Marianna Univ. Yokohama-city Seibu Hopsital, St. Marianna Wnt inhibition Univ. Yokohama-City Seibu Hopsital Objective: Several cases of sporadic cancer, not colitic cancer in the patients with ulcerative colitis were reported. Differential diagnosis is critical, because the first-line therapy is different. Methods: Case: A 47 y/o female was referred to our hospital, after ulcerative colitis was confirmed pathologically. 5-ASA, steroid enema and azathioprine was given, however, the remission stage could not be obtained. On colonoscopy, multiple

inflammatory polyps were seen in the entire colon. A sessile polypoid lesion sized as 5 mm in diameter, surrounded by the inflammatory mucosa, was seen in the hepatic flexure, and biopsy specimen showed adenocarcinoma. Magnifying images with NBI and indigocarmine stain showed IV with partial VI type pit pattern. After obtained fully informed consent, endoscopic mucosal resection (EMR) underwent. Results: Pathological result was as follows: Tubular adenocarcinoma, tub1, pM, Intestinal type; INFb. Panobinostat cost ly0, v0, horizontal margin:-, vertical margin:-. Immunohistological result with p53 and Ki-67 presented that the neoplastic area was seen only on the top of the lesion without any dysplasia in the adjacent area. (“top-down” type) Discussion: It is difficult to distinguish colitic from sporadic cancer only in the endoscopic

images, therefore, histological confirmation is critical. We firstly diagnosed colitic cancer, because the extension of the lesion was entire colon type and the morbidity history was more than 10 years. However, the final result was sporadic cancer with ulcerative colitis. Conclusion: A case report of sporadic early colon cancer in the patient with ulcerative colitis was presented, difficult to differentiate from colitic cancer endoscopically. More cumulative case reports would be mandatory. Key Word(s): 1. colitic cancer; 2. sporadic cancer; 3. ulcerative colitis Presenting Author: HIROKI TANAKA Additional Authors: MAKI MIYAKAWA, RYOSUKE SAKEMI, MASANAO NASUNO, SATOSHI MOTOYA, AKIMICHI IMAMURA

Corresponding Author: HIROKI TANAKA Affiliations: Sapporo Kosei General Hospital, Sapporo Kosei General Hospital, Sapporo Kosei General Hospital, Sapporo Kosei General Hospital, Sapporo Kosei General Hospital Objective: Very check details few studies have reported on Japanese patients with CD who received adalimumab maintenance treatment. We evaluated the effectiveness of adalimumab as a maintenance treatment in patients with CD and the prognostic factors related to the treatment results. Methods: We investigated all patients who were treated with adalimumab for luminal CD between October 2010 and March 2013. The effectiveness of adalimumab maintenance treatment was evaluated using the sustained treatment success rates, which were estimated using the Kaplan–Meier method. Sustained treatment success was defined as a lack of treatment failure.

2A, Supporting Table 2). Analysis of cyclin B1 and Cdk1 expression by western blot confirmed mitotic delay. These results clearly demonstrate dysregulated cell cycle progression in the hepatocytes of β2SP+/− mice and suggest that, whereas mutant hepatocytes

seem to have an accelerated G1/S phase, there is a definite delay in progression through the G2 and M phases. Given evidence of dysregulated cell cycle in β2SP+/− mice following PHx, we then assessed the expression of the checkpoint proteins p53 and p21 in wildtype and mutant mouse livers. Analysis of selleck products p53 and p21 expression by western blot demonstrated a significant impairment in their expressions at different timepoints post-PHx in β2SP+/− mouse livers in comparison to wildtype mouse livers (Fig. 3, Supporting Table 2). Moreover, the peak in p53 and p21 expression in mutant mice correlated with diminished levels of cyclin A and Cdk1 and delayed expression of p-histone (Ser10) (Fig. 2), suggesting that p53 and p21 may activate the G2/M-phase cell cycle checkpoint following PHx. To evaluate whether elevated p53 expression in mutant mice was secondary to impaired p53 regulation, we assessed transformed 3T3 cell double minute 2 (MDM2) and phosphatase and tensin homolog (PTEN) expression by western blot. PTEN may protect p53 from MDM2-mediated degradation and enhance p53 stability, whereas p53 can enhance

the transcription of PTEN.19 We demonstrated identical levels of PTEN and significantly Silmitasertib in vivo lower expression of MDM2 in mutant mice at 24 and 48 hours post-PHx (Supporting Fig. 1), suggesting enhanced p53 expression secondary to cellular or genotoxic stress and the DNA-damage response. G2/M-phase delay was further confirmed by analysis of phosphorylated Cdk1 (Thr14) (Fig.

2B, Supporting Table 2) and pSTAT3 (Tyr705) (Fig. 3, Supporting Table 2) expression. We then performed the Transferase-Mediated dUTP Nick-End Labeling (TUNEL) assay to determine whether p53 may mediate increased apoptosis leading to impaired regeneration. Cleaved caspase expression was virtually absent or significantly reduced in mutant mice compared with wildtype mice, particularly click here at 48 hours post-PHx. There was no evidence of correlating cleaved caspase-3 expression with either elevated p53 or p21 in mutant mice (Fig. 3). Similarly, results for the TUNEL assay were also negative at 48 hours (Supporting Fig. 2). These results further confirm a temporary p53-p21-mediated G2/M-phase arrest leading to delayed liver regeneration in β2SP+/− mice. Activation of p53 in response to DNA damage is mediated by phosphorylation on serine 15 and 20 by the kinases ATM/ATR and Chk2. Phosphorylation of p53 then results in an activated protein with numerous transcriptional targets necessary for cell cycle arrest, DNA repair, or apoptosis.

Low baseline HBsAg levels were associated with HBsAg clearance (40% for baseline HBsAg levels ≤ 20 IU/mL and 2% for levels > 20 IU/mL, P < 0.05). Interestingly, a 50% decrease in the HBsAg level from the baseline to week 12 was associated with a reduced likelihood of HBV DNA reactivation in patients with serum HBV DNA levels that were undetectable at the baseline (PPV = 89.5%).43 This raises the possibility that we might be able to identify those HCV/HBV-coinfected patients who are likely to experience HBV reactivation and may need additional therapy with

NAs. HBsAg declines during NA therapy appear more apparent in HBeAg-positive patients than HBeAg-negative patients, Selleckchem Inhibitor Library at least in the short term (Table 3). Although differences in the inclusion criteria preclude a comparison of HBsAg reduction across studies, one study involving both HBeAg-positive patients and HBeAg-negative patients showed that a substantial HBsAg decline during entecavir (ETV) therapy was restricted to HBeAg-positive patients.29 BVD-523 nmr A small study from Korea showed that a decrease > 1 log10 IU/mL in serum HBsAg levels during therapy (5 of 28 patients) was associated with a much higher cumulative incidence of HBeAg loss (80% versus 30%, P = 0.034) after 1

year of ETV therapy.28 Notably, one study showed that the HBsAg decline during ETV therapy was restricted to patients with baseline ALT levels greater than or equal to 2 times the upper limit of normal (P = 0.007), and it was most profound in those who lost HBeAg.29 This suggests that the HBsAg decline might be linked to increased immunological activity. HBsAg seroclearance is sometimes reported during NA therapy in HBeAg-positive patients. With tenofovir (TDF), HBsAg seroclearance rates of 3%, 6%, and 8% were reported after 1, 2, and 3 years of therapy in HBeAg-positive patients, but seroclearance was not observed in HBeAg-negative patients.44 HBsAg seroclearance rates for HBeAg-positive patients treated with ETV or LAM after 96 weeks on treatment and 24 weeks off therapy were 5%

and 3%, respectively.45 Recent studies have shown that a rapid decline in HBsAg levels during the first year of NA therapy learn more in HBeAg-positive patients is associated with a higher probability of HBsAg seroclearance: 8 of 32 patients with a rapid HBsAg decline > 1 log10 IU/mL during telbivudine (LdT) therapy achieved HBsAg clearance in year 3, whereas 0 of 56 patients with steady HBsAg levels achieved this (P = 0.0024).30 Similarly, patients with HBsAg loss during TDF therapy, who were most frequently infected with genotype A or D, exhibited a rapid HBsAg decline, and the HBV DNA decline pattern in patients with or without HBsAg loss was similar.31 There would be a considerable advantage in being able to determine whether a patient could stop NA therapy after a successful response.

4A). Similar trends were observed from the samples treated with GW4064 for a short time only (1 hour) (Supporting Fig. 12), which is consistent with a direct effect of FXR on gene expression, rather than delayed indirect responses. For the genes unique to obese mice, mRNA levels were increased significantly for 5 of 13 genes and decreased significantly in one (Fig. 4B). These results suggest that a large fraction of potential FXR target genes examined are likely repressed by agonist-activated FXR. Direct gene repression by agonist-activated FXR was expected to be rare, because

learn more nearly all of the direct FXR target genes have been reported to be activated.2, 3, 19 We therefore further examined epigenetic

histone markers of gene activation and repression, as well as occupancy by RNAPII.21, 24, 25 Genes with increased expression, as well as representative genes that were repressed or not find more significantly affected (Fig. 4A), were examined. Two-step re-ChIP and qRT-PCR analyses were performed, and the known FXR target gene, Shp, was first analyzed as a control. Co-occupancy of RNAPII with FXR and acetylated histone H3K9/K14 at the Shp promoter was increased, whereas co-occupancy of RXRα with FXR was not changed after GW4064 treatment (Fig. 5A). As expected, mRNA levels for Shp were increased after a 1-hour treatment with GW4064 (Fig. 5B). For selected potential FXR genomic targets, occupancy of FXR was increased in nearly all of the genes examined after GW4064 treatment (Fig. 5C). For the three genes with increased mRNA levels after GW4064 treatment (Fig. 4A), aldehyde dehydrogenase 1 and 2 (Aldh1/2), 3-oxoacid coenzyme A transferase 2B (Oxct2b), and cell division cycle-associated 4 (Cdca4), co-occupancy of RXRα and RNAPII with FXR was increased and acetylated histone H3K9/K14 levels were increased, see more as expected, for activated genes (Fig. 5D-F). For the remaining genes, RNAPII

occupancy and acetylated histone H3 levels were decreased or unchanged, which would be consistent with either no induction or suppression of these genes, as observed from the mRNA levels. Finally, to directly determine whether binding of agonist-activated FXR leads to the repression of genes examined, ChIP assays were performed to measure the levels of known epigenetic histone marks for gene repression, such as H3K9 di- and H3K27 tri-methylation.24, 25 After treatment with GW4064, occupancies of FXR and RNAPII were increased and tri-methylated H3K9 and H3K27 levels were decreased at the control Shp gene promoter (Fig. 6A). For the potential FXR target genes with increased expression, such as Ald1/2, Oxc2b, and Cdca4, levels of repressed histone marks (H3K27 and H3K9) were unchanged or decreased after GW4064 treatment (Fig. 6B).

These children with HBV breakthrough infection need careful, long-term follow-up, and the current immunization strategy may need modification to further eliminate the perinatal transmission of HBV. The GS-1101 datasheet authors thank Pei-Jer Chen and Shiou-Hwei Yeh for their professional opinion and technical support. They also thank Hui-Chuan Lee, Pei-Lin Tsai, and Shih-Ting Chiu for their help with subject follow-up and administrative work. Laboratory work performed

by Cheng-Lun Chiang and De-Shiuan Su is highly appreciated. “
“Alcoholic liver disease (ALD) is a primary consequence of heavy and prolonged drinking. ALD contributes to the bulk of liver disease burden worldwide. Progression of ALD is a multifactorial and multistep process that includes many genetic and environmental risk factors. The molecular

pathogenesis of ALD involves alcohol metabolism and secondary mechanisms such as oxidative stress, endotoxin, cytokines and immune regulators. The histopathological manifestation of ALD occurs as an outcome of complex but controlled interactions between hepatic cell types. Hepatic stellate cells (HSCs) are the key drivers of fibrogenesis, but transformation of hepatocytes to myofibroblastoids also implicate parenchymal cells as playing an active role in hepatic fibrogenesis. Recent discoveries indicate that lipogenesis during the early stages of ALD is a risk for advancement to cirrhosis. Other recently identified novel molecules and Lenvatinib cost physiological/cell

signaling pathways include fibrinolysis, osteopontin, transforming growth factor-β-SMAD and hedgehog signaling, and involvement of novel cytokines in hepatic fibrogenesis. The observation that ALD and non-alcoholic steatohepatitis share common pathways learn more and genetic polymorphisms suggests operation of parallel pathogenic mechanisms. Future research involving genomics, epigenomics, deep sequencing and non-coding regulatory elements holds promise to identify novel diagnostic and therapeutic targets for ALD. There is also a need for adequate animal models to study pathogenic mechanisms at the molecular level and targeted therapy. Alcohol-induced liver disease (ALD) remains a major cause of morbidity and mortality worldwide. Of the 60 types of diseases and injuries associated with alcohol consumption, ALD is the most common endpoint.1 It is estimated that for each 1-L increase in alcohol consumption per capita, there is an increase in liver cirrhosis of 14% in males and 8% in females.2 In Australia, ALD is the major cause of alcohol-related mortality exceeding that attributable to cancer and cardiovascular disease.

These children with HBV breakthrough infection need careful, long-term follow-up, and the current immunization strategy may need modification to further eliminate the perinatal transmission of HBV. The BMS-354825 mw authors thank Pei-Jer Chen and Shiou-Hwei Yeh for their professional opinion and technical support. They also thank Hui-Chuan Lee, Pei-Lin Tsai, and Shih-Ting Chiu for their help with subject follow-up and administrative work. Laboratory work performed

by Cheng-Lun Chiang and De-Shiuan Su is highly appreciated. “
“Alcoholic liver disease (ALD) is a primary consequence of heavy and prolonged drinking. ALD contributes to the bulk of liver disease burden worldwide. Progression of ALD is a multifactorial and multistep process that includes many genetic and environmental risk factors. The molecular

pathogenesis of ALD involves alcohol metabolism and secondary mechanisms such as oxidative stress, endotoxin, cytokines and immune regulators. The histopathological manifestation of ALD occurs as an outcome of complex but controlled interactions between hepatic cell types. Hepatic stellate cells (HSCs) are the key drivers of fibrogenesis, but transformation of hepatocytes to myofibroblastoids also implicate parenchymal cells as playing an active role in hepatic fibrogenesis. Recent discoveries indicate that lipogenesis during the early stages of ALD is a risk for advancement to cirrhosis. Other recently identified novel molecules and Ibrutinib order physiological/cell

signaling pathways include fibrinolysis, osteopontin, transforming growth factor-β-SMAD and hedgehog signaling, and involvement of novel cytokines in hepatic fibrogenesis. The observation that ALD and non-alcoholic steatohepatitis share common pathways check details and genetic polymorphisms suggests operation of parallel pathogenic mechanisms. Future research involving genomics, epigenomics, deep sequencing and non-coding regulatory elements holds promise to identify novel diagnostic and therapeutic targets for ALD. There is also a need for adequate animal models to study pathogenic mechanisms at the molecular level and targeted therapy. Alcohol-induced liver disease (ALD) remains a major cause of morbidity and mortality worldwide. Of the 60 types of diseases and injuries associated with alcohol consumption, ALD is the most common endpoint.1 It is estimated that for each 1-L increase in alcohol consumption per capita, there is an increase in liver cirrhosis of 14% in males and 8% in females.2 In Australia, ALD is the major cause of alcohol-related mortality exceeding that attributable to cancer and cardiovascular disease.

8% vs. 59.2%, P < 0.05); patients on combined consolidation therapy > 2-years with lower baseline HBV-DNA (< 105copies /mL) had a low cumulative relapse rate of 15.4%. Eight cases had HBsAg seroconversion without relapse. Baseline HBV-DNA and HBsAg at the end of treatment were two factors predictive of relapse. Conclusions: This study demonstrated that a Alvelestat 50% of relapse in NUCs-naïve CHB patients under LdT and LAM treatment. Most of the relapses

occurred within 4-years. Lower relapse rate as an ideal long-term durability could be observed in patients who achieved EVS with extended consolidation therapy and had lower baseline HBV-DNA. HBsAg seroconversion was a solid indicator

for sustained viral response. Disclosures: The following people have nothing to disclose: Hong-Ying Pan, Hong-Yi Pan, Li Chen, DanHong Yang, HaiJun Huang, YongXi Tong, Cui-Rong Chen, XingJiang Jian Background/Aim : Although entecavir (ETV) has high potency for hepatitis B virus (HBV) infection, partial virological response (PVR) has been shown in some patients. There are limited data of long-term ETV therapy in PVR patients. Saracatinib molecular weight The aim of this study was to determine the probability of response during long-term ETV therapy in PVR patients and to analyze tenofovir diso-proxil (TDF) efficacy on these patients. Methods: We retrospectively studied 120 patients with PVR (detectable HBV DNA at 12 months of therapy) to ETV. We compared the cumulative probability of complete virological response

selleck inhibitor (defined as HBV DNA <20 IU/ml), HBV DNA levels, and HBe Ag loss during prolonged therapy in nucleot(s)ide analogue (NUC)- naTve patients to NUC-experienced patients. We also analyzed CVR rate in patient switched from ETV to TDF Results: Among 120 patients, 96 (80.0%) were NUC- naTve. The cumulative probability of achieving CVR was significantly high in NUC- naTve group (51.2% vs. 39.5% at 12months, 71.1% vs. 39.4% at 24months, 77.3% vs. 39.4% at 36months of treatment from the time of PVR, p=0.036). There were no differences in change of HBV DNA and HBe Ag loss rate in two groups. Upon multi-variate analysis, HBV DNA at PVR (p=0.001) and NUC- experience (p=0.013) were associated with CVR at 24months from the time of PVR. In prediction of CVR at 24month, HBV DNA ≤177 IU/ml at the time of PVR showed 76.2% of sensitivity and 81.6% of specificity (AUROC 0.804, p=0.000). In subgroup analysis in patients switched to TDF or added TDF, the cumulative probability of CVR was 93.1% at 6 months of therapy. Conclusion: TDF therapy is effective for achieving CVR in ETV PVR patients. We should consider TDF therapy in patients with PVR, if patient have NUC- experience or HBV DNA is above 177 IU/ml at the time of PVR.

Administered dosages were tapered towards a normal prophylactic regimen of 15–25 IU

FVIII kg−1 three times a week, according to previously described intermediate dose prophylaxis [11]. When FVIII treatment was started because of a life threatening bleed or surgery, and the inhibitor level was less than 10 BU mL, an initial bolus with FVIII was given to neutralize the inhibitor [4], followed by 25 IU kg−1 FVIII twice daily for Kinase Inhibitor Library high throughput 1–2 weeks, depending on the clinical status of the patient and the anamnestic response to FVIII. During ITI in patients with a high titre inhibitor, surgical procedures, such as insertion of a PAC system, were covered with recombinant factor VIIa (rVIIa, Novoseven®; NovoNordisk, Copenhagen, Denmark). Bleeds were treated with both APCC (Feiba®; Baxter, Vienna, www.selleckchem.com/products/Liproxstatin-1.html Austria) or rVIIa (Novoseven®). Plasma sampling  Plasma samples to determine FVIII levels

and inhibitor assays were collected using standard techniques: 4.5 mL venous blood was drawn in a vacutainer in which 0.5 mL sodium citrate (109 mol L−1) was added as an anticoagulant. After centrifugation at 3000 × g for 15 min at 4°C, the platelet-poor plasma was carefully pipetted off and plasma was stored at −20°C. In small children 1 mL cups were used, containing 0.1 mL sodium citrate to which 0.9 mL blood was added. Inhibitor assays  Factor VIII antibodies were initially performed according to the Bethesda check details method as described by Kasper et al. [12]. In 1995, the Nijmegen modification was introduced [13]. This modification was subsequently used in our laboratory. Antibody titres of ≥1 BU mL−1 were defined as positive in the original test, whereas antibody titres >0.3 BU mL−1 were considered positive in the Nijmegen modification. With exception of patient one, all samples tested with the original Bethesda assay were retested with the Nijmegen assay. For this study, only the results of the Nijmegen assay were used. Inhibitor patients were tested every 4–8 weeks during their ITI treatment and the first 6 months

after successful ITI. Subsequently inhibitor tests were carried out once or twice yearly until end of follow-up. Factor VIII assay  Factor VIII assays were performed using the one stage method and expressed as a percentage of FVIII present in normal pooled human plasma. In vivo recovery and factor VIII half life  To determine in vivo recovery in patients with an inhibitor titre below 10 BU mL−1, blood samples were taken before, and 15–30 min after FVIII infusion. Recovery was defined as the level of FVIII measured in relation to the expected level of FVIII, calculated according to Lee et al. [14]. A FVIII recovery of 66% or more was considered normal. Factor VIII half life was determined after a wash out period of 72 h.

The present study aimed to assess and compare the efficacy of two separate clarithromycin including sequential regimens in Turkey which is well known with high clarithromycin and metronidazole resistance to H. pylori. Methods:  MLN0128 Consecutive H. pylori -positive patients with non-ulcer dyspepsia were randomly allocated to one of the two sequential regimens; the first group was given lansoprazole 30 mg b.i.d. plus amoxicillin 1 g b.i.d. for

the first week, followed by lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg t.i.d. for the second week (LA-CM). The second arm was given the same regimen but tetracycline500 g q.i.d. instead of metronidazole (LA-CT). H. pylori was detected with urea breath test (UBT) and histology before enrollment. UBT was repeated at 6th weeks after treatment. Results:  A total of 200 patients were enrolled in groups and 179 of them completed their protocols. The cumulative per protocol (“PP”) and intention-to-treat (“ITT”) eradication rates were 74.3% and 66.5% in BGB324 mouse all patients, respectively. Both “PP” (78.2% vs 70.1%) and “ITT” (72% vs 61%) eradication rates were better in LA-CT group than LA-CM group, but the differences were not statistically significant (p > .05). Both regimens were well tolerated, and the incidence of adverse effects was

comparable. Conclusion:  Two weeks clarithromycin including sequential regimens with metronidazole or tetracycline were not achieved acceptable eradication rates in Turkey. “
“Background and Aim:  Fluoroquinolone resistance of Helicobacter pylori is known to be dependent on mutations in the QRDR of gyrA. This study was performed to investigate the distribution of gyrA point mutations and to evaluate the impact of the mutations

on second-line H. pylori eradication therapy. Methods:  After H. pylori isolation from gastric mucosal specimens, fluoroquinolone resistance was examined using the agar dilution method. DNA sequencing of this website the QRDR of gyrA was performed in 89 fluoroquinolone-resistant and 27 fluoroquinolone-susceptible isolates. Transformation experiments were performed to confirm mutations in the resistant strains. The eradication rates of moxifloxacin-containing triple therapy were evaluated depending on the resistance of fluoroquinolone. Results:  The gyrA mutations were detected in 75.3% (55 of 73 strains) of the primary resistant strains and 100% (16 strains) of the secondary resistant strains. The most common mutations were Asp-91 (36.0%) and Asn-87 (33.7%). The MIC values in the transformed strains differed depending on the gyrA mutations, N87, and D91. Six patients with fluoroquinolone-resistant strains received moxifloxacin-containing triple therapy as the second-line therapy, and two of three patients with Asn-87 mutations (66.7%) failed in the eradication. By contrast, three patients with Asp-91 mutations had successful eradication treatment. Conclusions:  Fluoroquinolone resistance of H.

The present study aimed to assess and compare the efficacy of two separate clarithromycin including sequential regimens in Turkey which is well known with high clarithromycin and metronidazole resistance to H. pylori. Methods:  Selleck GDC-973 Consecutive H. pylori -positive patients with non-ulcer dyspepsia were randomly allocated to one of the two sequential regimens; the first group was given lansoprazole 30 mg b.i.d. plus amoxicillin 1 g b.i.d. for

the first week, followed by lansoprazole 30 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg t.i.d. for the second week (LA-CM). The second arm was given the same regimen but tetracycline500 g q.i.d. instead of metronidazole (LA-CT). H. pylori was detected with urea breath test (UBT) and histology before enrollment. UBT was repeated at 6th weeks after treatment. Results:  A total of 200 patients were enrolled in groups and 179 of them completed their protocols. The cumulative per protocol (“PP”) and intention-to-treat (“ITT”) eradication rates were 74.3% and 66.5% in Lenvatinib purchase all patients, respectively. Both “PP” (78.2% vs 70.1%) and “ITT” (72% vs 61%) eradication rates were better in LA-CT group than LA-CM group, but the differences were not statistically significant (p > .05). Both regimens were well tolerated, and the incidence of adverse effects was

comparable. Conclusion:  Two weeks clarithromycin including sequential regimens with metronidazole or tetracycline were not achieved acceptable eradication rates in Turkey. “
“Background and Aim:  Fluoroquinolone resistance of Helicobacter pylori is known to be dependent on mutations in the QRDR of gyrA. This study was performed to investigate the distribution of gyrA point mutations and to evaluate the impact of the mutations

on second-line H. pylori eradication therapy. Methods:  After H. pylori isolation from gastric mucosal specimens, fluoroquinolone resistance was examined using the agar dilution method. DNA sequencing of selleck compound the QRDR of gyrA was performed in 89 fluoroquinolone-resistant and 27 fluoroquinolone-susceptible isolates. Transformation experiments were performed to confirm mutations in the resistant strains. The eradication rates of moxifloxacin-containing triple therapy were evaluated depending on the resistance of fluoroquinolone. Results:  The gyrA mutations were detected in 75.3% (55 of 73 strains) of the primary resistant strains and 100% (16 strains) of the secondary resistant strains. The most common mutations were Asp-91 (36.0%) and Asn-87 (33.7%). The MIC values in the transformed strains differed depending on the gyrA mutations, N87, and D91. Six patients with fluoroquinolone-resistant strains received moxifloxacin-containing triple therapy as the second-line therapy, and two of three patients with Asn-87 mutations (66.7%) failed in the eradication. By contrast, three patients with Asp-91 mutations had successful eradication treatment. Conclusions:  Fluoroquinolone resistance of H.