Nakayama Y, Inoue H, Hamada Y, et?al. Castiella A. Liver fat and iron at in-phase and oppossed-phase MR imaging. 2001;9: 961C4. [PubMed] P0009?NON-ALCOHOLIC FATTY LIVER DISEASE IS ASSOCIATED WITH CORONARY ARTERY CALCIFICATION IN ASYMPTOMATIC INDIVIDUALS K.M. Sohn1, Y. Jeon2 (US-FLI)) allows the grading steatosis severity using ultrasound (US) and correlates with its histological features when assessed with liver biopsy. Aims and Methods: We aimed to assess the correlation of US-FLI with the controlled attenuation parameter (CAP) in patients with non-alcoholic fatty liver disease (NAFLD). Initially, inter-observer agreement for the score was assessed between 3 physicians using a sample of 31 patients. Later, 96 patients with NAFLD were included and several anthropometric, clinical and analytical parameters were assessed and US and transient elastography was performed. Results: Physicians showed an excellent absolute agreement regarding the total score, with an average Interclass Correlation Coefficient of 0.972 (95% CI 0.949C0.986). Patients had a median US-FLI of 6??3 points and a mean CAP of 311??48 dB/m. Comparing US-FLI with CAP, and considering the previously defined cutoff for steatosis >S1 (268dB/m) and >S2 (280dB/m), we verified that US-FLI had a good discriminative capacity for both grades, with areas under the curve (AUC) of 0.88 (p<0.001) and 0.90 (p<0.001), respectively. We also verified that a US-FLI3 points had a negative predictive value of 100% for steatosis >S2 and that values of US-FLI 6 points had a positive predictive value (PPV) of 94.0% for steatosis >S2. When comparing the clinical score (FLI) for the same CAP cutoffs, it showed a weak discriminative capacity for both grades with AUC of 0.65 (p?=?0.030) and 0.66 (p?=?0.017). When comparing AUC for US-FLI and FLI scores, we verified that these were significantly diferente for both cutoffs (p<0.001). Conclusion: US-FLI has an excellent reproducibility and a good discriminative capacity for the different steatosis grades. Scores 3 points allow us to exclude significant steatosis and scores 6 points have a PPV of 94.0% for steatosis >S2. US-FLI was significantly superior to the clinical score FLI in the discrimination between steatosis grades. Disclosure: Nothing to disclose P0017?IDENTIFYING THE NEXT TREATMENT FOR POLYCYSTIC LIVER DISEASE USING A DRUG SCREENING LIBRARY L.F.M. van de Laarschot, A. van Spijk, K. van der Ende, R.H.M. Morsche, J.P.H. Drenth in the majority of patients. Pharmaceutical treatment of polycystic liver disease is aimed at curtailing cyst volume and limited to the use of somatostatin analogues. Disadvantages of somatostatin analogues are the moderate efficacy, common frequency of side effects, and high costs. There is an urgent need for a safe treatment that decreases cyst proliferation, and hence cyst volume. The aim of our study is to design a diagnostic pipeline that is able to identify pharmaceutical compounds that target pathways related to hepatic cystogenesis: cell proliferation and fluid secretion caused by decreased calcium and subsequently increased cAMP levels.1 Aims and Methods: The Selleckchem FDA-approved drug screening library contains 1442 compounds with a wide spectrum of therapeutic targets. knockout H69 cholangiocytes were used as model for polycystic liver disease. Cells were incubated with compounds at 10 microM concentration for 24 hours in triplicate. Proliferation was measured as absorbance after addition of WST-1 proliferation reagent (Sigma-Aldrich) for 3 hours. Compounds changing proliferation >20% compared to DMSO controls were selected for incubation in wildtype H69 cholangiocytes. Compounds showing >50% of proliferation compared to control and >20% absolute difference between knockout and wildtype H69 cells were identified as most promising. Compounds were further tested for their effect on cyclic AMP levels after 24 hours incubation using ELISA (Cayman). Results: 1278 compounds showed proliferation rates of 80C120% relative to control in knockout H69 cholangiocytes. 26 compounds increased proliferation >120% of control and 138 compounds decreased proliferation below 80% of control proliferation rate. These 164 compounds were further tested in wildtype H69 cholangiocytes, while octreotide was added as reference. 18 compounds showed proliferation >50% of control proliferation rate and >20%.Urano7, N. IS ASSOCIATED WITH CORONARY ARTERY IU1-47 CALCIFICATION IN ASYMPTOMATIC INDIVIDUALS K.M. Sohn1, Y. Jeon2 (US-FLI)) allows the grading steatosis severity using ultrasound (US) and correlates with its histological features when assessed with liver biopsy. Aims and Methods: We aimed to assess the correlation of US-FLI with the controlled attenuation parameter (CAP) in patients with non-alcoholic fatty liver disease (NAFLD). Initially, inter-observer agreement for the score was assessed between 3 physicians using a sample of 31 patients. Later, 96 patients with NAFLD were included and several anthropometric, clinical and analytical parameters were assessed and US and transient elastography was performed. Results: Physicians showed an excellent absolute agreement regarding the total score, with an average IU1-47 Interclass Correlation Coefficient of 0.972 (95% CI 0.949C0.986). Patients had a median US-FLI of 6??3 points and a mean CAP of 311??48 dB/m. Comparing US-FLI with CAP, and considering the previously defined cutoff for steatosis >S1 (268dB/m) and >S2 (280dB/m), we verified that US-FLI had a good discriminative capacity for both grades, with areas under the curve (AUC) of 0.88 (p<0.001) and 0.90 (p<0.001), respectively. We also verified that a US-FLI3 points had a negative predictive value of 100% for steatosis >S2 and that values of US-FLI 6 points had a positive predictive value (PPV) of 94.0% for steatosis >S2. When comparing the clinical score (FLI) for the same CAP cutoffs, it showed a weak discriminative capacity for both grades with AUC of 0.65 (p?=?0.030) and 0.66 (p?=?0.017). When comparing AUC for US-FLI and FLI scores, we verified that these were significantly diferente for both cutoffs (p<0.001). Conclusion: US-FLI has an excellent reproducibility and a good discriminative capacity for the different steatosis grades. Scores 3 points allow us to exclude significant steatosis and scores 6 points have a PPV of 94.0% for steatosis >S2. US-FLI was significantly superior to the clinical score FLI in the discrimination between steatosis grades. Disclosure: Nothing to disclose P0017?IDENTIFYING THE NEXT TREATMENT FOR POLYCYSTIC LIVER DISEASE USING A DRUG SCREENING LIBRARY L.F.M. van de Laarschot, A. van Spijk, K. van der Ende, R.H.M. Morsche, J.P.H. Drenth in the majority of patients. Pharmaceutical treatment of polycystic liver disease is aimed at curtailing cyst volume and limited to the use of somatostatin analogues. Disadvantages of somatostatin analogues are the moderate efficacy, common frequency of side effects, and high costs. There is an urgent need for a safe treatment that decreases cyst proliferation, and hence cyst volume. The aim of our study is to design a diagnostic pipeline that is able to identify pharmaceutical compounds that target pathways related to hepatic cystogenesis: cell proliferation and fluid secretion caused by decreased calcium and subsequently increased cAMP levels.1 Aims and Methods: The Selleckchem FDA-approved drug screening library contains 1442 compounds with a wide spectrum of therapeutic targets. knockout H69 cholangiocytes were used as model for polycystic liver disease. Cells were incubated with compounds at 10 microM concentration for 24 hours in triplicate. Proliferation was measured as absorbance after addition of WST-1 proliferation reagent (Sigma-Aldrich) for 3 hours. Compounds changing proliferation >20% compared to DMSO controls were selected for incubation in wildtype H69 cholangiocytes. Compounds showing >50% of proliferation compared to control and >20% absolute difference between knockout and wildtype H69 cells were identified as most promising. Compounds were further tested for their effect on cyclic AMP levels after 24 hours incubation using ELISA (Cayman). Results: 1278 compounds showed proliferation rates of 80C120% relative to control in knockout H69 cholangiocytes. 26 compounds improved proliferation >120% of control and 138 compounds decreased proliferation below 80% of control proliferation rate. These 164 compounds were further tested in wildtype H69 cholangiocytes, while octreotide was added as research. 18 compounds showed proliferation >50% of control proliferation rate and >20% complete difference between knockout and wildtype H69 cholangiocytes. These compounds were then screened for his or her effect on cyclic AMP levels. Of these, 3 compounds reduce proliferation more in knockout cells than wildtype cells and decreased cyclic AMP levels. These included 2 anti-cancer medicines and 1 antimicrobial agent. Octreotide showed no difference in proliferation between incubated cells.In fact, many guidelines recommend alternative regimens such as sequential and concomitant therapy. Aims and Methods: We compared the effectiveness, adverse events, and drug compliance of standard triple, sequential, and concomitant therapy for eradication. quantification of hepatic iron concentration. 2004; 230: 479C84. [PubMed] 4. Alstiza JM, Castiella A. Liver excess fat and iron at in-phase and oppossed-phase MR imaging. 2001;9: 961C4. [PubMed] P0009?NON-ALCOHOLIC FATTY LIVER DISEASE IS ASSOCIATED WITH CORONARY ARTERY CALCIFICATION IN ASYMPTOMATIC INDIVIDUALS K.M. Sohn1, Y. Jeon2 (US-FLI)) allows the grading steatosis severity using ultrasound (US) and correlates with its histological features when assessed with liver biopsy. Seeks and Methods: We targeted to assess the correlation of US-FLI with the controlled attenuation parameter (CAP) in individuals with non-alcoholic fatty liver disease (NAFLD). In the beginning, inter-observer agreement for the score was assessed between 3 physicians using a sample of 31 individuals. Later, 96 individuals with NAFLD were included and several Mouse monoclonal to CD152 anthropometric, medical and analytical guidelines were assessed and US and transient elastography was performed. Results: Physicians showed an excellent complete agreement regarding the total score, with an average Interclass Correlation Coefficient of 0.972 (95% CI 0.949C0.986). Individuals experienced a median US-FLI of 6??3 points and a mean CAP of 311??48 dB/m. Comparing US-FLI with CAP, and considering the previously defined cutoff for steatosis >S1 (268dB/m) and >S2 (280dB/m), we verified that US-FLI experienced a good discriminative capacity for both marks, with areas under the curve (AUC) of 0.88 (p<0.001) and 0.90 (p<0.001), respectively. We also verified that a US-FLI3 points had a negative predictive value of 100% for steatosis >S2 and that ideals of US-FLI 6 points experienced a positive predictive value (PPV) of 94.0% for steatosis >S2. When comparing the clinical score (FLI) for the same CAP cutoffs, it showed a poor discriminative capacity for both marks with AUC of 0.65 (p?=?0.030) and 0.66 (p?=?0.017). When comparing AUC for US-FLI and FLI scores, we verified that these were significantly diferente for both cutoffs (p<0.001). Summary: US-FLI has an superb reproducibility and a good discriminative capacity for the different steatosis grades. Scores 3 points allow us to exclude significant steatosis and scores 6 points possess a PPV of 94.0% for steatosis >S2. US-FLI was significantly superior to the clinical score FLI in the discrimination between steatosis marks. Disclosure: Nothing to disclose P0017?IDENTIFYING THE NEXT TREATMENT FOR POLYCYSTIC LIVER DISEASE USING A DRUG SCREENING LIBRARY L.F.M. vehicle de Laarschot, A. vehicle Spijk, K. vehicle der Ende, R.H.M. Morsche, J.P.H. Drenth in the majority of individuals. Pharmaceutical treatment of polycystic liver disease is aimed at curtailing cyst volume and limited by the usage of somatostatin analogues. Drawbacks of somatostatin analogues will be the moderate efficiency, common regularity of unwanted effects, and high costs. There can be an urgent dependence on a secure treatment that reduces cyst proliferation, and therefore cyst quantity. The purpose of our research is to create IU1-47 a diagnostic pipeline that’s able to recognize pharmaceutical substances that focus on pathways linked to hepatic cystogenesis: cell proliferation and liquid secretion due to decreased calcium mineral and subsequently elevated cAMP amounts.1 Goals and Strategies: The Selleckchem FDA-approved medication screening collection contains 1442 substances with a broad spectral range of therapeutic goals. knockout H69 cholangiocytes had been utilized as model for polycystic liver organ disease. Cells had been incubated with substances at 10 microM focus every day and night in triplicate. Proliferation was assessed as absorbance after addition of WST-1 proliferation reagent (Sigma-Aldrich) for 3 hours. Substances changing proliferation >20% in comparison to DMSO handles had been chosen for incubation in wildtype H69 cholangiocytes. Substances displaying >50% of proliferation in comparison to control and >20% total difference between knockout and wildtype H69 cells had been defined as most guaranteeing. Compounds had been further tested because of their influence on cyclic AMP amounts after a day incubation using ELISA (Cayman). Outcomes: 1278 substances showed proliferation prices of 80C120% in accordance with control in knockout H69 cholangiocytes. 26 substances elevated proliferation >120% of control.Alves1, D. J, Castiella A, et?al. MR quantification of hepatic iron focus. 2004; 230: 479C84. [PubMed] 4. Alstiza JM, Castiella A. Liver organ fats and iron at in-phase and oppossed-phase MR imaging. 2001;9: 961C4. [PubMed] P0009?NON-ALCOHOLIC FATTY Liver organ DISEASE IS CONNECTED WITH CORONARY ARTERY CALCIFICATION IN ASYMPTOMATIC People K.M. Sohn1, Y. Jeon2 (US-FLI)) enables the grading steatosis intensity using ultrasound (US) and correlates using its histological features when evaluated with liver organ biopsy. Goals and Strategies: We directed to measure the relationship of US-FLI using the managed attenuation parameter (Cover) in sufferers with nonalcoholic fatty liver organ disease (NAFLD). Primarily, inter-observer contract for the rating was evaluated between 3 doctors using a test of 31 sufferers. Later, 96 sufferers with NAFLD had been included and many anthropometric, scientific and analytical variables had IU1-47 been evaluated and US and transient elastography was performed. Outcomes: Physicians demonstrated an excellent total agreement regarding the full total rating, with the average Interclass Relationship Coefficient of 0.972 (95% CI 0.949C0.986). Sufferers got a median US-FLI of 6??3 factors and a mean CAP of 311??48 dB/m. Evaluating US-FLI with Cover, and taking into consideration the previously described cutoff for steatosis >S1 (268dB/m) and >S2 (280dB/m), we confirmed that US-FLI got an excellent discriminative convenience of both levels, with areas beneath the curve (AUC) of 0.88 (p<0.001) and 0.90 (p<0.001), respectively. We also confirmed a US-FLI3 factors had a poor predictive worth of 100% for steatosis >S2 which ideals of US-FLI 6 factors got a positive predictive worth (PPV) of 94.0% for steatosis >S2. When you compare the clinical rating (FLI) for the same Cover cutoffs, it demonstrated a fragile discriminative convenience of both marks with AUC of 0.65 (p?=?0.030) and 0.66 (p?=?0.017). When you compare AUC for US-FLI and FLI ratings, we confirmed that these had been considerably diferente for both cutoffs (p<0.001). Summary: US-FLI comes with an superb reproducibility and an excellent discriminative convenience of the various steatosis grades. Ratings 3 factors enable us to exclude significant steatosis and ratings 6 factors possess a PPV of 94.0% for steatosis >S2. US-FLI was considerably more advanced than the clinical rating FLI in the discrimination between steatosis marks. Disclosure: Nothing to reveal P0017?IDENTIFYING ANOTHER TREATMENT FOR POLYCYSTIC Liver organ DISEASE UTILIZING A Medication SCREENING Collection L.F.M. vehicle de Laarschot, A. vehicle Spijk, K. vehicle der Ende, R.H.M. Morsche, J.P.H. Drenth in nearly all individuals. Pharmaceutical treatment of polycystic liver organ disease is targeted at curtailing cyst quantity and limited by the usage of somatostatin analogues. Drawbacks of somatostatin analogues will be the moderate effectiveness, common rate of recurrence of unwanted effects, and high costs. There can be an urgent dependence on a secure treatment that reduces cyst proliferation, and therefore cyst quantity. The purpose of our research is to create a diagnostic pipeline that’s able to determine pharmaceutical substances that focus on pathways linked to hepatic cystogenesis: cell proliferation and liquid secretion due to decreased calcium mineral and subsequently improved cAMP amounts.1 Seeks and Strategies: The Selleckchem FDA-approved medication screening collection contains 1442 substances with a broad spectral range of therapeutic focuses on. knockout H69 cholangiocytes had been utilized as model for polycystic liver organ disease. Cells had been incubated with substances at 10 microM focus every day and night in triplicate. Proliferation was assessed as absorbance after addition of WST-1 proliferation reagent (Sigma-Aldrich) for 3 hours. Substances changing proliferation >20% in comparison to DMSO settings had been chosen for incubation in wildtype H69 cholangiocytes. Substances displaying >50% of proliferation in comparison to control and >20% total difference between knockout and wildtype H69 cells had been defined as most guaranteeing. Compounds had been further tested for his or her influence on cyclic AMP amounts after a day incubation using ELISA (Cayman). Outcomes: 1278 substances showed proliferation prices of 80C120% in accordance with control in knockout H69 cholangiocytes. 26 substances improved proliferation >120% of control and 138 substances reduced proliferation below 80% of control proliferation price. These 164 substances had been further examined in wildtype H69 cholangiocytes, while octreotide was added as research. 18 compounds demonstrated proliferation >50% of control proliferation price and >20% total difference between knockout and wildtype H69 cholangiocytes. These substances had been then screened for his or her influence on cyclic AMP amounts. Of the, 3 compounds decrease proliferation even more in knockout cells than wildtype cells and reduced cyclic AMP amounts. These included 2 anti-cancer medicines and 1 antimicrobial agent. Octreotide demonstrated no difference in proliferation between incubated cells and.Franceschi6, F. Alstiza JM, Castiella A. Liver organ extra fat and iron at in-phase and oppossed-phase MR imaging. 2001;9: 961C4. [PubMed] P0009?NON-ALCOHOLIC FATTY Liver organ DISEASE IS CONNECTED WITH CORONARY ARTERY CALCIFICATION IN ASYMPTOMATIC People K.M. Sohn1, Y. Jeon2 (US-FLI)) enables the grading steatosis intensity using ultrasound (US) and correlates using its histological features when evaluated with liver organ biopsy. Seeks and Strategies: We targeted to measure the relationship of US-FLI using the managed attenuation parameter (Cover) in sufferers with nonalcoholic fatty liver organ disease (NAFLD). Originally, inter-observer contract for the rating was evaluated between 3 doctors using a test of 31 sufferers. Later, 96 sufferers with NAFLD had been included and many anthropometric, scientific and analytical variables had been evaluated and US and transient elastography was performed. Outcomes: Physicians demonstrated an excellent overall agreement regarding the full total rating, with the average Interclass Relationship Coefficient of 0.972 (95% CI 0.949C0.986). Sufferers acquired a median US-FLI of 6??3 factors and a mean CAP of 311??48 dB/m. Evaluating US-FLI with Cover, and taking into consideration the previously described cutoff for steatosis >S1 (268dB/m) and >S2 (280dB/m), we confirmed that US-FLI acquired an excellent discriminative convenience of both levels, with areas beneath the curve (AUC) of 0.88 (p<0.001) and 0.90 (p<0.001), respectively. We also confirmed a US-FLI3 factors had a poor predictive worth of 100% for steatosis >S2 which beliefs of US-FLI 6 factors acquired a positive predictive worth (PPV) of 94.0% for steatosis >S2. When you compare the clinical rating (FLI) for the same Cover cutoffs, it demonstrated a vulnerable discriminative convenience of both levels with AUC of 0.65 (p?=?0.030) and 0.66 (p?=?0.017). When you compare AUC for US-FLI and FLI ratings, we confirmed that these had been considerably diferente for both cutoffs (p<0.001). Bottom line: US-FLI comes with an exceptional reproducibility and an excellent discriminative convenience of the various steatosis grades. Ratings 3 factors enable us to exclude significant steatosis and ratings 6 factors have got a PPV of 94.0% for steatosis >S2. US-FLI was considerably more advanced than the clinical rating FLI in the discrimination between steatosis levels. Disclosure: Nothing to reveal P0017?IDENTIFYING ANOTHER TREATMENT FOR POLYCYSTIC Liver organ DISEASE UTILIZING A Medication SCREENING Collection L.F.M. truck de Laarschot, A. truck Spijk, K. truck der Ende, R.H.M. Morsche, J.P.H. Drenth in nearly all sufferers. Pharmaceutical treatment of polycystic liver organ disease is targeted at curtailing cyst quantity and limited by the usage of somatostatin analogues. Drawbacks of somatostatin analogues will be the moderate efficiency, common regularity of unwanted effects, and high costs. There can be an urgent dependence on a secure treatment that reduces cyst proliferation, and therefore cyst quantity. The purpose of our research is to create a diagnostic pipeline that’s able to recognize pharmaceutical substances that focus on pathways linked to hepatic cystogenesis: cell proliferation and liquid secretion due to decreased calcium mineral and subsequently elevated cAMP amounts.1 Goals and Strategies: The Selleckchem FDA-approved medication screening collection contains 1442 substances with a broad spectral range of therapeutic goals. knockout H69 cholangiocytes had been utilized as model for polycystic liver organ disease. Cells had been incubated with substances at 10 microM focus every day and night in triplicate. Proliferation was assessed as absorbance after addition of WST-1 proliferation reagent (Sigma-Aldrich) for 3 hours. Substances changing proliferation >20% in comparison to DMSO handles had been chosen for incubation in wildtype H69 cholangiocytes. Substances displaying >50% of proliferation in comparison to control and >20% overall difference between knockout and wildtype H69 cells had been defined as most appealing. Compounds had been further tested because of their influence on cyclic AMP amounts after a day incubation using ELISA (Cayman). Outcomes: 1278 substances showed proliferation prices of 80C120% in accordance with control in knockout H69 cholangiocytes. 26 substances elevated proliferation >120% of control and 138 substances reduced proliferation below 80% of control proliferation price. These 164 substances had been further examined in wildtype H69 cholangiocytes, while octreotide was added as guide. 18 compounds demonstrated proliferation >50% of control proliferation price and >20% overall difference between knockout and wildtype H69 cholangiocytes. These substances had been then screened because of their influence on cyclic AMP amounts. Of the, 3 compounds decrease proliferation even more in knockout cells than wildtype cells and reduced cyclic AMP amounts. These included 2 anti-cancer medications and 1 antimicrobial agent. Octreotide demonstrated no difference in proliferation between incubated handles and cells, nor between knockout and wildtype cells. Needlessly to say octreotide decreased cyclic AMP amounts in both cell lines. Bottom line: We discovered 3 FDA accepted drugs that decrease proliferation prices in knockout cholangiocytes without huge influence on proliferation prices in wildtype H69 cells..