[Critical value of citrulline for complications of intestinal transplant graft].

Objective: A biochemical marker for detection of acute cellular rejection following small intestine transplantation has been sought. Citrulline, a non- protein amino acid synthesized mainly by functioning enterocytes, has been proposed. Trial sensitivity has been reportedly high but with low specificity.

Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation.

Background: Serum citrulline is a marker for acute cellular rejection (ACR) after intestinal transplantation; however, its clinical utility has not yet been established. The goal of this study was to determine clearcut serum levels beyond which the diagnosis of acute rejection could be supported or refuted, and predictors of citrulline levels posttransplant from which more accurate estimates of sensitivity and specificity could be obtained.

Methods: Since March 2004, we obtained 2135 dried blood spot (DBS) citrulline samples from 57 intestinal transplant recipients at or beyond 3 months posttransplant.

An association of lower serum citrulline levels within 30 days of acute rejection in patients following small intestine transplantation.

Introduction: In a prospective protocol we studied whether serum citrulline level within 30 days of an acute rejection was predictive of the episode.

Methods: An acute rejection episode was defined as the date of occurrence of any biopsy-proven rejection in which treatment was initiated until two successive biopsies showed no further rejection. We compared the mean citrulline level based on values determined within 30 days of the start of an acute rejection episode with the mean citrulline level measured on the same patient during a rejection-free period.

Utilization of dried blood spot citrulline level as a noninvasive method for monitoring graft function following intestinal transplantation.

Background: Citrulline concentrations have been proposed as a marker for intestinal allograft rejection. We instituted dried blood spot (DBS) specimen monitoring of citrulline to simplify sample collection posttransplant. This study demonstrates the correlation between plasma and dried blood spot specimen citrulline concentrations after intestinal transplantation.

K+ channel blockers inhibit tissue factor expression by human monocytic cells.

Human monocytes express the important procoagulant protein, tissue factor (TF), after stimulation by a variety of agents, including bacterial lipopolysaccharide (LPS). Monocyte TF expression may contribute to intravascular coagulation in a number of disease states. The present studies show that monocytic cell TF expression can be inhibited by several agents known to block cellular K+ channels.

Effects of prostacyclin analogs on the synthesis of tissue factor, tumor necrosis factor-alpha and interleukin-1 beta in human monocytic THP-1 cells.

Previous studies have shown that prostacyclin analogs can inhibit the expression of tissue factor (TF) procoagulant activity by human monocytes. The present studies have investigated this phenomenon further, by using a plasma coagulation assay to measure cellular TF activity, an immunoassay to measure TF antigen and reverse transcription/polymerase chain reaction with appropriate oligomer primers to measure TF mRNA. Iloprost and cicaprost inhibited lipopolysaccharide-induced increases in TF activity, antigen and mRNA (50% inhibition, 2-8 nM), with no apparent effect on TF mRNA stability.

Effects of prostacyclin analogues on human endothelial cell tissue factor expression.

Prostacyclin analogues have been reported to inhibit the expression of tissue factor procoagulant activity in human monocytes, primarily by elevating intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP). The present studies have investigated whether prostacyclins can also inhibit tissue factor expression in endothelial cells. Iloprost, carbacyclin, and ciprostene had no effect on human umbilical vein endothelial tissue factor activity induced by lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), or interleukin-1 beta (IL-1 beta).

Prostacyclin analogues inhibit tissue factor expression in the human monocytic cell line THP-1 via a cyclic AMP-dependent mechanism.

Increased expression of tissue factor procoagulant by peripheral blood monocytes has been implicated in a number of thrombotic disorders. The present studies were undertaken to determine whether stable analogues of prostacyclin, a potent endothelium-derived platelet inhibitor and vasodilator, could inhibit tissue factor expression by human monocytic cells. Exposure of monocytic tumor THP-1 cells to 100 ng/ml endotoxin, 2 units/ml interleukin-1 beta, or 5 ng/ml tumor necrosis factor-alpha for 4 hours led to increased tissue factor procoagulant activity.

Endotoxin-induced secretion of an active plasminogen activator inhibitor from bovine pulmonary arterial and aortic endothelial cells.

Treatment of bovine pulmonary arterial and aortic endothelial cells for 24 h with 10-20 ng/ml endotoxin appeared to suppress urokinase secretion by over 90%. Immunodepletion of urokinase from conditioned medium revealed high levels of a fully active plasminogen activator inhibitor (PAI). In contrast, medium from aortic cells not treated with endotoxin expressed low levels of a latent PAI.

Endotoxin induction of an inhibitor of plasminogen activator in bovine pulmonary artery endothelial cells.

We have examined the effects of bacterial lipopolysaccharide (endotoxin) on the fibrinolytic activity of bovine pulmonary artery endothelial cells. Endotoxin suppressed the net fibrinolytic activity of cell extracts and conditioned media in a dose-dependent manner (threshold dose, 0.1 ng/ml; maximal dose, 10-100 ng/ml).

Serum-dependent induction of plasminogen activator in human fibroblasts by catecholamines and comparison with the effects of prostaglandin E1.

Human foreskin fibroblasts produce the protease plasminogen activator, as shown by the ability of cell extracts to lyse 125I-labelled fibrin in the presence of plasminogen. Cellular plasminogen activator was stimulated up to 3-fold by 0.01-10 microM epinephrine, norepinephrine, or isoproterenol.

Stimulation of fibrinolytic activity in human skin fibroblasts by prostaglandins E1, E2 and I2.

The effects of prostaglandins on the fibrinolytic activity of cultured human foreskin fibroblasts have been measured by a [125I]fibrin dish assay. Prostaglandin (PG) E1, added to fibroblasts in serum-containing medium, produced dose-dependent increases in the fibrinolytic activity of both cellular extracts and conditioned medium. PGE2 and PGI2, but not PGD2 or 6-keto-PGF1 alpha, also stimulated fibrinolytic activity.

Induction of plasminogen activator and prostaglandin biosynthesis in HeLa cells by 12-O-tetradecanoylphorbol-13-acetate.

Recent reports suggest that many of the biological effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate are mediated via intracellular prostaglandin biosynthesis. We have investigated whether the induction of plasminogen activator by 12-O-tetradecanoylphorbol-13-acetate in cultured HeLa cells is similarly mediated. 12-O-Tetradecanoylphorbol-13-acetate (0.