“
“Vitamin D3 improves portal hypertension (PH) through the activation of vitamin D receptor (VDR) and calcium

sensing receptor (CaSR) in cirrhotic rats. Propranolol is a nonselective β–blocker that is recommended for the treatment of PH. The present study aims to investigate the detail systemic and hepatic mechanisms of vitamin D3 and propranolol, alone or in combination, in cirrhotic rats. Common bile duct-ligated (BDL) and thioacetamide (TAA) cirrhotic rats were treated with vehicle, propranolol (30mg.kg-1.day-1), vitamin D3 (0.5μg.100g-1.day-1, twice weekly), or propranolol+ selleck compound vitamin D3, separately. Significantly, propranolol and vitamin D3 produced a similar magnitude of reduction in portal venous pressure (PVP) in cirrhotic rats through different mechanisms: whereas propranolol decreased PVP by reducing splanchnic hyperemia and cardiac index, vitamin D3 decreased PVP by decreasing intrahepatic resistance (IHR). However, propranolol plus vitamin D3 did not further decrease PVP in cirrhotic rats. Notably, a marked decrease in hepatic VDR and CaSR expressions was noted in cirrhotic human/rat livers compared to non-cirrhotic human/rat livers. In cirrhotic rats, vitamin D3 administration decreasing IHR by inhibiting the renin-angiotensin system, hepatic oxidative stress, inflammation/fibrosis,

ANGII production, Venetoclax purchase CaSR-mediated angiotensin II (ANGII) hyper-responsiveness, ANGII-induced hepatic stellate cells contraction, and correcting hepatic endothelial dysfunction through up-regulation of hepatic VDR, CaSR and eNOS expressions. Chronic vitamin D3 treatment alone results in comparative

portal hypotensive effects as propranolol alone in cirrhotic rats with PH. Taken together, chronic vitamin D3 administration was an ideal alternative strategy to effectively improve PH without unwanted systemic side effects. “
“Chronic hepatitis B (CHB) is a major global health issue. The role of rare genetic variants in CHB has not been elucidated. We aimed to identify rare allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB patients who had no identifiable risk factors for CHB selleck and 40 controls who were healthy and hepatitis B surface antibody-positive, but had never received hepatitis B vaccination. We selected six rare variant alleles and followed up their association with disease status by Sanger sequencing in a case-control study comprising 1,728 CHB patients and 1,636 healthy controls. The latter had either not been immunized with hepatitis B vaccine or had uncertain vaccination status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with CHB, with P values of <1.0 × 10−7, 2.76 × 10−5, 5.08 × 10−5, 2.

CTGF mRNA and protein expressions were determined through RT-qPCR and western blotting in MIR375

precursor transfected HT-29 cells, respectively. Conclusion: The results showed a significant decrease of CTGF transcripts and protein expression levels in MIR375 precursor treated cells. These results suggest that miR375 could play an important role in the pathogenesis of colon cancer. Key Word(s): 1. microRNA; 2. CTGF; 3. MIR375; 4. colorectal cancer Cyclopamine datasheet Presenting Author: TZE WEI CHRISTOPHER CHIA Additional Authors: SASHA DEVI THURMURTHY, YUAN MAH YUN, KIT JUNE CHAN, STEPHEN KIN KWOK TSAO Corresponding Author: TZE WEI CHRISTOPHER CHIA Affiliations: University of Aberdeen, Monash University, University of Melbourne, Tan Tock Seng Hospital Objective: The current practice of routinely resecting AG-014699 research buy all diminutive (1–5 mm) and small (6–9 mm) colonic polyps and submitting them for histopathologic assessment may not be cost-effective. The resect-and-discard (RD) strategy has been proposed to reduce retrieval of diminutive and small polyps for histology (thought not to have advanced histologic features). In this cross-sectional study, we aim to find the prevalence of small and diminutive polyps resected that shows advanced histologic features such as high grade dysplasia (HGD) or carcinoma and determine if RD policy is feasible

in the local tertiary setting. Methods: Data were retrieved from January-December 2009 with assistance from the Pathology Department to identify all submitted colonic polyp specimens. Each patient also had their colonoscopy report(s) and detailed histology report reviewed by 2 separate colleagues for data consistency. Results: The colonic distribution of the polyps was 45.4% right-sided, 46.1% left-sided and 8.5% rectal. There were 844 diminutive polyps, 447 small polyps and 191 large

polyps with proportion of HGD being 18.7%, 37.6% and 56.5%, respectively. The percentage of HGD present in these polyps was relatively high. There were no concurrent carcinomas click here seen in all polyps. Conclusion: These findings showed that a significant proportion of diminutive polyps (18.7%) and small polyps (37.6%) harboured features of HGD, which is much higher than current literature. Based on size alone without the aid of image enhanced endoscopy (IEE), we find that RD strategy is not readily applicable in our local setting. Key Word(s): 1. colonic polyps; 2. high grade dysplasia; 3. colorectal cancer; 4. resect and discard strategy; 5. image enhanced endoscopy Presenting Author: HYUN HO CHOI Additional Authors: HYUN HO CHOI, HYUNG KEUN KIM, SUNG SOO KIM, HIUN SUK CHAE, KYUNG JIN SEO Corresponding Author: YOUNG-SEOK CHO Affiliations: Seoul St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, Uijeongbu St.

CTGF mRNA and protein expressions were determined through RT-qPCR and western blotting in MIR375

precursor transfected HT-29 cells, respectively. Conclusion: The results showed a significant decrease of CTGF transcripts and protein expression levels in MIR375 precursor treated cells. These results suggest that miR375 could play an important role in the pathogenesis of colon cancer. Key Word(s): 1. microRNA; 2. CTGF; 3. MIR375; 4. colorectal cancer Rucaparib chemical structure Presenting Author: TZE WEI CHRISTOPHER CHIA Additional Authors: SASHA DEVI THURMURTHY, YUAN MAH YUN, KIT JUNE CHAN, STEPHEN KIN KWOK TSAO Corresponding Author: TZE WEI CHRISTOPHER CHIA Affiliations: University of Aberdeen, Monash University, University of Melbourne, Tan Tock Seng Hospital Objective: The current practice of routinely resecting JAK inhibitor all diminutive (1–5 mm) and small (6–9 mm) colonic polyps and submitting them for histopathologic assessment may not be cost-effective. The resect-and-discard (RD) strategy has been proposed to reduce retrieval of diminutive and small polyps for histology (thought not to have advanced histologic features). In this cross-sectional study, we aim to find the prevalence of small and diminutive polyps resected that shows advanced histologic features such as high grade dysplasia (HGD) or carcinoma and determine if RD policy is feasible

in the local tertiary setting. Methods: Data were retrieved from January-December 2009 with assistance from the Pathology Department to identify all submitted colonic polyp specimens. Each patient also had their colonoscopy report(s) and detailed histology report reviewed by 2 separate colleagues for data consistency. Results: The colonic distribution of the polyps was 45.4% right-sided, 46.1% left-sided and 8.5% rectal. There were 844 diminutive polyps, 447 small polyps and 191 large

polyps with proportion of HGD being 18.7%, 37.6% and 56.5%, respectively. The percentage of HGD present in these polyps was relatively high. There were no concurrent carcinomas this website seen in all polyps. Conclusion: These findings showed that a significant proportion of diminutive polyps (18.7%) and small polyps (37.6%) harboured features of HGD, which is much higher than current literature. Based on size alone without the aid of image enhanced endoscopy (IEE), we find that RD strategy is not readily applicable in our local setting. Key Word(s): 1. colonic polyps; 2. high grade dysplasia; 3. colorectal cancer; 4. resect and discard strategy; 5. image enhanced endoscopy Presenting Author: HYUN HO CHOI Additional Authors: HYUN HO CHOI, HYUNG KEUN KIM, SUNG SOO KIM, HIUN SUK CHAE, KYUNG JIN SEO Corresponding Author: YOUNG-SEOK CHO Affiliations: Seoul St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, Uijeongbu St. Mary’s Hospital, Uijeongbu St.

2% were postpubertal (Tanner stage 5). The distribution of histologic features is also summarized in Table 1. Briefly, the prevalence of severe steatosis (G3) was 39.3%, severe lobular inflammation (G2-3) was 8.9%, hepatocyte ballooning (G1-2) was 23.2%, more than mild portal inflammation Akt inhibitor (G2) was 23.6%, and advanced fibrosis was 37.8%. Simple steatosis was seen in 20 cases (35.7%). Features of SH were noted in the remaining 36 cases (64.3%). Histology was suspicious for SH in 26 cases, including nine cases (35%) with the pediatric pattern and 17 cases (65%) with the adult pattern. Definite SH was diagnosed in 10 cases, two of which (20%) demonstrated the pediatric pattern; the eight remaining cases

of definite SH (80%) exhibited the adult pattern. Thus, simple steatosis was present in a minority of our cohort. The larger subgroup had features of SH, with roughly Torin 1 one-third of those individuals demonstrating pediatric pattern SH and the remaining two-thirds exhibiting the more classical, adult SH pattern. When comparing the severity of the histologic features between boys and girls, we noted

that steatosis grade and fibrosis stage were significantly higher in boys (Wilcoxon rank sum test: P = 0.037 for steatosis and P = 0.02 for fibrosis). Regardless of gender, age was found to correlate with portal inflammation (ANOVA: P = 0.0005); patients with G1-2 portal inflammation were younger than patients with no portal inflammation (G0) (Tukey test: P < 0.05). Although univariate analyses did not show significant associations between pubertal stages and histologic features, there was a trend toward higher grades of portal inflammation in earlier pubertal stages (Wilcoxon rank sum test, P = 0.08). The median SHh grade was 2.5 [2, 4] in the available cohort (n = 20). Univariate analysis showed that

SHh grade was significantly associated with fibrosis stage (P = 0.0008, Fig. 1A-D) and steatosis grade (P = 0.022, Fig. 1D). SHh grades were higher in cases with advanced fibrosis (S3-4) compared to cases with no fibrosis (S0, P = 0.0007) and cases with mild to moderate fibrosis (S1-2, P = 0.009) (Fig. 1A-D). SHh grades were higher in cases with moderate steatosis selleck inhibitor (G2) than in cases with no to mild steatosis (G0-1, P = 0.0091, Fig. 1D). In the ordinal logistic regression model including steatosis grade, fibrosis stage, and gender, the association between SHh grade and fibrosis stage remained significant (P = 0.002), although steatosis grade did not (P = 0.241). There were no significant associations between SHh expression and grades of lobular inflammation, ballooned hepatocytes, or portal inflammation. Liver progenitor cells are known to be Hh-responsive. Therefore, we stained liver sections for the progenitor cell marker, keratin 7 (K7), and Gli2 (a marker of Hh-responsiveness). The median numbers of Gli2+ and K7+ cells per HPF were 227 [121, 380] and 17 [14, 25], respectively (n = 26 for both stains).

Second, most studies validated APO866 their results in an internal validation cohort from the same population with the training cohort. We validated our results in an external validation cohort that included chronic HBV carriers from Shanghai, Fujian Province, and Jiangsu Province, China. The geographic diversity of the training and validation cohort helped us to

find out models of stable accuracy irrespective of where the patient comes from. We notice that the diagnostic indices of the S index in the training cohort (Table 4) are slightly lower than those in the validation cohort (Table 5). These might be due to higher S1-2 prevalence in the training cohort, which is more difficult for a noninvasive predictive model to give a correct classification. Third,

our predictive model was based only on routine laboratory markers. GGT, PLT and ALB are all routine tests readily available to most clinicians managing patients with chronic GSK3 inhibitor HBV infection, so no additional tests are needed. The diagnostic accuracy of models consisting of simple routine tests was compared with models introducing special tests such as HA and A2M. To our knowledge, such validation and comparison were not carried out in chronic HBV carriers before. We noticed that the SLFG model and Hepascore performed better in identifying significant fibrosis than the Forns score and APRI, but the superiority was not significant in identifying check details advanced fibrosis or cirrhosis. The result was similar to a validation study in CHC patients,10 indicating that such special tests might improve the sensitivity of a diagnostic model in predicting early fibrosis. But including tests unavailable in daily practice makes standardization, validation and routine bedside use difficult. Fourth, the S index is easily calculated. Most of the previous models, except the APRI, involved complex formulas, which require a logarithmic calculator for calculations. The simplicity of the S index and APRI allows them to be determined in the clinic or bedside easily. But the APRI

was conducted in CHC patients and one of its two parameters is AST, which did not show a significant correlation with liver fibrosis staging of CHB patients in our study. This may explain the low AUROC of APRI compared with other models. The S index consisted of the most significant predictors of fibrosis among routine markers (GGT, PLT and ALB) and was simplified from three complicated regression functions. Despite a slightly lower AUROC than the respective function in each histological endpoint, the S index allows both significant fibrosis and cirrhosis to be identified using one simple formula. There are some limitations in our study. An incorrigible defect in studies of diagnostic models is the questionable gold standard we have to use. Liver biopsy is not a perfect gold standard for fibrosis evaluation due to sampling error and observer variability.

Second, most studies validated selleck their results in an internal validation cohort from the same population with the training cohort. We validated our results in an external validation cohort that included chronic HBV carriers from Shanghai, Fujian Province, and Jiangsu Province, China. The geographic diversity of the training and validation cohort helped us to

find out models of stable accuracy irrespective of where the patient comes from. We notice that the diagnostic indices of the S index in the training cohort (Table 4) are slightly lower than those in the validation cohort (Table 5). These might be due to higher S1-2 prevalence in the training cohort, which is more difficult for a noninvasive predictive model to give a correct classification. Third,

our predictive model was based only on routine laboratory markers. GGT, PLT and ALB are all routine tests readily available to most clinicians managing patients with chronic buy Vemurafenib HBV infection, so no additional tests are needed. The diagnostic accuracy of models consisting of simple routine tests was compared with models introducing special tests such as HA and A2M. To our knowledge, such validation and comparison were not carried out in chronic HBV carriers before. We noticed that the SLFG model and Hepascore performed better in identifying significant fibrosis than the Forns score and APRI, but the superiority was not significant in identifying selleckchem advanced fibrosis or cirrhosis. The result was similar to a validation study in CHC patients,10 indicating that such special tests might improve the sensitivity of a diagnostic model in predicting early fibrosis. But including tests unavailable in daily practice makes standardization, validation and routine bedside use difficult. Fourth, the S index is easily calculated. Most of the previous models, except the APRI, involved complex formulas, which require a logarithmic calculator for calculations. The simplicity of the S index and APRI allows them to be determined in the clinic or bedside easily. But the APRI

was conducted in CHC patients and one of its two parameters is AST, which did not show a significant correlation with liver fibrosis staging of CHB patients in our study. This may explain the low AUROC of APRI compared with other models. The S index consisted of the most significant predictors of fibrosis among routine markers (GGT, PLT and ALB) and was simplified from three complicated regression functions. Despite a slightly lower AUROC than the respective function in each histological endpoint, the S index allows both significant fibrosis and cirrhosis to be identified using one simple formula. There are some limitations in our study. An incorrigible defect in studies of diagnostic models is the questionable gold standard we have to use. Liver biopsy is not a perfect gold standard for fibrosis evaluation due to sampling error and observer variability.

Materials and Methods: Five implants of Astra Tech, Bego, Camlog, Friadent, Nobel Biocare, and Straumann were separately embedded in stainless steel tubes using polyurethane, for a total of 30 specimens. Specimens were statically loaded under an angle of 30° with respect to the implant axis in a universal testing machine using a test setup according to ISO 14801. Failure was indicated by a load drop of 100 N in force. Load–displacement curves Metabolism inhibitor were analyzed, and maximum force and force at which permanent deformation occurred were recorded. Statistical

analysis was performed using one-way ANOVA with the level of significance set at 0.05. Results: Statistical analysis revealed that the type of implant–abutment connection design has a significant influence on load bearing capacity (p < 0.001). The mean maximum forces ranged between 606 N (Straumann) and 1129 N (Bego); the forces where plastic deformation set in ranged between 368 N (Friadent) and 955 N (Bego). Failure modes differed between the various implant–abutment connection types tested. Conclusions:

Implant–abutment connection design has a significant influence on load bearing capacity and failure mode of implants; however, all implant–abutment connection designs tested would be expected to withstand clinically relevant forces. “
“Purpose: To assess Lumacaftor the effect of three implant abutment angulations and two types of fibers selleckchem on the fracture resistance of overlaying Ceramage single crowns. Materials and Methods: Three groups, coded A to C, with different implant abutment angulations (group A/0°, group B/15°, and group C/30° angulation) were restored with 45 overlay composite restorations; 15 Ceramage crowns for each angulation. Groups A, B, and C were further subdivided into three subgroups (n = 5) coded: 1, crowns without fiber reinforcement; 2, crowns with Connect polyethylene reinforcement; and 3, crowns with Interlig glass reinforcement. All crowns were constructed by one technician using the Ceramage System. The definitive restorations (before cementation) were stored in distilled water at mouth temperature (37°C) for 24 hours prior to testing. Before

testing, the crowns were cemented using Temp Bond. The compressive load required to break each crown and the mode of failure were recorded. The speed of testing was 1 mm/min. The results were statistically analyzed by two-way ANOVA (p < 0.05). The tested crowns were examined using a stereomicroscope at 40×, and selected crowns (five randomly selected from each group) were further examined by scanning electron microscopy (SEM) to reveal the composite–fiber interface. Results: Fracture resistance of single crowns was not affected (p > 0.05) by the different abutment angulations chosen (0°, 15°, 30°) or fiber reinforcement (Connect and Interlig fibers). Crowns in group A exhibited average loads to fracture (N) of A1 = 843.57 ± 168.20, A2 = 1389.20 ± 193.

Conclusion: The symptom burden in PBC, which is unrelated to disease severity or ursodeoxycholic acid response, is significant and complex and results in significant quality of life deficit. The complexity of symptom burden, and its lack of relation to disease severity and treatment response, suggest that specific approaches to symptom

management are warranted that address both symptom biology and social impact. (Hepatology 2013;58:-) Primary biliary cirrhosis (PBC), the commonest autoimmune liver disease, affects the lives of patients in numerous ways, including through progression to cirrhosis and endstage liver disease with complications of liver failure, portal hypertension, and hepatocellular carcinoma. Symptoms, which include Decitabine chemical structure the archetypal cholestatic pruritus, are reported by many patients. Recent advances in primary therapy with ursodeoxycholic acid (UDCA) and transplantation

HIF-1 cancer have reduced the risk to life from PBC substantially,4, 5 and approaches to primary and second-line disease processes are outlined in treatment guidelines.6, 7 Patient reports suggest, however, that the clinical impact of PBC is more complex than that of a slowly progressive chronic liver disease complicated in some by treatable pruritus.8 There is significant impairment of quality of life (QOL) in a substantial proportion.9, 10 The factors underpinning this QOL impairment appear to be multiple and complex, but include fatigue, cognitive symptoms, symptoms of social and emotional dysfunction, sleep disturbance, and depression.11 There is also significant debate as to whether these symptoms are a manifestation of the disease process itself, associated processes, or a reflection of the age, gender, and comorbidity of the selected PBC patient populations studied.12, 13 The uncertainty about the nature of the complex symptoms of PBC

is compounded by the fact that studies addressing these issues have often been performed in small, selected study populations and in centers with a particular interest in such symptoms. The aim of the current study was to use the unique resource of the UK-PBC Patient Cohort, the largest in the world, find more which has recruited participants from every clinical center in the UK to address the issue of QOL impairment in PBC and those factors underpinning it. A cross-sectional cohort study of patients recruited to the UK-PBC Patient Cohort, which was established initially to undertake a UK PBC genome-wide association study (GWAS).14, 15 Patients were phenotyped with regard to symptoms and QOL using established and validated measures.16 In order to compare the symptom values for PBC-related symptoms quantified using the PBC-40, a version of this measure suitable for completion by control subjects was developed and validated as part of the study protocol.

Conclusion: The symptom burden in PBC, which is unrelated to disease severity or ursodeoxycholic acid response, is significant and complex and results in significant quality of life deficit. The complexity of symptom burden, and its lack of relation to disease severity and treatment response, suggest that specific approaches to symptom

management are warranted that address both symptom biology and social impact. (Hepatology 2013;58:-) Primary biliary cirrhosis (PBC), the commonest autoimmune liver disease, affects the lives of patients in numerous ways, including through progression to cirrhosis and endstage liver disease with complications of liver failure, portal hypertension, and hepatocellular carcinoma. Symptoms, which include C59 wnt cell line the archetypal cholestatic pruritus, are reported by many patients. Recent advances in primary therapy with ursodeoxycholic acid (UDCA) and transplantation

MAPK inhibitor have reduced the risk to life from PBC substantially,4, 5 and approaches to primary and second-line disease processes are outlined in treatment guidelines.6, 7 Patient reports suggest, however, that the clinical impact of PBC is more complex than that of a slowly progressive chronic liver disease complicated in some by treatable pruritus.8 There is significant impairment of quality of life (QOL) in a substantial proportion.9, 10 The factors underpinning this QOL impairment appear to be multiple and complex, but include fatigue, cognitive symptoms, symptoms of social and emotional dysfunction, sleep disturbance, and depression.11 There is also significant debate as to whether these symptoms are a manifestation of the disease process itself, associated processes, or a reflection of the age, gender, and comorbidity of the selected PBC patient populations studied.12, 13 The uncertainty about the nature of the complex symptoms of PBC

is compounded by the fact that studies addressing these issues have often been performed in small, selected study populations and in centers with a particular interest in such symptoms. The aim of the current study was to use the unique resource of the UK-PBC Patient Cohort, the largest in the world, check details which has recruited participants from every clinical center in the UK to address the issue of QOL impairment in PBC and those factors underpinning it. A cross-sectional cohort study of patients recruited to the UK-PBC Patient Cohort, which was established initially to undertake a UK PBC genome-wide association study (GWAS).14, 15 Patients were phenotyped with regard to symptoms and QOL using established and validated measures.16 In order to compare the symptom values for PBC-related symptoms quantified using the PBC-40, a version of this measure suitable for completion by control subjects was developed and validated as part of the study protocol.

Conclusion: The symptom burden in PBC, which is unrelated to disease severity or ursodeoxycholic acid response, is significant and complex and results in significant quality of life deficit. The complexity of symptom burden, and its lack of relation to disease severity and treatment response, suggest that specific approaches to symptom

management are warranted that address both symptom biology and social impact. (Hepatology 2013;58:-) Primary biliary cirrhosis (PBC), the commonest autoimmune liver disease, affects the lives of patients in numerous ways, including through progression to cirrhosis and endstage liver disease with complications of liver failure, portal hypertension, and hepatocellular carcinoma. Symptoms, which include http://www.selleckchem.com/products/Everolimus(RAD001).html the archetypal cholestatic pruritus, are reported by many patients. Recent advances in primary therapy with ursodeoxycholic acid (UDCA) and transplantation

PXD101 have reduced the risk to life from PBC substantially,4, 5 and approaches to primary and second-line disease processes are outlined in treatment guidelines.6, 7 Patient reports suggest, however, that the clinical impact of PBC is more complex than that of a slowly progressive chronic liver disease complicated in some by treatable pruritus.8 There is significant impairment of quality of life (QOL) in a substantial proportion.9, 10 The factors underpinning this QOL impairment appear to be multiple and complex, but include fatigue, cognitive symptoms, symptoms of social and emotional dysfunction, sleep disturbance, and depression.11 There is also significant debate as to whether these symptoms are a manifestation of the disease process itself, associated processes, or a reflection of the age, gender, and comorbidity of the selected PBC patient populations studied.12, 13 The uncertainty about the nature of the complex symptoms of PBC

is compounded by the fact that studies addressing these issues have often been performed in small, selected study populations and in centers with a particular interest in such symptoms. The aim of the current study was to use the unique resource of the UK-PBC Patient Cohort, the largest in the world, selleck chemicals llc which has recruited participants from every clinical center in the UK to address the issue of QOL impairment in PBC and those factors underpinning it. A cross-sectional cohort study of patients recruited to the UK-PBC Patient Cohort, which was established initially to undertake a UK PBC genome-wide association study (GWAS).14, 15 Patients were phenotyped with regard to symptoms and QOL using established and validated measures.16 In order to compare the symptom values for PBC-related symptoms quantified using the PBC-40, a version of this measure suitable for completion by control subjects was developed and validated as part of the study protocol.