EHBF was stable in all Sham groups, and all Sham groups Vadimezan had no evidence of liver injury or tissue edema. Discussion: Despite adequate RES after HS to restore central hemodynamic function, liver blood flow was compromised at 4 hours post-RES. Minocycline treatment at the time of RES prevented liver injury (serum ALT) but did not significantly improve liver

blood flow. One therapeutic mechanism of action of minocycline might be that minocycline effectively inhibited hepatic apoptosis in the reperfusion period. We postulate that minocycline might provide a beneficial effect to trauma patients undergoing standard of care treatment fluid resuscitation after hemorrhagic shock. Disclosures: Craig J. McClain – Consulting: Vertex, Gilead, Baxter, Celgene, Nestle, Danisco, Abbott, Genentech; Grant/Research Support: Ocera, Merck, Glaxo SmithKline; Speaking and Teaching: Roche The following people have nothing to disclose: Paul J. Matheson, Jason Smith, Keith C. Falkner,

Jane Frimodig, Cynthia Downard, Richard N. Garrison Background: Serum levels of microRNA-122 (miR-122) are variably elevated in patients with chronic hepatitis C (CHC). To further examine its clinical role, we aimed to identify which demographic or laboratory variables were associated with miR-122. Methods: miR-122 values were determined in sera from 43 CHC patients, measured in triplicate using the mirVana™ PARIS™ kit. Banked sera were pulled from two CHC databases from clinics at the University of Texas Southwestern Medical Center and Parkland Health and Hospital System. The following Selleckchem Fulvestrant demographic and clinical data were retrospectively collected from the date of initial serum banking: HIV co-infection, sex, race, HCV genotype, cirrhosis, white blood cell count, hemoglobin, platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, albumin, total and direct

bilirubin, and HCV viral load. Using SPSS V21, univariate non-parametric testing was performed, followed by a multivariate linear regression for variables Thalidomide meeting univariate significance of p<0.05. Unavailable data were censored from analysis. Results: In univariate analysis, HIV co-infection was the only categorical variable significantly associated with miR-122, where co-infection was associated with lower miR-122 levels (p=0.016), and significant positive Spearman’s correlations were identified for hemoglobin (rho=0.361, p=0.028), ALT (rho=0.602, p<0.001), AST (rho=0.331, p=0.045), and albumin (rho=0.417, p=0.042). Multivariate linear regression including these five variables was significant (p<0.001), with ALT (p<0.001) and albumin (p=0.030) remaining significant in the model. Conclusions: Since miR-122 has been investigated as a marker for hepatic injury, ALT and AST were significant as expected. However, it was surprising to identify associations with variables unrelated to injury: HIV co-infection, hemoglobin, and albumin.

The authors thank Mari Brill and Bambang

Adiwijaya from Vertex Pharmaceuticals for supplying the data underlying their published kinetic studies,6, 17 and Harel Dahari and Vitaly Ganusov for their insightful comments. Additional Supporting Information may be found in the online version of this article. “
“Background and Aim:  The aim of this study was to Ku-0059436 manufacturer investigate the diagnostic reliability of multidetector-row computed tomography (MDCT) for the evaluation of tumor spread in hilar cholangiocarcinoma. Methods:  Images obtained from a 16-detector row scanner of 22 patients were interpreted. The diagnostic accuracy of longitudinal ductal spread, vertical invasion (including hepatic parenchyma), and lymph node metastasis was assessed with reference to histopathological findings. Results:  The

location of the tumor was correctly diagnosed in 95% of cases (21/22), but in five of these cases, the cut end of the intrahepatic bile duct was positive, resulting in 77% diagnostic accuracy for longitudinal spread. Among the patients with a negative bile duct surgical margin, there was selleck screening library a significant difference in the measurement of tumor spread between MDCT and microscopic investigation (P < 0.001). For vertical invasion, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDCT were 69%, 100%, 100%, and 69% for the liver parenchyma, respectively. The sensitivity, for specificity, PPV, and NPV of MDCT for lymph node metastasis were 50%, 75%, 43%, and 80%, respectively. Conclusions:  The diagnostic accuracy of MDCT for tumor location and vertical invasion was satisfactory, but ductal spread was underestimated in comparison with microscopic measurements. “
“Patients with unresectable

hepatocellular carcinoma (HCC) often undergo transcatheter arterial chemoembolization (TACE). Miriplatin is a lipophilic cisplatin derivative used in TACE that is effective in HCC. However, the difference in antitumor efficacy between warmed versus room temperature miriplatin is unclear. Chemotherapy efficacy was evaluated by dynamic computed tomography 1–3 months after TACE, according to the Modified Response Evaluation Criteria in Solid Tumors. A total of 203 patients with HCC who received TACE with miriplatin for the first time were included in a follow-up study to retrospectively investigate its efficacy and safety. Overall, 45 patients underwent TACE with warmed (40°C) miriplatin and 158 patients received TACE with room temperature miriplatin. Seventy patients (44.3%) treated with room temperature miriplatin and 32 patients (71.1%) who received warmed miriplatin experienced complete or partial responses. Multivariate analysis identified miriplatin temperature (warmed miriplatin, risk ratio (RR) = 2.26, P = 0.

The median follow-up period was 49.5 months. Results: Hepatic cysts were successfully managed in 38 patients

(90.5%) by ethanol sclerotherapy. The symptom did not resolve without reduction of cystic volume after ethanol sclerotherapy in 3 patients and there was cyst infection after sclerotherapy in one patient. Three patients underwent surgical resection of hepatic cysts. Among 38 successfully treated patients, 5 patients had hepatic cyst completely disappeared and 33 patients showed reduction of hepatic cysts from 1047.0 ml (12.6 cm in diameter) to 17.2 ml (3.2cm in diameter). There were no immediate complications related to procedure except pain which was manageable with analgesics. Conclusion: Treatment of hepatic cyst is indicated when the cysts are enlarging, cause symptoms or associated with complications. We conclude that check details huge symptomatic hepatic cyst can be safely treated Tyrosine Kinase Inhibitor Library ic50 with percutaneous

ethanol injection in selected patients. Disclosures: Won Young Tak – Advisory Committees or Review Panels: Gilead Korea; Grant/Research Support: SAMIL Pharma; Speaking and Teaching: BMS Korea The following people have nothing to disclose: Se Young Jang, Soo Young Park, Young Oh Kweon, Jung Gil Park, Sun Young Ahn, Yu Rim Lee, Eun Jeong Kang Background: Recently, non-invasive assessment of liver disease has become important, since liver biopsy has cost implications and associated complications. This study aimed to compare two technigues for the non-invasive evaluation of liver fibrosis: Acoustic Radiation Force Impulse Pomalidomide chemical structure (ARFI) and transient elastography (TE) using liver biopsy as the gold standard comparator. Methods: 75 patients underwent same-day liver biopsy, and measurement of liver fibrosis with TE and ARFI. Liver biopsy was un-interpretable in 3 patients. Statistical analysis was conducted in 72 patients. Liver

fibrosis and necroinflammatory activity were evaluated semiguantitatively according to the METAVIR scoring system and fibrosis was also staged according to the Ishak scoring system. ARFI technology is a software integrated in a conventional ultrasound machine. The measurement was taken at three different sites: 10 measurements in the left part of liver (ARFI L): 10 in the right part of the liver (ARFI R) and 10 in the spleen (ARFI S) for each subject. TE was performed with Fibroscan. Ten valid measurements were taken. Statistical analysis was conducted using graphPad PRISM and Medcalc. The histological staging was correlated with median ARFI and TE and values of the biopsy, both with Metavir and Ishak score. Pearson’s correlation coefficient calculated. P values of less than 0.05 were considered statistically significant. Results: 75 consecutive patients with chronic liver disease were enrolled.

84 ± 0.07-fold of control, n = 4). Moreover, expression levels of the microglial activation marker proteins CD74 and CD6812 remained unchanged after NH4Ac treatment (Fig. 6B,C), and ramified microglial morphology was preserved in NH4Ac-treated rats (Fig. 6A). This contrasts the in vitro finding depicted in Fig. 1 and may be due to different ammonia concentrations in rats in vivo.7 As shown by real-time PCR and western blot analysis,

neither iNOS nor COX-2 mRNA and protein expression in the cerebral cortex were affected by ammonium acetate treatment in vivo (Supporting Information Fig. 3A-D). In addition, mRNA expression of the proinflammatory cytokines TNF-α, IL-1α/β, or IL-6 in the cerebral cortex was not significantly affected after acute ammonium acetate challenge (Supporting

Information Fig. 4). As shown by western p38 MAPK activity blot analysis (Fig. 7A,B), expression of the microglial activation marker Iba-1 was significantly increased in post mortem cortical brain tissue from patients with liver cirrhosis and HE, but not from patients with cirrhosis SB203580 clinical trial who did not have HE. This indicates that HE, but not cirrhosis per se, is associated with microglia activation. As shown recently for iNOS protein,9 iNOS mRNA levels in the cerebral cortex were not significantly different between controls without cirrhosis and patients with cirrhosis, regardless of whether HE was present or not (Supporting Information Fig. 5A). Similar findings were obtained for the expression of COX-2 protein and mRNA (Supporting Information Fig. 5B-D). There were also no significant selleck products differences in the mRNA expression levels of the proinflammatory cytokines TNF-α,

IL-1α/β, or IL-6 (Fig. 8A) or the chemokine monocyte chemoattractive protein-1 (MCP-1) (Supporting Information Fig. 6) in the cerebral cortex in patients with liver cirrhosis and HE when compared with controls or patients with cirrhosis who do not have HE. In these human brain samples, protein levels for TNF-α and cleaved IL-1β protein were below the detection limit, whereas the IL-1β precursor protein was detectable. In contrast, IL-1β precursor as well as TNF-α proteins were both up-regulated in the cerebral cortex of a patient with multiple sclerosis that served as a positive control (Fig. 8B) It is widely accepted that HE represents a primary gliopathy in which ammonia, cell swelling, and oxidative/nitrosative stress play key roles. Studies on ammonia effects in cultured rat astrocytes suggest that astrocytes may contribute to cerebral neuroinflammation in HE through the release of glutamate, prostanoids, and reactive oxygen/nitrogen species due to ammonia-induced up-regulation of iNOS and NADPH-oxidase activation.5, 6, 25 Impaired neurotransmission associated with microglia activation and increased cerebral cytokine synthesis has been shown in different animal models for chronic HE.10, 26, 27 However, the role of microglia in the pathogenesis of acute ammonia toxicity and HE is largely unknown.

Elgible paients were given 300 mg TDF daily befoe breakfast. Treatment duration was for 4 years. Enrolled patients were seen in out patient ever 12 week basis. Complete blood cell count, ALT, urea, creatinine

and HBV-DNA Rquantitative was done every 12 week basis. HBV-DNA <60 IU/ml was considered complete virological response (VR). Results: Results: We are reporting 36 months treatment results of this cohort. Median age at baseline was 45, 60% were male and 40% were female, 70% were HBeAg negative. Mean HBV-DNA was 6 log IU/ml, mean ALT was 80. Virological response (VR) was 70%, 85% and 90% at 12, 24 and 36 months respectively. There were no significat AT9283 mw side effects especially no abnormal renal function. These patienst are continuing this treatment for another 12 months. Conclusion: Conclusion: TDF shows significant and sustained antiviral activity against HBV. It has a very favorable safety profile. Key Word(s): 1. tenofovir; 2. chronic hepatitis B; 3. naive patients; Presenting selleck chemicals Author: MUZAFFAR GILL Additional Authors: UZMA GILL, HAFSA AZIZ, FARAH SALMAN Corresponding Author: MUZAFFAR GILL Objective: Background: Entecavir is one of the most commonly used nucleo(s) tide

analogue in the treatment of chronic Hep B patients. we are using this product in our practice for the last 5 years now. We wanted to study the efficacy and safety of this compound in treatment eligible chronic

HBV patients. Methods: Methods: we prospectively enrolled 100 treatment Phosphoglycerate kinase naive patients with chronic HBV. Enrollment period was from january 2008 to june 2008. patients with Hep B surface antigen positive, ALT >80 and HBV-DNA >20, 000 IU/ml were included this study Patients with established diagnosis of cirrhosis were excluded from this study. Elgible paients were given 0.5 mg Entecavir daily befoe breakfast. Treatment duration was for 4 years. Enrolled patients were seen in ou t patient basis at every 12 week.Complete blood cell count, ALT, urea, creatinine and HBV-DNA quantitative was done every 12 week basis. HBV-DNA <60 IU/ml was considered complete virological response (VR). Results: Results: We are reporting 36 months treatment results of this cohort.Median age at baseline was 40, 60% were male and 40% were female, 70% were HBeAg negative. Mean HBV-DNA was 6 log IU/ml, mean ALT was 80.Virological response (VR) was 70%, 80% and 90% at 12, 24 and 36 months respectively.There were no significat side effects especially no abnormal renal function.These patienst are continuing this treatment for another 12 months. Conclusion: Conclusion: Entecavir shows significant and sustained antiviral activity against HBV. It has a very favorable safety profile. Key Word(s): 1. chronic hepatitis B; 2.

These reductions were similar in magnitude and duration of effect to those observed in the mouse HBV models receiving similar doses. The efficacy and Opaganib chemical structure safety of ARC-520 in a large primate demonstrate its promise as

a new class of therapeutic for patients chronically infected with HBV. HBsAg in chimpanzee Disclosures: Robert E. Lanford – Grant/Research Support: Arrowhead Research Christine I. Wooddell – Employment: Arrowhead Research Corporation Qili Chu – Employment: Arrowhead Madison Bruce Given – Board Membership: Icon plc, Calando Pharmaceuticals; Consulting: Leonardo Biosystems, Inc; Employment: Arrowhead Research Corp David L. Lewis – Employment: Arrowhead Research Corporation The following people have nothing to disclose: Deborah Chavez, Claudia Oropeza, Holly L. Hamilton, Alan McLachlan, Christopher R. Anzalone Background/Aims: Previous analyses demonstrated lower genetic distance within HBV polymerase/reverse transcriptase (pol/RT) and HBsAg genes in HBeAg+ GT A and D CHB subjects who lost HBsAg compared to control subjects who maintained high HBsAg levels through 192 weeks of TDF treatment. This study evaluated the differences in mean pairwise genetic distance across the core and HBx genes in this subject cohort. Methods: Study GS-US-174-0103 HBeAg+ subjects

were randomized 2:1 to receive TDF or ADV for 48 weeks followed by open-label TDF. After 4 years, 23/266 (8.6%) experienced HBsAg loss, including 14 GT A and 7 GT D subjects. 17 GT A and 10 GT D subjects Lumacaftor who maintained high HBsAg levels with similar baseline HBV DNA and ALT were selected as case controls. Population sequencing was performed on baseline samples and pair-wise genetic distance matrices for segments across HBx and core genes were used to calculate viral diversity. Non-parametric Levene test for homogeneity of variances in control and HBsAg loss groups was performed for each region, and equality of mean genetic distances within regions was evaluated using the Mann-Whitney-Wilcoxon test. The Hochberg

procedure was used to control for multiple testing. Results: For GT A and GT D, in general, segments corresponding to non structural regulatory elements (URR, NRE, CURS, and EnhII within HBx gene and precore) showed higher viral diversity within HBsAg loss patients compared Amino acid to controls. In contrast, the core gene, which encodes a structural element, the opposite pattern was observed with lower viral diversity in HBsAg loss patients. Similar to previous observations across the pol/RT and HBsAg genes, genotype-specific differences were observed across the core and HBx genes. For GT A, 6/9 segments had significant genetic diversity differences between HBsAg loss and control subjects, while only 4/9 segments had significant differences for GT D. In addition, GT A subjects had lower mean pairwise genetic distance in the majority of HBx and core gene segments evaluated compared to GT D subjects.

Revascularization of chronic vertebrobasilar occlusions is technically feasible. Due to the high-risk nature, it should be reserved as an option only for selected group of patients with recurrent ischemic symptoms and progressive disability despite maximal medical therapy. Further prospective study is helpful to clarify the role of this intervention. “
“The azygous anterior cerebral artery (Az) is a rarely observed anomaly of the anterior cerebral artery, and its associated aneurysm is even rarer. Our aim was to evaluate 3-dimensional

time-of-flight magnetic resonance angiography (3-D-TOF MRA) in the diagnosis of Az and associated aneurysms. Three thousand five hundred seventy-two Silmitasertib chemical structure consecutive patients underwent 3-D-TOF MRA at 3.0 T. Postprocessing techniques, including volume rendering (VR) and single artery highlighting, were performed by a 3-D specialist. All MRA data and clinical information were recorded and stored in a database for further analysis. Fourteen patients (.39%) were identified as having an Az. Among these cases, 3 males (21.43%) had an aneurysm located at the distal bifurcation

of the Az, with a mean size of 9.43 ± 3.33 mm. In MRA, the common trunk of the Az was slightly larger in diameter than the A1 segment (2.62 ± .35 mm vs. 2.54 ± .35 mm; P = .008). With the VR technique, 3-D-TOF MRA is feasible and valuable in detecting an Az and associated aneurysm. Our MRA-based study has proved that the Az is a rare anomaly but has a relatively high incidence of associated aneurysms. The azygous anterior cerebral artery (Az) is comprised of a single common trunk of the distal anterior cerebral Pritelivir nmr artery (ACA) fused with two sides of the proximal ACA.[1-4] The reported incidence of Az in the literature ranges from 0 to 5%, representing a relatively uncommon developmental anomaly of the circle of Willis in man.[1-4] The Az should be identified from other anomalies of the ACA, including bihemispheric ACA and triplicate ACA in angiography.[1] Digital subtraction (DS) angiographic distinction between the Az and

the bihemispheric ACA is difficult because the hypoplastic Chorioepithelioma A2 segment in the bihemispheric ACA is often poorly visualized and the pattern of DS angiography (based on one-artery angiography at a time) cannot visualize the whole cerebral artery network in one scanning series.[1] For Az, unilateral DS angiography need contralateral carotid compression. With gross visualization of all cerebral arteries, magnetic resonance angiography (MRA) can overcome the inherent disadvantage of DS angiography, especially with the aid of post-processing techniques, including volume rendering (VR). Thus, MRA may be more useful in the detection of an Az and associated aneurysms. The presence of an Az is closely related to aneurysm formation and is often associated with other anomalies of the central nervous system.

Demographic characteristics, body mass index (BMI) and condition of fatty liver were retrospectively reviewed. The prognosis of patients was compared between the fatty liver and the non fatty liver group. Results: Fatty liver was diagnosed in 29.17% (35/120) of our patients. Fatty liver correlated with higher incidence of SAP (62.9% vs. 29.4%, p = 0.001), systemic inflammatory response syndrome (SIRS) (57.1% vs. 37.6%, p = 0.050), pulmonary failure (45.7% vs. 20.0%,

p = 0.004), severe metabolic disturbance (37.1% vs. 12.9%, p = 0.003), higher level of APACHE-II score (p = 0.007) and SIRS score Selleck SCH772984 (p = 0.009). Higher level of BMI was also detected in patients with fatty liver (p < 0.001). Multiple analysis demonstrated that only fatty liver independently correlated with SAP (OR 3.95, 95%CI 1.43–10.93), systemic complications

(OR 4.22, 95%CI 1.49–11.95) and pulmonary failure (OR 4.02, 95%CI 1.38–11.73). Conclusion: Fatty liver is an independent risk factor for SAP and systemic complications of AP. It is probable that fatty liver correlates more closely with the severity of AP than obesity. Key Word(s): 1. acute pancreatitis; 2. fatty liver; 3. prognosis; Table 2. Logistic analysis for obesity and fatty liver in the prognosis of AP   p OR 95% CI Age, sex, and etiology were also entered into the logistic analysis but were not found to be relevant to the incidence of SAP, systemic complication or pulmonary failure. Presenting Author: GUOYING WANG Additional Authors: JIAN ZHANG, GUI-HUA CHEN Corresponding Author: GUOYING WANG Affiliations: GSK2126458 Liver Transplantation Center, the third affiliated hospital of sun yat-sen university Objective: Alpha-fetoprotein (AFP) has been proposed to correlate with vascular invasion of hepatocellular carcinoma (HCC) and predict tumor recurrence after liver transplantation (LT). However, the prognostic value of AFP in patients with HCC without vascular invasion during the waiting list for LT has not been clearly defined. In this study, we determined the prognostic role of preoperative AFP in patients who underwent LT for HBV-associated HCC

without vascular invasion. Methods: We analyzed the outcome of 80 patients who underwent LT for HBV-associated HCC without vascular invasion. Vascular invasion was defined as the presence of tumor emboli within the lobar or segmental branches of the portal or hepatic others veins, which was diagnosed or highly suspected by preoperative imaging examination. Patients were divided into two groups according to different AFP cut-off level (20 ng/mL, 100 ng/mL, 200 ng/mL, and 400 ng/mL). Results: The 1-, 3- and 5-year disease-free and overall survivals were 97.1%, 89.1%, and 79.9%, and 92.1%, 81.5%, and 72.7%, respectively. Ten patients developed tumor recurrence and 13 patients died during 6 years of follow-up. Univariate analysis revealed that multiple tumor number was the only preoperative predictor of disease-free survival (DFS).

Rather, they are valued for their proven relation to important patient outcomes. The important step for a new method is the same: not “does it predict the biopsy

result,” but “does it predict the patient result.” Long-term follow-up of patients after extracting the new measure should be our target, along with serious thought about what that measure or measures should be. That is the gold standard for whether a new method is an important addition to the practice. “
“A 25-year-old woman from Vietnam presented with 3 weeks of yellowing of the skin. On admission, her alanine aminotransferase (ALT) level was 329 IU/L and her total bilirubin (TBI) level was 5.7 mg/dL. Serological markers for hepatitis A, B, C, and antinuclear and antimitochondrial antibodies were negative, www.selleckchem.com/products/cb-839.html but her anti–smooth muscle antibody (1:20) was weakly positive. Her serum ceruloplasmin level was normal. Corneal Kayser-Fleischer rings were not found. We initiated prednisolone 75

mg/day and made a tentative diagnosis of autoimmune hepatitis. ALT, alanine aminotransferase; ICAH, improved cholestasis but aggravated hepatitis; Ig, immunoglobulin; IHC, immunohistochemistry; PCR, polymerase chain reaction; TBI, total bilirubin. Two weeks later, the patient’s ALT level was 91 IU/L, and her TBI level was 1.6 mg/dL. After 3 weeks, her TBI level decreased to 1.0 mg/dL, but her ALT level increased to 360 IU/L. Orientia tsutsugamushi AZD6244 supplier immunoglobulin (Ig) M and polymerase chain reaction (PCR) analyses

were negative. A rapid plasma regain test (1:8) and Treponema pallidum hemagglutination assay (1:80) for syphilis were both inconclusive. Leptospira-specific IgG/IgM analysis was positive, but nested Protein Tyrosine Kinase inhibitor Leptospira PCR analysis was negative. A liver biopsy specimen revealed portal lymphocytic infiltration with blurred interface, bilirubinostasis with bile pigment within hepatocytes and Kupffer cells, and canalicular bile plugs (Fig. 1A, hematoxylin and eosin [magnification ×100]). Silver staining demonstrated a one-end hooked wavy spirochete (Fig. 1B, arrowhead [magnification ×400]). A long wavy Leptospira (arrowhead) and other leptospiral forms, including short rods (R), aggregates (Ar), and cocci (arrows), were revealed by way of leptospiral immunohistochemistry (IHC) staining using polyclonal rabbit anti–Leptospira interrogans antiserum (Fig. 1C [magnification ×400]). Initially, improved cholestasis but aggravated hepatitis (ICAH) occurred, during which the patient’s TBI level decreased while her ALT level increased (Fig. 1D, dotted circle). Finally, her aspartate aminotransferase and ALT levels decreased gradually to normal within 3 weeks after tapering prednisolone and using doxycycline followed by penicillin G. Leptospirosis is caused by Leptospira species endemic in nonurban areas. The clinical manifestations range from subclinical infection to febrile illness, jaundice, renal failure, and pulmonary hemorrhage.

For this purpose, the iron chelator dpp was added to unadhered

as well as AGS-adhered H. pylori. It has previously been reported that dpp at a concentration learn more of 200 μmol/L does not affect viability of H. pylori [35]. To examine whether dpp actually removes available iron under the experimental conditions used in this study, the effect of dpp on the expression of two Fur-regulated genes, amiE and pfr, was examined in unadhered and adhered H. pylori. Expression of amiE is known to be repressed by Fe-Fur [36] as such, addition of dpp resulted in a large increase in amiE expression (about 27-fold) in unadhered H. pylori although a much more modest increase (about 7-fold) was observed in AGS-adhered H. pylori (Fig. S1). On the other hand, expression of the pfr gene that is known to be repressed by apo-Fur [10] was decreased by about 2.5-fold C646 in vivo in dpp-treated unadhered H. pylori, although in adhered H. pylori, practically no decrease was observed (Fig. S1). These results suggested that dpp effectively chelates iron in unadhered H. pylori leading largely to the conversion of Fe-Fur to apo-Fur, but dpp is much less effective in adhered bacteria (a possible reason is discussed). Addition of dpp to the unadhered H. pylori cells had practically no effect on cagA expression

consistent with the observation that Fur had practically no effect on cagA expression in H. pylori in the unadhered state (Fig. 3). Surprisingly, however, although previous observation indicated that Fur has a role in cagA upregulation

in AGS-associated H. pylori (Fig. 2), addition of dpp to adhered H. pylori had little effect on cagA expression (Fig. 3) and about 5-fold upregulation of cagA was observed in the AGS-adhered H. pylori strain even in the presence of dpp. In contrast, dpp treatment reduced vacA expression (about 3-fold) in both adhered and unadhered H. pylori, suggesting that vacA is activated by Fe-Fur (Fig. 3). It may be noted that although vacA expression was reduced in dpp-treated AGS-adhered H. pylori, the expression Astemizole was still higher than in the corresponding dpp-treated unadhered bacteria (Fig. 3). Wild-type H. pylori or the Δfur mutant strain was added to semiconfluent monolayers of AGS cells at MOI 50, and at different times, the cell cultures were washed to remove unadhered bacteria and observed by phase contrast microscopy (Fig. 4 and Fig. S2). Although more than 50 percent of the AGS cells were vacuolated within 2 hours of adherence of wild-type H. pylori, vacuolation was observed in only about 10 percent AGS cells at 2 hours after adherence of the Δfur mutant strain. At 6 hours after adherence of the wild-type H. pylori, more than 80 percent of AGS cells were vacuolated, whereas less than 40 percent were vacuolated following adherence of the Δfur mutant strain. Furthermore, by 6 hours postadherence, H. pylori induced scattering and elongation in more than 60 percent AGS cells.