grade 3 steatosis was higher in patients with the GG genotype versus those with the CG and CC genotypes (P < 0.05).

The simultaneous change in these factors precludes an understanding of their independent effects on the ecophysiology Poziotinib of phytoplankton. In addition, there is a lack of data regarding the interactive effects of these

factors on phytoplankton cellular stoichiometry, which is a key driving factor for the biogeochemical cycling of oceanic nutrients. Here, we investigated the effects of pCO2 and iron availability on the elemental composition (C, N, P, and Si) of the diatom Pseudo-nitzschia pseudodelicatissima (Hasle) Hasle by dilute batch cultures under 4 pCO2 (~200, ~380, ~600, and ~800 μatm) and five dissolved inorganic iron (Fe′; ~5, ~10, ~20, ~50, and ~100 pmol · L−1) conditions. Our experimental procedure successfully overcame the problems associated with simultaneous changes PI3K Inhibitor Library manufacturer in pCO2 and Fe′ by independently manipulating carbonate chemistry and iron speciation, which allowed us to evaluate the individual effects of pCO2 and iron availability. We found that the C:N ratio decreased significantly only with an increase in Fe′, whereas the C:P ratio increased significantly only with an increase in pCO2. Both Si:C and Si:N ratios decreased with increasing pCO2 and Fe′. Our results indicate that changes in pCO2 and iron availability could influence the biogeochemical cycling of nutrients in future oceans with high-

CO2 levels, and, similarly, during the time course of phytoplankton blooms. Moreover, pCO2 and iron availability may also have affected oceanic nutrient biogeochemistry in the past, as these conditions have changed markedly over the Earth’s history. “
“Department of Biological Sciences, University of Rhode Island, Kingston, Rhode Island, USA The freshwater red algal genus Batrachospermum has been shown to be paraphyletic since the first molecular studies of the Batrachospermales. Previous research, along with this study, provides strong support for the clade Batrachospermum section Helminthoidea. This study has found

that heterocortication, MCE公司 the presence of both cylindrical and bulbous cells on the main axis, is an underlying synapomorphy of this clade. Based on support from DNA sequences of the rbcL gene, the COI barcode region and the rDNA ITS 1 and 2, along with morphological studies, the new genus Sheathia is proposed. Seven heterocorticate species were recognized from the molecular clades. Sheathia boryana and S. exigua sp. nov. appear to be restricted to Europe, whereas S. confusa occurs in Europe and New Zealand. Sheathia involuta is widespread in the USA and reported for the first time from Europe. Sheathia americana sp. nov., has been collected in the USA and Canada, and S. heterocortica and S. grandis sp. nov. have been collected only in the USA. Sheathia confusa and S.

Research on several new concepts and technologies discussed herein can clearly benefit ALD research. Exploring nuclear receptors such as PPARα and RXR is an area for research to investigate targets for therapeutic interventions. Advantage should also be taken of the understanding gained from research in other liver diseases, particularly NAFLD/NASH, that show increasing parallels with ALD/ASH development,

for example PNPLA3, hedgehog and osteopontin pathways. Recent advances in newer technologies enabling genome-wide search for millions of SNPs, whole genome deep sequencing, global epigenetics (DNA methylation) profiles, non-coding regulatory elements (miRNA, snRNA, tiRNA), CH5424802 manufacturer are the future research areas to construct the undefined genetic architecture of ALD and identifying new targets for therapy. Advances in live cell and whole animal imaging techniques provide extraordinary possibilities to investigate actions of alcohol in real-time within the cell, tissue and small animals. A global concerted effort is required to invest in future research to provide a

better understanding of ALD pathogenesis. Research in these areas will define the important steps along the therapeutic pipeline by identifying potential novel and specific therapeutics to targets in ALD, which remains the most common form of human liver disease. DS is the main contributor for this review,

WKS and AMD contributed to liver repair and hedgehog signaling, PH provided PLX3397 order guidance on clinical aspects and assistance for section on genetic basis of ALD was provided by CPD. “
“An excess of coinhibitory signals has been proposed to drive the T-cell exhaustion characteristic MCE公司 of persistent viral infections. In this study we examined the contribution of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 (CTLA-4) to CD8 T cell tolerance in chronic hepatitis B virus (HBV) infection (CHB). CD8 T cells in patients with CHB have an increased propensity to express the coinhibitory receptor CTLA-4 and this correlates with viral load. CTLA-4 is up-regulated on those HBV-specific CD8 T cells with the highest levels of the proapoptotic protein Bim, which we have previously shown mediates their premature attrition; abrogation of CTLA-4-mediated coinhibition can reduce Bim expression. Longitudinal study of CHB patients beginning antiviral therapy reveals that HBV DNA suppression induces transient reconstitution of HBV-specific CD8 T cells but does not reprogram their CTLA-4hiBimhi tolerogenic phenotype. Blocking CTLA-4 is able to increase the expansion of interferon gamma (IFN-γ)-producing HBV-specific CD8 T cells in both the peripheral and intrahepatic compartments. The rescue of anti-HBV responses by either CTLA-4 or PD-L1 blockade is nonredundant.

To address many of these issues, the International Prophylaxis Study Group was formed in 2001 [35]. Pharmacokinetics have become a requisite for prophylactic

Deforolimus in vitro dosing. During the 1990s, it could be shown that shortening of dose interval, keeping trough levels, reduced cost at sustained prophylactic efficacy [36, 37]. Even daily dosing has a potential to be feasible in some patients [38]. Pharmacokinetics have more recently been studied in larger international cohorts [39, 40] and the trend is to personalize dosing according to clinical response and individual pharmacokinetics. Long-acting FVIII and FIX concentrates are under study and have a potential to improve prophylaxis, either by using longer intervals than with traditional products, or by raising trough levels. BIBW2992 research buy Longer intervals for dosing would improve convenience and compliance. Raising the trough levels has a potential to dramatically increase the long-term medical effect as even patients

receiving so-called high-dose prophylaxis have substantially reduced levels compared to haemostatically normal people. Cost remains the main hurdle for prophylaxis and therefore perhaps the most important wish for the future, irrespective of the type of concentrate used, is a price reduction Gene therapy and cure of haemophilia will totally change the history, but that is another story. The author stated that he had no interests which might be perceived as posing a conflict or bias. “
“Psychosocial outcomes are important in the perspective of boys with haemophilia. However, health-related quality of life (HRQoL) is based on self-report, and assumes adequate literacy. Yet, literacy

is rarely assessed prior to data collection. This study sought to identify criteria that might indicate the level of literacy of children being recruited for clinical trials and to develop a simple method to prescreen those whose literacy was uncertain. We developed a brief screening tool in the form of two stories, MCE公司 at a grade 3 reading level, followed by comprehension questions. We applied the screening test to a sample of haemophilic boys between the ages of 7 and 13 years to assess their literacy. The data were analysed to determine the best criteria to use in identifying the ability to independently self-report for HRQoL studies. Twenty-four Brazilian boys (7.9–12.8) completed the testing. The results showed that 17 (70.8%) were literate (were able to both read and comprehend), and could complete a questionnaire without assistance. All boys over 11.0 years of age were sufficiently literate. Grade level was not found to be a helpful criterion. We recommend that all children under the age of 11.0 years be prescreened before providing self-reported HRQoL data. Those with limited literacy should be provided assistance to ensure comprehension of the questions. This is important to ensure high-quality data on HRQoL for future clinical trials.

[273] New medical therapies for A-1ATD are being investigated.[274] Inborn errors resulting in bile acid synthesis disorders (BASD) most commonly present as neonatal cholestasis or neonatal hepatitis, but can present as chronic liver disease in older children.[275-277] These diseases are characterized by a failure to produce normal bile acids and Y-27632 mw an accumulation of unusual bile acids and bile acid intermediaries.[278] Unlike most cholestatic diseases, patients with inborn errors of bile acid synthesis generally present with the hallmark features

of normal or low serum levels of primary bile acids, normal GGT concentrations, and the absence of pruritus.[279] For a definitive diagnosis, fast atom bombardment-mass spectrometry (FAB-MS) and gas chromatography-mass spectrometry (GC-MS) analyses of serum and urine is recommended, but is only available in a few specialized referral laboratories.[280] Early diagnosis of some defects of bile acid synthesis can be treated effectively with cholic acid and/or chenodeoxycholic acid, which down-regulate endogenous bile acid synthesis resulting in clinical, biochemical, and histologic improvement if therapy is initiated before significant liver disease is established.[281, 282] LT is indicated for progression to endstage liver disease.[283]

click here 63. Bile acid replacement therapy should be initiated as early as possible in children with a confirmed bile acid synthetic disorder; LT should MCE公司 be considered only in patients with progressive endstage liver disease due to inborn errors of bile acid synthesis or those known to be refractory to medical therapy. (1-B) Hereditary tyrosinemia type 1 (HT) is a multisystem disorder often presenting in infancy with a profound coagulopathy despite minimally elevated or normal serum aminotransferase levels.[284] Older

children and even adults can present with features of chronic liver disease. Treatment with NTBC (2-(2nitro-4-fluoromethybenzoyl)−1,3-cyclohexanedione) results in rapid clinical and biochemical improvement, manifested by undetectable levels of succinylacetone in the urine within 24 hours, and has reduced early complications as well as the need for LT. There has been an increase in mean age at transplantation from 1.82 ± 2.86 years between 1988-1998 to 3.70 ± 4.42 years between 1999-2008.[285] Failure to respond to NTBC within a week may be due to noncompliance or subtherapeutic NTBC, manifested by persistence of succinylacetone in the urine, or a fulminant course despite therapy. The child that survives initial presentation without LT can experience an extended interval of good health. Hepatic nodules, if present initially, may persist, regress, or disappear on a combination of NTBC therapy and a low tyrosine / low phenylalanine diet. The AFP is elevated at presentation, but will normalize or fall to levels less than 10 ng/L on NTBC therapy.

Result: We obtained about 9.0 million 32-mer short reads on average per sample, and mapping rates to miRBase were 15.5%. In the statistical analysis, the p-value and the expression levels of 110 miRNAs were found to be differentially expressed in the 3 groups. 16 miRNAs

were up-regulated in CH-B patients with miR-3591-5p being the most enriched. To set up the condition of miRNA-mRNA pairings with perfect matching of the seed region, RNAhybrid 2.2 analysis predicted that human hepatic cells might use 8 out of 16 miRNAs to down regulate the expression of HBV P and S genes. Then, eight HBV genomic segments containing putative target sites for human miRNAs were separately cloned in the psiCheck-2 vector. The HBV genomic segment predicted to be targeted by miR-125b-5p inhibited Saracatinib research buy remarkably the expression of the reporter in HepG2 and Huh-7 cells. Transfection of miR-125b-5p mimic in HepG2 cells increased the reporter silencing effect.

Moreover, LBH589 transfection of the inhibitor in the cells reduced the reporter silencing activity. Conclusion: We demonstrated that 16 miRNAs were up-regulated in patients with HBV chronic infection. miR-125b-5p, one of the 16 miRNAs, may be responsible for the silencing effect on the HBV genome segment. Disclosures: The following people have nothing to disclose: Masashi Ninomiya, Yasuteru Kondo, Takayuki Kogure, Eiji Kakazu, Osamu Kimura, Tatsuki Morosawa, Tomoaki Iwata, Yasuyuki Fujisaka, Tooru Shimosegawa Background and Aims: Long-term treatment with tenofovir (TDF) is effective in suppressing viral replication in HBeAg-ve and +ve chronic hepatitis B (CHB) patients, but loss of HBsAg is rare. The effect of stopping TDF in a CHB patient with long-term HBV-DNA suppression or HBsAg loss is uncertain. Methods: Among 25 TDF-treated CHB patients with persistently undetectable HBV-DNA for a median time of 7.46 years, therapy was stopped in 7 prospectively followed-up patients. Hepatitis B virus (HBV) quasispecies between codons rt163-rt278 was studied

by ultra-deep pyrosequencing MCE公司 (UDPS, GS-FLX/Junior, Roche) in patients in whom amplification of HBV-DNA at baseline (BA) and after TDF discontinuation (Post) was possible. Results: At BA, median HBV-DNA and HBsAg levels (qHBsAg) were 5.61 (4.82-8.59) and 3.33 (1.95-5.31) logIU/mL respectively, median age 54.81 (43.07-62.86) years, HBV genotype A 1, D 4 and F 1. At end of treatment, all patients were HBeAg-ve, HBV-DNA undetectable, and median qHBsAg was 2.99 (2.02-3.70) logIU/mL. After stopping TDF fora median of 7.29 weeks, no patient cleared HBsAg and HBV-DNA was detectable in all cases (median, 4.52 [1.75-5.34] logIU/mL) with no changes in ALT or qHBsAg. UDPS analysis of HBV quasispecies in 3 patients showed no changes in the master sequence between BA and Post despite 7 years’ complete suppression of HBV replication, but low-frequency variants between positions rtG21 0 and rtS238 were detected at Post: 1 patient showed variants rtV214A (0.26%), rtQ215S (0.

The shear test was performed in a universal test machine (1 mm/min). Results: ANOVA and Tukey (5%) tests noted no statistically significant difference in the bond strength values between the two surface check details treatments (p = 0.7897). The bond strengths (MPa) for both surface treatments reduced significantly after aging (SB-24: 8.2 ±

4.6; SB-Aging: 3.7 ± 2.5; SC-24: 8.6 ± 2.2; SC-Aging: 3.5 ± 3.1). Conclusion: Surface conditioning using airborne particle abrasion with either 50 μm alumina or 30 μm silica particles exhibited similar bond strength values and decreased after long-term TC and water storage for both methods. “
“Purpose: The aim of this study was to determine the condylar form, incline, and movement characteristics during protrusive movement in fully edentulous complete denture wearers. The study went on to analyze the occlusal consequences

on the setup of artificial posterior teeth and the occlusal grinding phase. Materials and Methods: The study included 60 complete denture wearers (aged 58 to 74 years), who received a new set of complete dentures for this study. The patients did not present signs of muscular or articular pain. Protrusive STA-9090 nmr movements were recorded by a SAM® electronic axiography system. Results: Condylar paths exhibited fairly specific characteristics in the completely edentulous patients, particularly path forms, which had highly specific patterns. Three condylar path forms were determined: the classic form following a convex curve (41% of cases), a sinusoidal form that flattened out in the first 2 mm before following a convex curve (51%), and a rectilinear path (9%). The mean condylar angles also exhibited

specific patterns. The mean started in the first millimeter of protrusive movement, at 32.2°± 14.9°, and then increased in the second millimeter to 40.4°± 11.9°, reaching 44.5°± 9° at 5 mm. Conclusion: During protrusive movement in completely edentulous patients, the condylar path patterns were different than conventionally described patterns. In particular, 上海皓元医药股份有限公司 the sinusoidal form was frequently found, and the incline of the condylar slope was low. These factors need to be taken into account during the final occlusal selective grinding for new sets of complete dentures. “
“Prosthetic management of maxillectomy cases is challenging, and a multidisciplinary approach is usually needed. This clinical report describes the treatment provided to a patient who presented with a moderately differentiated squamous cell carcinoma. A two-stage surgical protocol was followed for this purpose. At the first surgery, the anterior maxilla was resected, and the oral and nasal mucosal and osseous defect was reconstructed with an osteocutaneous flap from the radial forearm. At the second surgery, all fascias and the connective tissue between the skin and the bone were resected to provide an optimal thickness for denture stability.

[12] The phosphorylation allows SHP1 or SHP2 recruitment to SIRPα that, in turn, dephosphorylates specific substrates involved in various physiological effects.[14, 15] SIRPα can bind to either widely expressed transmembrane buy YAP-TEAD Inhibitor 1 ligand CD47 or soluble ligands, such as the surfactant proteins A and D.[16] It is suggested that the SIRPα/CD47 signaling axis is important in tumor therapy.[17, 18] Our previous work has shown that SIRPα negatively regulate Toll-like receptor (TLR) signaling in Mψ.[16, 19] However, it is still unknown whether SIRPα expression on tumor-polarized

Mψ can act on tumor progression. We demonstrate here that SIRPα expression is reduced on Mψ obtained from peritumoral tissues of HCC patients. Down-regulated SIRPα expression is coincident with transiently activated Mψ during the early stage of exposure to tumor. Moreover, adoptive transfer of SIRPα-KD Mψ could promote tumor growth in vivo. These findings provide a new role of SIRPα on tumor-polarized Mψ and tumor progression. Peripheral blood samples of healthy donors (n = 20) and untreated http://www.selleckchem.com/products/AZD0530.html HCC patients (n = 22) as well as HCC tumor samples (n = 25) were obtained. Tumor tissues were collected from the areas of tumor nest, while the peritumoral samples were obtained near the tumor tissues (0.5-1 cm from tumor margin). The patients were pathologically confirmed

as HCC at the Eastern Hepatobiliary Surgery Hospital, Shanghai, China. Detailed information about the patients and their tumors are shown

in Supporting Table. 1. Written informed consent was obtained and the protocols were approved by the Review Board of the Eastern Hepatobiliary Surgery Hospital. The circulating mononuclear cells were obtained by Ficoll density gradient centrifugation. 上海皓元医药股份有限公司 The infiltrated leukocytes were isolated according to the following protocols: specimens were cut into small pieces and digested with 0.05% collagenase IV, 0.002% DNase I (Sigma-Aldrich), and 20% fetal bovine serum (FBS) (Gibco) at 37°C for 1 hour. The dissociated cells were filtered through 150-μm mesh and separated by Percoll centrifugation. The obtained cells were washed for the fluorescent-activated cell sorter (FACS) analysis. Male C57BL/6 mice and Balb/c mice (6-8 weeks old) were obtained from the Chinese Science Academy, Shanghai, China, and maintained under pathogen-free conditions. All animals received humane care according to the criteria outlined in the Guide for the Care and Use of Laboratory Animals, prepared by the National Institutes of Health. Experiments were performed repeatedly and representative data are shown. Continuous variables were compared with the Student t test, ordinal variables with the Mann-Whitney U test. P 0.05 was considered significant. Data analysis was performed with SPSS 16.0 for Windows (Chicago, IL). A detailed description of Patients and Methods can be found in the online Supporting Information.

“
“Summary.  Haemophilia A is characterized by the occurrence of frequent spontaneous

intra-articular and intramuscular bleeding. If inadequately treated, it results in progressive damage to joints and muscles leading to crippling deformities and musculoskeletal dysfunction. These complications result in lifelong chronic Selleckchem KU-60019 pain and disability that may greatly affect the patients’ mood. We aimed to evaluate the musculoskeletal function in our haemophilia A patients and its correlation to depressed mood in these patients and determine the impact of degree of factor VIII deficiency, different replacement therapy regimens and frequency of hemarthrosis, on both musculoskeletal function and mood. A cross-sectional study was carried out on 50 adolescent haemophilia A patients. Musculoskeletal function was assessed using Functional Independence Score for Hemophilia (FISH) and mood status was assessed using Idelalisib molecular weight Beck Depression Inventory—Short Form (BDI-SF). The mean FISH

score was 23.32 ± 4.69 (range 13–28) and the tasks that obtained lower scores were step climbing, squatting and walking. Of our 50 patients included, 16(32%) were not depressed, 18(36%) were with mild depression, 11(22%) were with moderate depression and 5(10%) were with severe depression. There was a highly significant negative correlation between mean FISH score and mean BDI-SF score (P < 0.001). The better the replacement therapy regimen, the better the musculoskeletal function that could be obtained in haemophilia A patients and the better the mood. "
“IB1001 trenacog alfa is an investigational recombinant factor IX (FIX) for the treatment and prevention of bleeding in individuals with haemophilia B. To compare the pharmacokinetics (PK) of IB1001 with nonacog alfa in individuals MCE公司 with haemophilia B and to assess the relationship between sialylation and PK of IB1001 (NCT00768287). A randomized, double-blind, non-inferiority, cross-over study conducted in participants aged ≥12 years weighing ≥40 kg, with severe or moderately severe haemophilia B (FIX activity ≤2 IU dL −1). PK parameters were derived using observed FIX concentration levels and actual PK sampling times,

and repeated in a subset of participants who had received IB1001 prophylaxis for 4–18 months. A retrospective analysis was conducted in subgroups according to the sialylation levels of IB1001 (50.8, 57.8–59.0%, or 71.7%). In the 32 adolescent and adult males evaluated, there were no clinically meaningful differences in PK parameters between those receiving IB1001 75 IU kg−1 or nonacog alfa. The lower limit of the one-sided 95% confidence interval for the ratio of AUC0-t and AUC0-∞ (IB1001/nonacog alfa) was 0.90, establishing non-inferiority. Terminal phase half-lives were similar (29.7 ± 18.2 h for IB1001 and 33.4 ± 21.2 h for nonacog alfa). The PK results were stable for up to 18 months of IB1001 exposure; the impact of sialylation levels was not clinically meaningful.