Disrupted NF- kappa B activation after partial hepatectomy does not impair hepatocyte proliferation in rats.

Aim: To analyze the effects of NF- kappa B inhibition by antioxidant pyrrolidine dithiocarbamate (PDTC) or TNF inhibitor pentoxifylline (PTX) on liver regeneration after partial hepatectomy (PH).

Methods: Saline, PDTC or PTX were injected 1 h before PH and rats were killed at 0.5 and 24 h after PH.

Molecular events associated with accelerated proliferative response in rat livers when partial hepatectomy is preceded by a sham operation.

Background: When a sham operation is performed 6 h before partial hepatectomy (PH), the regenerative response is accelerated suggesting that sham operation itself contributes to cellular events leading to proliferation.

Materials And Methods: In order to examine the mechanisms implicated in this acceleration, we compared the activation of several factors associated with the progression through the cell cycle at various times after PH and after PH preceded by sham operation (S6 h + PH). The effect of a single sham (S) and two combined sham operations (S6 h + S) was also examined.

Retrorsine: a kinetic study of its influence on rat liver regeneration in the portal branch ligation model.

Background: Retrorsine, a naturally occurring pyrrolizidine alkaloid, impairs liver regeneration after partial hepatectomy by mechanisms that are still unclear.

Aim: The aim of the study was to clarify the influence of retrorsine on cell cycle progression in the regenerating liver lobes of rats after portal branch ligation (PBL).

Methods: Liver weight, protein and DNA contents, DNA synthesis (5'-bromodeoxyuridine (BrdU) incorporation) and cellular levels of Cyclin E, CDK-2, CDK-4 and proliferating cell nuclear antigen (PCNA) were assessed before and 24, 48, 72 and 168 h after PBL.

Steatosis is not sufficient to cause an impaired regenerative response after partial hepatectomy in rats.

Background/aims: Fatty liver is known to be associated with increased mortality and morbidity after liver resection. The ability of fatty liver to regenerate after two-thirds partial hepatectomy was studied in three different models of steatosis in rats: obese Zucker rats, orotic acid-fed Wistar rats and Wistar rats fed a methionine-low, choline-deficient diet.

Methods: Liver regeneration was assessed 24 h after partial hepatectomy by bromodeoxyuridine incorporation (immunohistochemistry), proliferating cell nuclear antigen, cyclin E and cyclin-dependent kinase 2 protein expression (Western blot analysis) and cyclin-dependent kinase 2 activity (kinase assays using histone H1 as a substrate).

Expression of presumed specific early and late factors associated with liver regeneration in different rat surgical models.

Experiments performed on the portal branch ligation (PBL) model indicate that early changes observed after surgery are not related to the regenerative process because they also occur in atrophying lobes. To further confirm the lack of specificity of the early events and to exclude the influence of circulatory factors released by proliferating lobes on their occurrence, we investigated this response after sham operation (SO) and portacaval shunt (PCS), a model characterized by liver atrophy. We also attempted to determine expression of later events associated specifically with regeneration, ie, expression of p53 or c-Ha-ras, or inhibition of proliferation, ie, interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) after partial (PH) and temporary partial (TPH) hepatectomy, SO and PCS.

After portal branch ligation in the rat, cellular proliferation is associated with selective induction of c-Ha-ras, p53, cyclin E, and Cdk2.

Background: In liver regeneration after portal branch ligation we previously showed that early cellular changes are observed in both the proliferating and atrophying liver lobes. They are therefore not indicative of future proliferative response. In this study we attempted to define precisely, in the same model, the time at which the cellular processes diverge between the lobes by measuring various parameters associated with cellular proliferation.

Early down-regulation of cytochrome P450 3A and 2E1 in the regenerating rat liver is not related to the loss of liver mass or the process of cellular proliferation.

Aims/background: Conflicting data have been reported concerning the modification of cytochrome P450 expression in the regenerating liver. Ligation of branches of the portal vein (PBL) perfusing 70% of the liver parenchyma, which produces regeneration and atrophy within the same liver, constitutes an ideal model to study the relative specificity of the early events in the regenerating liver and their relationship to the loss of liver mass.

Methods: In this PBL model and in sham models, we studied the expression and the metabolic activities of two major cytochromes, CYP3A and CYP2E1, and the expression of inducible nitric oxide synthase protein (iNOS).

The compensatory hyperplasia (liver regeneration) following ligation of a portal branch is initiated before the atrophy of the deprived lobes.

Background/aims: In rats, partial ligation of portal branches produces atrophy of the deprived lobes and hypertrophy of the intact lobes. The hepatocyte proliferation observed in the nondeprived lobes is viewed as a compensatory hyperplasia, implying that the atrophy somewhat precedes the initiation of the proliferative response. As this has not been demonstrated, the time course and magnitude of those two sequences of events were investigated and compared with the well-defined response to a partial hepatectomy.

Saccharomyces boulardii upgrades cellular adaptation after proximal enterectomy in rats.

Background: Saccharomyces boulardii is a non-pathogenic yeast which exerts trophic effects on human and rat small intestinal mucosa.

Aims: To examine the effects of S boulardii on ileal adaptation after proximal enterectomy in rats.

Methods: Wistar rats, aged eight weeks, underwent 60% proximal resection or transection and received by orogastric intubation either 1 mg/g body wt per day lyophilised S boulardii or the vehicle for seven days.

After portal branch ligation in rat, nuclear factor kappaB, interleukin-6, signal transducers and activators of transcription 3, c-fos, c-myc, and c-jun are similarly induced in the ligated and nonligated lobes.

Several studies have emphasized the involvement of transcription factors, cytokines, and proto-oncogenes in initiating the regenerative process after partial hepatectomy. To assess whether these events do specifically occur in a cellular system undergoing regeneration, we studied the induction of nuclear factor kappaB (NFkappaB), interleukin-6 (IL-6), signal transducers and activators of transcription 3 (Stat3), c-fos, c-myc, c-jun, after portal branch ligation (PBL), which produces atrophy of the deprived lobes (70% of the liver parenchyma), whereas the perfused lobes undergo compensatory regeneration. Nuclear extracts and total RNA were prepared from control livers as well as from atrophying and regenerating lobes at 0.

Early hepatocyte, endothelial, and bile duct cell injury after pediatric liver transplantation from cadaveric or living-related donors.

Background: When compared with cadaveric grafts (Cad), the potential advantages of pediatric orthotopic liver transplantation (OLT) from living-related (LR) donors may include better graft quality, shorter ischemic time, appropriate preparation of the recipient, and better immunologic compatibility.

Methods: The aim of this study was to analyze early hepatocyte, endothelial, and bile duct cell injury following pediatric OLT using LR (n=15) or uncomplicated Cad reduced-size (n=10) grafts. Median (range) total ischemic times were 190 min (105-261) versus 760 min (418-948) in LR and Cad groups, respectively (P<0.

The monoethylglycinexylidide test does not correctly evaluate lidocaine metabolism after ischemic liver injury in the rat.

Although the monoethylglycinexylidide (MEGX) test defined as a single determination of MEGX plasma concentration after lidocaine injection has been proposed as a liver function test, some discrepancies appeared in assessing the quality of liver donor for transplantation as well as the severity of liver disease. The present study used a severe ischemia-reperfusion liver injury (IRI) in rat to evaluate the various factors able to influence the level of MEGX. The metabolism of lidocaine was studied on microsomes isolated from intact rats and from rats submitted to this liver injury.

Control of rate and extent of the proliferative response after partial hepatectomy.

To examine the role of the early changes occurring in the liver within the first hours after a partial hepatectomy and in an attempt to demonstrate the involvement of subsequent regulatory mechanisms, the size of the remnant liver was modified at various times and by different surgical techniques. Male Wistar rats were submitted to a two-thirds "temporary partial hepatectomy" produced by a 3-h occlusion of the pedicle of the anterior lobes protected by local hypothermia. Various indexes of cell proliferation ([3H]thymidine uptake and 5-bromo-2'-deoxyuridine and proliferating cell nuclear antigen labeling) were not increased despite a c-myc expression as high as that observed after a two-thirds partial hepatectomy.

14C-Propoxyphene demethylation in the rat. An example of differences between liver and intestinal drug-presystemic metabolism.

Presystemic metabolism is believed to occur mainly in the liver with some minor intestinal participation. The aim of this study was to investigate the respective part of each of these two organs in the metabolism of the analgesic d-propoxyphene (DP). Pharmacological doses of DP were given in the duodenum (ID), the portal vein (IP), and the femoral vein (IV) of male Wistar rats.

[Prevention of acute hepatic failure after "90%" hepatectomy by portal branch ligation in rats].

In this study, ligation of portal branches feeding 90% liver mass was performed in rats. After the ligation, 10% liver mass with portal blood perfusion underwent a progressive hypertrophy. It gained weight against the control by about 5-fold at the 14th day.

Effect of sialoadenectomy and epidermal growth factor administration on liver regeneration after partial hepatectomy.

Epidermal growth factor (EGF), a mitogen in vitro for hepatocytes, produces in various cell lines changes similar to those observed very rapidly in hepatocytes after partial hepatectomy (PH). These changes include ion movements, membrane hyperpolarization and proto-oncogene expression. A stimulatory effect of EGF on liver regeneration can therefore tentatively be associated with the events occurring within the first 3 hours after a PH, sometimes referred to as the "priming phase.

Prior ligation of portal branches improves survival after a 90% portal hepatectomy in the rat.

The ligation of portal branches is known to induce an atrophy of the deprived lobes and a hypertrophy of the nonligated lobes. In this work, we examined if this response occurs when the ligation affects 90% of the liver mass and if it is able to influence the survival rate after a hepatectomy of this magnitude. In male Wistar rats, major portal branches were ligated, keeping open only a small branch supplying the papillary lobes.

Intestinal transport of calcium in rat biliary cirrhosis.

The characteristics of intestinal calcium transport in chronic cholestasis remain largely unknown. Using an experimental model of biliary cirrhosis in the rat, we aimed to investigate changes in calcium transport at the jejunal and ileal levels. Two methods were used: 1) uptake of 45Ca in brush border membrane vesicles and 2) measurements of transepithelial fluxes of calcium in Ussing chambers.

Branched chain amino acids improve body composition and nitrogen balance in a rat model of extra hepatic biliary atresia.

Malnutrition and growth retardation remain a major complication in infants with extrahepatic biliary atresia associated cholestasis. The purpose of this study was to investigate whether oral supplementation with branched chain amino acids (BCAA) can correct malnutrition in a rat model of biliary atresia. Four groups of 15 rats, 30 d old, were used.

CT of the portal vein after portacaval shunt with arterialization.

Objective: Our goal was to assess the state of the portal vein in cirrhotic patients treated with a portacaval shunt associated with an arterialization of the portal vein.

Materials And Methods: We reviewed the follow-up CT of 23 patients treated by portacaval shunt with arterialization of the portal vein.

Results: Five patients demonstrated an aneurysm of the portal vein.

Preformed antibody and complement rebound after plasma exchange: analysis of immunoglobulin isotypes and effect of splenectomy.

Unlabelled: Splenectomy (Sx) has been proposed to attenuate post-PE (plasma exchange) rebound of isoagglutinins and xenogenic (XG) antibody (Ab) in both ABO-incompatible allografts and discordant xenografts. This study analyses the qualitative nature and kinetics of serum immunoglobulins as well as complement resynthesis after PE in sham-operated (PE) and splenectomized (PE+Sx) syngeneic LOU/C rats; non-PE sham-operated or splenectomized animals were used as controls. PE was performed in unanesthetized, unheparinized rats.

Brain tumor imaging with PET and 2-[carbon-11]thymidine.

Methods: To assess the potential of thymidine for imaging brain tumors, 20 patients with untreated (n = 14) and recurrent (n = 6) supratentorial intracranial tumors were studied with PET by using 2-[11C]thymidine (Tdr), and the results were compared with [18F]fluorodeoxyglucose (FDG) PET data.

Results: Blood analysis consistently revealed a rapid clearance of the intact Tdr together with the appearance of CO2/HCO3- that, with time, accounted for approximately 70% of the total blood activity. As soon as 10 min after tracer injection, brain images showed a low and homogeneous Tdr distribution over the normal brain structures (cortex-to-blood ratio approximately 1).

In vivo IgM depletion by anti-mu monoclonal antibody therapy. The role of IgM in hyperacute vascular rejection of discordant xenografts.

Xenoreactive natural antibodies (XNA) and complement activation are thought to be the 2 main factors responsible for the hyperacute vascular rejection (HVR) of discordant xenografts. The aim of this work was to study the role of IgM XNA in the HVR of guinea pig to rat cardiac xenografts, a discordant model. Adult LOU/C rats were depleted of circulating IgM and therefore of IgM XNA using an anti-mu mAb (mouse anti-rat IgM mAb 7 [MARM-7]).

Measurement of the vasoconstrictive substances endothelin, angiotensin II, and thromboxane B2 in cold storage solution can reveal previous renal ischemic insults.

In a rat model, the left kidney was subjected to 60 min of normothermic ischemia followed by 15 min of reperfusion, whereas the right kidney, serving as a paired control, was not rendered ischemic. Both kidneys were then perfused in situ with either Euro-Collins (EC) solution (n = 12) or University of Wisconsin (UW) solution (n = 6) for 10 min. Each kidney was then harvested and stored at 4 degrees C in its respective solution.