Rôle du foie dans le métabolisme des nutriments en nutrition artificielle

The liver is a prominent organ in nutritional homeostasis. Due to unique metabolic properties, it plays a main role in the metabolism of the three macronutrients ‘as well as the micronutrients’ (vitamins and minerals) storage. Although it represents only 2.5% of the body mass, it consumes 20% of total resting energy expenditure and a similar percentage of the amino acid mixture absorbed via the gut during and after a meal. Due to a peculiar vascularization (portal vein, the entire gastrointestinal venous flux is directed towards the liver with all hydrosoluble nutrients, only water-unsoluble lipids being excluded from this obligatory ‘first-pass mechanism’). Since it is the location for glycogen storage, VLDL synthesis and ketogenesis, the liver is crucial in the fed-to-fasted metabolic alternation. While fat is not physiologically stored in the liver, it is a very important organ in lipid metabolism. Except immunoglobulins, all plasma proteins are synthetised by the liver together with the constitutive proteins, explaining that it is a very powerful organ for protein synthesis. Finally, due to a very active amino acid metabolism, the liver can reshape the amino acid-mixture coming from the gut in the absorptive state. Such a phenomenon has a major implication in the nutritional physiology of amino acid metabolism according to the route: enteral or parenteral. Indeed, in the latter case the remodelling by the liver does not occurs.     

Effects of cholecalciferol and calcium on experimental hepatic osteodystrophy in rats

To investigate cholecalciferol (vitamin D) metabolism disorders in hepatic osteodystrophy (HOD) and the effects of vitamin D, its metabolites, and calcium (Ca) on HOD, an experimental HOD model in rats was developed using carbon tetrachloride. In the serum level of 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol, and 24R,25-dihydroxycholecalciferol, there were no significant differences between normal and control cirrhotic rats. Vitamin D supplementation significantly inhibited the atrophy of intestinal villi, reduction of bone calcium content, elevation of bone resorption, reduction of osteoid volume, and reduction of bone volume. Ca supplementation significantly increased the serum free Ca index and inhibited the elevation of bone resorption, the reduction of bone ash and Ca content, and the reduction of bone volume. This experimental study demonstrates that: (1) no marked vitamin D hydroxylation disorder was found in HOD; (2) vitamin D supplementation was effective in inhibiting HOD; and (3) sufficient Ca supplementation was also effective in inhibiting HOD.A portion of this work was presented at the 13th Annual Meeting of the Japanese Society for Bone and Mineral Research, July 1995, Fukuoka, Japan.     

Increase of mexiletine plasma levels due to delayed hepatic metabolism in patients with chronic liver disease

The clinical relevance of changes in pharmacokinetics of oralmexiletine (600 mg daily dose) was studied in 82 patients withventricular arrhythmias and impaired liver, renal or heart function(control group n = 51, patients with liver cirrhosis n = 9,with renal insufficiency n = 14, or heart failure n = 8). Increasedplasma levels of mexiletine were found in patients with chronicliver disease (2.21 ± 0.94 µg/ml, versus, 0.63± 0.22µg/ml of controls, P < 0.01). Plasma levels in patients with renal insufficiency or heartfailure were not significantly different from the controls.The resulting elevated plasma levels in patients with livercirrhosis emphasize the importance of hepatic metabolism inthe elimination of mexiletine. Drug monitoring must be considerednecessary in patients with impaired liver function.     

Correlation Between the Inhibitory Effects of Basic Drugs on the Uptake of Cardiac Glycosides and Taurocholate by Isolated Rat Hepatocytes

The role of the multispecific bile acid transporter for cardiac glycoside uptake is still controversial. This study was designed to examine the inhibitory effects of basic drugs (verapamil, dipyridamole, nifedipine, chlorpromazine, disopyramide, quinidine, propranolol, and lidocaine) on taurocholate uptake by isolated rat hepatocytes and to compare these effects with inhibition of ouabain uptake. Sodium-dependent taurocholate uptake was significantly reduced, to 50-70% of the control value, by 50 µM verapamil, dipyridamole, and nifedipine. Sodium-independent taurocholate uptake was more extensively inhibited, to 20-40%, by these basic drugs. The inhibition of ouabain uptake correlated better with sodium-independent taurocholate uptake ( = 0.918) than with sodium-dependent taurocholate uptake ( = 0.714). Taurocholate competitively inhibited ouabain uptake in the absence of sodium. These results indicate that the cardiac glycoside transport system is similar to the sodium-independent taurocholate transport system.     

Cytologic diagnosis of cavernous hemangioma of the liver with fine-needle biopsy.

We present the cytopathologic findings in seven cases of cavernous hemangiomas of the liver diagnosed by direct "squash" smears made on tissue obtained through image-guided fine-needle biopsy. The diagnosis in each case was confirmed histologically. Utilizing this simple cytologic technique, the morphologic findings in these common hepatic lesions are as accurate and diagnostic as histologic examination.     

Sonographic patterns of Caroli's disease: report of 5 new cases.

We have reviewed 5 cases of Caroli's disease, studied from 1982 to 1987, in order to define the validity of its sonographic signs. The "intraluminal portal vein" sign, found in all the cases, is emphasized. This sign may be easily identified and it is never encountered in other diseases. Recessive polycystic kidney disease was present in 3 cases, and congenital hepatic fibrosis was demonstrated in the 2 cases studied by liver biopsy.     

Technical aspects of hepatic portal dissection in biliary atresia.

During the past 8 yr, 37 patients with a noncorrectable type of biliary atresia have undergone hepatic portoenterostomy or portocholecystostomy at the Kobe Children's Hospital. The hepatic portal dissections employed in this series were classified as "supraportal" (9 procedures), "portal" (25 procedures), and "infra-portal" (3 procedures) based on the level at which the fibrous mass at the porta hepatis was transsected as determined by the operative record and the pathologic findings. Successful biliary drainage was achieved in 19 out of 25 patients (76%) with a "portal" type of dissection, while 1 out of 9 with "supra-portal" and none out of 3 with "infra-portal" type dissections were successful in this respect. Of the 19 patients who achieved significant biliary flow, 8 have lived for 2--7 yr without jaundice and 3 others are jaundice-free for shorter intervals.     

Hepatic clearance of drugs. II. Experimental evidence for acceptance of the “well-stirred” model over the “parallel tube” model using lidocaine in the perfused rat liverin situ preparation

Theoretical analysis of two models of hepatic drug clearance revealed that one powerful discriminator between them is the effect of changes of hepatic blood flow on either the emergent drug concentration or the availability of a highly extracted compound when operating under linear conditions. Lidocaine (extraction ratio 0.997) was employed in the discriminatory studies. The behavior of this drug under linear conditions (input lidocaine concentrations < 5 mg/ liter) to changes in hepatic blood flow rate (10–16 ml/min per liver) was examined in the perfused rat liver in situpreparation. The steady-state output lidocaine concentration in the blood leaving the liver was predicted better by a well-stirred model than by a parallel tube model. As anticipated, the clearance of a poorly extracted compound, antipyrine (extraction ratio 0.08),was unaltered by changes in hepatic blood flow. These experimental findings, and the data from the literature, point to the acceptance of the well-stirred model, which describes the liver as a well-stirred compartment with the drug in the hepatic venous blood being in equilibrium with that in the liver.Supported in part by National Institutes of Health Grant GM 16496 and the Patent Fund, Graduate Division, University of California, San Francisco.Abstracted in part from a dissertation submitted by K. Sandy Pang to the Graduate Division, University of California, San Francisco, California, in partial fulfillment of the Doctor of Philosophy degree requirements.     

当归对大鼠免疫性肝损伤的保护作用

目的 研究当归对免疫性肝损伤大鼠的保护作用。方法 采用牛血清白蛋白(BSA)致大鼠免疫肝损伤模型,观察当归大、小剂量对其肝功能、超氧化物歧化酶(SOD)、丙二醛(MDA)及肝细胞膜功能的影响。结果当归尤其是小刘量当归具有明显提高肝细胞SOD、降低MDA(P<0.05).并提高肝细胞膜ATP酶(ATPase)活性(P<0.05)的作用。结论提示当归具有明显的抗肝损伤作用.机制可能与其抗脂质过氧化作用及改善肝细胞功能有关。     

茵陈提取液对实验性动物肝损伤的作用

目的　研究茵陈提取液对实验性肝损伤的作用。 方法　 用茵陈提取液连续给小鼠灌胃 7d后 ,采用四氯化碳 (CCL4 )腹腔内注射造成小鼠急性肝损伤 ,造型 2 0h后摘除眼球取血 ,测ALT、AST、ALP、TP、G、A等指标 :给大鼠每周二次皮下注射 10 %CCL4油液 0 .5ml/ 10 0g ,造成慢性肝损伤 ,于中毒第三个月初起开始 ,每日用茵陈提取液连续给大鼠灌胃一个月 ,于末次给药 2 4h眶静脉取血 ,分离血清 ,AT、AST、总蛋白、白蛋白、白蛋白 /球蛋白 (A/G)等指示。 结果　CCL4造成小鼠急性肝脏损伤 ,出现明显肝功能异常 ,茵陈提取液治疗组小鼠各项指标较CCL4模型组均有所降低 ,但差异无显著性意义 (P >0 .0 5 ) ;在CCL4所致大鼠慢性肝损伤模型中 ,茵陈提取液治疗组可显著地降低大鼠由CCL4造成的AST活性升高 ,与模型组比较 ,P <0 .0 1。 结论　 茵陈提取液对CCL4所致大鼠慢性肝损伤有较好的治疗作用 ,但对CCL4造成小鼠急性肝伤模型没有保护作用。