Serotonin protects mouse liver from cholestatic injury by decreasing bile salt pool after bile duct ligation.

Unlabelled: Obstructive cholestasis induces liver injury, postoperative complications, and mortality after surgery. Adaptive control of cholestasis, including bile salt homeostasis, is necessary for recovery and survival. Peripheral serotonin is a cytoprotective neurotransmitter also associated with liver regeneration.

Partial bile duct ligation in mice: a novel model of acute cholestasis.

Background: The standard model for research in cholestasis is the total ligation of the bile duct (tBDL). Because this model causes severe hepatic injury in mice, we developed a novel model of cholestasis using a partial bile duct ligation (pBDL) and evaluate different mechanisms of injury.

Methods: Male C57Bl/6 mice were subjected to sham operation, tBDL, or pBDL.

Serotonin regulates macrophage-mediated angiogenesis in a mouse model of colon cancer allografts.

Serotonin, a neurotransmitter with numerous functions in the central nervous system (CNS), is emerging as an important signaling molecule in biological processes outside of the CNS. Recent advances have implicated serotonin as a regulator of inflammation, proliferation, regeneration, and repair. The role of serotonin in tumor biology in vivo has not been elucidated.

Aggravation of viral hepatitis by platelet-derived serotonin.

More than 500 million people worldwide are persistently infected with hepatitis B virus or hepatitis C virus. Although both viruses are poorly cytopathic, persistence of either virus carries a risk of chronic liver inflammation, potentially resulting in liver steatosis, liver cirrhosis, end-stage liver failure or hepatocellular carcinoma. Virus-specific T cells are a major determinant of the outcome of hepatitis, as they contribute to the early control of chronic hepatitis viruses, but they also mediate immunopathology during persistent virus infection.

Extralymphatic virus sanctuaries as a consequence of potent T-cell activation.

T helper cells can support the functions of CD8(+) T cells against persistently infecting viruses such as murine lymphocytic choriomeningitis virus (LCMV), cytomegalovirus, hepatitis C virus and HIV. These viruses often resist complete elimination and remain detectable at sanctuary sites, such as the kidneys and other extralymphatic organs. The mechanisms underlying this persistence are not well understood.

Routine stenting reduces urologic complications as compared with stenting "on demand" in adult kidney transplantation.

Objectives: To examine the impact of the chosen surgical technique and of systematic versus "on-demand" placement of a primary stent on the incidence of urologic complications in adult kidney transplantation.

Methods: Data of 497 consecutive patients undergoing kidney transplantation at a single center were retrospectively analyzed with respect to urologic complications. Three different surgical strategies for the ureteroneocystostomy were compared: (1) transvesical anastomosis with stenting "on demand," (2) extravesical anastomosis with stenting "on demand," and (3) extravesical anastomosis with routine stenting.

Serotonin mediates oxidative stress and mitochondrial toxicity in a murine model of nonalcoholic steatohepatitis.

Background And Aims: Nonalcoholic steatohepatitis (NASH) is one of the most common causes of liver enzyme elevation in the West. Its prevalence is likely to increase further, paralleling the epidemic increase of the metabolic syndrome. Serotonin degradation by monoamine oxidase A (MAO-A) was recently implicated as an important source of reactive oxygen species.

Platelets and platelet-derived serotonin promote tissue repair after normothermic hepatic ischemia in mice.

Unlabelled: Hepatic ischemia and reperfusion (I/R) leads to the formation of leukocyte-platelet aggregates. Upon activation, platelets generate reactive oxygen species and release proapoptotic and proinflammatory mediators as well as growth factors. In cold hepatic ischemia, adhesion of platelets to endothelial cells mediates sinusoidal endothelial cell apoptosis.

Increased susceptibility to bacterial superinfection as a consequence of innate antiviral responses.

The reason why severe localized or systemic virus infections enhance and aggravate bacterial superinfection is poorly understood. Here we show that virus-induced IFN type I caused apoptosis in bone marrow granulocytes, drastically reduced granulocyte infiltrates at the site of bacterial superinfection, caused up to 1,000-fold higher bacterial titers in solid organs, and increased disease susceptibility. The finding that the innate antiviral immune response reduces the antibacterial granulocyte defense offers an explanation for enhanced susceptibility to bacterial superinfection during viral disease.

Immunoprivileged status of the liver is controlled by Toll-like receptor 3 signaling.

The liver is known to be a classical immunoprivileged site with a relatively high resistance against immune responses. Here we demonstrate that highly activated liver-specific effector CD8+ T cells alone were not sufficient to trigger immune destruction of the liver in mice. Only additional innate immune signals orchestrated by TLR3 provoked liver damage.

Kupffer cell-dependent TNF-alpha signaling mediates injury in the arterialized small-for-size liver transplantation in the mouse.

Implantation of small liver grafts causes liver injury and defective regeneration leading to graft failure. We investigated whether Kupffer cell-dependent TNF-alpha signaling contributes to this poor outcome. Partial 30% liver transplantation was performed in C57BL/6 wild-type mice (control group), and in three groups with down-regulation of the TNF-alpha pathway: (i) TNF receptor 1 knockout [TNFR-1(-/-)] mice, and mice pretreated with (ii) gadolinium chloride or (iii) pentoxifylline (PTX).

Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical implications.

Widespread application of cadaveric split or living donor liver transplantation bears considerable potential to increase the pool of available organs and thus alleviate the problem of organ shortage. Although splitting of a cadaveric liver into two grafts for adult recipients can be performed successfully, sufficient function of undersized grafts is a major concern. To minimize the risk for living donors, transplant surgeons aim at procuring the least necessary liver volume, also leading to potentially small grafts.