早期光疗对早产儿黄疸的影响

目的:探讨在经皮胆红素监测下早期蓝光干预对早产儿高胆红素血症的防治作用。方法:选择2009年10月-2011年10月我院新生儿科收治的86例出生体重≤2000 g,无出生窒息史的早产儿,按住院号单双号分为观察组46例和对照组40例。对照组按照我国2000年制定的新生儿黄疸干预推荐方案的干预标准进行光疗。观察组于出现黄疸和/或经皮胆红素85.50μmol/L,但尚未达方案的干预标准就进行光疗,监测经皮胆红素至黄疸消失。经皮胆红素值达187.5μmol/L以上时同时查静脉血监测血清总胆红素。比较2组早产儿经皮胆红素峰值及恢复正常时间。结果:观察组与对照组比较经皮胆红素峰值较低,黄疸持续时间较短,两组比较P均0.05,有统计学差异。结论:早产儿在经皮胆红素监测下进行早期蓝光干预有利于降低早产儿胆红素峰值,缩短黄疸持续时间,有效预防早产儿胆红素脑病。     

Decreased astrocytic thrombospondin‐1 secretion after chronic ammonia treatment reduces the level of synaptic proteins: in vitro and in vivo studies

Chronic hepatic encephalopathy (CHE) is a major complication in patients with severe liver disease. Elevated blood and brain ammonia levels have been implicated in its pathogenesis, and astrocytes are the principal neural cells involved in this disorder. Since defective synthesis and release of astrocytic factors have been shown to impair synaptic integrity in other neurological conditions, we examined whether thrombospondin‐1 (TSP‐1), an astrocytic factor involved in the maintenance of synaptic integrity, is also altered in CHE. Cultured astrocytes were exposed to ammonia (NH₄Cl, 0.5–2.5 mM) for 1–10 days, and TSP‐1 content was measured in cell extracts and culture media. Astrocytes exposed to ammonia exhibited a reduction in intra‐ and extracellular TSP‐1 levels. Exposure of cultured neurons to conditioned media from ammonia‐treated astrocytes showed a decrease in synaptophysin, PSD95, and synaptotagmin levels. Conditioned media from TSP‐1 over‐expressing astrocytes that were treated with ammonia, when added to cultured neurons, reversed the decline in synaptic proteins. Recombinant TSP‐1 similarly reversed the decrease in synaptic proteins. Metformin, an agent known to increase TSP‐1 synthesis in other cell types, also reversed the ammonia‐induced TSP‐1 reduction. Likewise, we found a significant decline in TSP‐1 level in cortical astrocytes, as well as a reduction in synaptophysin content in vivo in a rat model of CHE. These findings suggest that TSP‐1 may represent an important therapeutic target for CHE.

     

Variant CJD

It is now 18 years since the first identification of a case of vCJD in the UK. Since that time, there has been much speculation over how vCJD might impact human health. To date there have been 177 case reports in the UK and a further 51 cases worldwide in 11 different countries. Since establishing that BSE and vCJD are of the same strain of agent, we have also shown that there is broad similarity between UK and non-UK vCJD cases on first passage to mice. Transgenic mouse studies have indicated that all codon 129 genotypes are susceptible to vCJD and that genotype may influence whether disease appears in a clinical or asymptomatic form, supported by the appearance of the first case of potential asymptomatic vCJD infection in a PRNP 129MV patient. Following evidence of blood transfusion as a route of transmission, we have ascertained that all blood components and leucoreduced blood in a sheep model of vCJD have the ability to transmit disease. Importantly, we recently established that a PRNP 129MV patient blood recipient with an asymptomatic infection and limited PrP^Sc deposition in the spleen could readily transmit disease into mice, demonstrating the potential for peripheral infection in the absence of clinical disease. This, along with the recent appendix survey which identified 16 positive appendices in a study of 32 441 cases, underlines the importance of continued CJD surveillance and maintaining control measures already in place to protect human health.     

Effects of inhibition of ornithine aminotransferase on thioacetamide-induced hepatogenic encephalopathy

Repeated administration of thioacetamide (TAA) to CD1 mice produced hepatic failure and biochemical and behavioral effects characteristic of hepatogenic encephalopathy (HE). The symptoms in mice resembled those previously observed in rats after similar treatments. It is, howeve, obvious that both in rats and mice the severity of symptoms depends not only on dose and dosing schedule of TAA, but also on strain and body weight (age). Administration of 5-fluoromethylornithine (5FMOrn), a selective inactivator of ornithine aminotransferase (OAT), significantly reduced mortality, and it ameliorated most of the TAA-induced pathologic symptoms, such as hypothermia, decreased locomotor and exploratory behavior, pathologic liver function and amino acid patterns. The most prominent biochemical consequence of 5FMOrn administration is the elevation of ornithine concentrations in tissues, including the brain, and in body fluids. Elevated ornithine concentrations are, therefore, the most likely basis for the therapeutic effects of 5FMOrn. In agreement with this notion is the enhancement of citrulline and urea formation. These findings and the observation that administration of ornithine in combination with a branched-chain 2-oxoacid ameliorated the pathologic symptoms of portal-systemic encephalopathy suggest inhibition of OAT in the treatment of this disease. The liver protective effect of 5FMOrn is not yet understood; the enhancement of regenerative processes is a likely explanation.Abbreviations GABA 4-aminobutyrate - GABA-T 4-aminobutyrate aminotransferase - GOT plasma glutamate oxaloacetate transaminase - HE hepatogenic encephalopathy - LDH plasma lactate dehydrogenase - MAO monoamine oxidase - OAT ornithine aminotransferase - TAA thioacetamide - 5FMOrn 5-fluoromethylornithine Special issue dedicated to Dr. Claude Baxter.     

双歧杆菌四联活菌片联合乳果糖对轻微型肝性脑病患者炎症性肠黏膜损伤的保护作用

目的探讨双歧杆菌四联活菌片联合乳果糖对轻微型肝性脑病(MHE)患者炎症性肠黏膜损伤的保护作用,为该类患者的治疗提供参考。方法选择2018年1月至2019年12月我院内科住院治疗的90例MHE患者,随机分为联用组和单用组各45例。两组患者给予低盐饮食、护肝降转氨酶、维持水电解质平衡及防治并发症等基础治疗。单用组患者给予乳果糖口服液20 mL/次,3次/d,口服。联用组患者在单用组基础上加用双歧杆菌四联活菌片1.5 g/次,3次/d,温开水送服。两组患者连用8周。观察两组患者治疗前后血清丙氨酸转氨酶(ALT)、数字连接试验(NCT)时间、血清炎症因子[白介素(IL) 6、肿瘤坏死因子(TNF) α]和肠黏膜损伤指标[血清肠脂肪酸结合蛋白(IFABP)、中晚期糖基化终末产物(AGEs)]水平变化,并比较临床型肝性脑病(HE)的进展率。结果治疗8周后,两组患者ALT、IL 6、TNF α、IFABP、AGEs水平和NCT时间均较治疗前明显下降,且联用组患者下降幅度大于单用组(均P<0.05)。联用组患者临床型HE的进展率为8.89%(4/45),明显低于单用组的24.44%(11/45),差异有统计学意义(χ²=3.920,P=0.047 1)。结论双歧杆菌四联活菌片联合乳果糖能改善MHE患者肝功能和智力测验结果,降低临床型HE的进展率,其作用机制可能与其能抑制IL 6、TNF α水平,保护肠黏膜相关。     

New avenues to treatment of liver cirrhosis

<正>Liver cirrhosis is the pathologic end stage of multiple liver diseases.The major complications of liver cirrhosis,such as hepatic encephalopathy,spontaneous bacterial peritonitis and esophageal variceal bleeding are characterized by remarkable changes of the gut microbiota,which indicates that enteric dysbiosis might play an important role in the progression of liver cirrhosis[1,2].The human gastrointes-     

Effect of Ammonia on Brain Serotonin Metabolism in Relation to Function in the Portacaval Shunted Rat

Four weeks following portacaval anastomosis (PCA) in the rat, severe liver atrophy, sustained hyperammonemia, and increased plasma and brain tryptophan are observed. Administration of ammonium acetate (NH4Ac) to rats with PCA precipitates severe signs of hepatic encephalopathy (HE) (loss of righting reflex progressing to loss of consciousness and ultimately deep coma). To evaluate the relationship between the deterioration of neurological status in HE and serotonin (5-HT) metabolism, the levels of 5-HT, its precursor 5-hydroxytryptophan, and its major metabolite 5-hydroxy-indole-3-acetic acid (5-HIAA) were measured by HPLC with ion-pairing and electrochemical detection in three well-defined areas of the cerebral cortex: anterior cingulate, piriform and entorhinal, and frontoparietal; as well as in the caudate-putamen, the raphe nuclei, and the locus ceruleus in rats with PCA at different stages of HE, before and after injection of NH4Ac, as well as in sham-operated controls. The results demonstrate increased 5-HIAA/5-HT ratios after PCA and NH4Ac loading, suggesting increased 5-HT turnover in the brains of these animals. However, these changes do not appear to be related to the precipitation of coma as no significant difference in 5-HT turnover was observed between precoma and coma stages of HE. Increased 5-HT turnover in brain of shunted rats may be related to early symptoms of HE such as altered sleep patterns and disorders of motor coordination.     

Reversible Alterations of Cerebral γ-Aminobutyric Acid in Pyrithiamine-Treated Rats: Implications for the Pathogenesis of Wernicke''s Encephalopathy

Treatment of rats with the central thiamine antagonist, pyrithiamine, results in severe neurological symptoms such as loss of righting reflex. Measurement of gamma-aminobutyric acid (GABA) content of brain tissue from symptomatic pyrithiamine-treated (PT) rats revealed significant reductions in thalamus, cerebellum, and pons. GABA content of cerebral cortex, however, was unaltered. Activities of the thiamine-dependent enzyme alpha-ketoglutarate dehydrogenase (alpha KGDH) were reduced in parallel with the GABA changes. On the other hand, activities of the GABA-synthetic enzyme glutamic acid decarboxylase (GAD) remained within normal limits, with the exception of a small but significant decrease in thalamus of symptomatic PT rats. Affinities and densities of high-affinity [3H]muscimol binding sites on crude cerebral membrane preparations from symptomatic PT rats were unchanged. Thiamine administration to symptomatic animals resulted in correction of abnormal righting reflexes and in normalization of decreased GABA levels and reduced alpha KGDH activities in cerebellum and pons. Thalamic GABA levels and alpha KGDH activities, on the other hand, remained significantly lower than normal. These results suggest that the reversible symptoms of pyrithiamine treatment may result from imparied GABA synthesis in cerebellum and pons of these animals. Similar mechanisms may play a role in the pathogenesis of the reversible symptoms of Wernicke's encephalopathy in man.     

不同严重程度缺氧缺血性脑病患儿血清MMP-9、MMP-2、UA水平的表达及临床意义

目的:研究不同严重程度缺氧缺血性脑病患儿血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-2(MMP-2)、尿酸(UA)水平的表达及临床意义。方法:选取2015年4月-2017年4月本院收治的缺氧缺血性脑病患儿50例记为研究组,另取同期本院健康新生儿50例记为对照组,分别比较两组新生儿血清MMP-9、MMP-2及UA水平,对比研究组不同时期不同严重程度患儿血清MMP-9、MMP-2及UA水平,采用Preason相关性分析缺氧缺血性脑病病情严重程度与血清MMP-9、MMP-2、UA水平的关系。结果:研究组患儿发病后1d、发病后3d、发病后7d血清MMP-9、MMP-2及UA水平均明显高于对照组,差异有统计学意义(P0.05),且MMP-9水平先升高后降低,MMP-2、UA水平呈逐渐升高的趋势(P0.05)。轻度组、中度组、重度组患儿发病后3d的MMP-9、MMP-2、UA水平高于发病后1d,且随着病情的加重,呈逐渐上升的趋势,差异有统计学意义(P0.05)。经Preason相关性分析可得:缺氧缺血性脑病病情严重程度与血清MMP-9、MMP-2、UA水平均呈正相关(P0.05)。结论:缺氧缺血性脑病患儿随着病情的逐渐加重,其血清MMP-9、MMP-2及UA水平不断升高,呈正相关关系。