磁共振波谱技术及脑干听觉诱发电位在新生儿早期胆红素脑损伤中的评估作用

目的 探讨新生儿胆红素脑损伤时磁共振波谱技术（MRS）及脑干听觉诱发电位（BAEP）的变化特征，为新生儿胆红素脑损伤的早期干预治疗提供临床依据。方法 选取2013年7月至2016年3月入住安徽省儿童医院新生儿科114例高胆红素血症患儿为研究对象，根据头颅核磁共振（MRI）检查是否有脑损伤，分为观察组（胆红素脑损伤）和对照组（无脑损伤），同时分别进行MRS分析及BAEP检测，MRS分析所测定的代谢产物包括：N-乙酰天门冬氨酸（NAA）；肌酸复合物（Cr）；胆碱复合物（Cho）；并以Cr的峰下面为内参照物，计算NAA/Cr、Cho/Cr、NAA/Cho比值。比较两组MRS及BAEP的差异。结果 观察组NAA/Cr比值（1.34±0.26）较对照组（1.50±0.36）低，差异有统计学意义（P<0.05），NAA/Cho及Cho/Cr在两组之间差异无统计学意义（P>0.05）；观察组BAEP异常率明显高于对照组，差异有统计学意义（P<0.05），两组之间血清总胆红素水平差异无统计学意义（P>0.05）。结论 在MRI基础上，MRS联合BAEP检查有助于新生儿胆红素脑损伤的早期判断。     

Characterization of endogenous markers of hepatic function in patients receiving itraconazole treatment for prophylaxis of deep mycosis

BackgroundLong-term use of itraconazole (ITZ) is associated with a risk of inducing hepatotoxicity. This study aimed to evaluate the associations of plasma concentrations of ITZ and its hydroxylated metabolite (OH-ITZ) with endogenous markers of hepatic function.MethodsThirty six patients treated with oral ITZ solution for prophylaxis of deep mycosis were enrolled. Plasma concentrations of ITZ and OH-ITZ were determined on the 14th day or later after administration of ITZ. Their associations with endogenous marker levels of hepatic function including plasma coproporphyrin (CP)-I and OATP1B1 genotypes were assessed.ResultsThe serum level of total bilirubin (T-Bil) was moderately correlated with the plasma concentration of total ITZ (tITZ) and OH-ITZ (tOH-ITZ). T-Bil elevation above 0.3 mg/dL was observed in 19% of patients, although statistically significant difference was not identified. The plasma concentration of tITZ had no correlation with other endogenous markers levels including AST, ALT, albumin, and plasma CP-I. The serum AST and plasma CP-I levels were correlated with the plasma concentration of free OH-ITZ (fOH-ITZ). T-Bil and plasma CP-I, a marker of OATP1B1 activity, were not correlated with each other, and neither was associated with the OATP1B1 genotypes.ConclusionsPlasma ITZ and OH-ITZ had a positive association with T-Bil. The patients with a higher fOH-ITZ level had lower OATP1B1 activity on the basis of plasma CP-I level. ITZ and OH-ITZ have the potential to slightly increase endogenous marker levels of hepatic function, although most likely by different mechanisms.     

Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine,liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin

Body is equipped with organic cation transporters (OCTs). These OCTs mediate drug transport and are also involved in some disease process. We aimed to investigate whether liver failure alters intestinal, hepatic and renal Oct expressions using bile duct ligation (BDL) rats. Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure, associated with decreased intestinal absorption and increased urinary excretion. Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2. In vitro cell experiments show that chenodeoxycholic acid (CDCA), bilirubin and farnesoid X receptor (FXR) agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1, which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR. Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL, which are confirmed using CDCA-treated and bilirubin-treated rats. A disease-based physiologically based pharmacokinetic model characterizing intestinal, hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats. In conclusion, BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats, finally, decreasing plasma exposure and impairing hypoglycemic effects of metformin. BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.     

新诊2型糖尿病患者血清总胆红素与外周动脉内膜中膜厚度的关系

目的 初步探讨新诊2型糖尿病患者血清总胆红素与外周动脉内膜中膜厚度的关系.方法 357例新诊2型糖尿病患者,根据是否有外周动脉内膜中膜增厚分为内膜中膜增厚组(178例)和内膜中膜正常组(179例),比较两组血清总胆红素浓度;根据患者血清总胆红素浓度由低到高将患者分为四组:低胆红素组、较低胆红素组、较高胆红素组、高胆红素组,比较四组患者外周动脉内膜中膜厚度;采用Logistic回归分析法分析新诊2型糖尿病患者外周动脉内膜中膜厚度增厚的危险因素.结果 内膜中膜增厚组血清总胆红素浓度比内膜中膜正常组降低,两组比较差异有显著性(P<0.05).根据血清总胆红素浓度进行分组的四组患者,外周动脉内膜中膜厚度低胆红素组高于高胆红素组,差异有显著性(P<0.01).Logistic回归分析显示,血清总胆红素、年龄和收缩压进入回归方程.结论 低血清总胆红素可能是新诊2型糖尿病外周动脉内膜中膜增厚的独立危险因素.