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发布于:2019-3-15 14:04:25  访问:4 次 回复:0 篇
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1HNMR of the isolated cortex was performed to study the brain metabolism of ammonia. Results: Induction Selleckchem Anti-infection Compound Library of hyper-ammonemia to pathophysiological concentrations (340.9 �� 32 WT-NH3, 247.6�� 18.7 TLR4-/��NH3 ) resulted in significant liver (albumin 30.3�� 0.9 WT-NH3 vs 26.27�� 0.9 TLR4-/�� NH3, urea 8.3�� 0.1 WT-NH3 vs 7.2�� 0.4 TLR4-/��NH3 ) and renal (creatinine) injury (11.84��0.7 WT-NH3 vs 7.19�� 0.3 TLR4-/��NH3) in WT mice, which was significantly abrogated in the TLR4-KO mice (p<0.006, p<0.001, p<0.0001 respectively). Hyperammonemia resulted in a significant increase in brain water in WT animals, which was significantly reduced in the TLR4-KO cohort (p 0.05).1H NMR spectroscopy of the cortical brain revealed that lactate and glutamine were significantly selleck chemical lower in hyperammonemic WT vs groups TLR4?/? (p<0.05, p<0.004 respectively). Conclusion: The results of this study strongly support the concept that ammonia act as a DAMP producing multiple organ injury and inflammation through a TLR4 dependant pathway. For the first time, the data from this study show that TLR4 modulates brain ammonia metabolism and accumulation of lactate and glutamine leading to brain swelling explaining the synergy between ammonia and inflammation in the pathogenesis of HE. We conclude that TLR4 inhibition may reduce ammonia induced brain swelling and is therefore an important target of therapy. Disclosures: Nathan Davies - Patent Held/Filed: UCL Rajiv Jalan - Consulting: Ocera Therapeutics, Conatus; Grant/Research Support: Grifols, Gambro The following people have nothing to disclose: Yalda Sharifi, Gavin Wright, Francesco De Chiara, Laia Chavarria, Marc Oria, Francesco Scaravilli Background and aims: The aim of this study was to prospectively evaluate whether the characteristics of hepatic blood flow change in patients with nonalcoholic fatty liver disease (NAFLD) occurred at a milder stage of fibrosis compared with patients with chronic hepatitis due ATP7A to hepatitis C virus (CH-C). Methods: A total of 995 subjects were enrolled. Hepatic blood flow was measured by Doppler ultrasonography, and the arterio-portal ratio (A/P ratio) was calculated. Elasticity of the spleen was measured, and the SEP score (splenic elasticity ��1.63-2.88) was calculated. In a pilot study, hepatic blood flow was measured in 142 patients with NAFLD and 121 patients with CH-C diagnosed histologically. In a validation set, hepatic blood flow was measured in 753 subjects with NAFLD based on ultra-sonographic findings to confirm accuracy and reproducibility. The institutional review board approved this study, and patients provided written informed consent prior to entry into the study. Results: In the NAFLD group, median A/P ratios in F0, F1, F2, F3, and F4 patients were 1.8, 2.0, 2.5, 3.2, and 3.7, respectively. The A/P ratio was significantly higher in stage 2 than in stage 0 patients with NAFLD (P<0.01).
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