fibrin and Acute-Phase-Reaction

To measure the inflammatory reaction in the anterior chamber after lens extraction in a rabbit model and to evaluate the effect of nonsteroidal antiinflammatory drugs (NSAIDs) or steroids on the amount of inflammation as measured by fibrinogen levels in the aqueous humor.. Animal laboratory, Goldschleger Research Institute, Tel Aviv University, Sheba Medical Center, Ramat Gan, Israel.. Experimental study.. Twenty-six eyes of New Zealand white rabbits had lens extraction surgery. One day later, aqueous humor (∼0.1 mL) was withdrawn from the anterior chamber and examined for fibrinogen concentration. Control rabbits received no treatment (9 eyes) or artificial tear eyedrops (5 eyes). One study group received NSAID drops (diclofenac) (6 eyes), and another study group received steroid drops (dexamethasone-neomycin) (6 eyes). All rabbits were treated hourly for 9 applications. Aqueous humor (∼0.1 mL) was withdrawn from the anterior chamber and examined for fibrinogen concentration 1 day later. Fibrinogen levels were also measured in the aqueous in 8 unoperated eyes.. Steroid-treated eyes achieved the lowest inflammatory score, followed by NSAID eyes, artificial tears eyes, and untreated eyes. The mean fibrinogen concentrations in the aqueous humor were 69.1 mg% untreated, 52.0 mg% artificial tears, 18.5 mg% NSAIDs, and 2.8 mg% steroids (P=.002).. Measurement of aqueous fibrinogen after lens extraction surgery in a rabbit animal model was simple and provided a useful parameter for precise evaluation of postoperative intraocular reaction. Steroids and NSAIDs were effective in reducing postoperative inflammation. Steroids reduced inflammation to almost undetectable values.. No author has a financial or proprietary interest in any material or method mentioned.

Topics: Acute-Phase Reaction; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aqueous Humor; Cataract Extraction; Dexamethasone; Diclofenac; Fibrin; Fibrinogen; Glucocorticoids; Inflammation; Male; Postoperative Complications; Rabbits

Thrombin-activable fibrinolysis inhibitor (TAFI) has recently been identified as a positive acute phase protein in mice, an observation that may have important implications for the interaction of the coagulation, fibrinolytic, and inflammatory systems. Activated TAFI (TAFIa) inhibits fibrinolysis by removing the carboxyl-terminal lysines from partially degraded fibrin that are important for maximally efficient plasminogen activation. In addition, TAFIa has been shown to be capable of removing the carboxyl-terminal arginine residues from the anaphylatoxins and bradykinin, thus implying a role for the TAFI pathway in the vascular responses to inflammation. In the current study, we investigated the ability of acute phase mediators to modulate human TAFI gene expression in cultured human hepatoma (HepG2) cells. Surprisingly, we found that treatment of HepG2 cells with a combination of interleukin (IL)-1 and IL-6 suppressed endogenous TAFI mRNA abundance in HepG2 cells (~60% decrease), while treatment with IL-1 or IL-6 alone had no effect. Treatment with IL-1 and/or IL-6 had no effect on TAFI promoter activity as measured using a luciferase reporter plasmid containing the human TAFI 5'-flanking region, whereas treatment with IL-1 and IL-6 in combination, but not alone, decreased the stability of the endogenous TAFI mRNA. Treatment with the synthetic glucocorticoid dexamethasone resulted in a 2-fold increase of both TAFI mRNA levels and promoter activity. We identified a functional glucocorticoid response element (GRE) in the human TAFI promoter between nucleotides 92 and 78. The GRE was capable of binding the glucocorticoid receptor, as assessed by gel mobility shift assays, and mutation of this element markedly decreased the ability of the TAFI promoter to be activated by dexamethasone.

Topics: Acute-Phase Proteins; Acute-Phase Reaction; Animals; Arginine; Base Sequence; Blotting, Northern; Carboxypeptidase B2; Cell Line; Cells, Cultured; Dexamethasone; Fibrin; Genes, Reporter; Glucocorticoids; Humans; Interleukin-1; Interleukin-6; Luciferases; Mice; Molecular Sequence Data; Mutagenesis, Site-Directed; Plasmids; Plasminogen; Promoter Regions, Genetic; Protein Binding; Response Elements; RNA; RNA, Messenger; Time Factors; Tumor Cells, Cultured

Circulating D-dimer and thrombomodulin (TM) levels are now routinely measured in clinical laboratories. Plasma levels of D-dimer are used as a marker of fibrin formation and degradation, and serum TM is used to assess the state of endothelial cell injuries. While the levels of circulating D-dimer and TM have been investigated in many diseases, to our knowledge they have not been studied in patients with measles. We measured circulating levels of D-dimer in patients with measles to discuss whether fibrin formation and degradation occur and TM whether endothelial injury occur.. The plasma levels of D-dimer and serum levels of alanine aminotransferase (ALT) and creatinine were measured of 14 adolescent and adult Japanese patients with measles, and the serum or plasma levels of TM of 10 of these 14 patients were measured in the acute febrile phase and convalescent afebrile phase with commercially available kits.. Plasma D-dimer levels were significantly higher in the acute febrile phase than in the convalescent afebrile phase in patients with measles, and no significant difference was shown in serum and plasma TM levels between the two phases. Plasma D-dimer levels were not correlated with serum or plasma TM levels in either phase. No significant differences were identified in the serum ALT and creatinine levels between the acute febrile and convalescent afebrile phases, and the levels of plasma D-dimer were not significantly correlated with the serum ALT levels.. Our results indicate that while clot formation and fibrinolysis may tend to occur in patients with the acute febrile phase of measles, there may be little risk that such patients will suffer endothelial injury.

Topics: Acute Disease; Acute-Phase Reaction; Adolescent; Adult; Alanine Transaminase; Convalescence; Creatinine; Endothelium; Fever; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Measles; Morbillivirus; Thrombomodulin

The influence of an acute phase reaction on the size, weight, and fibrin content of experimental venous thrombi was examined in 10 pairs of rabbits. Jugular vein thrombosis was provoked by venous stasis plus mechanical injury 36 hours after one member of each pair received 0.5 ml/kg sterile turpentine in olive oil by subcutaneous injection. Fibrinogen level, factor VIII activity, and antithrombin III activity were significantly higher at the time of thrombus formation in turpentine treated rabbits, as were thrombus size (assessed by visual scoring), dry weight of thrombi, and their fibrin content (derived by measuring 125I-fibrinogen incorporation). In addition, the fibrinogen concentration correlated significantly with size, weight, and fibrin content of thrombi when results from turpentine treated and control animals were pooled, suggesting that plasma fibrinogen concentration at the time of thrombus formation may strongly influence the extent of thrombosis. This effect could help explain observations of a "hypercoagulable state" after injury.

Topics: Acute-Phase Reaction; Animals; Antithrombin III; Factor VIII; Fibrin; Fibrinogen; Inflammation; Rabbits; Thrombophlebitis; Turpentine