Institute of Cellular Medicine, The Medical School, Newcastle University, NE2 4HH Newcastle u Tyne, UK.
Metab Brain Dis. 2013 Jun;28(2):201-7. doi: 10.1007/s11011-012-9362-2. Epub 2012 Nov 23.
Induction of hyperammonaemia with nitrogen challenge in man can be used to study the pathogenesis and treatment of hepatic encephalopathy complicating cirrhosis. Initially 20 g of glutamine was given orally as a flavored solution which resulted in doubling of blood ammonia concentration and this was associated with a deterioration in performance of the choice reaction time. The effect could have been due to a direct effect of glutamine rather than the ammonia generated so in subsequent experiments a glutamine free mixture of amino acids resembling the composition of haemoglobin was used (gastrointestinal bleeding is a known precipitant of hepatic encephalopathy). In Child grade B and C patients, 2-3 h after 54 g, slowing of the EEG was observed. The cerebral effects of induced hyperammonaemia were studied with diffusion weighted imaging and MR spectroscopy after giving 54 g of a mixture of threonine, serine and glycine when apparent diffusion coefficient increased. Also the change in ammonia levels correlated with the change in cerebral glutamine levels (r = 0.78, p = 0.002) suggesting intra cerebral formation of glutamine from ammonia and this may have accounted for the fall in cerebral myoinositol concentrations observed. Finally a colonic source for ammonia was confirmed by administering urea using colon coated capsules when ammonia concentrations slowly increased from 5 h after administration and rapidly after 10 h. In two patients the hyperammonaemia was ameliorated by pre treatment with Rifaximin 1200 mg per day for 1 week. Nitrogen challenge studies are thus a valuable model for studying new treatments for hepatic encephalopathy without the need to simultaneously treat precipitating factors.
用氮负荷诱导人体高氨血症可用于研究肝硬化合并肝性脑病的发病机制和治疗。最初，口服 20 克谷氨酰胺调味溶液，导致血氨浓度增加一倍，这与选择反应时间的表现恶化有关。这种影响可能是由于谷氨酰胺的直接作用，而不是生成的氨，因此在后续实验中，使用了一种类似于血红蛋白组成的不含谷氨酰胺的氨基酸混合物（胃肠道出血是肝性脑病的已知诱发因素）。在 Child B 和 C 级患者中，在给予 54 克氨基酸混合物后 2-3 小时，观察到脑电图减慢。在用苏氨酸、丝氨酸和甘氨酸混合物给予 54 克后，通过弥散加权成像和磁共振波谱研究了诱导高氨血症的脑效应，此时表观扩散系数增加。此外，氨水平的变化与脑谷氨酰胺水平的变化相关（r = 0.78，p = 0.002），表明氨在脑内形成谷氨酰胺，这可能解释了观察到的脑肌醇浓度下降。最后，通过用结肠包被胶囊给予尿素，证实了氨的结肠来源，氨浓度在给药后 5 小时缓慢增加，10 小时后迅速增加。在两名患者中，通过每天预用 Rifaximin 1200 毫克治疗 1 周，高氨血症得到改善。因此，氮负荷研究是一种研究新的肝性脑病治疗方法的有价值模型，而无需同时治疗诱发因素。
