Treatment of refractory cholestatic pruritus after liver transplantation with albumin dialysis.

Albumin dialysis has been shown to improve the outcome in patients with cholestatic liver failure caused by chronic liver disease. This study reports 7 liver transplant recipients who were treated with albumin dialysis for intractable pruritus of different origin (ductopenic graft rejection, non-anastomotic strictures, and recurrence of hepatitis C). Treatment with histamine (H1) blockers, opioid antagonists, and cholestyramine had not been effective.

Pharmacokinetics of amphotericin B lipid complex in critically ill patients on continuous veno-venous haemofiltration.

Pharmacokinetics of amphotericin B lipid complex (ABLC) was determined in two critically ill patients requiring continuous veno-venous haemofiltration (CVVH) because of acute renal failure. ABLC was administered at a mean daily dose of 4.94 mg/kg for suspected invasive mycosis.

Heparan sulfate proteoglycans are involved in opiate receptor-mediated cell migration.

Opioid receptors are expressed in cells of the immune system, and potent immunomodulatory effects of their natural and synthetic ligands have been reported. In some studies, the opiate receptor antagonist naloxone itself displayed immunomodulatory actions. We investigated effects of naloxone on leukocyte chemotaxis.

Syndecan-4-dependent signaling in the inhibition of endotoxin-induced endothelial adherence of neutrophils by antithrombin.

Circulating endotoxin is elevated in sepsis and plays a role in endothelial dysfunction whereas antithrombin is decreased by virtue of its consumption during complex formation with clotting factors and by proteolytic degradation by granulocyte elastase. Dysfunction of endothelium results in enhanced leukocyte rolling and diapedesis into tissues leading to edema formation and injury. Antithrombin exerts beneficial effects on endothelial function in sepsis.

CD40 ligand-dependent maturation of human monocyte-derived dendritic cells by activated platelets.

Atherosclerosis is defined as an inflammatory immunological disease that is triggered by platelet activation, endothelial injury and consequent innate and adaptive immune processes. Dendritic cells are critical for the cell-mediated arm of the immune response as they activate naïve T cells after maturation. Platelets play a crucial role in thrombus formation in the injured vessel walls.

Expression and function of the vascular endothelial growth factor receptor FLT-1 in human eosinophils.

Vascular endothelial growth factor (VEGF) is highly expressed in the airway of patients with asthma. Whether VEGF affects eosinophil function in vitro and if VEGF receptors are involved was tested. Eosinophils were from venous blood of healthy donors.

Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression.

In vivo evidence suggests that interleukin-18 (IL-18) shapes the development of adaptive immunity toward T-helper cell type 1 (Th1) responses. Monocyte-derived dendritic cells 1 (DC1s) preferentially induce a Th1 response, while plasmacytoid DC-derived DC2s have been linked to a Th2 response. We analyzed the role of IL-18 during the initiation phase of a Th response in vitro to elucidate the basis of these in vivo observations.

Agonist function of the neurokinin receptor antagonist, [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P, in monocytes.

G-protein-coupled bombesin receptors are capable of signaling through the G(i) protein even when receptor-coupling to G(q) is blocked by [D-Arg1,D-Phe5,D-Trp7,9,Leu11]substance P (SpD), a neurokinin-1 receptor antagonist and "biased" agonist to bombesin receptors. As bombesin is a monocyte and tumor cell attractant, we were interested in the effects of SpD on cell migration. Chemotaxis of monocytes was tested in micropore filter assays.

Endothelial protein C receptor-dependent inhibition of human eosinophil chemotaxis by protein C.

Background: Eosinophil infiltration is a characteristic feature of allergic inflammation. Allergic responses are associated with local activation of the coagulation pathway and accumulation of fibrin.

Objective: We tested whether protein C and activated protein C (APC), which are endogenous anti-inflammatory coagulation inhibitors, affect eosinophil function.

Leukocyte motility in response to neuropeptides is heparan sulfate proteoglycan dependent.

Activation of neuropeptide receptors on leukocytes induces chemotaxis. We determined in Boyden chambers with micropore filters, whether in human monocytes and lymphocytes this migratory response is heparan sulfate proteoglycan (HSPG) dependent. Chemotaxis toward calcitonin gene-related peptide, secretoneurin, vasoactive intestinal peptide (VIP), and substance P (SP) was abolished by removal of heparan sulfate side chains from cell surface proteoglycans or by addition of anti-syndecan-4 antibodies.

Inhibition of neutrophil migration and oxygen free radical release by metipranolol and timolol.

Propanolol and metoprolol exert adrenoceptor-independent effects including scavenging of free radicals and inhibition of protein kinase C leading to inhibition of leukocyte migration and radical release as a consequence. Whether topically used metipranolol and timolol exert such effects is unknown. Neutrophil chemotaxis was tested using modified Boyden microchemotaxis chambers.

Toll-like receptor 4 and atherogenesis.

Toll-like receptor 4 (TLR4) is a pattern recognition receptor involved in the innate immune response to various microorganisms and other exogenous and endogenous stress factors. Recently, evidence emerged that important inflammatory processes implicit in human atherogenesis are mediated in part via the TLR4/nuclear factor-kappaB pathway. Polymorphisms of TLR4, which attenuate receptor signalling, enhance the risk of acute severe infections but may have opposite effects on atherogenesis.

Expression and function of the endothelial protein C receptor in human neutrophils.

Activation of protein C by thrombin bound to thrombomodulin is enhanced by endothelial protein C receptor. This pathway may inhibit inflammation. We investigated effects of protein C and activated protein C on neutrophils as well as whether an endothelial protein C receptor is involved in mediating protein C effects.

Sphingosine kinase-dependent migration of immature dendritic cells in response to neurotoxic prion protein fragment.

The concept that circulating dendritic cells mediate neuroinvasion in transmissible spongiform encephalopathies received strong support from recent observations that prion protein is expressed in myeloid dendritic cells. We observed that prion protein fragment 106-126 is a chemoattractant for monocyte-derived immature but not mature dendritic cells. Signaling events in chemotaxis involved enzymes downstream of G(q) protein and were inhibited by blockade of sphingosine kinase, suggesting transactivation of sphingosine-1-phosphate-dependent cell motility by prion protein.

Parthenolide and its photochemically synthesized 1(10)Z isomer: chemical reactivity and structure-activity relationship studies in human leucocyte chemotaxis.

The present study has achieved the photochemical conversion of a germacrolide into a melampolide. The investigation on their chemical properties allowed us to evaluate the minimum interatomic distance needed for transannular bridging of C(10) ring in germacrolides and to explain the regiochemical selectivity of electrophilic cyclizations. The antiinflammatory activity of parthenolide and its semisynthetic derivatives was evaluated by in vitro chemotaxis assay with human neutrophiles.

Amphotericin B lipid formulations in critically ill patients on continuous veno-venous haemofiltration.

Objectives: The pharmacokinetics of lipid-formulated amphotericin B (AMB), and of AMB that has dissociated from its lipid moiety and bound to lipoproteins in plasma, were separately determined in critically ill patients.

Patients And Methods: Eleven patients required continuous veno-venous haemofiltration (CVVH). Five of them were treated with liposomal AMB (AmBisome) and seven with AMB colloidal dispersion (Amphocil).

New insights into the pharmacological and toxicological effects of thalidomide.

The molecular activity of thalidomide comprises a wide range of mechanisms. Alteration of cytokine synthesis and release may be as important as changes in lymphocyte trafficking and leukocyte migration. Since endothelial cells play an important role in leukocyte extravasation and maintenance of inflammatory processes in the affected tissue, thalidomide-induced alterations of cellular adhesion molecules, and consequently changes of interaction of leukocytes with the endothelial cell layer, will result in modulation of the response in inflammation and immunity.

Neuropeptide-induced inhibition of IL-16 release from eosinophils.

Objectives: Eosinophils are prominent inflammatory cells that respond to peripheral neuropeptides in vitro and in vivo. At inflammatory sites, cytokines activate distinct cellular and biochemical pathways that act in a coordinated fashion. We investigated whether peripheral neuropeptides can act as immunomodulators by influencing cytokine release from eosinophils.

Marburg I polymorphism of factor VII--activating protease: a prominent risk predictor of carotid stenosis.

Background: Atherothrombosis is a main pathomechanism in the evolution of vessel stenosis and is counteracted by endogenous fibrinolysis. Recently, the plasmatic serine protease "factor seven-activating protease" (FSAP) was recognized as a potent activator of prourokinase in vitro. The Marburg I polymorphism of FSAP impairs this potential and may thus facilitate arterial thrombosis.