The statistical analyses were performed with a StatView computer

The statistical analyses were performed with a StatView computer program (SAS institute, Abacus concepts incorporation, Berkeley, CA, USA). The effects of bolus 5-FU vs continuous 5-FU regimens, chemoradiation vs chemotherapy only, L. rhamnosus GG vs no dietary supplements, and guar gum vs no guar gum were compared using univariate and multivariate inhibitor Imatinib Mesylate logistic regression models. The results are given as odds ratios with 95% confidence intervals. Mann�CWhitney U-test was used to compare the treatment groups with respect to quantitative response variables. Frequency tables were analysed using the ��2 test. RESULTS Patient characteristics and compliance The treatment arms were balanced with gender, the WHO performance status, primary tumour site, Dukes’ stage, and radiation therapy given (Table 1).

The median age at randomisation was 60 (range: 31�C75); 51% of the participants were men. Sixteen (11%) subjects did not complete the scheduled 6 months of adjuvant chemotherapy due to either adverse events (n=7, six of whom received bolus 5-FU), cancer recurrence (n=5), or a concomitant disease (n=4). Two patients (both in the continuous 5-FU group) who did not receive any of the study treatments due to postoperative complications were not included in safety or efficacy analyses leaving 148 patients for these analyses. None of the patients were lost to follow-up. Table 1 Patient characteristics Chemotherapy dose intensity and tolerability The scheduled 5-FU dose intensity, calculated as the percentage of the scheduled dose as milligrams of 5-FU given per square metre per week of the scheduled cumulative dose, was maintained better among the patients who received the simplified de Gramont regimen than among those treated with the Mayo regimen (median 93 vs 78%, respectively; P<0.

0001). The simplified de Gramont regimen was tolerated better than the Mayo regimen (Table 2). Any grade 3 or 4 adverse effect was present in 87% (65 out of 75) of the patients treated with the Mayo regimen as compared with only 45% (33 out of 73) of those treated with the simplified de Gramont regimen, when the vascular access device (VAD)-related toxicity was included in this analysis (P<0.0001, Table 2). Vascular access device-related complications occurred in seven (10%) patients who received continuous Entinostat 5-FU infusions; three were classified as serious. The Mayo regimen was more frequently associated with stomatitis, diarrhoea, and neutropenia than the simplified de Gramont regimen, whereas mild-to-moderate hand�Cfoot syndrome was more common among the patients who received the simplified de Gramont regimen (P<0.0001). There were no treatment-related deaths.

Acknowledgments This study was supported by the French Associatio

Acknowledgments This study was supported by the French Association Vaincre la Mucoviscidose and by the Minist��re de l’Education Nationale, de la Recherche et de la Technologie. We thank C. Baritaud for his technical assistance.
Hepatocellular carcinoma selleck chem (HCC) is a major cause of cancer death and morbidity worldwide (Johnson, 1996) It is frequently complicated by pre-existing chronic liver disease, limiting therapeutic options. While early disease can be managed by resection or local ablation, decreased hepatic reserve may limit the options for surgery or systemic therapy. Furthermore, response rates for systemic therapy are low: no single agent has a response rate higher than approximately 20%, and none improves survival (Leung and Johnson, 2001).

Multiagent therapy using cis-platinum, doxorubicin, 5-fluorouracil, or interferon-alpha may show higher response rates (Leung et al, 1999). However, because patients with HCC frequently have advanced liver disease and associated comorbidities, they are often unable to tolerate intensive and toxic treatment. On the basis that some HCCs have hormone receptors, hormonal approaches (including tamoxifen in a variety of doses) have been evaluated; however, none of these has shown a survival advantage over best supportive care (Chow et al, 2002). A small randomised trial conducted by Kouroumalis et al (1998) suggested that survival was longer in a group treated with short-acting octreotide than in an untreated control group (median survival 13 vs 4 months, 12-month survival 56 vs 13%, P=0.002).

High-affinity somatostatin receptors capable of binding octreotide are present in approximately 40% of HCC, and not in adjacent liver. However, the numbers of high-affinity receptors are lower than reported for neuroendocrine tumours (Reubi et al, 1999). Somatostatin is a potent inhibitor of several growth factors and angioneogenesis (Florio et al, 2003); it also has immune-modulating properties (Lambrecht, 2001). Neuroendocrine and epithelial tumour cell growth can be inhibited in vitro and in vivo by the semisynthetic somatostatin analogue, octreotide (Lamberts et al, 1990). The long-acting depot form of octreotide (sandostatin long-acting release (LAR)) is formulated in microspheres, enabling treatment to be delivered by monthly intramuscular (i.m.) injection.

It is currently used for the treatment of acromegaly (Freda, 2002) and functional neuroendocrine tumours (de Herder and Lamberts, 2002). Little information is available about its elimination kinetics in cirrhosis, although the short-acting form has been studied (Jenkins et al, 1998). In patients with portal hypertension, octreotide has been used extensively in the management of acute variceal bleeding and other complications, Dacomitinib where it reduces portal blood pressure in patients with poor liver function (Jenkins et al, 1997).

shigatox net/ecmlst/cgi-bin/strainquery and the sequence of ECA-B and the sequence of ECA-B was provided by Dr. Kenneth kinase inhibitor MEK162 Simpson. Allele, st7 and clonal group were determined using the EcMLST web-based software ( Bovine Primary Endometrial Cell Isolation and Culture Primary endometrial epithelial and stromal cells were isolated and cultured as described previously [18]. Briefly, bovine uteri were collected from post-pubertal non-pregnant animals with no evidence of genital disease or microbial infection at a local abattoir and kept on ice until further processing in the laboratory. The stage of the reproductive cycle was determined by observation of ovarian morphology and genital tracts with an ovarian Stage II corpus luteum were selected for endometrial culture [40].

The endometrium from the horn ipsilateral to the corpus luteum was cut into strips and placed into PBS (Sigma, Poole, UK) supplemen
Imatinib is a selective inhibitor of tyrosine kinases, comprising Bcr-Abl fusion protein in chronic myeloid leukaemia (CML) and the c-kit proto-oncogene in gastrointestinal stromal tumour (GIST). It has demonstrated an impressive clinical efficacy in both malignancies. Inducing durable responses and achieving prolonged survival, imatinib has become the standard of care for the treatment of these diseases. However, imatinib treatment is not devoid of toxicity and resistance occurs in some instances. Besides cellular mechanisms of resistance (gene amplification and mutation), variability in binding to ��1-acid glycoprotein (AGP) can modulate its activity [1, 2�C5].

Indeed, only the free drug is likely to equilibrate with the intracellular milieu to exert its pharmacological action. Moreover, a small change in the extent of protein binding may result in a significant impact on imatinib free fraction and on its concentration�Ceffect relationships [5, 6]. Although there are many circulating proteins in plasma capable of binding drugs, the majority of drugs bind to human serum albumin (HSA) and AGP [7]. HSA is the most abundant protein in plasma, whereas the normal AGP concentrations are much lower, resulting in a lower capacity to bind drugs and a more rapid saturation of the protein [8]. Both are capable of binding a broad variety of drugs with sufficient affinity to impact on the pharmacologically active free fraction.

HSA is the primary binding protein for acidic drugs, while binding to AGP is more commonly observed with basic lipophilic agents. Changes in the concentration, conformation, and/or other physicochemical characteristics of these proteins may result in significant changes in the Cilengitide drug free fraction [9]. Alterations in albumin concentrations in plasma occur as a result of altered synthesis, loss, or a shift of fluids between body compartments.

Based on these preliminary experiments, interactions of segmen

.. Based on these preliminary experiments, interactions of segments 40-130 and 130-261 fused to CFP or YFP were investigated Palbociclib IC50 by FRET. As shown in Fig. Fig.2B,2B, these N- and C-terminal fragments were found to interact both with themselves and with each other. These results demonstrate that several determinants contribute to the oligomerization of NS4B, through homotypic (i.e., occurring between the same protein segment) and heterotypic (i.e., occurring between different protein segments) interactions. Whether the heterotypic interaction between the N- and C-terminal fragments occurs as an intermolecular or intramolecular association in the context of the full-length protein remains unknown. Confirmation of FRET results by coimmunoprecipitation. To corroborate the results obtained by FRET, we performed coimmunoprecipitation analyses.

To this end, the HA or FLAG tag was fused to the C terminus of full-length HCV NS4B or DV NS4B, as well as to fragments 40-130 and 130-261 from HCV NS4B. Lysates from cells coexpressing different combinations of these constructs were subjected to immunoprecipitation and Western blot analyses using anti-HA and anti-FLAG antibodies. As shown in Fig. Fig.3A,3A, these analyses revealed a specific self-interaction of HCV NS4B, while as expected, no interaction was observed between the NS4B proteins from HCV and DV. In addition, coimmunoprecipitation analyses confirmed the specificity of the homotypic and heterotypic interactions observed between the N- and C-terminal NS4B fragments 40-130 and 130-261 (Fig. (Fig.3B).3B).

Taken together, the results from the coimmunoprecipitation analyses confirm the oligomerization of HCV NS4B through several determinants. FIG. 3. Confirmation of FRET results by coimmunoprecipitation. (A) Constructs pCMVNS4B-HA, pCMVNS4B-FLAG, pCMVDV4B-HA, and pCMVDV4B-FLAG were transfected into U-2 OS cells as indicated, followed by immunoprecipitation (IP) of cell lysates with anti-FLAG M2 agarose … Oligomerization of NS4B proteins from different HCV genotypes. In order to assess whether our observations can be extended to other HCV strains and to gain insights into the genotype specificity of the identified interactions, we investigated FRET between NS4B sequences derived from the HCV H77 consensus (genotype 1a) and JFH-1 (genotype 2a) clones.

The overall amino acid sequence identity AV-951 between these two NS4B sequences is 72%, while the 40-130 and 130-261 fragments display 70% and 82% identity, respectively (see Fig. S1 in the supplemental material). A schematic representation of the percent amino acid identity along the NS4B sequence, derived from the sequence alignment shown in Fig. S1, highlights the regions that are conserved between these relatively distant HCV strains (Fig. (Fig.4A4A). FIG. 4. Oligomerization of NS4B proteins from different HCV genotypes.

For immunolocalization of TLR4/MD2, confocal images were obtained

For immunolocalization of TLR4/MD2, confocal images were obtained (Radiance system 2100; Bio-Rad Labs, Hercules, CA) and for immunolocalization selleck inhibitor of occludin fluorescent images were obtained with an Olympus Provis AX70 microscope (Olympus, Melville, NY); images were analyzed with Scion Image software (Scion, Frederick, MD). Measurement of phosphorylated myosin light chain by Western blot. Phosphorylated myosin light chain (p-MLC) expression was measured by Western blot of ileum as previously described (17). Briefly, 30 g of proteins were used, samples were loaded in precast 7% Tris acetate gel, and the gel was run for 60 min at 125 volts (Invitrogen Power Case 500). The proteins were transferred (1 h at 30 V, 220 mA) from the gel to a Fluorotrans polyvinylidene difluoride membrane (Pall, East Hills, NY).

Skim milk (10%) in TBS-Tween 20 (TBST) was used to block. Primary antibody dilution was 10 ��l in 10% milk-TBST [glyceraldehyde-3-phosphatase dehydrogenase (GAPDH) (14C10) rabbit monoclonal antibody, no. 2118 (Cell Signaling, Beverly, MA); p-MLC (18Thr)-R, no. sc-19848-R (Santa Cruz Biotechnoloy)]. Milk-TBST (10 ��l in 25%) of secondary antibody [anti-rabbit IgG horseradish peroxidase-linked, no. 7074 (Cell Signaling), were used as well as horseradish peroxidase (1:2,000; Cell Signaling). The membrane was exposed to film for 30 min and developed in a 100 Plus automatic X-Ray film Processor (All Pro Imaging, Hicksville, NJ). The film was analyzed by Imagequant version 5.1 software (Amersham, Biosciences, Amersham, UK) (17).

Quantitative assessment of gut microbiota order abundance by sequence analysis of the microbial 16S rRNA gene. The materials and methods are described in detail [see supplemental information and Ref. 20 (Supplemental data for this article may be found on the American Journal of Physiology: Gastrointestinal and Liver Physiology website.)]. Cecal contents were removed and maintained on dry ice for same-day processing by phenol-chloroform-sodium acetate-ethanol- and bead beating-based cellular lysis and nucleic acid isolation/purification methods. Each quantitative PCR (qPCR) well was run in triplicate and contained 10 ��l of 2�� Takara Perfect Real Time master mix (7.2 ��l of water, 0.

8 ��l of a 10 ��M F/R primer mix, 2 ��l of either an optimized dilution of 1:500 of extracted template DNA in DNase/RNase-free water for specimen analysis or a serial dilution series of Carfilzomib bacterial reference genomic DNA for standard curves); all reactions were paralleled by a nontemplate water control analysis. Cycling conditions were as follows: 95��C for 20 s; 40 repeats of the following steps: 95��C for 4 s, 30 s annealing. SYBR green fluorescence was detected with a Bio-Rad Chromo4 Real Time PCR Detector on a Dyad Disciple Peltier Thermal Cycler. Melting curves were obtained from 55 to 90��C, with fluorescence measurements taken at every 1��C increase in temperature.

Methods Subjects The data for this paper

Methods Subjects The data for this paper selleck kinase inhibitor come from a longitudinal study of the natural history of smoking among adolescents. The study uses a multimethod approach to assess adolescents at multiple time points (baseline, 6, 15, and 24 months). The data collection modalities include paper-and-pencil questionnaires, in-person interviews, and for subsets of participants, more intensive measurement modalities including family observations, psychophysiological assessments, and week-long time/event ecological momentary assessment sampling via hand-held palmtop computers (referred to as ��Electronic Diary��). The NDSS instrument examined in this study was collected from questionnaires.

Out of the 1,263 baseline adolescents who had smoked and were eligible to respond to the NDSS items, 1,034 responded to at least 1 out of the 10 NDSS items and are included in the baseline analysis (Model I in the analysis and result sections). An averaged NDSS score was created for subjects who responded to at least five NDSS items at a given wave of data collection, resulting in a sample of 1,032 adolescents for the longitudinal NDSS score analysis (Model II). Those subjects who responded to at least one NDSS item at one or more time points are included in the longitudinal analysis of item responses (Model III), resulting in the largest sample size among the three sets of analyses, N = 1,097. Of the 1,097, the adolescents were either in Grade 9 (n = 545, 49.7%) or Grade 10 (n = 552, 50.3%), and 612 (55.8%) were female students. The ethnicity groups include Non-Hispanic White (618, 56.

3%), Non-Hispanic Black (172, 15.7%), Hispanic (204, 18.6%), Asian/Pacific Island (39, 3.6%), and other (64, 5.8%). Measures The 10 NDSS items were rated on a four-category ordinal scale (1 = not at all true; 2 = not very true; 3 = fairly true; 4 = very true). About one-fifth of the subjects missed information on at least one item at each wave. Brefeldin_A An average NDSS score was obtained for those individuals who responded to at least five items at a given time point. Descriptions and summary statistics for the items and the averaged score across waves are listed in Table 1. The subjects had a consistently high rating to Item 2, Since I started smoking, I have increased how much I smoke. Two other relatively highly rated items were: Item 1, Compared with when I first started smoking, I need to smoke a lot more now in order to be satisfied, and Item 3, After not smoking for awhile, I need to smoke to relieve feelings of restlessness and irritability.

3 �� 1 2 nmol/mg protein per 10 s in control mice to 17 3 �� 2 8

3 �� 1.2 nmol/mg protein per 10 s in control mice to 17.3 �� 2.8 nmol/mg protein per 10 s in TNBS mice (n = 3; P = 0.028) (Fig. 1A). Western blot with BBMV protein showed that TNBS administration also decreased NaPi-IIb immunoreactive protein abundance (indicated by the ratio of optical densities of the NaPi-IIb band enough to that of the ��-actin band) from 1.97 �� 0.45 in control mice to 0.73 �� 0.18 in TNBS mice (n = 3; P = 0.017) (Fig. 1B). Fig. 1. Effect of inflammation on intestinal phosphate absorption and type IIb sodium-phosphate cotransporter (NaPi-IIb) expression in trinitrobenzene sulfonic acid (TNBS) colitis mice. Six-week-old male mice were treated with TNBS (2 mg/mouse) and were harvested … Effect of TNBS colitis on NaPi-IIb expression in rat intestine.

Male rats received TNBS (1 mg/rat in 50% ethanol) or PBS buffer in a total volume of 250 ��l by an enema into the colonic lumen. Six days after TNBS administration, rats were killed and jejunal mucosa was harvested for BBMV and RNA purification. Western blot was used to determine NaPi-IIb protein abundance from BBMV protein. Real-time PCR was used to determine NaPi-IIb mRNA expression. Western blot results showed that NaPi-IIb immunoreactive protein abundance was reduced by ~53% in TNBS colitis rats, from 1.23 �� 0.11 in control rats to 0.59 �� 0.26 in TNBS rats (n = 3; P = 0.04) (Fig. 2A). Real-time PCR data indicated that the expression of NaPi-IIb mRNA was decreased by ~42% in TNBS colitis rats compared with control rats, from 1.09 �� 0.02 in control rats to 0.63 �� 0.07 in TNBS rats (n = 3; P = 0.004) (Fig.

2B). Fig. 2. Effect of inflammation on NaPi-IIb expression in TNBS colitis rats. Three-week-old rats were treated with TNBS (1 mg/rat) and were harvested 6 days after TNBS administration. A: BBMVs were isolated from the jejunal mucosa of rats treated with PBS or TNBS … Effect of TNF-�� on phosphate uptake and NaPi-IIb expression in Caco-2 cells. The endogenous NaPi-IIb expression in Caco-2 cells has been shown in our previous work (38). To study the effect of TNF-�� on cellular phosphate absorption, Caco-2 cells were grown in 24-well plates and treated with normal or TNF-��-containing medium (20 ng/ml) for 40 h. Cellular phosphate uptake assays were performed to measure the rate of phosphate uptake in Caco-2 cells. Western blot detection was used to assess NaPi-IIb protein levels in Caco-2 cells. Real-time PCR was conducted to determine the expression of NaPi-IIb mRNA in Caco-2 cells. As shown in Fig. 3, sodium-dependent phosphate absorption was significantly decreased in Caco-2 cells after TNF-�� treatment, from 2.51 �� 0.27 nmol/mg protein per 15 min in control cells Brefeldin_A to 1.14 �� 0.37 nmol/mg protein per 15 min in TNF-��-treated cells (n = 3; P = 0.013) (Fig. 3A).

To our knowledge, only a few adolescent twin studies of depressio

To our knowledge, only a few adolescent twin studies of depression and smoking have been carried out, all of which were conducted in U.S. and European settings. A study of Finnish adolescent twin pairs who were discordant for depressive disorders found that history of depressive disorder occurring prior to age 14 predicted use of smokeless tobacco by age 17.5 increased risk for daily smoking, but did not predict smoking initiation (Sihvola et al., 2008); this study did not utilize genetic modeling approaches. In a genetic modeling study of U.S. adolescent twins, Silberg, Rutter, D��Onofrio, and Eaves (2003) found that early experimental smoking and depression were genetically correlated in girls but environmentally correlated among boys. Finally, in U.S.

adolescent twin pairs, McCaffery, Papandonatos, Stanton, Lloyd-Richardson, and Niaura (2008) found that nonshared environmental factors explained the relation between level of depressive symptoms and smoking involvement and that there was a common genetic source of depression�Csmoking covariation in girls. Given the substantial public health burden of smoking in Asian countries, such as China (Qian et al., 2010), it is important to understand influences on smoking initiation in Chinese adolescents. A sizeable number of Chinese begin smoking in adolescence, with evidence that for boys, the hazard of smoking initiation is very low (<2%) before 7 years of age, increases rapidly after age 10 years, and peaks at 14�C15 years, whereas the hazard for girls is low (<1%) until 12 years of age before it increases by age 15 years, but the overall prevalence of smoking is higher in boys than in girls (Chen et al.

, 2001). The cultural characteristics of Asia are different from western societies, which may modulate the expression of genetic vulnerabilities on depressive symptoms, smoking initiation, and their association (Unger et al., 2011). For example, although most Asian countries have laws restricting Entinostat youth access to tobacco, enforcement of these policies is inconsistent, and it is common for adults to offer cigarettes to adolescents on special occasions or as a rite of passage into adulthood (Okamoto et al., 2010). Adolescents in China often report high levels of academic stress because admission to prestigious high schools is very competitive, and they tend to report smoking to cope with stress while studying for stressful exams (Booker et al., 2007; Okamoto et al., 2010). Also, Asian populations also have different allele frequencies for genetic variants implicated in depression and smoking (e.g., Kang, Palmatier, & Kidd, 1999).

Terminology AP is a sudden inflammation of the pancreas It can h

Terminology AP is a sudden inflammation of the pancreas. It can have severe complications and high mortality despite treatment. While mild cases are often successfully treated with conservative measures and aggressive intravenous fluid rehydration, severe cases may require admission to the intensive care unit or even surgery to deal with complications of the disease process. Peer 17-AAG solubility review The role of SSM is mainly deleterious and also anti inflammatory and antimicrobial, what in literature has support about the protective effect of SSM in AP. The study is designed reasonably and the methods and the results seem mostly proper to show interesting protective effect of SSM on AP. Footnotes Supported by National Research Foundation of Korea grant funded by the Korea government MEST, No.

2010-0029498 P- Reviewers Sumi S, Kumar A S- Editor Jiang L L- Editor A E- Editor Xiong L
Fusogenic viral envelope glycoproteins are multimeric proteins that facilitate the fusion of viral and target cell lipid membranes during the initiation of infection. The membrane fusion process is energetically favorable and essentially irreversible, but has a considerable kinetic energy barrier [1]. These proteins allow rapid membrane fusion by drawing the opposing membranes together and either stabilizing or providing the activation energy to surmount the transition state [1], [2]. In this way, they behave in many aspects like a fusion catalyst. Because they effect a macromolecular process that involves large scale conformational changes in the substrate membranes and the proteins themselves, these proteins possess multiple interacting surfaces that could be targeted by inhibitors [3].

There are several distinct types of viral fusion proteins, including the class I, primarily alpha helical proteins (such as HIV TM and influenza HA), the class II, primarily beta sheet proteins (such as the flavivirus E and alphavirus E1), and mixed helix/sheet proteins (including herpes virus gB and rhabdovirus G) [3], [4]. To date, most progress with viral fusion protein inhibitors has focused on class I alpha helical proteins. The HIV TM protein provides an excellent example of targeting distinct, interacting surfaces for inhibition. The HIV TM functions as a homotrimer with each monomer contributing two alpha helical regions that interact to form a post-fusion six-helix bundle.

Inhibition of the formation of this six-helix bundle can be accomplished by exogenous peptides mimicking either of the two reciprocally interacting helices [5]�C[7]. Only a few examples of viral entry inhibitors with activity against the primarily beta sheet envelope proteins (E) from flaviviruses have been described [8]�C[10]. However, few of these have taken advantage of the available GSK-3 crystal structures of flavivirus E proteins, including both pre-fusion and post-fusion forms [11]�C[22].

However, it remains important to note that the two groups after W

However, it remains important to note that the two groups after Week 24�C telbivudine and telbivudine plus tenofovir �C were not randomized and hence statistical comparisons are limited. In particular, the lack of randomization, and confounding by Week 24 response to telbivudine, precludes efficacy comparison between the telbivudine and telbivudine plus tenofovir groups. Results Patient Disposition The efficacy population comprised 100 patients and the safety population 105 patients (Figure 2). Patient demographics and baseline characteristics are shown in Table 1, stratified according to treatment after Week 24. Compared with those who remained on telbivudine monotherapy, a higher proportion of intensification patients had baseline HBV DNA ��9 log10 copies/mL (73.3% versus 36.

4% of those remaining on monotherapy; P<0.001). Mean baseline ALT was also higher in those who remained on monotherapy (167.2 U/L versus 93.2 U/L; P=0.0045). Other characteristics were broadly similar between those who did and did not receive intensification. Table 1 Demographics and baseline characteristics (efficacy population) according to post-Week 24 treatment. A total of 99/100 patients in the efficacy population (99%) completed Week 52. There was one discontinuation in the telbivudine plus tenofovir group for loss to follow-up after Week 30. Efficacy At Week 24, 55 of 100 patients (55%) in the efficacy population had undetectable HBV DNA and continued to receive monotherapy. All of these 55 patients remained undetectable at Week 52 on telbivudine monotherapy.

The remaining 45 patients (45%) received telbivudine plus tenofovir after Week 24, of whom 38 (84.4%) had undetectable DNA at Week 52. Of these 45 patients, 12 had baseline HBV DNA <9 log10 copies/mL (of whom 3 also had baseline ALT ��2��ULN) and 33 had ��9 log10 copies/mL. All (12/12) of the patients with baseline HBV DNA <9 log10 copies/mL, and 78.8% (26/33) of those with ��9 log10 copies/mL, achieved undetectable DNA at week 52. The overall rate of undetectable HBV DNA at Week 52 (primary endpoint) was therefore 93% (93/100) by LOCF analysis. This value was the same by a strict ITT missing=failure analysis, as one patient lost to follow-up after Week 30 had detectable HBV DNA (2.67 log) at last visit. Primary and secondary efficacy endpoints are shown in Table 2.

Figure 3 shows mean changes from baseline in HBV DNA by visit for the two treatment groups. By LOCF Anacetrapib analysis, mean reduction from baseline in HBV DNA at Week 24 was ?6.2 log10 copies/mL in patients who continued to receive telbivudine alone, versus ?6.0 log10 copies/mL in those who subsequently received tenofovir. The Week 24 mean reduction remained stable at ?6.2 log10 through Week 52 in those who continued telbivudine monotherapy, while the addition of tenofovir resulted in an additional 1.4 log10 reduction at Week 52 in the intensification group.