Role of cysteinyl-leukotrienes for portal pressure regulation and liver damage in cholestatic rat livers.

Kupffer cells (KCs) have a major role in liver injury, and cysteinyl-leukotrienes (Cys-LTs) are known to be involved as well. The KC-mediated pathways for the production and secretion of Cys-LT in cholestatic liver injury have not yet been elucidated. Here, we hypothesized that KC activation by Toll-like receptor ligands results in Cys-LT-mediated microcirculatory alterations and liver injury in acute cholestasis.

Portal pressure regulation following Kupffer cell activation: control of prostaglandin production by heme oxygenases.

Background: Portal pressure (PP) results from the interplay of vasoconstrictors and vasodilators. Recently, we have shown that Kupffer cell (KC) activation increases PP.

Aims: The role of the vasodilating compounds nitric oxide (NO) and carbon monoxide (CO) was studied.

Tacrolimus preconditioning of rat liver allografts impacts glutathione homeostasis and early reperfusion injury.

Objective: To characterize the immunosuppressant tacrolimus as a protective antioxidant in rat liver transplantation.

Methods: Livers of male Lewis rats underwent 24 h of hypothermic preservation in UW solution and were rinsed with tacrolimus or placebo directly before transplantation. Markers of liver injury, such as enzymes and bile flow, were determined during a 2 h reperfusion period.

GSH attenuates organ injury and improves function after transplantation of fatty livers.

Ischemia-reperfusion injury (IRI) is increased after transplantation of steatotic livers. Since those livers are increasingly used for transplantation, protective strategies must be developed. Reactive oxygen species (ROS) play a key role in hepatic IRI.

Treatment with the leukotriene inhibitor montelukast for 10 days attenuates portal hypertension in rat liver cirrhosis.

Unlabelled: The mechanisms underlying intrahepatic vasoconstriction are not fully elucidated. Here we investigated the Kupffer cell (KC)-dependent increase in portal pressure by way of actions of vasoconstrictive cysteinyl leukotrienes (Cys-LTs). Liver cirrhosis was induced in rats by bile duct ligation (BDL for 4 weeks; controls: sham-operation) and thioacetamide application (18 weeks).

Intraperitoneal LPS amplifies portal hypertension in rat liver fibrosis.

Recent studies have shown that the risk of variceal bleeding in patients with liver cirrhosis increases with infections such as spontaneous bacterial peritonitis (SBP). In this study, we hypothesized that pretreatment with intraperitoneal LPS may escalate portal hypertension. In fibrotic livers (4 weeks after bile duct ligation, BDL), the activation of Kupffer cells (KCs) by zymosan (150 microg/ml) in the isolated non-recirculating liver perfusion system resulted in a transient increase in portal perfusion pressure.

Kupffer cell activation by hydrogen peroxide: a new mechanism of portal pressure increase.

This study aimed to investigate the effects of reactive oxygen species on the hepatic macrophages, the Kupffer cells (KC), and to identify the relevant targets of vasoconstrictors involved in the regulation of intrahepatic microcirculation and therefore portal pressure. The effects of hydrogen peroxide (H2O2), xanthine/xanthine oxidase or a thromboxane (TX) analogue (U46619; 0.1 microM) were tested in sham-operated and fibrotic livers (bile duct ligation over 4 weeks) during isolated rat liver perfusion and in vivo with or without additional KC blockade (gadolinium chloride, 10 mg kg(-1) body weight, 48 and 24 h, i.

Kupffer cell activation in normal and fibrotic livers increases portal pressure via thromboxane A(2).

Background/aims: Cirrhotic patients show an increased risk of variceal bleeding upon bacterial infections. Kupffer cells (KC) constitute the first macrophage population to become activated by bacterial beta-glucans and endotoxins derived from the gut. We therefore investigated whether and how KC activation increases portal pressure.

IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro.

The IL-10-like cytokine IL-22 is produced by activated T cells. In this study, we analyzed the role of this cytokine system in hepatic cells. Expression studies were performed by RT-PCR and quantitative PCR.

Role of Kupffer cells in host defense and liver disease.

Kupffer cells (KC) constitute 80-90% of the tissue macrophages present in the body. They reside within the lumen of the liver sinusoids, and are therefore constantly exposed to gut-derived bacteria, microbial debris and bacterial endotoxins, known to activate macrophages. Upon activation KC release various products, including cytokines, prostanoides, nitric oxide and reactive oxygen species.

Perforation of the colon: a rare complication of hepatocellular carcinoma.

Direct infiltration of the colon by hepatocellular carcinoma (HCC) is a rare condition. Only a few reports can be found in the literature. Here we present a case of direct infiltration of the ascending colon by an exophytic growing HCC of the right posterior liver lobe, in which treatment with transarterial chemoembolization (TACE) had been performed.

PI 3-kinase pathway is responsible for antiapoptotic effects of atrial natriuretic peptide in rat liver transplantation.

Aim: To investigate the in vivo effect of atrial natriuretic peptide (ANP) and its signaling pathway during orthotopic rat liver transplantation.

Methods: Rats were infused with NaCl, ANP (5 microg/kg), wortmannin (WM, 16 microg/kg), or a combination of both for 20 min. Livers were stored in UW solution (4 degrees C) for 24 h, transplanted and reperfused.

Characterization of organic anion transporter regulation, glutathione metabolism and bile formation in the obese Zucker rat.

Background/aims: Alterations in hepatobiliary transporters may render fatty livers more vulnerable against various toxic insults.

Methods: We therefore studied expression and function of key organic anion transporters and their transactivators in 8-week-old obese Zucker rats, an established model for non-alcoholic fatty liver disease.

Results: Compared to their heterozygous littermates, obese animals showed a significant reduction in canalicular bile salt secretion, which was paralleled by significantly diminished Oatp2 mRNA and protein levels together with reduced nuclear HNF3beta, while expression of bile salt export pump, organic anion transporter (Oatp) 1 and multidrug resistance-associated protein (Mrp) 4 were unchanged.

Suramin inhibits death receptor-induced apoptosis in vitro and fulminant apoptotic liver damage in mice.

Suramin is a polysulfonated derivative of urea and has been widely used both to treat infections and as a chemotherapeutic drug. Suramin has been shown to inhibit growth factor signaling pathways; however, its effect on apoptosis is unknown. Here we show that suramin inhibits apoptosis induced through death receptors in hepatoma and lymphoma cells.

ANP-induced decrease of iron regulatory protein activity is independent of HO-1 induction.

Atrial natriuretic peptide (ANP)-preconditioned livers are protected from ischemia-reperfusion injury. ANP-treated organs show increased expression of heme oxygenase (HO)-1. Because HO-1 liberates bound iron, the aim of our study was to determine whether ANP affects iron regulatory protein (IRP) activity and, thus, the levels of ferritin.

Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation.

Aim: To investigated the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation.

Methods: Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting. During a 2-h reperfusion period either saline (controls, n=8) or GSH (50 or 100 micromol/(h/kg), n=5 each) was continuously administered via the jugular vein.

ANP preconditioning does not increase protection against experimental pancreatitis, observed after general anesthesia and jugular vein catheterization.

It has been widely shown that preconditioning, inducing heat shock proteins, can protect against experimentally induced pancreatitis. Solid evidence indicates that HSP70 plays a central role in this context, possibly by inhibition of premature intracellular trypsinogen activation. Current preconditioning protocols such as whole body hyperthermia are, however, quite strenuous and clinically not applicable.

Selective retroinfusion of GSH and cariporide attenuates myocardial ischemia-reperfusion injury in a preclinical pig model.

Objective: Reperfusion after ischemia may contribute to loss of myocardial function and increase in infarct size. Scavenging of reactive oxygen species (ROS) by glutathione (GSH) and inhibition of the sodium-proton-exchanger by cariporide are both capable of reducing myocardial reperfusion injury. We tested the efficacy of both agents applied regionally into the myocardium immediately before reperfusion.

Glutathione protects the rat liver against reperfusion injury after prolonged warm ischemia.

Objective: To evaluate the potential of postischemic intravenous infusion of the endogenous antioxidant glutathione (GSH) to protect the liver from reperfusion injury following prolonged warm ischemia.

Background Data: The release of reactive oxygen species (ROS) by activated Kupffer cells (KC) and leukocytes causes reperfusion injury of the liver after warm ischemia. Therefore, safe and cost-effective antioxidant strategies would appear a promising approach to prevent hepatic reperfusion injury during liver resection, but need to be developed.

[52-year-old patient with subcutaneous space-occupying lesion in immunosuppression].

We report the case of a 52-years-old male patient, who was diagnosed with subcutaneous alveolar echinococcosis 6 months after liver transplantation for HCV-related cirrhosis. Nether the explanted nor the transplantated liver revealed an echinococcus focus. Therefore a rare primary extrahepatic manifestation was likely.

Atrial natriuretic peptide preconditioning protects against hepatic preservation injury by attenuating necrotic and apoptotic cell death.

Background/aims: Preconditioning of livers with the atrial natriuretic peptide (ANP) markedly reduces hepatic ischemia-reperfusion injury. Aim of this study was to characterize the influence of ANP preconditioning on necrotic and apoptotic cell death and on proliferation.

Methods: Rat livers were perfused with Krebs-Henseleit buffer with or without ANP or its second messenger analogue 8-Bromo cyclic guanosine monophosphate (8-Br cGMP) for 20 min, stored in cold University of Wisconsin solution (24 h), and reperfused for up to 120 min.

Rapid development of esophageal squamous cell carcinoma after liver transplantation for alcohol-induced cirrhosis.

Liver transplant recipients have an increased risk of developing de novo malignancies. It is generally accepted that chronic alcohol abuse is a contributive factor in the pathogenesis of several malignancies, in particular, of oropharyngeal squamous cell carcinoma (SCC). Thus, patients with end-stage alcohol-induced cirrhosis could be at risk of esophageal SCC following orthotopic liver transplantation (OLT).

Kupffer-cell specific induction of heme oxygenase 1 (hsp32) by the atrial natriuretic peptide--role of cGMP.

Background/aims: Pretreatment with atrial natriuretic peptide (ANP) attenuates ischemia-reperfusion injury of livers via cGMP. Heme oxygenase-1 (HO-1) is known as a protective mediator in ischemia-reperfusion injury. The aim of this study was to investigate whether ANP affects the expression of HO-1.

Induction of cellular resistance against Kupffer cell-derived oxidant stress: a novel concept of hepatoprotection by ischemic preconditioning.

Ischemic preconditioning (IP) triggers protection of the liver from prolonged subsequent ischemia. However, the underlying protective mechanisms are largely unknown. We investigated whether and how IP protects the liver against reperfusion injury caused by Kupffer cell (KC)-derived oxidants.

Improved quality of life in patients with refractory or recidivant ascites after insertion of transjugular intrahepatic portosystemic shunts.

Background: We have recently shown that the transjugular intrahepatic portosystemic shunt (TIPS) is more effective than paracentesis in the treatment of cirrhotic patients with severe ascites and can prolong survival in selected patients. Although an improved quality of life (QOL) has been suggested in these patients after the TIPS procedure, so far there are no data available to substantiate this assumption. Therefore, the aim of this study was to determine the effect of TIPS on the QOL in cirrhotic patients with refractory or recidivant ascites.