3% were female. Etiology of liver fibrosis were 46.9% HBV, 15.6% HCV and 37.5% miscellanous. Results of Spearman rank test

level of hyaluronic acid (r = 0.436; p = 0.014), YKL-40 (r = 0.43; p = 0.014), Type IV collagen (r = 0.509; p = 0.003), laminin (r = 0.733; p = 0.001). Double linear regression selleck screening library test with stepwise method on all of the determinant factors show that the most significant determinant factor was type IV collagen (r = 0.463; p < 0.001). Conclusion: There was significant positive correlation between serum extracellular matrix (hyaluronic acid, laminin, YKL-40, type IV collagen) and liver stiffness in liver fibrosis patients. The most significant determinant factor was type IV collagen. Key Word(s): 1. liver stiffness; 2. liver fibrosis; 3. serum extracellular matrix (hyaluronic acid, laminin, Ykl-40, Type Iv collagen)

Presenting Author: XIU QING WEI Additional Authors: JIN TAO, ZUOFU WEN, BIN WU drug discovery Corresponding Author: XIUQING WEI Affiliations: The Third Affiliated Hospital of Sun Yat-Sen University; Third Affiliated Hospital, Sun Yat-Sen University; The Third Affiliated Hospital of Sun Yat-Sen Unive Objective: To introduce an uncommon cause of anorexia and jaundice. Methods: The medical course of a rare patient with anorexia and jaundice was presented in brief. Results: A 65-year-old woman was admitted to our hospital because of fatigue, anorexia and food avoidance during the past 6 months and jaundice for one month. Serum level of AST, ALT, total bilirubin and direct bilirubin MCE were elevated at 174 U/L, 89 U/L , 163.9 umol/L and 117.9 umol/L respectively. Testes for serum cortisol level at the following time points: 0 am 76.67 nmol/L, 8 am 42.12 nmol/L,

4 pm 74.23 nmol/L, and ACTH was markedly low at 1.23 pmol/L. Hormones on other pituitary axes were within normal range. The patient responded quickly to hydrocortision and all the symptoms relieved totally one month later. Conclusion: Addision’s disease can be presented as hepatitis and anorexia in some rare cases. Key Word(s): 1. Addision’s disease; 2. hepatitis Presenting Author: MUSTOKO NEGORO WIBOWO Additional Authors: ARITANTRI DAMAYANI, PAULUS KUSNANTO, TRIYANTA YULI PRAMANA, TANTORO HARMONO Corresponding Author: MUSTOKO NEGORO WIBOWO Affiliations: Fk Uns – Dr Moewardi Hospital, Fk Uns – Dr Moewardi Hospital, Fk Uns – Dr Moewardi Hospital, Fk Uns – Dr Moewardi Hospital Objective: The aim of our study was to evaluate a possible correlation between HBV DNA, HCV RNA viral load and liver fibrosis assessed by Fibroscan among chronically infected subject Methods: Restrospective analysis of 64 patients with hepatitis B and hepatitis C undergoing Fibroscan in Dr. Moewardi Hospital Surakarta from January 2012 to March 2014. Statical analysis with Chi Square Test. Exclusion criteria were the presence of diabetes mellitus, advanced cancer and pregnancy.

3% were female. Etiology of liver fibrosis were 46.9% HBV, 15.6% HCV and 37.5% miscellanous. Results of Spearman rank test

level of hyaluronic acid (r = 0.436; p = 0.014), YKL-40 (r = 0.43; p = 0.014), Type IV collagen (r = 0.509; p = 0.003), laminin (r = 0.733; p = 0.001). Double linear regression MDV3100 in vitro test with stepwise method on all of the determinant factors show that the most significant determinant factor was type IV collagen (r = 0.463; p < 0.001). Conclusion: There was significant positive correlation between serum extracellular matrix (hyaluronic acid, laminin, YKL-40, type IV collagen) and liver stiffness in liver fibrosis patients. The most significant determinant factor was type IV collagen. Key Word(s): 1. liver stiffness; 2. liver fibrosis; 3. serum extracellular matrix (hyaluronic acid, laminin, Ykl-40, Type Iv collagen)

Presenting Author: XIU QING WEI Additional Authors: JIN TAO, ZUOFU WEN, BIN WU Rucaparib Corresponding Author: XIUQING WEI Affiliations: The Third Affiliated Hospital of Sun Yat-Sen University; Third Affiliated Hospital, Sun Yat-Sen University; The Third Affiliated Hospital of Sun Yat-Sen Unive Objective: To introduce an uncommon cause of anorexia and jaundice. Methods: The medical course of a rare patient with anorexia and jaundice was presented in brief. Results: A 65-year-old woman was admitted to our hospital because of fatigue, anorexia and food avoidance during the past 6 months and jaundice for one month. Serum level of AST, ALT, total bilirubin and direct bilirubin 上海皓元医药股份有限公司 were elevated at 174 U/L, 89 U/L , 163.9 umol/L and 117.9 umol/L respectively. Testes for serum cortisol level at the following time points: 0 am 76.67 nmol/L, 8 am 42.12 nmol/L,

4 pm 74.23 nmol/L, and ACTH was markedly low at 1.23 pmol/L. Hormones on other pituitary axes were within normal range. The patient responded quickly to hydrocortision and all the symptoms relieved totally one month later. Conclusion: Addision’s disease can be presented as hepatitis and anorexia in some rare cases. Key Word(s): 1. Addision’s disease; 2. hepatitis Presenting Author: MUSTOKO NEGORO WIBOWO Additional Authors: ARITANTRI DAMAYANI, PAULUS KUSNANTO, TRIYANTA YULI PRAMANA, TANTORO HARMONO Corresponding Author: MUSTOKO NEGORO WIBOWO Affiliations: Fk Uns – Dr Moewardi Hospital, Fk Uns – Dr Moewardi Hospital, Fk Uns – Dr Moewardi Hospital, Fk Uns – Dr Moewardi Hospital Objective: The aim of our study was to evaluate a possible correlation between HBV DNA, HCV RNA viral load and liver fibrosis assessed by Fibroscan among chronically infected subject Methods: Restrospective analysis of 64 patients with hepatitis B and hepatitis C undergoing Fibroscan in Dr. Moewardi Hospital Surakarta from January 2012 to March 2014. Statical analysis with Chi Square Test. Exclusion criteria were the presence of diabetes mellitus, advanced cancer and pregnancy.

The primary outcome was the modified Rankin score (mRS) at 90-days with a good outcome defined by mRS of 0-2.000. There were 114 (50.7%) patients in the LVO and 111 (49.3%) in the No-LVO group. A good outcome was seen in 28 (24.6%) patients in the LVO and 77 (69.4%) patients in the No-LVO

group (OR .14; 95% CI: .08-.26; P < .0001). Mortality was observed in 13 (11.7%) patients in the No-LVO group and 48 (42.1%) patients in the LVO group (OR .18; 95% CI: .09-.36; P < .0001). Significant EX 527 hemorrhage was seen in 14 (12.5%) patients in the LVO and 0 (0%) patients in the No-LVO group (P < .0001). Older age (OR .96; 95% CI: .93-.98; P = .002) and presence of LVO (OR .29; 95% CI: .12-.68; P = .004) were significant independent predictors of poor outcome. CTA identification of proximal occlusions is associated with significantly poor outcomes in patients receiving

intravenous stroke thrombolysis. “
“To reveal the characteristics of susceptibility-weighted imaging (SWI) under low cerebral blood flow (CBF) induced by hyperventilation (HV). This study was approved by the institutional review board. Informed consent was obtained. Six healthy volunteers (5 men, 1 woman; mean age, 29 years; range, 24-33 years) underwent SWI and arterial spin labeling perfusion imaging under normal ventilation (NV) and HV at 3.0 T. Regions of interest (ROIs)

were placed on gray matter (GM) and white matter Staurosporine ic50 (WM) of the frontal lobe (FL) and occipital lobe (OL). Intensities of ROIs were compared between NV and HV. Contrast of veins compared with adjacent MCE cerebral parenchyma (CV) was also compared between NV and HV. CBF during HV (CBFHV) was decreased compared with CBF during NV (CBFNV) (29.1 ± 4.6%). FL-GMHV and OL-GMHV showed significant signal decreases compared with FL-GMNV and OL-GMNV, respectively (P= .018, .017). CVHV was significantly increased compared with CVNV (164.1 ± 29.9%) (P= .00019). SWI sensitively reflects HV-induced decreases in CBF. The present results might assist in the interpretation of SWI in clinical practice, since CBF decreases might also influence signal changes on SWI. “
“Various anastomosis and aberrant origins of the middle meningeal artery (MMA) have been documented in literature. However, there has been no report of its origin from the posterior inferior cerebellar artery (PICA) or its branches. In this report, we discuss an anomalous origin of the MMA from the PICA. Also, we discuss the embryological and anatomical development of the MMA. Imaging identification of the origin of the MMA is important while planning surgical and endovascular interventions in the region of the skull base.

The primary outcome was the modified Rankin score (mRS) at 90-days with a good outcome defined by mRS of 0-2.000. There were 114 (50.7%) patients in the LVO and 111 (49.3%) in the No-LVO group. A good outcome was seen in 28 (24.6%) patients in the LVO and 77 (69.4%) patients in the No-LVO

group (OR .14; 95% CI: .08-.26; P < .0001). Mortality was observed in 13 (11.7%) patients in the No-LVO group and 48 (42.1%) patients in the LVO group (OR .18; 95% CI: .09-.36; P < .0001). Significant Roxadustat hemorrhage was seen in 14 (12.5%) patients in the LVO and 0 (0%) patients in the No-LVO group (P < .0001). Older age (OR .96; 95% CI: .93-.98; P = .002) and presence of LVO (OR .29; 95% CI: .12-.68; P = .004) were significant independent predictors of poor outcome. CTA identification of proximal occlusions is associated with significantly poor outcomes in patients receiving

intravenous stroke thrombolysis. “
“To reveal the characteristics of susceptibility-weighted imaging (SWI) under low cerebral blood flow (CBF) induced by hyperventilation (HV). This study was approved by the institutional review board. Informed consent was obtained. Six healthy volunteers (5 men, 1 woman; mean age, 29 years; range, 24-33 years) underwent SWI and arterial spin labeling perfusion imaging under normal ventilation (NV) and HV at 3.0 T. Regions of interest (ROIs)

were placed on gray matter (GM) and white matter C59 wnt cost (WM) of the frontal lobe (FL) and occipital lobe (OL). Intensities of ROIs were compared between NV and HV. Contrast of veins compared with adjacent MCE cerebral parenchyma (CV) was also compared between NV and HV. CBF during HV (CBFHV) was decreased compared with CBF during NV (CBFNV) (29.1 ± 4.6%). FL-GMHV and OL-GMHV showed significant signal decreases compared with FL-GMNV and OL-GMNV, respectively (P= .018, .017). CVHV was significantly increased compared with CVNV (164.1 ± 29.9%) (P= .00019). SWI sensitively reflects HV-induced decreases in CBF. The present results might assist in the interpretation of SWI in clinical practice, since CBF decreases might also influence signal changes on SWI. “
“Various anastomosis and aberrant origins of the middle meningeal artery (MMA) have been documented in literature. However, there has been no report of its origin from the posterior inferior cerebellar artery (PICA) or its branches. In this report, we discuss an anomalous origin of the MMA from the PICA. Also, we discuss the embryological and anatomical development of the MMA. Imaging identification of the origin of the MMA is important while planning surgical and endovascular interventions in the region of the skull base.

Rat colitis model (group B, C and D) was established by intrarectal administration with 100 mg/kg body weight of TNBS (in 0.25 ml 50% ethanol), group A was administered the same dose of 0.9% sodium chloride solution in 0.25 ml 50% ethanol using the same technique. Then group C was treated with 100 mg/kg body of curcumin and the same dose of SASP for group D by intragastric administration daily. Rats in group A and B were respectively treated with 100 mg/kg body weight of 0.9% sodium chloride solution. Colon intestinal

and serum sample were collected after 8 days. Evaluated Selleckchem PCI-32765 weight loss, stool consistency, and blood in feces in each group. The disease activity index (DAI) was calculated by assigning well-established and validated scores for parameters. Evaluated colonic mucosa damage index (CMDI) and histological activity index (HAI). Determined IL-17 and IL-23 levels with immunohistochemistry in colonic mucosa, and with enzyme-linked immunosorbent assay (ELISA) in serum. Results: Compared

with the TNBS-induced colitis group, the scores of DAI, CMDI, HAI, the expression of IL-17, IL-23 in colonic mucosa and serum were all decreased in the curcumin-treated group (P < 0.05). While there was no significant difference in DAI, CMDI, HAI, expression of IL-17, IL-23 see more between the curcumin-treated group and SASP-treated group (P > 0.05). Conclusion: Curcumin can attenuates inflammation through inhibition of IL-17 and IL-23 in experimental rats colitis. Key Word(s): 1. curcumin; 2. colitis; 3. IL-17; 4. IL-23; Presenting Author: ZHANG JING Additional Authors: LIBI MIN Corresponding Author: LIBI MIN Affiliations: First affiliated hospital of nanchang university Objective: To explore the effect of NF-κB Decoy ODN enema on the BALB/C mice with chronic intestinal fibrosis induced by TNBS/50% EtOH, and

research the best treatment of NF-κB Decoy ODN to intestinal fibrosis. To observe the experimental mice disease activity MCE公司 index (DAI), analyze the change of histological pathological, find the hyperplasia degree of collagen fibers, research the expression of IL-1β, TNF-α, Col-III mRNA and NF-κB, TGF-β1 protein. So that we can study the mechanism of NF-κB Decoy ODN on the BALB/C mice with chronic intestinal fibrosis induced by TNBS, and provide the experimental basis for IBD treatment. Methods: 1. Establishment of IBD mice models BALB/C mice are fasting but free for water for 24 hours, ether anesthesia, use 3.5 F catheter insert into the intestine from anus and the depth is about 5.5 cm. Give 2 mg TNBS/50% EtOH 100 ul enema, and inverse the mice for 60 seconds. Last for 6 weeks, once for a week, all groups of mice get executed one week after the last enema. 2.

The dual blood supply of the liver is a unique feature of the hepatic vasculature.5 Both vascular systems share an intimate modulatory relationship called the “hepatic arterial ALK inhibitor buffer response,” where compensatory hepatic arterial blood flow can occur in response to changes in portal venous flow.6 Even with the protection of a dual blood supply, coupled with the liver’s capacity for anaerobic metabolism of glycogen, hypoxic damage can still occur. Occlusion of the hepatic artery and portal vein by cross-clamping the porta hepatis

with a vascular clamp is known as the Pringle maneuvre. It is a useful technique commonly employed in hepatic resection and liver transplantation, but inherent to the Pringle maneuvre is the inevitable risk of warm IR injury. The models used to study hepatic IR injury can be classified into three groups: in vivo models, in vitro cell culture systems and ex vivo intact organ models. Rodents are the most commonly used species for whole organ and cell culture studies. Two main in vivo models of hepatic IR injury have been described. Livers may be subjected to global or total hepatic ischemia by occluding the hepatic artery, portal vein and common bile duct.7 The period

of hepatic ischemia using this technique is limited (20 min) as longer occlusion times result in high mortality. Kawamoto NVP-BGJ398 demonstrated that irreversible hemodynamic instability and severe splanchnic congestion occurred following global ischemic periods of more than 30 min.8 A model of partial hepatic ischemia was first described by Yamauchi et al. in 1982, where the left and median lobes were rendered ischemic by occluding the pertinent arterial and portal vein branches.9 This resulted in ischemia to 70% of the liver. This model was further developed by other investigators.10–15 In this model, portal decompression is possible via the right and caudate lobes, thereby preventing mesenteric congestion and portal endotoxemia. In models employing the isolated

perfused liver, the excised organ is perfused MCE via the portal vein using a non-recirculating system with buffer as perfusate; buffer flow rates can be adjusted to mimic low-flow hypoxia,16 or the oxygen content altered to simulate hypoxia-reoxygenation.17 Regardless of whether an in vivo or ex vivo system was studied, each model demonstrated clear evidence for IR injury on the basis of leakage of intracellular hepatic enzymes (lactate dehydrogenase [LDH], alanine aminotransferase [ALT] or aspartate aminotransferase [AST] ) into blood or perfusate, and histological evidence of hepatocellular necrosis.18,19 Cell culture studies have been useful in study the pathophysiology of IR in vitro.

Similar results were obtained for NS5A by western blotting (Supporting Fig. 3). All together, these data show that EGCG does not inhibit viral replication or virion assembly and egress. Because EGCG has an antiviral activity at an early step of the HCV life cycle, we further investigated its mode of action on HCV entry. To test whether EGCG would act on the viral particle or on the target cells, HCVcc was preincubated with EGCG before contact with target cells. Tanespimycin chemical structure In these conditions, EGCG should have a higher inhibitory effect, especially if it acts on the viral particle. In contrast, the antiviral action of EGCG should not be modified if EGCG acts

on the cell. Preincubation of the virus with 50 μM of EGCG, followed by a dilution to 5 μM during infection, led to a stronger inhibition of infection than the one observed with the same concentration of EGCG during the inoculation, with no preincubation (Fig. 5A). Together with the inhibition of HCVpp infectivity, this website these data strongly suggest that EGCG inhibits HCV entry by affecting the HCV envelope. The mechanism of HCV entry is a complex multistep process involving binding of the viral particle to the cell surface, interaction with several entry factors followed by endocytosis, and fusion of the viral envelope with an internal membrane. To determine which step of HCV entry is impaired by

EGCG, virus binding was performed at 4°C. Then, the cells were shifted to 37°C to allow endocytosis and fusion, with EGCG being added at different times (Fig. 5B). Heparin, a known inhibitor of HCV binding, was used as a positive control. 29 A strong decrease in HCV infection was observed when

EGCG was added at 4°C during the first hour (i.e., binding step), whereas no inhibition was observed when EGCG was added after virus binding, even before endocytosis. As expected, similar results were obtained with heparin. 上海皓元医药股份有限公司 These results are consistent with a direct action of EGCG on the viral particle, as suggested before, for the antiviral effect to take place. To determine whether EGCG impairs directly the binding of particles to the cell surface or a later step of virus entry, we analyzed virus binding in the presence of EGCG. Cells were inoculated with purified HCVcc at 4°C in the presence of EGCG or heparin, and the amount of bound viruses was determined by quantifying HCV genomic RNA (gRNA). As expected, heparin strongly reduced HCV attachment to the cell surface (Fig. 5C). In the presence of EGCG, a strong decrease in virus binding was also observed. Together, these results show that EGCG, likely by acting on the virion, inhibits virus entry by impairing virus binding to the cell surface. After infection of Huh-7 cells with HCVcc, progeny viruses are transmitted to adjacent cells, resulting in focal areas of spreading infection (i.e., foci).

18 Flow cytometry at day 11 confirmed depletion efficiencies of >95%. Following cardiac perfusion with phosphate-buffered saline, livers were aseptically removed and mechanically disrupted between sterile frosted microscope slides. Cell suspensions were passed twice through 70 μm filters before cell isolation. Liver CD11b+ cells were isolated using anti-CD11b magnetic beads and positive selection columns (Miltenyi) per the manufacturer’s protocol. Gr1+ cells were isolated using phycoerythrin-tagged

anti-Gr1 (RB6-8C5; eBioscience) and positive immunomagnetic separation using a phycoerythrin selection kit (StemCell Technologies, Inc.). CD11b+Ly6GhiLy6Clo cells were isolated via positive selection employing biotinylated anti-Ly6G and anti-biotin Fulvestrant manufacturer magnetic microbeads (Miltenyi). CD11b+Ly6G−Ly6Chi cells were isolated by negative selection of Ly6G− cells followed by positive selection with biotinylated anti-Ly6C and anti-biotin magnetic microbeads (Miltenyi). Flow cytometry verified that all cell isolations yielded >90% pure populations. Bead-isolated CD4+ T cells were

cultured for 3 days with plate-bound anti-CD3ε (10.0 μg/mL), soluble anti-CD28 (1.0 μg/mL; BD Biosciences) recombinant interleukin-12 (IL-12) (10 ng/mL; Peprotech) and anti-IL-4 (10 μg/mL; NCI). Th1 effector development was confirmed by intracellular IFN-γ staining. Cells were incubated with Fc Block (anti-CD16/CD32; eBioscience)

for 20 minutes at 4°C then washed twice. Cells were stained with antibodies to CD4, CD11b, Gr1, F4/80, programmed Selleck RO4929097 death ligand 1 (PD-L1; eBioscience, San Diego), Ly6G (Clone 1A8), Ly6C (Clone 1G7.G10), major histocompatibility complex class II (BD Biosciences), or CD14 (Biolegend) and acquired on either BD FACSCalibur (eBiosciences) or Accuri C6. Data analysis was performed with FlowJo, version 8.8.6 (Tree Star) software. Cells obtained from suppression assay cultures at 48 hours were surface stained as described above, fixed and permeabilized (CytoFix/CytoPerm; BD Biosciences), stained with rabbit anti-mouse iNOS (BD Biosciences), followed MCE by blocking with 10% normal goat serum, and secondary staining with goat anti-rabbit (Jackson ImmunoResearch). Surface-marker-appropriate isotype and intracellular staining with secondary antibody alone served as negative control. RAW 264.7 cells cultured for 24 hours with lipopolysaccharide and IFN-γ served as positive control. Cells were acquired by flow cytometry. Prior to inclusion in cocultures, bead-isolated CD4+ or CD8+ T cells from wild-type mouse spleens were stained with 5.0 μM 5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester (CFSE; Invitrogen) for 10 minutes and quenched by washing twice in Roswell Park Memorial Institute medium 1640/10% fetal bovine serum. Isolated Tgfb1+/− or Tgfb1−/− CD11b+ cells were added at 3.0 × 105 (“300K”) or 1.

18 Flow cytometry at day 11 confirmed depletion efficiencies of >95%. Following cardiac perfusion with phosphate-buffered saline, livers were aseptically removed and mechanically disrupted between sterile frosted microscope slides. Cell suspensions were passed twice through 70 μm filters before cell isolation. Liver CD11b+ cells were isolated using anti-CD11b magnetic beads and positive selection columns (Miltenyi) per the manufacturer’s protocol. Gr1+ cells were isolated using phycoerythrin-tagged

anti-Gr1 (RB6-8C5; eBioscience) and positive immunomagnetic separation using a phycoerythrin selection kit (StemCell Technologies, Inc.). CD11b+Ly6GhiLy6Clo cells were isolated via positive selection employing biotinylated anti-Ly6G and anti-biotin buy EMD 1214063 magnetic microbeads (Miltenyi). CD11b+Ly6G−Ly6Chi cells were isolated by negative selection of Ly6G− cells followed by positive selection with biotinylated anti-Ly6C and anti-biotin magnetic microbeads (Miltenyi). Flow cytometry verified that all cell isolations yielded >90% pure populations. Bead-isolated CD4+ T cells were

cultured for 3 days with plate-bound anti-CD3ε (10.0 μg/mL), soluble anti-CD28 (1.0 μg/mL; BD Biosciences) recombinant interleukin-12 (IL-12) (10 ng/mL; Peprotech) and anti-IL-4 (10 μg/mL; NCI). Th1 effector development was confirmed by intracellular IFN-γ staining. Cells were incubated with Fc Block (anti-CD16/CD32; eBioscience)

for 20 minutes at 4°C then washed twice. Cells were stained with antibodies to CD4, CD11b, Gr1, F4/80, programmed Crizotinib solubility dmso death ligand 1 (PD-L1; eBioscience, San Diego), Ly6G (Clone 1A8), Ly6C (Clone 1G7.G10), major histocompatibility complex class II (BD Biosciences), or CD14 (Biolegend) and acquired on either BD FACSCalibur (eBiosciences) or Accuri C6. Data analysis was performed with FlowJo, version 8.8.6 (Tree Star) software. Cells obtained from suppression assay cultures at 48 hours were surface stained as described above, fixed and permeabilized (CytoFix/CytoPerm; BD Biosciences), stained with rabbit anti-mouse iNOS (BD Biosciences), followed medchemexpress by blocking with 10% normal goat serum, and secondary staining with goat anti-rabbit (Jackson ImmunoResearch). Surface-marker-appropriate isotype and intracellular staining with secondary antibody alone served as negative control. RAW 264.7 cells cultured for 24 hours with lipopolysaccharide and IFN-γ served as positive control. Cells were acquired by flow cytometry. Prior to inclusion in cocultures, bead-isolated CD4+ or CD8+ T cells from wild-type mouse spleens were stained with 5.0 μM 5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester (CFSE; Invitrogen) for 10 minutes and quenched by washing twice in Roswell Park Memorial Institute medium 1640/10% fetal bovine serum. Isolated Tgfb1+/− or Tgfb1−/− CD11b+ cells were added at 3.0 × 105 (“300K”) or 1.

2 Lamina propria DCs are situated to pick up any material transported between or through the epithelial cells. Indeed, a more important role has been recently ascribed to the lamina propria than the Peyer’s patches in inducing immune responses in the small intestine.3 After their loading with mucosal antigens, DCs are trafficked to the MLNs to present the processed antigen to naïve T

cells. In cirrhosis, there is an increased susceptibility selleck chemicals llc to spontaneous bacterial infections, mainly those caused by Gram-negative aerobic bacteria. Most of these infections are of enteric origin and arise from the translocation of bacteria from the gut lumen to the MLNs. Indeed, an increased rate of gut bacterial translocation (GBT) has been observed both in patients and in experimental models of cirrhosis with ascites.4-7 Attempts to explain the high rate of GBT in cirrhosis include intestinal barrier damage, which leads to increased intestinal permeability and an increased enteric bacterial load.6, 8 However, the potential contribution of another component of the intestinal barrier (the immune system) to GBT and, specifically, the part played by a pivotal regulatory element of the innate and adaptive immune response (the Carfilzomib solubility dmso DC) has not been addressed so far. Damage to gut DCs could be the consequence of splanchnic hyperactivity of the sympathetic

nervous system,9, 10 liver insufficiency,11 and/or its exhaustion after chronic stimulation by enteric bacterial

overload.12-14 The present study was designed to examine in rats with ascitic cirrhosis (1) the distribution, activation state, and functions of DCs isolated from the MLNs and small intestine lamina propria and (2) possible correlations between the observed abnormalities and GBT. APC, allophycocyanin; Bact-DNA, bacterial DNA; CCL21, (C-C motif) ligand 21; CFU, colony-forming units; DCs, dendritic cells; DMEM, Dulbecco’s modified Eagle’s medium; FITC, fluorescein isothiocyanate; GBT, MCE gut bacterial translocation; HBSS, Hank’s balanced salt solution; LPS, lipopolysaccharide; mAbs, monoclonal antibodies; MFI, mean fluorescence intensity; MHC, major histocompatibility complex; MLNs, mesenteric lymph nodes; PBS, phosphate-buffered saline; PE, phycoerythrin; TNF-α, tumor necrosis factor alpha. Cirrhosis was induced in male pathogen-free Wistar rats (120-140 g initial weight) by intragastric weekly CCl4 administration (Farmitalia-Carlo Erba, Milan, Italy). Phenobarbital (Química Farmacéutica Bayer, Barcelona, Spain) was given in drinking water.15 The initial 20-μL dose of CCl4 was increased depending on the animal’s weekly change in body weight. CCl4 was continued for 2 weeks after ascites onset. Experiments were performed 7 days after the last CCl4 dose and according to the Guide for the Care and Use of Laboratory Animals (National Institutes of Health publication 86-23, revised 1985) and fulfilled local regulations.