L-Ornithine phenylacetate (OP): a novel treatment for hyperammonemia and hepatic encephalopathy

Hepatic encephalopathy (HE) is a common neuropsychiatric complication of liver disease affecting about 20-30% patients with cirrhosis. HE may only affect quality of life (e.g. impairments in attention; coordination; driving ability), but in some patients this progresses to coma and death; defining mortality in those with acute liver failure. HE is thought to occur through accumulation of ammonia as a by-product of protein metabolism. In liver failure ammonia accumulates to toxic levels, resulting in ammonia-associated brain swelling. Presently, there is no proven therapy for HE though recent studies suggest that during liver failure, ammonia removal by skeletal muscle (by conversion to glutamine) can be manipulated; also that ammonia and amino acid metabolism should be viewed in terms of their interorgan relationship. This led us to develop a novel concept for ammonia removal. Preliminary studies provide the proof of concept that the combination of L-ornithine (amino acid) with phenylactetate, as L-ornithine phenylacetate (OP), reduces toxic levels of ammonia by (1) L-ornithine acting as a substrate for glutamine synthesis from ammonia in skeletal muscle and (2) phenylacetate excreting the ornithine-related glutamine as phenylacetylglutamine in the kidneys. As both L-ornithine and phenylacetate are already available for human use, data showing its usefulness in ammonia lowering could translate quickly into providing the much needed therapy for HE patients.     

谷氨酰胺改善艾滋病患儿肠道功能和预后的观察

目的 观察含有谷氨酰胺（Gln）的肠内营养制剂对艾滋病（AIDS）患儿肠道屏障功能及临床预后指标的影响。方法 将50例符合入选标准的AIDS患儿,随机分为对照组（常规肠内营养）和研究组（谷氨酰胺干预组）,每组各25例,营养干预28d分别观察患儿临床预后指标和胃肠道并发症发生率。结果 研究组胃肠道并发症发生率15.4%,对照组37.5%（P﹤0.05）;研究组平均住院日较对照组缩短（14.6±4.4 vs 17.5±4.8）（P﹤0.05）;感染相关并发症发生率研究组较对照组发生率低（16.7%vs32.1%）（P﹤0.01）。结论 对AIDS患儿应用含有Gln的肠内营养治疗对减少胃肠道并发症及改变患儿临床预后有一定的作用,具有较好的临床应用价值。     

Amino acid signatures in the developing mouse retina

This study characterizes the developmental patterns of seven key amino acids: glutamate, γ-amino-butyric acid (GABA), glycine, glutamine, aspartate, alanine and taurine in the mouse retina. We analyze amino acids in specific bipolar, amacrine and ganglion cell sub-populations (i.e. GABAergic vs. glycinergic amacrine cells) and anatomically distinct regions of photoreceptors and Müller cells (i.e. cell bodies vs. endfeet) by extracting data from previously described pattern recognition analysis. Pattern recognition statistically classifies all cells in the retina based on their neurochemical profile and surpasses the previous limitations of anatomical and morphological identification of cells in the immature retina. We found that the GABA and glycine cellular content reached adult-like levels in most neurons before glutamate. The metabolic amino acids glutamine, aspartate and alanine also reached maturity in most retinal cells before eye opening. When the overall amino acid profiles were considered for each cell group, ganglion cells and GABAergic amacrine cells matured first, followed by glycinergic amacrine cells and finally bipolar cells. Photoreceptor cell bodies reached adult-like amino acid profiles at P7 whilst Müller cells acquired typical amino acid profiles in their cell bodies at P7 and in their endfeet by P14. We further compared the amino acid profiles of the C57Bl/6J mouse with the transgenic X-inactivation mouse carrying the lacZ gene on the X chromosome and validated this animal model for the study of normal retinal development. This study provides valuable insight into normal retinal neurochemical maturation and metabolism and benchmark amino acid values for comparison with retinal disease, particularly those which occur during development.     

早期肠外给予谷氨酰胺对急性重症胰腺炎患者预后的临床研究

目的观察消旋卡多曲治疗成人急性腹泻的治疗效果,探讨消旋卡多曲治疗急性腹泻的临床应用价值。方法选取我科2013年5月至2014年4月收治的急性重症胰腺炎患者28例,将其随机分为研究组和对照组各14例,对照组给予常规肠外营养治疗,研究组在对照组的基础上给予谷氨酰胺支持治疗,治疗7天。比较两组患者APACHE-Ⅱ评分,血清前白蛋白及免疫球蛋白含量,氮平衡及C3、C4的变化。结果治疗第7天研究组患者的APACHE-Ⅱ评分比对照组下降显著,差异有统计学意义(P<0.01);研究组患者的氮平衡测定比对照组改善得更明显(P<0.01);两组患者血清前白蛋白值均高于治疗前,研究组与对照组相比差异显著(P<0.01);研究组IgG、IgM、IgA值明显回升,与对照组相比差异显著(P<0.01);研究组C3、C4值升高,与对照组相比差异显著(P<0.01)。结论早期肠外给予谷氨酰胺可改善急性重症胰腺炎患者营养状况,降低APACHE-Ⅱ评分,改善负氮平衡,减少感染,可有效改善急性重症胰腺炎的临床预后,值得推广。     

海洋芽孢杆菌B-9987中macrolactin生物合成基因簇分析及反式酰基转移酶高表达

目的 对海洋芽孢杆菌B-9987中macrolactin生物合成基因簇及其关键基因进行分析、鉴定及功能研究。方法 通过生物信息学手段对基因簇的基因组成和功能结构域进行了分析;构建了用于酰基转移酶基因高表达的大肠杆菌—芽孢杆菌穿梭载体,采用电击转化方法导入B-9987之中进行高表达。 结果 macrolactins是由位于同一个操纵子的8个基因bmmA-I所编码的反式酰基转移酶聚酮合酶体系组装而成,反式酰基转移酶(trans-acyltransferase,trans-AT)BmmA的高表达使macrolactin A的产量提高了约0.6倍。结论 macrolactin生物合成基因簇在具有生物防治活性的芽孢杆菌中普遍存在,且高度保守;反式酰基转移酶的高表达能够增加macrolactin A的产量。     

益生菌联合谷氨酰胺对腹泻型肠易激综合征患者肠道微生物的影响

目的探讨益生菌联合谷氨酰胺对腹泻型肠易激综合征患者肠道微生物的影响。方法收集46例确诊为腹泻型肠易激综合征的患者,随机分为对照组和治疗组,每组23例。对照组给予常规综合治疗,治疗组在对照组的基础上给予益生菌联合谷氨酰胺治疗。分别在治疗前1 d及治疗4周后检测两组患者肠道菌群的变化,并观察疗效。结果治疗前,两组患者肠道菌群比较差异无统计学意义(P>0.05);与对照组相比,治疗组腹痛及腹泻恢复时间缩短。治疗后,治疗组患者乳杆菌属和肠球菌属的菌落数均明显增加(P<0.05),且多于对照组(P<0.05);酵母样真菌菌落数显著降低(P<0.05),与对照组比较差异有统计学意义(P<0.05)。结论益生菌联合谷氨酰胺可增加腹泻型肠易激综合征患者肠道乳杆菌等益生菌,维持肠道微生态平衡,促进腹痛腹泻等症状的缓解,临床疗效确切。     

Diversification of Ergot Alkaloids in Natural and Modified Fungi

Several fungi in two different families––the Clavicipitaceae and the Trichocomaceae––produce different profiles of ergot alkaloids, many of which are important in agriculture and medicine. All ergot alkaloid producers share early steps before their pathways diverge to produce different end products. EasA, an oxidoreductase of the old yellow enzyme class, has alternate activities in different fungi resulting in branching of the pathway. Enzymes beyond the branch point differ among lineages. In the Clavicipitaceae, diversity is generated by the presence or absence and activities of lysergyl peptide synthetases, which interact to make lysergic acid amides and ergopeptines. The range of ergopeptines in a fungus may be controlled by the presence of multiple peptide synthetases as well as by the specificity of individual peptide synthetase domains. In the Trichocomaceae, diversity is generated by the presence or absence of the prenyl transferase encoded by easL (also called fgaPT1). Moreover, relaxed specificity of EasL appears to contribute to ergot alkaloid diversification. The profile of ergot alkaloids observed within a fungus also is affected by a delayed flux of intermediates through the pathway, which results in an accumulation of intermediates or early pathway byproducts to concentrations comparable to that of the pathway end product.     

Clinical Heterogeneity of Interstitial Lung Disease in Polymyositis and Dermatomyositis Patients With or Without Specific Autoantibodies

Background

The aim of this study was to compare the heterogeneity of interstitial lung disease (ILD) in patients with polymyositis and dermatomyositis (PM/DM) according to serological type.

脂多糖对大鼠不同组织中一氧化氮合成酶基因表达的影响

通过Northernblot和NADPH－心肌黄酶染色显示一氧化氮合成酶活性的组织化学分析方法，观察了脂多糖对大氧心脏、主动脉和肾组织中诱导型一氧化氮合成酶基因表达的影响及诱导型一氧化氮合成酶被脂多糖诱导表达的动力学。结果表明，未经脂多糖处理的大鼠诱导型一氧化氮合成酶基因在所检测的三种组织中表达活性很低，脂多糖作用于大鼠2h，心、肾和主动脉中的诱导型一氧化氮合成酶mRNA开始增加，6h达到峰值，此后，逐渐下降，24h回复到对照水平。一氧化氮合成酶组织化学染色显示，对照大鼠的组织细胞内存在较低的组成型一氧化氮合成酶活性，被脂多糖处理不同时间后，三种组织中的一氧化氮合成酶活性均显著升高，到24h仍维持在较高水平，提示诱导型一氧化氮合成酶被合成后，在组织细胞内较为稳定。