Kinetics of hepatic transport of 4-methylumbelliferone in rats. Analysis by multiple indicator dilution method

Hepatic elimination of 4-methylumbelliferone (4MU), which has been used as a model compound for conjugative metabolism, was studied by means of a multiple indicator dilution (MID) method in the isolated perfused rat liver. Using this method, three intrinsic hepatic clearances, CL _int,inf , CL _{int,eff, and} CL _{int,seq, which represent the influx, efflux, and sequestration processes, respectively, were obtained. When the dose was increased from a low dose (50 g/rat liver) to a high dose (3000 g/rat liver), the hepatic availability of 4MU increased from 0.11 to 0.73. With increasing dose, the} CL _{int,eff value increased approximately two times, while the} CL _{int,seq value decreased to approximately one-third. The remarkable dose dependence of hepatic availability was due to nonlinearity in both} CL _{int,eff and} CL _{int,seq values. However, the} CL_int,inf value was almost independent of dose. The dose-dependent change in CL_int,seq might be explained by the saturation of conjugative metabolism of 4-MU, while the increase in the CL _{int,eff value with increasing dose might be partly explained by the nonlinear tissue binding of 4-MU, since the tissue unbound fraction determined by an ultrafiltration method using liver homogenate increased approximately 1.5 times at higher concentration of 4-MU compared to that at lower concentrations. In addition, based on a comparison of the individual intrinsic clearances, i.e.}, CL _int,inf , CL _{int,eff, and} CL _{int,seq, the major determining process of the apparent hepatic intrinsic clearance of 4MU is thought to be the sequestration process at the high dose. However, at the low dose, the membrane transport process (influx and efflux processes) as well as the sequestration process also determine the apparent hepatic intrinsic clearance}.     

Artificial Liver: Present and Future

Early in 1956, the first model of a biological artificial liver, using a live dog's liver incorporated in a cross-hemodialyzer, was placed in an experimental animal with portocaval encephalopathy. This "biological artificial liver," a hybrid artificial liver in the present terminology, was the first in the world. In October 1958, the first human patient, a young male patient in hepatic coma due to liver cirrhosis, was placed on the laboratory-made biological artificial liver composed of four parabiotic cross-hemodialyzers connected with four live dogs' livers to which the "hepatic reactors" for ammonium adsorption and acid-base balance were additionally equipped. This first case was very successful, resulting in the patient's recovery from coma. This article introduces the past history of the artificial liver, research of which has mainly been conducted in Japan since the early 1950s by the author, M. Mito, and Y. Nosé. Until recently, little progress has been made in this field through the application of blood purification principles such as hemoadsorption, plasmapheresis, and other modifications and combinations. Accumulation of clinical experiences with such conventional methods has stimulated the third generation of the artificial liver to a return to a hybrid organ applying modern science and technology. A concept of hybrid organs in comparison with organ transplants is introduced. The Japanese national project of developing a new artificial liver system, as conducted by the author as the chairman and his associates, is introduced.     

肝包虫病合并HBV感染患者Th17、CD4+细胞表面PD-1/PD-L1的表达水平及意义

目的探讨肝包虫合并乙型肝炎病毒(HBV)感染患者辅助性T细胞17(Th17)、CD4⁺细胞表面程序性死亡分子-1/程序性死亡分子1配体(PD-1/PD-L1)的表达水平及其临床意义。方法选取2014年9月一2019年9月新疆医科大学第一附属医院收治的肝包虫病患者作为研究对象﹐其中100例肝包虫病合并HBV感染患者为合并HBV感染组,肝包虫病无HBV感染患者88例为非HBV感染组﹐采用流式细胞仪检测外周血Th17,CD4⁺细胞表面PD-1,PD-L1表达水平。结果合并HBV感染组患者乙型肝炎家族史,B~C Child分级占比均高于非HBV感染组(P<0.05);肝功能指标[谷丙转氨酶(ALT)、谷草转氨酶(AST),γ-谷氨酰转肽酶(γ-GT)]水平以及Th17 PD-1、Th17 PD-L1,CD,PD-1,CD4⁺PD-L1表达水平均高于非HBV感染组(P<0.05);Child分级A级肝包虫病患者的Th17 PD-1,Th17 PD-L1,CD4⁺PD-1,CD4⁺PD-L1表达水平均低于Child分级B~C级患者(P<0.05)。结论HBV感染会影响肝包虫病患者的肝功能及外周血Th17,CD4⁺细胞表面PD-1,PD-L1表达水平,肝功能严重程度可能与外周血Th17,CD4⁺细胞PD-1,PD-L1表达存在关系。     

肝癌细胞分泌物对凝血系统的直接影响

目的：探讨肝癌细胞分泌物对凝血系统的直接影响。方法：以一期法测定肝癌细胞分泌物对APTT、PT、TT及Ⅷ、Ⅴ因子活性的影响。结果：肝癌细胞分泌物使正常血浆APTT缩短、TT延长、Ⅷ因子活性增加、V因子活性降低。异常血浆PT、TT延长。结论：肝癌细胞分泌物可直接改变血浆凝血像。     

LAMS抑制肝癌细胞增殖和促凝活性的实验研究

目的：观察LAMS抑制肝癌细胞增殖和促凝活性的效果。方法：比较LAMS处理的肝癌细胞生长曲线、AgNoRs含量变化;用一步法APTT测定LAMS拮抗肝癌细胞分泌物的促凝血作用。结果：LAMS处理后的肝癌细胞增殖受抑制、AgNoRs数量减少,LAMS能拮抗肝癌细胞分泌物对APTT的影响。结论：LAMS可有效地抑制肝癌细胞增殖和促凝活性。     

腹腔镜解剖性肝Ⅶ段切除术的难点与应对策略

腹腔镜解剖性肝Ⅶ段切除术是被公认难度较大的肝段切除手术方式之一。肝Ⅶ段因其位置与解剖特点,行解剖性肝切除术时存在显露不佳、操作困难、肝蒂解剖复杂、切除平面难以确定和断肝容易出血等问题。笔者在行腹腔镜解剖性肝Ⅶ段切除术时病人常规采取左侧半卧位,将Trocar布局整体向右季肋区偏移,根据术前三维重建个体化选择适宜的肝Ⅶ段肝蒂解剖方式,由肝Ⅵ和Ⅶ段间平面开始离断肝脏,以垂直方向寻找和显露肝右静脉主干,然后以肝右静脉作为肝内路标指引肝实质离断。笔者临床经验表明:通过选择合适手术策略能有效降低腹腔镜解剖性肝Ⅶ段切除术难度、提高手术安全性和可控性,同时保证肿瘤根治性效果。     

慢加急性肝衰竭合并自发性细菌性腹膜炎影响因素分析与预测模型构建

目的 探究慢加急性肝衰竭(acute - on - chronic liver failure,ACLF)患者合并自发性细菌性腹膜炎(spontaneous bacterial peritonitis,SBP)的影响因素并构建预测模型。方法 收集来自重庆市7家医疗机构2018年1月—2020年6月的627例ACLF患者,根据其是否发生自发性腹膜炎分为ACLF合并SBP组(n = 423)和ACLF组(n = 204)。将纳入研究患者资料随机抽取70%（436例）作为训练集构建预测模型,剩余30%（191例）作为测试集进行内部验证。采用ROC曲线评估模型临床效能,并将预测模型以公式和列线图形式表现出来。结果 经Lasso - logistic回归结果显示,肝肾综合征(OR = 9.570,95%CI:2.662～34.407)和直接胆红素(OR = 1.006,95%CI:1.004～1.008)是ACLF患者合并SBP的独立危险因素;白蛋白(OR = 0.890,95%CI:0.846～0.937)和凝血酶原活动度(OR = 0.915,95%CI:0.913～0.917)是ACLF患者合并SBP的保护因素。logistic预测模型表现为,X = 6.105 + 2.259×肝肾综合征 + 0.006×直接胆红素 - 0.116×白蛋白 - 0.089×凝血酶原活动度。预测模型ROC曲线下面积为0.843(95%CI:0.825～0.861),敏感度为79.6%,特异度为70.1%;内部验证ROC曲线下面积为0.825(95%CI:0.809～0.841),敏感度为77.8%,特异度为73.0%。结论 ACLF合并SBP风险预测模型能较好地预测SBP的发生风险,同时可为医务人员及时采取预防性管理措施提供参考。     

Anatomic basis of vascular distribution in combined removal of liver and pancreas (28.5.93)

Summary Based on the study of the arterial distribution of 120 hepatic grafts removed from brain-dead patients, the authors assess the possibilities of vascular partition in cases of combined removal of the liver and pancreas. The discussion deals with the vascular distribution of each organ. The presence of a right hepatic artery arising from the superior mesenteric a. (SMA) requires preservation of the SMA with the hepatic graft, while the pancreas is removed with the celiac trunk (CT) and its branches. The presence of a left hepatic artery arising from the CT requires its preservation with the hepatic graft, the pancreas being removed with the SMA and the splenic artery.

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Partage vasculaire des prélèvements hépatiques et pancréatiques combinés : bases anatomiques (28.5.93)

Résumé A partir de l'étude de la distribution artérielle de 120 greffons hépatiques prélevés sur des patients en état de mort cérébrale, les auteurs apprécient les possibilités de partage vasculaire en cas de prélèvement combiné foie-pancréas. La discussion porte sur la distribution vasculaire de chaque organe. L'existence d'une artère hépatique droite naissant de l'artère mésentérique supérieure (AMS) nécessite de conserver l'AMS avec le greffon hépatique, le pancréas est prélevé avec le tronc coeliaque (TC) et ses branches. La présence d'une artère hépatique gauche naissant du TC impose de le conserver avec le greffon hépatique, le pancréas est prélevé avec l'AMS et l'artère splénique.

     

JNK信号转导通路对白细胞介素-1β促肝星状细胞增殖的调控作用

目的：探讨JNK信号转导通路在白细胞介素- 1β（IL-1β）介导的促肝星状细胞（HSCs）增殖中的作用。方法:应用 Western印迹法检测JNK的活化程度。应用活细胞计数试剂盒-CCK-8检测HSCs增殖并观察JNK 特异性阻断剂SP600125对IL-1β促HSCs增殖的影响。结果：IL-1β有明 显促大鼠HSCs增殖作用，而经JNK特异性阻断剂 SP600125预处理后，IL-1β促HSCs增殖作用 受到抑制（1.560±0.110 vs 1.427±0.113，P<0.05）。IL-1β以时间依赖 方式激活JNK。IL-1β作用HSCs后0、5、15、30、60和120 min，JNK 活性分别为0.982±0 .299、1.501±0.720、2.133±0.882、3.360±0.452、2.181±0.789、1.385±0 .368。结论:IL-1β可刺激HSCs增殖，细胞内JNK信号转导通路参与了 IL-1β促HSCs增殖作用。     

Morphometry of terminal hepatic veins

Summary In the present study, hepatic venous distribution per unit of liver surface area on normal wedge biopsies from man (n=11) and baboon (n=8) were analysed and compared. Terminal hepatic veins (THV - man:n=100; baboon:n=200) morphometric size variables were obtained with a Leitz ASM 68K morphometric equipment. THV, defined as hepatic veins up to 150 m in internal diameter (ID), in the centrolobular position and with sinusoidal openings, represented 84% and 74% of hepatic veins of man and baboon, respectively. Four or more THV were generally found on 8 mm² of liver surface. Transversely sectioned THV selected by the ratio IDminimum/IDmaximum >0.67, was found to be only 25% of the total THV. In baboon, THV merge with other terminal veins and the interlobular veins present sinusoidal inlets. The baboon THV wall surface (WS) and wall thickness (WT) values were higher than in man. Positive correlations between the number of mesenchymal cells (Mc) in the vein wall and wall surface of terminal hepatic veins (man: r= 0.79; baboon: r=0.83) and between wall surface and internal surface (IS) (man: r=0.80; baboon: r=0.72) were found. Two ratios were selected as the most reliable parameters: (1) for the THV wall rim, wall surface/internal surface (WS/IS - man: 0.43±0.16; baboon: 0.63±0.23), regarding transversely sectioned THV; and (2) for the evaluation of wall cell density (WS/Mc-man: 550±231; baboon: 558±183 m²/cell) as they did not depend on THV caliber.Dr. Porto was supported by a fellowship from MEC-CAPES, Brazil. A grant for morphometric equipment was obtained from the Fondation pour la Recherche Médicale and from the Societé d'Hépatologie Expérimentale, 77 rue Pasteur, Lyon, France