AIM To prepare 5-fluorouracil solid lipid nanoparticles (5-FuE-SLN) with liver targeting.METHODS 5-Fu was employed as model drug to acylate with stearyl chloride and obtain 5-Fu precurser N1-stearyl-5-Fu (5-FuE). The precurser was determined by nuclear magnetic resonance and infraredspectrometry and used to prepare 5-FuE-SLN by the method of physical agglomeration. TransmissionElectron Microscopy (TEM) was employed to study the shape, mean size and particle distribution of 5-FuE-SLN. The drug loading, and releasing characteristics in vitro, the drug distribution and pharmacokinetics invivo were also investigated by HPLC method.RESULTS The average diameter was 240.19nm, and the drug loading was 20.53%. The releasingcharacteristics in vitro was fitted to first-order pharmacokinetic model. The distribution of 5-FuE-SLN inmice showed that 5-FuE-SLN had significant liver targeting being compared with 5-Fu injection. Theconcentration of 5-FuE-SLN group in mice liver was double over that of control group. The mainpharmacokinetics parameters in rabbits were as follows: Vc = 0.04336 L·kg-1, T1/2β- 1.2834 h, CL =0.1632 L·h-1CONCLUSION 5-FuE-SLN has the characteristic of liver targeting. Using 5-Fu precurser to enhance itsliposoluble properties and the method of preparation presented in this paper seems to have significantadvantages and important reference value.

AIM To investigate the effect of cold preservation on rat livers by modified storage method with self-madeHYD solution.METHODS The modified method was that the vascular bed of rat livers was expended with an additional20 mL, 30 mL and 40 mL self-made HYD solution / 100 g liver. After resection of the liver, the extra HYDsolution expressed as % liver weight was entrapped via portal infusion by tying off the supra- and infrahepatic inferior vena cava. According to the amount of extra HYD solution, 40 rats were randomly dividedinto four groups: control group with conventional storage method, 20% group, 30% group and 40% group.The preservation effect of modified storage method was compared with that of conventional storage methodusing isolated perfused rat liver model.RESULTS Bile production and all the indices of hepatic microcirculation including portal perfused pressure, endothelin in the effluent, Trypan blue distribution time and histology in modified method groupswere significantly superior to those in control group (P< 0.05). The liver enzymes in 30% group weremarkedly lower than those in control group (P<0.05). The preservative efficiency of rat liver in 30% groupwas the best among the modified method groups.CONCLUSION The cold preservative efficiency with modified storage method is obviously superior to thatwith conventional storage method. It is suggested that the modified cold storage method is effective and mayhave potential for liver preservation

Site-specific delivery of therapeutic drugs to their target cells is a major scientific challenge for the pharmaceutical sciences. It offers a number of advantages over conventional drug administration. With drug targeting, high local concentrations of the drug can be achieved, thus circumventing many unwanted side effects. Various carriers have been suggested for the delivery of drugs, including liposomes[1 - 5] and (neo ) glycoproteins[6-8]. The asialoglycoprotein receptor (ASGP-R) has frequently been utilized for targeting drugs to the parenchymal liver cell[6- 12]. Liposomes have several advantageous characteristics as drug carrier, and particularly, ligandtacked liposomes achieve a highly effective targeting[13]. Hara et al reported that asialofetuin (AF)-tacked liposomes distributed to rat hepatocytes selectively in vivo[14], and ASGP-R mediated the uptake of AF-liposomes encapsulating IFN-γ by isolated rat hepatocytes in vitro[15]. Lactosaminated human serum albumin (L-HSA) is a neoglycoprotein taking number of galactose residue as terminal sugar[6].

INTRODUCTIONEndothelins (ETs) has a potent and sustained vasoconstrictive effect on a variety of blood vessels.The vascular smooth muscle cell (VSMC) is the target for ETs. VSMC of the whole body contains endothelin receptor (ETR)[1]. A great number of experiments have shown that three distinct complementary DNAs of ETR have been identified i. e., endothelin A receptor (ETA receptor),endothelin B receptor ( ETB receptor ) and endothelin C receptor (ETc receptor). ETA receptor was expressed in VSMC responsible for the contraction[2]. The aim of this study is to confirm the effects of endotoxin on the activity of ETR, and the transcription and expression of ETA receptor mRNA in hepatic and intestinal tissues.

Objective　To document morphological changes in hepatic microcirculation in liver tissue with hepatitis B and the pathogenesis of hepatic microcirculatory disturbances.Methods　Liver tissue samples were obtained from patients with hepatitis B by liver biopsy. These samples were examined with a light microscope and transmission electron microscope. Results　Hepatic microcirculatory disturbances existed in patients with hepatitis B, including those with normal liver function, manifested by red blood cell aggregation in sinusoids seen under light microscope and sinusoidal capillarization seen under electron microscope. Weibel-Palade bodies in sinusoidal endothelial cells were seen in 26 out of 53 cases. Intimate contacts were found between lymphocyte/Kupffer cells and sinusoidal endothelial cells. Conclusions　Hepatic microcirculatory disturbances exist in patients with hepatitis B .The appearance of Weibel-Palade bodies in sinusoidal endothelial cells may be a key step in the development of hepatic microcirculatory disturbances.

Alveolar echinococcosis (AE) of liver associated with simultaneous lung and brain metastases is rare clinically. During a period of 15 years (1985-2000), 2 (1.9%) of 103 cases with liver AE diagnosed at our laboratory were associated with simultaneous lung or brain metastases.1 They were confirmed pathologically through surgical biopsy or autopsy respectively, and reported as follows.

目的:研究不同剂量的"常乐"对大鼠肝脏结构和功能的影响.方法:采用健康Wistar大鼠180只,每组30只,实验组分别以0.1、0.2、2.0、10.0、20.0 mg*kg-1常乐连续灌胃6个月,每日1次.应用常规组织化学、透射电镜技术及血清生化测定技术,观察动物肝脏的结构和功能变化.结果:各实验组动物体重随染毒剂量的减少而呈线性增长.20.0 mg*kg-1组肝细胞内糖原颗粒减少,肝细胞核有不同程度的变形,门管区有炎细胞浸润,其余各组肝脏结构与对照组相比无明显改变.各实验组动物肝脏Kupffer细胞及肝细胞中均可见到高电子密度的致密体及含电子密度较高颗粒的溶酶体,其数量随染毒剂量的增大而增多.20.0 mg*kg-1组血清ALP及GPT增高.结论:20.0 mg*kg-1"常乐"长期作用对大鼠肝脏结构和功能均有损害.

The hepatitis B virus (HBV) is a major pathogen of chronic inflammatory liver disease and liver cirrhosis and is known to be infected to the hepatocytes via HBV specific receptors[1]. However, the specific receptor for HBV has not yet been identified. The HBV envelops consist of three related proteins, called major-(S region), middle-(S + preS2) and large protein (S + preS2 + preS1).

OBJECTIVE:Use of cisplatin, a conventional anticancer drug, is restricted because it generates strong hepatotoxicity by accumulating in liver. Therefore its anticancer potential can only be fully exploited if its own toxicity is considerably reduced. Towards this goal, ethanolic extract of the plant, Boldo (Peumus boldus), known for its antihepatotoxic effects, was used simultaneously with cisplatin, to test its ability to reduce cisplatin’s cytotoxicity without affecting its anticancer potential. METHODS: The cytotoxicity of Boldo extract (BE) and cisplatin, administered alone and in combination, was determined in three cancer cell lines (A549, HeLa, and HepG2) and in normal liver cells (WRL-68). Drug-DNA interaction, DNA damage, cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP, ΔΨ) were also studied. Hepatotoxicity and antioxidant activity levels were determined by alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and glutathione assays in mice. The cytotoxicity of related proteins was tested by Western blotting. RESULTS:Co-administration of BE and cisplatin increased viability of normal cells, but had no effect on the viability of cancer cells. Boldo protected liver from damage and normalized different antioxidant enzyme levels in vivo and also reduced ROS and re-polarized MMP in vitro. Bax and cytochrome c translocation was reduced with caspase 3 down-regulation. Further, a drug-DNA interaction study revealed that BE reduced cisplatin’s DNA-binding capacity, resulting in a reduction in DNA damage. CONCLUSION: Results indicated that a low dose of BE could be used beneifcial y in combination with cisplatin to reduce its toxicity without hampering cisplatin’s anticancer effect. These ifndings signify a potential future use of BE in cancer therapy.

Wnt signaling in liver physiology and pathology

1 Wnt/β-catenin signalingThis signaling pathway is known to play key roles during development and in maintaining homeostasis in many adult tissues. Its aberrant activation is associated with cancers in many tissues such as breast, colon, pancreas, skin and liver.

BACKGROUND: A preoperative diagnosis of primary hepatic lymphoma (PHL) can have profound therapeutic and prognos-tic implications. Because of the rarity of PHL, however, there are few reports on diagnostic imaging.We reviewed the clinical and radiologic findings of 29 patients with PHL, the largest series to date, to evaluate the diagnostic features of this disease.
METHODS: Clinical data and radiologic findings at presen-tation were retrospectively reviewed for 29 patients with pathologically confirmed PHL from January 2005 to June 2013. Imaging studies, including ultrasound (US) (n=29) and contrast-enhanced computed tomography (CECT) (n=24), were performed within 2 weeks before biopsy or surgery.
RESULTS: Among the 29 patients, 23 (79%) were positive for hepatitis B virus (HBV) and 26 (90%) had a significantly ele-vated level of serum lactate dehydrogenase (LDH). There were two distinct types of PHL on imaging: diffuse (n=5) and nodu-lar (n=24). Homogeneous or heterogeneous hepatomegaly was the only sign for diffuse PHL on both US and CECT, without any definite hepatic mass. For the nodular type, 63% (15/24) of patients had solitary lesions and 38% (9/24) had multiple lesions. On US, seven patients displayed patchy distribution with an indistinct tumor margin and a rich color flow signal. CECT showed rim-like enhancement (n=3) and slightly ho-mogeneous or heterogeneous enhancement (n=14) in the arte-rial phase and isoenhancement (n=5) and hypoenhancement (n=12) in the portal venous and late phases. Furthermore, in five patients, CT revealed that hepatic vessels passed through the lesions and were not displaced from the abnormal area or appreciably compressed.
CONCLUSIONS: The infiltration type of PHL was associated with the histologic subtype. Considered together with HBV positivity and elevated LDH, homogeneous or heterogeneous hepatomegaly may indicate diffuse PHL, whereas patchy dis-tribution with a rich color flow signal on US or normal vessels extending through the lesion on CECT may be the diagnostic indicators of nodular PHL.

Objective: To introduce a safe and specific approachof 13C magnetic resonance spectrum (13C MRS )spectroscopy and investigate the alterations in hepaticanabolism.Methods: Relative anaplerotic, pyruvate recyclingand gluconeogenic fluxes were measured by 13C MRSisotopomer analysis of blood glucose from rats with 40%body surface area burn injury, and from rats exposed tosham injury. A short chain fatty acid, [U-13C] propionatewhich was avidly extracted by the liver, was infusedintravenously to deliver 13C into the citric acid cycle.Proton-decoupled 13C MRS of deproteinized plasma orextracts of the freeze-clamped liver were used to determinethe distribution of 13C in blood or hepatic glucose.Results: There was no difference in the multipletsdetected in the glucose carbon-2 anomer from blood or liverafter 45 or 60 minutes of the infusion of the propionate,indicating that steady-state isotopic conditions wereachieved. Gluconeogenesis relative to citric acid cycle fluxwas not altered by burn injury; in both sham and burngroups the rate of glucose production was about equal toflux through citrate synthase. In the sham group ofanimals, the rate of entry of carbon skeletons into the citricacid cycle was about 4 times than that in the burn group.Similarly, flux through pyruvate kinase (again relative tocitrate synthase) was significantly increased after the burninjury.Conclusions: Since results from analysis of the bloodglucose are the same as that of the hepatic glucose, 13Cdistribution in the glucose and hepatic metabolism can beassessed based on the 13C MRS analysis of the bloodglucose.