In normal rat cholangiocytes, siRNA against Ngn-3 blocked the proliferation stimulated by exendin-4. In addition, Ngn-3 knockdown neutralized the overexpression of insulin growth factor-1 (IGF1; promitotic effector) observed after exposure to exendin-4, but not that of PDX-1 or VEGF-A/C. Oligonucleotides anti-miR-7 inhibited the exendin-4-induced proliferation in normal rat DAPT concentration cholangiocytes, but did not affect Ngn-3 synthesis. Biliary hyperplasia and collagen deposition induced by DDC or BDL were significantly reduced in Ngn-3+/− mice compared to wild-type. Conclusion: Ngn-3-dependent activation of miR-7a

is a determinant of cholangiocyte proliferation. These findings indicate that the reacquisition of a molecular profile typical of organ development is essential for the biological response to injury by mature cholangiocytes. (Hepatology Alpelisib cell line 2014;60:1324–1335) “
“Elevated serum uric acid (UA) levels

strongly reflect and may even cause oxidative stress, insulin resistance, and metabolic syndrome, which are risk factors for the progression of liver disease. We sought to determine whether serum UA levels are associated with the development of cirrhosis or the presence of elevated serum liver enzymes. We used cohort data from the first National Health and Nutrition Examination Survey (NHANES I) to determine whether the baseline serum UA level was associated with the incidence of hospitalization or death due to cirrhosis among 5518 participants during a mean follow-up of 12.9 years (range = 4-21 years) after the exclusion of the first 4 years of follow-up. We also used cross-sectional data from NHANES 1988-1994 (n = 10,993) and NHANES 1999-2006 (n = 6186) to determine whether the serum UA level was associated with elevated serum alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT), two markers of hepatic necroinflammation. Compared to persons in the lower third of the distribution of serum UA (<4.8 mg/dL), those in the top

third (>6 mg/dL) had a higher risk of cirrhosis-related hospitalization or death [adjusted hazard ratio (AHR) = 2.8, 95% confidence interval (CI) =1.3-5.7], whereas the risk was not substantially increased in persons within the middle third (serum UA level = 2.6-4.8 mg/dL, Rucaparib AHR = 1.3, 95% CI = 0.6-2.7). A higher serum UA level was associated with greater mean serum ALT and GGT levels and a greater probability of elevated serum ALT and GGT. Conclusion: The serum UA level is associated with the development of cirrhosis and the presence of elevated serum liver enzymes after adjustments for important causes and risk factors of chronic liver disease. (HEPATOLOGY 2010;) In humans and higher primates, uric acid (UA) is the final oxidation product of purine metabolism and is excreted in urine. Hyperuricemia has long been recognized as a cause of gouty arthritis and kidney stones.

There may be an inhibition occurring when sumatriptan is used frequently in conjunction with naproxen sodium or that naproxen is protective while sumatriptan can increase migraine frequency.

When used as a combination, the effects Decitabine mouse may offset or balance each other. If true, this has important clinical implications in managing patients with frequent episodic migraine. Both medications were well tolerated, and there was little evidence that either product resulted in MOH. The authors wish to acknowledge Rebecca Browning for her statistical input. (a)  Conception and Design (a)  Drafting the Manuscript (a)  Final Approval of the Completed Manuscript “
“(Headache 2010;50:1017-1030) Objectives.— The goal of this study was to determine the vascular effects of protease-activated receptor-2 AZD6244 concentration (PAR-2) activation in the rat cranial vasculature. Background.— The role of PAR-2 in pain and inflammatory conditions has been established but the information available on its effects and receptor distribution in the trigeminal vascular axis is limited. We studied the dilatory function and expression of PAR-2 in the neuro-vascular

circuit, critical in migraine pathogenesis. We also investigated the interaction of PAR-2 with calcitonin gene-related peptide (CGRP) and dural mast cells. Methods.— We used an improved model of intravital microscopy on the closed cranial window in rats to study the vascular effects of PAR-2 activating peptides (PAR-2 APs; SLIGRL-NH2, 2-Furoyl-LIGRLO-NH2) in the dural vasculature. Measurement of immunoreactive CGRP in skull halves and in trigeminal nucleus caudalis was done by using an enzyme-linked immunosorbent assay. We also analyzed the presence of PAR-2 in different migraine relevant tissues by quantitative real-time PCR and Western blot analysis. Results.— PAR-2 APs and Doxacurium chloride trypsin induced a dose-dependent increase in dural artery diameter. The topical application of a nonspecific nitric oxide synthase (NOS) inhibitor, L-NG-Nitroarginine methyl ester,

attenuated SLIGRL-NH2 responses. Olcegepant, a CGRP receptor antagonist, did not a have significant effect on the SLIGRL-NH2 responses, though exogenous CGRP responses were completely blocked. There was no significant release of CGRP from skull halves incubated with SLIGRL-NH2 as compared with those incubated with the corresponding negative peptide. Chronic mast cell degranulation did not change the vascular effects of PAR-2 APs. mRNA and protein expression of PAR-2 were found throughout trigeminovasuclar axis. Conclusion.— PAR-2 activation leads to vasodilation of dural arteries and these responses are partially mediated by nitric oxide. As PAR-2 is present throughout trigeminovasuclar axis, it may have a role in migraine pathogenesis, independent of CGRP and mast cell mediated mechanism. “
“(Headache 2010;50:613-625) Objectives.

Histopathologic examination revealed epitheloid granulomatous with caseating necrosis and presence of Langerhan’s giant cells. Therefore, postoperative diagnosis HIF-1 activation was revealed tuberculosis of cholecystitis. The patient tolerated the procedure well and was discharge 1 week following surgery without any problems. The patient was started on anti tubercular treatment. Conclusion: Herein, we present a case of tuberculous cholecystitis with cholecysto-colonic fistula.

Key Word(s): 1. tuberculosis cholecystitis; 2. cholecysto-colonic fistula Presenting Author: JIN KYEONG CHO Additional Authors: Na Corresponding Author: JIN KYEONG CHO Affiliations: Seoul Medical Center Objective: Introduction After successful common bile duct (CBD) stone removal by endoscopic retrograde cholangiopancreatography (ERCP), high prolonged jaundice is very confused for the next decision (ERCP for remnant stone or other rare causes). With assurance of removal JQ1 research buy of CBD stone and no remnant stone, Liver biopsy may be useful for jaundice of parenchymal origin but invasive. In such cases, steroid challenge test is useful both diagnosis and treatment. Case description

A 62-year-old male presented with colicky right upper quadrant pain. Laboratory tests showed total bilirubin of 7.6 mg/dL, aspartate aminotransferase (AST) 60 IU/L, alanine aminotransferase (ALT) 15 IU/L, alkaline phosphatase (ALP) 60 IU/L and gamma-glutamyltranspeptidase

(γ-GT) 71 IU/L. At abdomen CT, There was single 1.3 cm sized distal CBD stone and diffuse dilatation of upstream bile duct and cystic duct. The patient underwent endoscopic retrograde biliary drainage (ERBD) by plastic stent because of long procedure time for cannulation. But 5 days after the ERBD, his total bilirubin increased to 18.7 mg/dL. A second ERCP was carried out, which revealed patent biliary stent and CBD stone was removed successfully. After 2 days of second ERCP, total bilirubin level increased to 19.5 mg/dL. At second abdomen CT, there was no remnant stone. It was presumed that intrahepatic cholestasis was occurred by intrahepatic bile duct inflammation from contrast agent or pethidine. Protein kinase N1 P rednisolone was started (30 mg/day) for three days, which caused a significant improvement of jaundice and bilirubin level. But 7 days later, his bilirubin raised up to 20.3 mg/dL. It was certain that prednisolone improved his cholestasis. Prednisolone started again and after use of 30 mg/day of prednisolone for 7 days, total bilirubin fell to 10 mg/dL, and his jaundice was progressively declined. Steroid was used and tapered off during a month. He had normal bilirubin level and normal liver function tests. Key Word(s): 1. ERCP; 2.

Among EGFR ligand secreted by MF in cancer, HB-EGF has emerged as a paracrine factor that contributes to intercellular communications between MF and tumor cells in uterine cervical[26] and breast[36] carcinoma. In human CCA specimens, HB-EGF immunoreactivity

was detected in MF. In addition to MF, we also detected an expression of HB-EGF in tumor cells. Therefore, we can assume that HB-EGF participates in the autocrine and paracrine activation of EGFR. HB-EGF produced by MF is likely to act only on tumor cells in CCA because EGFR was only detected in these cells. The expression of HB-EGF by MF prompted us to hypothesize that MF may constitute an additional source of ligands required to activate EGFR on the cancer cell surface. EGFR heterodimerizes with other receptors of the ErbB/HER family (i.e., ErbB/HER2 and ErbB/HER3). Upon

Selleckchem Kinase Inhibitor Library stimulation of CCA cells with HB-EGF, EGFR and, to a lesser extent, ErbB/HER2 and ErbB/HER3 are activated (data not shown). Thus, a potential contribution of ErbB/HER2 and/or ErbB/HER3 through EGFR heterodimerization cannot be excluded in the cross-talk between MF and tumor cells in CCA. To date, the role of HB-EGF in CCA has see more not been explored. In vitro, an HB-EGF-neutralizing Ab inhibited activation of EGFR and dispersion of CCA cells in response to HLMF-CM. Consistently, exogenous addition of HB-EGF to CCA cells caused cell migration and invasion, as previously described in many cancers.[37, 38] Although HB-EGF activated EGFR and downstream pathways, including ERK1/2, we were unable to show an effect of HB-EGF on CCA cell proliferation. Thus, stimulation of EGFR by HB-EGF in CCA cells is likely to play a role in tumor invasion and metastasis, which is consistent with the IHC and genomic profiling studies that demonstrated high EGFR expression in patients with aggressive phenotype and poor prognosis CCA.[7, 11, 12, 14, 39] In addition to EGFR overexpression, Sia et al. have recently showed an enrichment of EGFR activation in a subgroup

of CCA.[7] From our studies, we may hypothesize that activation of EGFR is related to EGFR ligand produced by Tau-protein kinase stroma cells. It would be worthwhile to explore the gene expression profiling of stroma in this subgroup of CCA tumors. Through the production of soluble factors, cancer cells have the ability to communicate with stromal myofibroblasts located arround them. This point has been stressed in several cancers, including HCC,[40] colorectal,[21] uterine cervical cancers,[26] and in CCA.[33] Our results showed that EGFR activation in CCA cells promotes the expression of TGF-β1. TGF-β1 is expressed in a vast majority of CCA. As previously reported,[41-43] we detected TGF-β1 in carcinoma cells and its receptor, TGF-β RII, both in carcinoma and stromal MF. Recently, Andersen et al.

[69] Monocytes in HCV-infected patients have impaired tolerance for repeated TLR4 challenge and greater TLR4 expression, leading to higher levels of serum and intrahepatic TNF-α, which contributes Crizotinib to inflammation in HCV infection.[64, 70] TLR3 is important for its antiviral immune effects, and TLR3-stimulated

non-parenchymal liver cells are able to regulate HCV replication through production of IFN-β.[71, 72] TLR3 mRNA is significantly increased in monocytes in chronic HCV infection.[73] An IFN-responsive element has been identified in the promotor region of the TLR3 gene, and it therefore seems likely that TLR3 expression is responsive to IFN treatment in HCV infection.[74] Myeloid DCs (mDCs) have normal functioning TLR3 and can produce IL-12, IL-6, IL-10, IFN-γ, and TNF-α with TLR3 stimulation despite HCV infection.[75] HCV genomic RNA has direct immunostimulatory effects on TLR7 and TLR8, leading to IFN-α production and activation of IRF7 and NFκB.[76] Plasmacytoid DCs (pDCs) can also be activated via TLR7 and TLR9 through the HCV RNA polyuridine tail.[76-81] TLR7 activation of hepatocytes also induces IFN-independent antiviral effects, reducing both HCV RNA levels and NS5A protein expression in cell lines.[82] There is also increased TLR7 and TLR8 expression on monocytes in HCV infection, although

the significance of this remains unclear.[64] HCV viral proteins are able to stimulate TLR signaling, which plays an important role in viral immune clearance. However,

HCV is able to simultaneously see more evade immune clearance through specifically targeting and impairing TLR signaling through several mechanisms. First, HCV interferes with signaling via the TRIF-TBK1-IRF3 pathway. The HCV NS3 protein induces degradation of TRIF, while the NS3/4A protein impedes IRF3 and NFκB activation by reducing the amount of TRIF in circulation and by generating cleavage products with dominant-negative activity.[83, 84] NS3/4A also interacts directly with TBK1 to reduce TBK1-IRF3 interaction and therefore inhibit IRF3 activation.[85] HCV also interferes with the TLR-MyD88 pathway through NS5A click here interaction with MyD88 to prevent IRAK1 recruitment and cytokine production in response to ligands for TLR2, TLR4, TLR7, and TLR9.[86] The HCV lipoviral particle interferes directly with TLR4 signaling in DCs, while HCV core protein suppresses TLR4 expression.[64, 87] Cellular expression of TLR2 and TLR4 in mDCs is controversial, being reported as both higher and lower in HCV infection patients compared with healthy controls, although signal transduction of TLR2 and TLR4 in mDCs is certainly impaired in HCV infection.[49, 56, 88] Greater anti-inflammatory IL-10 production by macrophages with TLR2 stimulation has been reported and may explain the dichotomous effects of TLR2 activation in different cellular compartments.

Glucose; 3. virulence factor; Presenting Author: BOLOR-ERDENE MANDKHAI Additional Authors:

JAV SARANTUYA, NAMDAG BIRA Corresponding Author: JAV SARANTUYA, NAMDAG BIRA Affiliations: Dpartment of Physiology and Molecular biology; Department of Molecular biology and Genetics; Department of Gastroenterology of HSUM Objective: Helicobacter pylori is one of the most common human infections worldwide. All consensus guidelines recommend eradication of H. pylori in symptomatic MK-1775 patients. Standard therapy combines a proton pump inhibitor, such as omeprazole, and two antibiotics, chosen from among amoxicillin, clarithromycin, and metronidazole. However, the eradication rate is decreasing, with as low as 60% success in some PD-1 inhibitor countries, and this is related to the increase in clarithromycin and metronidazole resistance reported worldwide. The resistance of H. pylori to the recently available antibiotic treatment regimens has been a growing problem. Therefore aim of study was to determine the prevalence of antibiotic resistance among H. pylori strains isolated from Mongolians. Methods: 262 samples of gastric biopsies were obtained

during upper gastrointestinal endoscopy from the patients referred for the exploration of clinical gastritis. Biopsy specimens were taken from the gastric antrum or body for the testing of H. pylori. The urease positive samples were cultured according to standard microbiological procedures. All H. pylori strains were grown under microaerophilic conditions on selective Pylori agar and the isolates were identified by Gram staining and biochemical tests for catalase, oxidase, and urease activities. The susceptibilities of the H. pylori isolates to clarithromycin, metronidazole, amoxicillin, tetracyclin, nitrofurantion and erytromycin were examined by Etest strip. Results: Total of 262 gastric biopsy specimens, 63.3% (166) were confirmed to have gastric H. pylori infection by CLO test. We have successfully obtained 68.6% (114) pure H. pylori isolates. The overall

eltoprazine H. pylori Etest antibiotic resistance rates were 52.8% for clarithromycin, 67,3% for metronidazole, 26,9% for amoxicillin, 33.3% for tetracycline, 43.5% for erythromycin and 13.7% for nitrofuranton. Both resistances were significantly higher in female than in male patients. Conclusion: The prevalence of H. pylori infection increased among Mongolian population. In the present study, H. pylori metronidazole and clarithromycin-resistant strains are more frequently found in Mongolians. Clarithromycin and metronidazole should be used with caution for H. pylori eradication treatment. Key Word(s): 1. Helicobacter pylori; 2. antibiotic; 3. resistance; Presenting Author: KETUT MARIADI Additional Authors: PANDE KETUT KURNIARI, I DEWA NYOMAN WIBAWA Corresponding Author: KETUT MARIADI Affiliations: sanglah hospital Objective: The prevalence of Helicobacter Pylori (H. pylori) infection is still high, approximately 41–45% in my region. Infection by H.

Being a carrier of haemophilia and having a haemophilic child was life changing. The women moved from a state of sad, guilty chaos to reconciling

themselves with the new situation. Our analysis revealed three acts in which phenomena appeared: the time after diagnosis, the turning point and GS1101 reconciliation with a changing life. Emerging as crucial to the process of reconciliation with a changing life was a sense of being fully informed and supported. The Haemophilia Treatment Centre (HTC) should create an environment that encourages learning, and the team should invite and encourage the woman’s partner to be actively involved in the child’s care. Moreover, the results indicate that it would be beneficial to invite female carriers to receive patient education at the HTC before

they plan to start a family. During this visit, the woman may gain a greater understanding of her carriership to prepare her for future decisions concerning prenatal diagnosis, for example. “
“Summary.  Haemophilia, if not properly managed, can lead to chronic disease and lifelong disabilities. The challenges and issues in infants/young children are different from those in older children and adults although episodes of bleeding still predominate as the diagnostic trigger. Awareness of clinical manifestations and treatment complications high throughput screening assay are crucial in instituting appropriate management and implementing preventive strategies. Currently, inhibitor development is a challenging complication of paediatric haemophilia and prophylaxis is emerging as the optimal preventive care strategy. In this section we will review some important aspects of haemophilia in children including early prophylaxis, current evidence relating to inhibitor development, including the aims of the SIPPET study

which is already ongoing and involves boys <6 years, and the potential of immune tolerance therapy for eradicating GNA12 the inhibitor and permitting a resumption of standard dosing schedules. In this section, dedicated to haemophilia during childhood, we will focus on two hot topics: prophylactic regimens and the development of inhibitors against FVIII. Primary prophylaxis, which has been used in Sweden for over 40 years, is the treatment of choice in severe haemophilia recommended by the World Health Organisation (WHO) and the World Federation of Haemophilia since 1994. The benefits of prophylaxis have been clearly demonstrated by numerous cohort studies and, more recently, by a randomized trial. Therefore, to prevent the development of haemophilic arthropathy, primary prophylaxis should be started after the first haemarthrosis during early childhood. However, the optimal regimen has not been fully established yet.

To date, there are only a handful of reports[60, 61] to support the feasibility of this technology. In addition, peroral cholangioscopy appears to be associated with a significantly higher rate of cholangitis, possibly because of the intermittent EPZ015666 datasheet intraductal irrigation required during the procedure.[62] pCLE is a new imaging technique that provides real-time microscopic information on the

tissue during ERCP.[63] Several investigators have reported the usefulness of pCLE in the diagnosis of CCA.[63-65] Recently, Miami criteria for the diagnosis of malignant biliary stricture have been proposed.[66] Thick dark and white bands, dark clumps, visible epithelium, and fluorescein leakage were criteria indicating malignancy. Although the diagnostic sensitivity was excellent, the specificity was still suboptimal (67%).[66] The criteria may need some refinement LDK378 mw and pilot them in a larger set of indeterminate biliary strictures before recommendation as a standard approach. 8. Abdominal ultrasonography (US) is frequently the initial imaging modality performed to evaluate patients with suspected biliary obstruction. Other imaging modalities are required for further characterization and staging of HCCA. Level of agreement: a—90%, b—10%,

c—0%, d—0%, e—0% Quality of evidence: II-2 Classification of recommendation: A Abdominal US is practically performed to confirm the presence of biliary obstruction, to Adenosine identify the extent of obstruction, and possibly to determine the cause of the obstruction.[67] In HCCA, US can demonstrate dilation of bilateral intrahepatic ducts. Occasionally, intraluminal masses may be discovered in papillary type HCCA, and US in a patient with infiltrative-type HCCA may show periductal thickening of bile ducts.[67] However, the sensitivity of US to identify the etiology of the obstruction

is lower than other modalities such as CT scan, magnetic resonance imaging (MRI), and direct cholangiography.[68, 69] Therefore, further delineation of HCCA for the detail of tumor characterization, vascular involvement, staging, and variation in biliary anatomy by other modalities is required. 9. Multidetector computed tomography (MDCT) and MRI/magnetic resonance cholangiopancreatography (MRCP) are the two best imaging modalities for diagnosis and staging of HCCA, as well as for determining its resectability. The role of positron emission tomography (PET)/computed tomography (CT) is not clearly defined. Level of agreement: a—74%, b—21%, c—0%, d—5%, e—0% Quality of evidence: II-2 Classification of recommendation: A The recent staging and registry for HCCA relies on the extent of the disease in the biliary system, the involvement of the hepatic vasculatures, the involvement of lymph nodes, distant metastases, and the volume of the future hepatic remnant (FLR) after resection.[17] CT scan and MRI are the two most practical imagings that serve this purpose.

Consecutive patients with new onset ascites were prospectively enrolled in this cross-sectional study. All patients had measurements of serum-ascites albumin gradient (SAAG), total protein concentration in ascitic fluid, serum, and ascites BNP. We enrolled 218 consecutive patients with ascites resulting from HF (n = 44), cirrhosis (n = 162), peritoneal disease (n = 10), and constrictive pericarditis (n = 2). Compared to SAAG and/or total protein LY2157299 in vivo concentration in ascites, the test that best discriminated HF-related ascites from other causes of ascites was serum BNP. A cutoff of >364 pg/mL (sensitivity 98%, specificity 99%, and diagnostic accuracy 99%) had the highest positive likelihood ratio (168.1); that is, it was the best to

rule in HF-related ascites. Conversely, a cutoff ≤182 pg/mL had the lowest negative

likelihood ratio (0.0) and was the best to rule out HF-related ascites. These findings find protocol were confirmed in a 60-patient validation cohort. Conclusions: Serum BNP is more accurate than ascites analyses in the diagnosis of HF-related ascites. The workup of patients with new onset ascites could be streamlined by obtaining serum BNP as an initial test and could forego the need for diagnostic paracentesis, particularly in cases where the cause of ascites is uncertain and/or could be the result of HF. (Hepatology 2014;59:1043–1051) “
“Background and Aim:  Needle-knife fistulotomy has commonly been used for overcoming difficult bile duct cannulation. Periampullary diverticula (PAD) can be an impediment to endoscopic retrograde cholangiopancreatography (ERCP) procedures. There are little data on needle-knife fistulotomy in patients

with PAD. We evaluated the efficacy and safety of needle-knife fistulotomy between patients with and without PAD. Methods:  Data from December 2005 to October 2010 were reviewed. Patients who underwent needle-knife fistulotomy were divided into the group with PAD and the group without PAD (control group). The technical success and complications were compared. Results:  A total of 3012 ERCP cases were analyzed. Needle-knife fistulotomy was performed in 154 out of 3012 cases (5.1%) with 138 of these patients (89.6%) experiencing successful bile duct cannulation. Nabilone The overall cannulation success rate was not significantly different between PAD group (n = 33) and control group (n = 121) (93.9% vs 88.4%; P = 0.523). There was no significant difference in pancreatitis, bleeding and perforation between the two groups. Conclusions:  Needle-knife fistulotomy can be performed effectively and safely in patients with periampullary diverticula and difficult bile duct cannulation. “
“Human MxA, an interferon-inducible cytoplasmic dynamin-like GTPase, possesses antiviral activity against multiple RNA viruses. Recently, MxA has also been demonstrated to have activity against the hepatitis B virus (HBV), a well-known DNA virus responsible for acute and chronic liver disease in humans.

This corresponds to ∼87% of the total amount injected. Within the first 4 hours the peptide-associated radioactivity in the liver remained constant. It slowly declined to 30.5 %ID/g at 24 hours after injection. At early points in time, minor levels were detectable in the blood (at 10 minutes: 2.8 %ID/g; at 1 hour: 2.0 %ID/g), in the kidneys (at 10 minutes: 2.7 %ID/g; at 1 hour: 2.3 %ID/g) and to a lower extend in heart, lung, and spleen (at 10 minutes:

3.8 %ID/g; at 1 hour: 2.6 %ID/g). No activity was associated with the brain, indicating no crossing of the blood-brain barrier. This confirms the results of noninvasive imaging obtained with genotype D HBVpreS/2-48myr-y-125I (Fig. 2A). Notably, the organ distribution pattern entirely changed when the N-terminal Tanespimycin in vivo fatty acids were removed. At 10 minutes p.i. >50% of the ID/g of HBVpreS/1-48-y-131I was detectable

in the kidneys (Fig. 3B). The signal declined to undetectable levels within the following 4 hours. At early timepoints higher peptide levels were detectable in the blood. No specific accumulation was observed in the liver when compared to other organs. Since a similar distribution was observed for a non-myristoylated scrambled peptide (data not shown), we conclude that myristic acid may mediate binding to a serum factor preventing the 5.4 kDa peptide from filtration in the kidney. In addition, association see more with a serum factor may enhance resistance against serum proteases. To substantiate the sequence-dependence for the hepatotropism of the peptide

we tested the point mutant HBVpreS/2-48stea(G12E)-y-131I. This mutant is defective in HBV infection inhibition.20 Remarkably, the single amino acid substitution completely changed the organ distribution of the peptide in NRMI mice (Fig. 3C). The pronounced association with the liver was lost and the peptide did not retain in the mouse for 24 hours. Thus, Carbohydrate acylated HBVpreS/2-48-peptides address a homologous target in mouse and human livers with comparable binding specificities for the HBVpreS1-sequence. Finally, we performed organ distribution studies using all peptides depicted in Fig. 3D. To quantify liver association, we calculated a liver enrichment factor and compared it with the inhibitory activity of the same peptide determined in infection inhibition assays (Fig. 3D). Mutants lacking their ability to interfere with HBV infection also lost their potential to accumulate in mouse livers. Inactive peptides (e.g., those with mutations in the essential receptor binding site 9-NPLGFFP-15) behaved like the scrambled mutant, while those with a residual inhibitory activity still retained some hepatotropism. This correlation supports the hypothesis that mice harbor an HBVpreS1-specific receptor which displays the same binding specificity as its human homolog. The unexpected finding that mice harbor an HBVpreS-specific receptor in the liver prompted us to perform in vivo distribution studies in other species.