Results: CDAA-elicited a typical histological picture of advanced NASH. Coffee administration significantly reduced HTG (117.46±23.59 in CDAA vs.81.74±28.5 in CDAA-C group p<0.05) and mRNA levels of both TNF-a and MCP-1. Also coffee administration was associated to lower scores of fibrosis (2.38±0.48 in CDAA group vs.1.5±0.58 in CDAA-C group, p<0.05) and partially corrected CDAA diet-induced mitochondrial dysfunction. In addition, HSC treated with caffeine exhibited a decrease (−60%) of a-SMA and collagen1

a 1 mRNA levels in a time- and dosedependent manner. Protein levels of a-SMA were also reduced after 72h of caffeine treatment (20mM). Treatment with selleck chemicals 1, 7DMX did not result in a reduction of α-SMA and/or collagen1 α 1. Caffeine (20mM) also reduced proliferative capacity of HSC by 50% after 96. CYP1A2 (the enzyme that metabolizes caffeine) was not detected in stellate cells by qPCR. Conclusion: Coffee administration has beneficial effects in a mouse model of NASH. This may be related to reduction in HTG and improvement in mitochondrial function. In addition, caffeine directly reduced HSC activation see more and proliferation in vitro, independent of its metabolites. These results may explain the protective effects of caffeine on

NASH and hepatic fibrogenesis. (FONDECYT 1110455, Conicyt, project ACT79/CARE Basal Project). Disclosures: The following people have nothing to disclose: Juan E. Oyarzun, Marjolein Tiebosch, Pablo Quintero, Margarita Pizarro, Nancy Solis, Klaas Nico Faber, Silvana Zanlungo, Han Moshage, Marco Arrese Background: Prior data suggests that GG genotype of the PNPLA3 SNP confers a higher likelihood of liver fat, inflammation, and ballooning in NASH patients. Conversely, it is unclear whether CC genotype is protective regarding histological disease in NASH. Methods:

33 patients (31 Caucasians, 1 East Indian, and 1 East Asian) with NASH underwent testing for PNPLA3 genotyping, lipids, BMI, and HOMA-IR. MRI imaging was performed to quantify steatosis. Histological data included NAS score, inflammation, ballooning, fibrosis, and steatosis, which was measured both by standard histopathological evaluation and computer-aided image analysis of photomicrographs. Unpaired t-tests compared baseline 上海皓元 data from subjects with CC genotype vs. GC+GG genotype. Seventeen patients were treated with fish oil and 16 received placebo for 1 year. We also performed paired t-tests to assess whether genotype predicted response to fish oil therapy. Results: Baseline HOMA scores were higher in the CC group compared with GC+GG (8.3 v.5.4, P = 0.07). Despite this finding, baseline histology tended to be significantly less severe in the CC group with lower fat on biopsy (1.7 v.2.2, P = 0.05), less ballooning (0.9 v.1.3, P = 0.04), less fibrosis (1.6 v.2.0, P = 0.33), and significantly lower NAS scores (4.5 v.5.5, P = 0.0027).

In chronic this website hepatitis C (CHC) infection, the immune response is a key determinant to outcome of the antiviral therapy.

In this study we hypothesised that impaired T cell glucose metabolism occurs in HCV infection and will impact response to antiviral therapy. Methods: Longitudinal peripheral blood mononuclear cells (PBMCs) from patients with CHC (n = 21) were examined at baseline -prior to standard antiviral therapy and post-treatment, which includes 13 responders to treatment and 8 non-responders. As a control group, PBMCs from 10 healthy controls were also examined. PBMCs from subjects were stimulated with HCV peptides and CD3/CD28 Dynabeads for 44 hrs. Flow cytometry was used to measure specific metabolic markers such as pAkt (a key molecule in glucose transport and metabolism and a marker for T cell energy) and glucose transporter-1 as well as a marker of exhaustion (PD-1) in T-cell subpopulations (CD4/CD8/T selleck products reg/naive/central and effector memory

& terminally differentiated). As a measure of functionality, cytokine multiplex assays will be employed to detect TH-1 and TH-2 cytokines produced by PBMCs. Results: Compared to normal subjects, patients with CHC had impaired T cell MCE (CD4 & CD8) glucose metabolism as assessed by pAkt and glucose uptake (p < 0.05). Clearance of HCV with antiviral therapy restored pAkt and glucose uptake to levels of healthy controls (p < 0.05). Active T cell populations (central and effector memory, terminally differentiated and T regulatory cells) in patients with CHC had significantly higher metabolic

activity (p < 0.05) as reflected by pAkt levels when compared to quiescent populations (naive cells). Compared to responders to antiviral therapy, non-responders had significantly reduced expression of pAkt (p < 0.05) in all CD8 T cell subpopulations. This significant reduction was found at both baseline and post-treatment time points. Low pAKT levels correlated with an exhausted T cell profile (increased PD-1) (p = 0.009, R2 = 0.52). Conclusions: The current study identifies for the first time a glucose metabolic defect (pAkt and glucose uptake) within T cells of patients with CHC when compared to healthy controls. This metabolic defect is found to recover after viral clearance, which could suggest a virus driven effect. Secondly, a decrease in metabolic activity is found in all T cell subpopulations in those who do not respond to treatment when compared to responders of treatment.

Supplementation of recombinant transforming growth factor beta (TGF-beta) enhanced the spheroid formation capacity of HCC cells, and this effect was abolished when cultured with neutralizing antibodies against TGF-beta. Co-injection of HCC cells with fibroblasts but not with stellate cells or endothelial cells resulted in

the high motility of mice with high frequency of lung metastasis. [Conclusions] Fibrotic liver microenvironment accelerates buy LY294002 the malignant natures of HCC with enrichment of EpCAM/CD1 33-positive cancer stem cells through activation of TGF-beta signaling. TGF-beta may be a good molecular target to reduce the risk of aggressive liver cancer development in liver cirrhosis patients. Disclosures: Mariko Yoshida – Grant/Research Support: Bayer Shuichi Kaneko – Grant/Research Support: MDS, Co., Inc, Chugai Pharma., Co., Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc, Dainippon Sumitomo, Co., Inc, Aji-nomoto Co., Inc, MDS, Co., Inc, Chugai Pharma., Co., Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc, Dainippon Sumitomo, Co., Inc, Ajinomoto Co., Inc, Bayer Japan The following people have nothing to disclose: Mitsumasa Kondo,

Taro Yamashita, Naoki Oishi, Kouki Nio, Sha Sha Zeng, Takehiro Hayashi, Yoshimoto Nomura, Tomoyuki Hayashi, Hikari Okada, Hajime Sunagozaka, Hajime Takatori, Honda Masao Background::The presence of liver cirrhosis is the main risk factor for the development of hepatocellular carcinoma (HCC). Activated hepatic stellate cells (aHSC) are recognized Obeticholic Acid manufacturer as a central event in the development of liver fibrosis, but which role in HCC is unclear. Objective:This study investigated angiogenetic activity of aHSC in HCC and angiogenetic effect on proliferation, metastasis of HCC. Methods:In vitro, we exposured microvascular endothelial cell (MEC) 上海皓元医药股份有限公司 to conditioned media(CM) from aHSC to observe the influence of the CM on MEC by quantifying MEC tube formation, and placed aHSC over an endothelial monolayer to assesse transendothelial migration of aHSC to hepatoma cells by examining the movement of CFSE labeled aHSC through the endothelial cell monolayer. For convenient viewing, aHSC were labeled

for CFSE (one green fluorescent dye). In vivo, we established orthotopic model of HCC with nude mice receiving an intraliver injection of aHSC plus hepatoma cells. After 7 weeks, tumor size,number of metas-tases were measured. Forthermore, tumors tissue were ashah-sessed by immunostaining for expression of aHSC and microvessel. Angiogenesis activities were assessed by immunostaining tumors for CD34, an endothelial cell marker and vascular endothelial growth factor (VEGF). Results: In vitro, The CM from aHSC stimulated the tube formation by MEC, and hepatoma cells stimulated transendothelial migration of aHSC. In vivo, compared with mice receiving hepatoma cells alone, mice injected with hepatoma cells plus aHSC exhibited the most increased tumor size and regional and distant metastasis.

Supplementation of recombinant transforming growth factor beta (TGF-beta) enhanced the spheroid formation capacity of HCC cells, and this effect was abolished when cultured with neutralizing antibodies against TGF-beta. Co-injection of HCC cells with fibroblasts but not with stellate cells or endothelial cells resulted in

the high motility of mice with high frequency of lung metastasis. [Conclusions] Fibrotic liver microenvironment accelerates Atezolizumab the malignant natures of HCC with enrichment of EpCAM/CD1 33-positive cancer stem cells through activation of TGF-beta signaling. TGF-beta may be a good molecular target to reduce the risk of aggressive liver cancer development in liver cirrhosis patients. Disclosures: Mariko Yoshida – Grant/Research Support: Bayer Shuichi Kaneko – Grant/Research Support: MDS, Co., Inc, Chugai Pharma., Co., Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc, Dainippon Sumitomo, Co., Inc, Aji-nomoto Co., Inc, MDS, Co., Inc, Chugai Pharma., Co., Inc, Toray Co., Inc, Daiichi Sankyo., Co., Inc, Dainippon Sumitomo, Co., Inc, Ajinomoto Co., Inc, Bayer Japan The following people have nothing to disclose: Mitsumasa Kondo,

Taro Yamashita, Naoki Oishi, Kouki Nio, Sha Sha Zeng, Takehiro Hayashi, Yoshimoto Nomura, Tomoyuki Hayashi, Hikari Okada, Hajime Sunagozaka, Hajime Takatori, Honda Masao Background::The presence of liver cirrhosis is the main risk factor for the development of hepatocellular carcinoma (HCC). Activated hepatic stellate cells (aHSC) are recognized Tanespimycin datasheet as a central event in the development of liver fibrosis, but which role in HCC is unclear. Objective:This study investigated angiogenetic activity of aHSC in HCC and angiogenetic effect on proliferation, metastasis of HCC. Methods:In vitro, we exposured microvascular endothelial cell (MEC) 上海皓元 to conditioned media(CM) from aHSC to observe the influence of the CM on MEC by quantifying MEC tube formation, and placed aHSC over an endothelial monolayer to assesse transendothelial migration of aHSC to hepatoma cells by examining the movement of CFSE labeled aHSC through the endothelial cell monolayer. For convenient viewing, aHSC were labeled

for CFSE (one green fluorescent dye). In vivo, we established orthotopic model of HCC with nude mice receiving an intraliver injection of aHSC plus hepatoma cells. After 7 weeks, tumor size,number of metas-tases were measured. Forthermore, tumors tissue were ashah-sessed by immunostaining for expression of aHSC and microvessel. Angiogenesis activities were assessed by immunostaining tumors for CD34, an endothelial cell marker and vascular endothelial growth factor (VEGF). Results: In vitro, The CM from aHSC stimulated the tube formation by MEC, and hepatoma cells stimulated transendothelial migration of aHSC. In vivo, compared with mice receiving hepatoma cells alone, mice injected with hepatoma cells plus aHSC exhibited the most increased tumor size and regional and distant metastasis.

The comparison of treatments for hepatocellular carcinoma (between liver transplantation and hepatectomy) was practically unchanged, but articles on living donor liver transplantation were also mentioned

in some passages. A previous CQ as to whether transarterial chemoembolization (TAE) before liver transplantation is effective was amended because treatment before transplantation is not limited to TAE transplantation; it was modified to make it a more comprehensive CQ instead of a question on the efficacy of previous treatment. Another previous CQ on the mode of recurrence after transplantation and treatments for it was deleted because it is not frequently asked, and a new question was formulated: “Are there any differences in results after transplantation according to differences in background liver diseases (HBV, HCV, alcohol, MG-132 datasheet primary biliary cirrhosis and cryptogenic)? Do indications change? CQ27 Does treatment for hepatocellular carcinoma before liver transplantation improve prognosis? There is no adequate scientific evidence that treatment for hepatocellular carcinoma before liver transplantation improves prognosis. (grade C1) The presence or absence of liver transplantation is the most influential factor for prognosis of hepatocellular SB203580 mw carcinoma patients with cirrhosis or hepatic failure. Because of a serious

lack of brain death donors and a risk for living donors, restrictions are made for the indication of liver transplantation for hepatocellular carcinoma. The following statements are made by limiting the viewpoint as to whether treatment of cancer before transplantation improves prognosis when liver transplantation is feasible. In a report by Mazzaferro et al. who proposed the Milan criteria, treatment was given to 28

[26 TACE, one percutaneous ethnol injection therapy (PEIT), one hepatectomy] of 48 patients waiting for transplantation. The 4-year 上海皓元 survival rate was 79% in the treated group and 69% in the non-treated group; not a significant difference (LF005401 level 2a). According to a retrospective, multicenter, case–control study conducted in France by Decaens et al. comparing 100 patients who underwent TACE and 100 who did not before liver transplantation (LF108692 level 2b), the 5-year survival rates in the TACE and non-TACE groups were 59.4% and 59.3%, respectively. An evaluation of the recurrence-free survival rate only in patients who survived for at least 3 months after transplantation also revealed that the 5-year survival rates were 67.5% and 64.1%, respectively, with no significant difference. In an evaluation of only patients meeting the Milan criteria, TACE was performed in 74 and not performed in 68. The 5-year survival rates were 68.8% and 67.1%, respectively; again, not a significant difference. In a study on the effect of response to treatment before transplantation, response is considered to reflect prognosis.

Finally, the image

documentation of endoscopic findings is becoming more obvious—and accessible. Thus, recommendations for normal procedures as well as for focal and diffuse pathology are presented. The recommendations are “minimal,” meaning that expansions and subcategories will likely be needed in most centers. Still, with a stronger common grounds, communication within endoscopy will still benefit. “
“Liver fibrogenesis is a process tightly controlled by endogenous anti- and pro-fibrogenic factors. Interferon gamma (IFNγ) is a potent antifibrogenic cytokine in vitro and might therefore represent a powerful therapeutic entity. However, its poor pharmacokinetics and adverse effects, due to the presence of IFNγ receptors on nearly all cells, prevented its clinical application so far. We hypothesized that delivery of IFNγ specifically to the disease-inducing cells and concurrently avoiding its binding to nontarget cells might increase therapeutic

efficacy JQ1 nmr and avoid side effects. We conjugated IFNγ to a cyclic peptide recognizing the platelet-derived Vemurafenib growth factor beta receptor (PDGFβR) which is strongly up-regulated on activated hepatic stellate cells (HSC), the key effector cells responsible for hepatic fibrogenesis. The IFNγ conjugates were analyzed in vitro for PDGFβR-specific binding and biological effects and in vivo in acute (early) and chronic (progressive and established) carbon-tetrachloride-induced liver fibrosis in mice. The targeted-IFNγ construct showed PDGFβR-specific binding to fibroblasts and HSC and inhibited their activation in vitro. In vivo, the targeted-IFNγ construct attenuated local HSC activation in an acute liver injury model. In the established liver fibrosis model,

it not only strongly inhibited fibrogenesis but also induced fibrolysis. In contrast, nontargeted IFNγ was ineffective in both models. Moreover, in contrast to unmodified IFNγ, our engineered targeted-IFNγ did not induce IFNγ-related side effects such as systemic inflammation, hyperthermia, elevated plasma triglyceride levels, and neurotropic effects. Conclusion: This study presents a novel HSC-targeted engineered-IFNγ, which in contrast MCE公司 to systemic IFNγ, blocked liver fibrogenesis and is devoid of side effects, by specifically acting on the key pathogenic cells within the liver. (HEPATOLOGY 2011;) Liver cirrhosis, characterized by the extensive accumulation of an abnormal extracellular matrix, is the major cause of liver-related morbidity and mortality worldwide.1, 2 Except for an effective treatment of the underlying etiology, which is an option for some patients, there exists no clinically proven antifibrotic therapy to prevent progression of chronic liver disease to cirrhosis or to its regression.3, 4 Activated hepatic stellate cells and portal fibroblasts (collectively named activated hepatic stellate cells, HSC) are the main effector cells of liver fibrogenesis, producing most of the excessive extracellular matrix (ECM) such as fibrillar collagens.

We now provide a temporal reference to further test this hypothesis about the evolution of HBV in its natural small primate host. In addition to data presented here, we have previously reported that M. sylvanus species can be transfected with an HBV-coding plasmid.[20] Moreover, in vitro transduction of primary macaque hepatocyte with baculovirus-HBV constructs secreted HBV particles.[21] Those results Copanlisib datasheet had already opened up the possibility of using the macaque model for HBV study, although chronic viral infection was not achieved in these experimental studies. Our current data support

the evidence of chronic HBV infection in some macaques and the possible transmission of the HBV strain to M. sylvanus from Morocco.

Moreover, our screening evaluation performed on 120 animals demonstrates, for the first time, that a high proportion of wild-living M. fascicularis in Mauritius Island is naturally infected with HBV. However, to date, most of the HBV infections in M. fascicularis were found to be cryptic, with very low titer or undetectable markers in the absence of liver disease. To date, we have no hypothesis how this prevalence can be maintened in natura, because very low peripheral viral load click here implies a poor transmission efficiency either within the macaque group or from macaque to human animal-care team. Such natural, low-grade infections in Mauritius macaques are similar to occult HBV infections in humans, which present a major concern in the hepatitis B field[42-45] and may therefore represent an excellent model and unique opportunity for their study and therapy for which no recommendations exist. The Mauritius M. fascicularis could represent MCE a particularly valuable model for novel anti-HBV immunotherapeutic approaches for evaluation because of their limited genetic diversity, notably in the Mhc class I region, that could influence the immune cellular response as it has been demonstrated for SIV infection.[46-48] Further characterization of this

novel small primate close to humans will make it possible, for the first time, to test innovative immunotherapeutical approaches, including therapeutic DNA vaccination,[49] alone or in combination with cytokines, possibly as an adjuvant to antiviral nucleos(t)ides for their ability to cure chronic HBV infection. Many thanks to B. Chomel for his interest and support. The authors are grateful to Nick Lerche and Souad Sekkat for their invaluable guidance and help in this study. Additional Supporting Information may be found in the online version of this article. “
“Serum hepatitis B surface antigen (HBsAg) levels may reflect the immunomodulatory efficacy of pegylated interferon (PEG-IFN). We investigated within a large randomized trial whether quantitative HBsAg levels predict response to PEG-IFN in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.

47-0.83), compared with subjects with WT homozygotes of the two SNPs. In stratified analyses, no obvious evidence of heterogeneity associations for the combined effects of these independence SNPs on HBV clearance and HCC risk was observed (Supporting Table 3). LD information of these four SNPs is shown in Supporting Table 4. We performed haplotype analysis to assess the effect of the haplotype

containing HLA-DP and HLA-DQ variant alleles (Supporting Table 5). When compared with the most frequent GGAG haplotype, all other haplotypes containing variant alleles of the four SNPs were significantly associated with HBV clearance (P value range from 1.75 × 10−3 to 3.12 × 10−11), which was consistent with the single SNP analysis. However, for HCC risk, the haplotype carrying rs3077 and selleck inhibitor rs2856718 (AAGG) showed a protective effect, but the haplotype carrying rs9277535 (GAAG) expressed a significant risk effect (compared to GGAG). In this study, we

investigated the associations between four SNPs in HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs2856718 and rs7453920) and risk of HBV clearance and HBV-related HCC in Southeast Han Chinese populations. Cell Cycle inhibitor This is the first study that validated the results of HLA-DQ variations and HBV persistence with a carefully selected control group, compared with the published GWAS,7, 8 and further expanded the data on HBV-related HCC. During the preparation and revision of the manuscript for this article, five studies replicated the associations of the two HLA-DP SNPs (rs3077 and rs9277535) and chronic HBV infection in Han Chinese, which were all consistent with our observations.9-13 For HBV-related HCC, only two studies9, 13 on rs9277535 and one study9 on rs3077 was published. We performed a mini meta-analysis with a dominant genetic model on these two SNPs and HCC risk by pooling our current data and the published data. rs9277535 was not associated with HCC risk, either using controls of chronic HBV infection or chronic HBV infection MCE公司 and cirrhosis (Supporting Fig. 2). However, compared with chronic

HBV infections, only one small study (265 HCC and 591 controls) genotyped the SNP rs3077 and found a comparable (but not significant) association with HBV-related HCC as ours (Supporting Fig. 2). No study reported the associations between the two HLA-DQ SNPs (rs2856718 and rs7453920) and HCC risk, much less the HLA-DP/DQ haplotypes. Compared with the most frequent haplotype GGAG, the haplotype carrying rs3077 and rs2856718 (AAGG) showed a protective effect, which was consistent with the single SNP effects. However, the haplotype-carrying rs9277535 (GAAG) expressed a significant risk effect, although the single SNP analysis did not show obvious associations. Thus, the effects by HLA-DP and HLA-DQ may not be independent; further fine mapping studies are recommended. In the current study, we also typed the previously reported susceptibility locus, KIF1B, at 1p36.22 (rs17401966) for HBV-related HCC.

Experimental and observational data suggest that intestinal inflammation arises from abnormal immune response to intestinal microbiota in genetically susceptible individuals. Not all subjects who carry common risk alleles develop the disease suggesting that environmental triggers are important

in disease expression.We hypothesis that norovirus may play a role in the pathogenesis of Crohn’s disease. In an observational pilot study, we aimed to determine the prevalence of norovirus in Crohn’s disease and ulcerative colitis subjects compared with controls. Methods: Stool samples were collected from consecutive subjects with confirmed Crohn’s disease (CD), ulcerative this website colitis (UC) and controls. Viral RNA was extracted and human norovirus detection was performed using real time polymerase chain reaction. Results: A total of 102 subjects with inflammatory bowel diseases (IBD) (61 CD; 41 UC; 19 active disease) and 102 healthy controls were included. All stool samples from cases and controls were tested negative for the norovirus genogroup II, the most prevalent group of norovirus circulating locally and elsewhere. Conclusion: Human norovirus is absent in the stool of subjects with IBD (active and inactive) and controls. Norovirus may only play a minor role, if any,

in pathogenesis or disease Regorafenib in vivo flare in IBD. Key Word(s): 1. IBD; 2. Norovirus; 3. Crohn’s disease; Presenting Author: YAO HE Additional Authors: SHUNHUA LONG, MINHU CHEN, KANG CAO, YUJUN CHEN, BAILI CHEN, REN MAO, SHENGHONG ZHANG, ZHIRONG ZENG, PINJIN HU Corresponding Author: MINHU CHEN, PINJIN HU Affiliations: The First Affiliated MCE Hospital of Sun Yat-Sen University; The First Affiliated Hospital of Nanchang University; The Sixth Affiliated Hospital of Sun Yat-Sen University Objective: The purpose of this study was to investigate the role of the PI3K/Akt/mTOR

signaling pathway and it’s negative feedback factor PTEN in the pathogenesis of Crohn’s disease(CD). Methods: Peripheral blood was collected from 24 patients with CD (n = 24) and 16 healthy donors (Control,n = 16). Tissue samples were obtained endoscopically from patients with CD as study group (n = 23) and patients with constipation as control (n = 12). Changes of PI3K/Akt/mTOR pathway and PTEN expression were evaluated by quantitative real time PCR(qPCR) and western blotting respectively in peripheral CD4+ T Cells, and by a standard immunohistochemical procedure in mucosal lymphocytes. Results: No significant difference of mRNA expression of PI3K, Akt, mTOR, 4E-BP1, P70 S6K was found in peripheral CD4+ T Cells between CD patients and control, though a tendency of up-regulation of these mRNA expressions in CD patients was noted.

While similar ultrastructural changes were also observed in patients with CD, they were not significantly different from the controls. Functionally, these patients showed increase in intestinal permeability along with dilated TJs. After 6 months of treatment in both the groups, there was improvement in the ultrastructural parameters of learn more the TJs. Conclusion: Disruption of integrity of tight junctions (loss of pentalaminar

structure, dilatation of TJs, disarrayed microvilli) are characteristic of both celiac disease and Crohn’s disease and forms the basis of increase in intestinal permeability. These changes are not disease specific. The ultrastructural changes of the tight junctions and microvilli improve (not completely) with healing of lesions at 6 months after treatment which is reflected functionally by improvement in intestinal permeability; however the improvement in ultrastructural changes are incomplete suggesting 6 months

is not good enough for complete normalization of ultra-structural changes. Key Word(s): 1. selleck chemicals llc Tight Junction; 2. Celiac Disease; 3. Crohn’s disease; 4. HPLC; Presenting Author: PRASENJIT DAS Additional Authors: POOJA GOSWAMI, ANILK VERMA, SIDDHARTHDATTA GUPTA, TAPOSHK DAS, TAPAS NAG, VINEET AHUJA, GOVINDK MAKHARIA Corresponding Author: GOVINDK MAKHARIA Affiliations: All India Institute of Medical Sciences Objective: The apical most part of intercellular junction

called tight junctions (TJ) are regulated by a host of transmembrane and cytoplasmic proteins, which in turn maintains the integrity of these junctions. Abnormalities in tight junctions have been implicated in the pathogenesis of celiac disease (CeD) and Crohn’s disease (CD). Since the mechanisms of abnormalities in intestinal permeability MCE公司 are different in CeD and CD; we planned to study if there was a differencein the expression and semiquantitation of a few key tight junction proteins in them at baseline and at six months after treatment. Methods: Endoscopic mucosal biopsies from treatment naïve patients with CeD (n = 24), activeCD (n = 28) and 15 control subjects were subjected to histological examination (Modified Marsh grade), immunohistochemical staining of key TJ proteins [transmembrane proteins (claudin-2, 3, 4, occludin and JAM) and cytoplasmic protein (ZO-1)]. The expression patterns of the TJ proteins were validated by western blot analysisfor the same set of proteins. The expression and semiquantitation of these proteins were assessed after 6 monthsof appropriate treatment. Functional analysis of tight junctions was assessed by estimating lactulose and mannitol ratio in urine using HPLC.