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41.
Jean de Ville de Goyet Raymond Reding Viktoria Hausleithner Jan Lerut Jean-Bernard Otte 《Transplant international》1995,8(4):280-285
This paper describes a quick procedure for cadaveric liver graft retrieval during multiple organ harvesting. The technique is based on minimal preliminary dissection, absence of in situ direct portal perfusion, and en bloc removal of the liver and pancreas, with an aortic patch encompassing the coeliac trunk and superior mesenteric artery. The results of 110 pediatric liver transplantations with 109 organs harvested using this technique are reported. There were no graft harvesting injuries. The liver graft primary nonfunction rate was 4.5% (5/110). The 3-month retransplantation rate was 10%. The actual patient survival rates were 93% at 3 months and 90% at 1 year; actual graft survival rates were 85.5% and 78%, respectively. The technique described was at least as safe as conventional procedures. A major advantage of the procedure is its flexibility, which allows for the easily combined procurement of other organs (whole pancreas and intestine). 相似文献
42.
Pia Lautala Maija Kivimaa Hannele Salomies Eivor Elovaara Jyrki Taskinen 《Pharmaceutical research》1997,14(10):1444-1448
Purpose. Nitrocatechol COMT inhibitors are a new class of bioactive compounds, for which glucuronidation is the most important metabolic pathway. The objective was to characterize the enzyme kinetics of nitrocatechol glucuronidation to improve the understanding and predicting of the pharmacokinetic behavior of this class of compounds.
Methods. The glucuronidation kinetics of seven nitrocatechols and 4-nitrophenol, the reference substrate for phenol UDP-glucuronosyltrans-ferase activity, was measured in liver microsomes from creosote-treated rats and determined by non-linear fitting of the experimental data to the Michaelis-Menten equation. A new method that combined densitometric and radioactivity measurement of the glucuronides separated by HPTLC was developed for the quantification.
Results. Apparent Km values for the nitrocatechols varied greatly depending on substitution pattern being comparable with 4-nitrophenol (0.11 mM) only in the case of 4-nitrocatechol (0.19 mM). Simple nitrocatechols showed two-fold Vmax values compared with 4-nitrophenol (68.6 nmol min–1 mg–1), while all disubstituted catechols exhibited much lower glucuronidation rate. Vmax/Km values were about 10 times higher for monosubstituted catechols compared to disubstituted ones. The kinetic parameters for COMT inhibitors were in the following order: Km nitecapone >> entacapone > tolcapone; Vmax nitecapone > entacapone > tolcapone; Vmax/Km tolcapone > nitecapone > entacapone.
Conclusions. Nitrocatechols can in principle be good substrates of UGTs. However, substituents may have a remarkable effect on the enzyme kinetic parameters. The different behaviour of nitecapone compared to the other COMT inhibitors may be due to its hydrophilic 5-substituent. The longer elimination half-life of tolcapone in vivo compared to entacapone could not be explained by glucuronidation kinetics in vitro. 相似文献
43.
Characterization of the human cytochrome P450 enzymes involved in the metabolism of dihydrocodeine 总被引:1,自引:0,他引:1
L. C. Kirkwood R. L. Nation & A. A. Somogyi 《British journal of clinical pharmacology》1997,44(6):549-555
Aims Using human liver microsomes from donors of the CYP2D6 poor and extensive metabolizer genotypes, the role of individual cytochromes P-450 in the oxidative metabolism of dihydrocodeine was investigated.
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K m values. The kinetic constants for O -demethylation were significantly different in extensive and poor metabolizers. The extensive metabolizers had a mean intrinsic clearance to dihydromorphine more than ten times greater than the poor metabolizer. The CYP2D6 chemical inhibitors, quinidine and quinine, and LKM1 antibodies inhibited O -demethylation in extensive metabolizers; no effect was observed in microsomes from a poor metabolizer.
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A. 相似文献
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A. 相似文献
44.
用小鼠胎肝细胞体外血浆凝块培养红系集落(Erythroid colong formig unit inculturc,E-CFUc)方法,以红细胞生成素(Erythropoietin,EPO)850323为标准试剂,测定正常人、贫血病人血清EPO浓度。实验用妊娠13~15d小鼠胎肝细胞。血清均经透析处理,培养液中加量最大不超过10%。EPO(850323)在培养液中浓度为2.5~100mU/ml。血清EPO(mU/ml)测定结果:28例正常人为48.O±17.7,12例再生障碍性贫血病人为946~>10000,1例巨幼细胞性贫血病人为500,1例缺铁性贫血病人为400和18例慢性肾功能衰竭病人则为94.2±87.6。结果表明:贫血病因对血清EPO浓度有影响。 相似文献
45.
Symptomatic liver cyst: Special reference to surgical management 总被引:2,自引:0,他引:2
Kenji Kakizaki Hidemi Yamauchi Shin Teshima 《Journal of Hepato-Biliary-Pancreatic Surgery》1998,5(2):192-195
We conducted a retrospective study of 14 patients with symptomatic liver cysts to evaluate current therapeutic interventions
for this condition. Abdominal pain (n = 7) or abdominal mass (n = 5) were the most frequent presentations. Three patients also had renal cyst. Percutaneous aspiration with ethanol sclerotheraphy
was carried out in 4 patients and all cysts so treated diminished in size, with relief of the symptoms. One patient was treated
by aspiration only and re-retension occurred. Cystectomy was performed in 2 patients, unroofing in 5, and fenestration in
2 patients. All patients gained relief of symptoms, with no recurrence of symptoms. Computed tomography revealed that the
cysts were diminished or were no longer observable after all the treatments. Our experience indicates that unroofing, fenestration,
and cystectomy are safe and suitable procedures for treatment of the condition. Ethanol sclerotherapy may be a feasible alternative
to surgical intervention in selected patients.
Received for publication on July 23, 1997; accepted on Dec. 25, 1997 相似文献
46.
甲基强的松龙对低温保存大鼠肝脏的保护作用 总被引:2,自引:1,他引:1
应用Wistar大鼠肝脏离体灌流模型,用CMU—1号液,含有甲基强的松龙的CMU—1号液,以及缺血前预用甲基强的松龙后再用CMU—1号液分别对肝脏进行灌洗保存。检测LDH、ALT、肝组织匀浆SOD活性和MDA含量,并观察肝组织结构。结果表明:甲基强的松龙对低温保存的离体大鼠肝脏具有保护作用 相似文献
47.
Eiji Takeuchi Yuji Nimura Shin-ichi Mizuno Hideaki Suzuki Shinsuke Iyomasa Masaki Terasaki Hiroshi Kuriki Keiko Tamiya-Koizumi Shonen Yoshida 《Journal of Hepato-Biliary-Pancreatic Surgery》1997,4(3):254-262
Hepatocyte regeneration has been widely investigated, with the mitotic index and the incorporation of [3H]thymidine being used as regeneration markers. We focused on the induction of DNA replication enzymes, particularly DNA polymerases
(pol) α, δ, and ε. Using rat models, we have shown that the activity of pol α in crude liver extract well represents the regenerating
capacity of hepatocytes. Using pol α as an indicator, we analyzed liver regeneration in rat models under various conditions:
obstructive jaundice, external or internal biliary drainage, and the obstruction of portal vein branches. It has been revealed
that the ligation of the common bile duct alone induces a certain amount of hepatocyte proliferation. It was striking that
external biliary drainage suppressed regeneration capacity in cholestatic rat liver after partial hepatectomy. The strong
regeneration in nonligated lobes induced by portal branch ligation was similar to the liver regeneration seen after partial
hepatectomy with respect to the induction of DNA polymerases. Taken together, the aspects of DNA replication, particularly
the induction of DNA polymerases, may contribute to shedding new light on the regeneration of human liver.
This work was supported in part by a Grant-in-Aid for General Scientific Research and for Cancer Research from the Ministry
of Education, Science and Culture, Japan, and by grants from the Uehara Memorial Foundation 相似文献
48.
A rat model of monitoring liver allograft rejection 总被引:5,自引:0,他引:5
Timi Martelius Heikki Mäkisalo Krister Höckerstedt Eero Taskinen Irmeli Lautenschlager 《Transplant international》1997,10(2):103-108
Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection,
monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 ± 20
days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation
in the FNAB [9.1 ± 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 ± 4.4 CIU), together
with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from
1 % ± 2 % to 21 % ± 13 %) and class II (from 20 % ± 9 % to 43 % ± 13 %) expressing lymphoid cells and induction of ICAM-1
in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology.
In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental
animals. This saves work, animals, and costs in the study of liver rejection.
Received: 2 July 1996 Accepted: 28 October 1996 相似文献
49.
T. Scholz Ø. Mathisen A. Bergan S. Osnes R. Innes T. Pedersen A. O. Aasen O. Søreide 《Transplant international》1997,10(3):180-184
We have introduced and evaluated several modifications of the conventional venovenous bypass (VVBP) in 29 adult patients
undergoing liver transplantation (OLT). A percutaneous technique for insertion of a jugular venous return cannula and a femoral
vein cannula was applied. The inferior mesenteric vein (IMV) was used for splanchnic decompression, which facilitated dissection
of the recipient liver and allowed portal anastomosis to be performed without disconnecting the portal bypass. A heat exchanger
was introduced into the bypass circuit to prevent heat loss. The percutaneous technique prevented complications related to
dissection in the axilla and groin. Hemodynamic characteristics corresponded to those found using the traditional technique.
Complications related to the VVBP were seen in only one patient in whom the femoral catheter was accidentally introduced into
the femoral artery. We conclude that percutaneous cannulas, use of the IMV for splanchnic decompression and the introduction
of a heat exchanger offer significant benefits and that they are safe and reliable.
Received: 23 August 1996 Received after revision: 14 January 1997 Accepted: 27 January 1997 相似文献
50.
Summary With the use of duplex Doppler ultrasound and color Doppler flow imaging(CDFI), the characteristics of blood supply in neoplasma
were studied in 51 cases of 60 liver tumors, and compared with the results of surgery, pathological examination and hepatic
anerial angiography. The result showed that: 1. Doppler blood flow signals could be detected in all hepatic carcinomas, and
in 10 cases of 18 hemangiomas, significant difference was observed (P<0.001); 2. Doppler blood flow spectra showed pulsatile pattern in 41 of 42 hepatic carcinomas, and in 6 of 10 hemangiomas
(P<0.01); and 3. the peak flow velocity was obviously lower in hemangioma group than in hepatic carcinoma group (20.34±23.93
vs 64.74±30.18 cm,P<0.001). The characteristics of CDFI show that hemangiomas and hepatocellular carcinomas are different. It can, therefore,
be concluded that the blood supply of hepatic carcinomas mainly comes from hepatic arterial system, and is of value in duplex
Doppler ultrasound and CDFI. 相似文献