Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FIBRIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources
PubMed2006

Controlling bone morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth using fibrin glue.

STUDY DESIGN: An in vitro and in vivo study. OBJECTIVE: To evaluate the ability of fibrin glue to limit diffusion of recombinant human bone morphogenetic protein (rhBMP)-2 and its ability to protect spinal nerves from rhBMP-2 stimulated bone growth. SUMMARY OF BACKGROUND DATA: Studies have shown bone morphogenetic protein (rhBMP-2) stimulated bone growth can encroach on the spinal canal and nerves, causing neural compression. More recently, rhBMP-2 use in the cervical spine has been associated with life-threatening swelling. Fibrin glue has been used as a biologic carrier but has not been evaluated for its ability to limit rhBMP-2. METHODS: In phase 1 of the study, rhBMP-2 soaked absorbable collagen sponges (ACS) were encapsulated in fibrin glue and immediately incubated in physiologic lactated ringers solution at 38 degrees C. Samples of solution were tested for rhBMP-2 concentration. In phase 2 of the study, rats were surgically treated with laminectomy and placement of rhBMP-2/ACS versus laminectomy and placement of fibrin glue before placement of rhBMP-2/ACS. After 8 weeks, animals were euthanized and imaged using micro-computerized tomography. RESULTS: The diffusion study showed a significant limitation in rhBMP-2 diffusion when encapsulated in fibrin glue. The laminectomy study revealed blockage of bone formation by fibrin glue and protection of the spinal canal. CONCLUSIONS: Fibrin glue can limit the diffusion of rhBMP-2, and, thus, it can be used to help protect the spinal canal and nerve roots from rhBMP-2 stimulated bone growth.

Animals↗
PubMed2006

Enoxaparin inhibits fibrin sheath formation and decreases central venous catheter colonization following bacteremic challenge.

OBJECTIVE: Inhibition of fibrin sheath formation by enoxaparin decreases catheter colonization. Fibrin-binding radioactive tracer and catheter weights quantify fibrin reduction. DESIGN: Controlled experimental study of central venous line colonization. SETTING: Animal laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Central venous lines were introduced into right external jugular veins of 254 animals in three groups: enoxaparin, Fibrimage, and catheter weight. The enoxaparin group (n = 196) received daily enoxaparin injections (n = 97) or catheter implantation only (n = 99); 176 received tail vein injections of Staphylococcus epidermidis on postoperative day (POD) 10. Twenty rats received saline injections as a control. On POD 13, catheters were removed and incubated in broth at 37 degrees C for 48 hrs. Turbid samples were plated. In the Fibrimage group (n = 39), 20 rats receiving enoxaparin were compared with 19 controls without enoxaparin; all received S. epidermidis injections on POD 10. Fibrimage, fibrin-binding radiolabeled tracer, was given 1 hr before catheter removal. In the weight group (n = 19), six rats received enoxaparin; 13 did not. All received injections of S. epidermidis on POD 10. MEASUREMENTS AND MAIN RESULTS: Positive plates underwent analytic profile index testing, ensuring correlation with inoculum. Results were compared using Fisher's exact or chi-square tests. Gamma counts were determined in the Fibrimage group. Catheter tip weights were recorded. Results from the Fibrimage and weight groups were compared using Student's t-test. The enoxaparin group had fewer catheters colonized (17 of 77) vs. no enoxaparin (42 of 99; p < .01). Pericatheter sheaths contained less fibrin compared with controls. Fibrimage group gamma counts were significantly decreased for the enoxaparin subgroup (x = 2244 counts per minute) vs. controls (x = 3767 counts per minute; p < .0002). The weight of catheter tips treated with enoxaparin (x = 39 mg) vs. controls (x = 90 mg) was also significantly decreased (p < .0001). CONCLUSIONS: Enoxaparin decreases the amount of fibrin surrounding central venous catheters. The incidence of catheter colonization decreases when the amount of fibrin within the pericatheter sheath decreases.

Animals↗
PubMed2003

Induction of vascular endothelial growth factor by fibrin as a dermal substrate for cultured skin substitute.

In the initial phase of wound healing, endogenous fibrin clots are known to form a provisional matrix and to promote angiogenesis. Growth factors such as vascular endothelial growth factor (VEGF) increase in wounds to stimulate angiogenesis. However, it remains unknown whether VEGF is induced when fibrin is used as a dermal substrate for cultured skin substitutes. The authors investigated the effect of fibrin gel as a dermal substrate for a cultured skin substitute, using human keratinocytes and dermal fibroblasts. A collagen-cultured skin substitute was also examined for comparison. VEGF in the culture supernatant in both types was measured by enzyme-linked immunosorbent assay, and VEGF mRNA was determined semiquantitatively by reverse-transcriptase polymerase chain reaction after 2 days of incubation. Experiments were performed using 12 cultured skin substitutes: four for histologic examination before transplantation, four for VEGF assay in vitro, and four for the transplantation to athymic mice. Three independent experiments were performed for each step. VEGF concentration in the fibrin-cultured supernatant was 84.3 +/- 11.8 pg/ml, whereas it was 27.8 +/- 4.68 pg/ml in the case of the collagen substrate. The relative levels of VEGF mRNA were 1.088 +/- 0.100 and 0.698 +/- 0.226, respectively. In in vivo transplantation, the fibrin-type cultured skin substitute showed an excellent take on the wound bed, and a normally proliferating keratinocyte layer with emergence of vascular endothelial cells in the transplanted floor was seen 3 days after transplantation. Vascular endothelial cells, which were identified using alkaline phosphatase stain, were significantly increased in the fibrin-type cultured skin substitute. The use of fibrin as a dermal substrate for cultured skin substitute increases the secretion of VEGF, improves regeneration of mature epidermal structure after in vivo transplantation, and promotes the migration of vascular endothelial cells.

Animals↗
PubMed2000

Quantification and macroscopic modeling of the nonlinear viscoelastic behavior of strained gels with varying fibrin concentrations.

The mechanical properties of fibrin gels under uniaxial strains have been analyzed for low fibrin concentrations using a free-floating gel device. We were able to quantify the viscous and elastic moduli of gels with fibrin concentration ranging from 0.5 to 3 mg/ml, reporting significant differences of biogels moduli and dynamical response according to fibrin concentration. Furthermore, considering sequences of successively imposed step strains has revealed the strain-hardening properties of fibrin gels for strain amplitude below 5%. This nonlinear viscoelastic behavior of the gels has been precisely analyzed through numerical simulations of the overall gel response to the strain steps sequences. Phenomenological power laws relating the instantaneous and relaxed elasticity moduli to fibrin concentration have been validated, with concentration exponent in the order of 1.2 and 1.0, respectively. This continuous description of strain-dependent mechanical moduli was then used to simulate the biogel behavior when continuously time-varying strains are applied. We discuss how this experimental setup and associated macroscopic modeling of fibrin gels enable a further quantification of cell traction forces and mechanotransduction processes induced by biogel compaction or stretching.

Biomedical Engineering↗
PubMed2005

Hyperproduction of fibrin and inefficacy of antithrombin III and alpha2 macroglobulin in the presence of bacterial porins.

Bacterial porins enhance the thrombin activity upon chromogen substrate chromozym. Should porin-dependent enhancement of thrombin activity take place also upon fibrinogen in vivo, this might greatly increase the fibrin production which, in turn, might lead to blood vessel obstruction. In this study, we demonstrate fibrin hyperproduction in a simplified coagulative system, consisting of fibrinogen and thrombin-pure molecules, in the presence of bacterial porins. In particular, bacterial porins, in the presence of thrombin, significantly increased the fibrin production compared with thrombin alone. Also, fibrin hyperproduction took place even in the presence of the thrombin inhibitors antithrombin III (AT III) or alpha2 macroglobulin (alpha2M). However, the thrombin-fibrinogen reaction in the presence of AT III or alpha2M did not generate fibrin, unless porins were present. In conclusion, porins not only enhance thrombin activity but also inhibit the antithrombin activity exerted by AT III or alpha2M. We hypothesize that, because of porins activity, fibrin is largely generated due to thrombin hyperactivation. Moreover, further fibrin is produced by thrombin, which is not blocked by two serpins for the presence of porins. These results might be relevant as to the occurrence of disseminated intravascular coagulation in sepsis by gram-negative bacteria, which are known to produce porins.

Antithrombin III↗
PubMed1993

The fibrinolytic response to ancrod therapy: characterization of fibrinogen and fibrin degradation products.

Ancrod is a purified coagulant venom which renders blood incoagulable by cleaving fibrinopeptide A (FPA) from fibrinogen, but the mechanism involved in the clearance of fibrin from the circulation is unknown. To investigate the fibrinolytic response to ancrod, and to increase understanding of clearance mechanisms, six patients with peripheral vascular disease causing claudication were infused with ancrod at 2 u/kg over 6 h followed by 2 u/kg at 12 h intervals for 38 h. Venous blood samples were taken at time 0, 3, 6, 25 and 49 h for assay of fibrinogen (Fbg), fibrinopeptide A (FPA), total fibrin(ogen) degradation products (TDP), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (tPA), urinary type plasminogen activator (u-PA), plasminogen, alpha 2 antiplasmin (alpha 2 AP) and plasminogen activator inhibitor-1 (PAI-1). Fibrinogen (median and range) was 2.3 (1.4-3.90) g/l at time 0 and thereafter was undetectable. FPA rose from 2.5 (1.8-3.6) to 600 and 188 pmol/l at 3 h and 6 h and remained elevated. TDP, FbDP and FgDP increased greatly following ancrod while there was no evidence of XL-FDP. The surprising increase in FgDP during defibrination suggests either that fibrinogen is digested following its incorporation into circulating fibrin protofibrils or that some of the fibrin subunits in the photofibril retain one of the two fibrinopeptide A's. tPA and uPA remained unchanged. Plasminogen fell from 125 (100-155)% to 79 (40-118)% at 49 h and alpha 2 AP fell from 91 (75-107)% to 24 (10-35)% at 49 h. The level of PAI-1 was depressed during defibrination, with the exception of the 6 h data. The results demonstrate that ancrod removes FPA from fibrinogen to produce non-cross-linked (soluble) fibrin. This is cleared from the circulation without evidence of an increase in the circulating activities of the plasminogen activators, tPA or UK, but with evidence of plasminogen activation and consumption.

Adult↗
PubMed1992

Pericapillary fibrin cuffs in venous ulceration. Persistence with treatment and during ulcer healing.

A recent hypothesis suggests that venous hypertension leads to ulceration through the formation of pericapillary fibrin cuffs, which are presumed to impede the exchange of oxygen and other nutrients. In this report, we evaluated by direct immunofluorescence the presence of pericapillary fibrin at the edge of venous ulcers during the course of treatment with elastic compression. In an initial group of 23 patients studied at baseline, pericapillary fibrin cuffs were detected in 20 (91%) of 22 patients. The intensity of fibrin staining, rated blindly on a scale of 0 to 3, could not be correlated with several baseline parameters, including the clinical presence and extent of lipodermatosclerosis, ulcer size, venous recovery time, and transcutaneous oxygen measurements (TcPO2) taken next to the ulcer. Eleven of this initial group of 23 patients were randomly selected to receive elastic compression treatment, and were evaluated for the persistence of pericapillary fibrin at 60 and 120 days. Although a reduction (mean +/- SD = 50.2% +/- 25.7) in ulcer size occurred in 10 of the 11 patients, pericapillary fibrin was still present at the ulcer edge and with undiminished intensity. We conclude that pericapillary fibrin cuffs in venous ulcers persist with compression treatment and in spite of healing, and are unlikely to be directly related to the development of ulceration.

Adult↗
PubMedDate not supplied

Treatment of nonunions with nonglycosylated recombinant human bone morphogenetic protein-2 delivered from a fibrin matrix.

OBJECTIVE: To report the results of the treatment of nonunions with nonglycosylated recombinant human bone morphogenetic protein-2 (nglBMP-2) delivered from a designed fibrin matrix. STUDY DESIGN: Experimental trial in rodents and prospective clinical study in dogs and cats with nonunion fractures. ANIMALS: Twenty adult female, albino, Sprague-Dawley rats; 8 client-owned cats and dogs. METHODS: After development of a fibrin matrix and evaluation of nglBMP-2 in a rodent femoral defect model, 8 consecutive long bone nonunion fractures (no progression in healing in > or = 3 months), were treated using 300 microg nglBMP-2 in a liquid fibrin precursor, injected into the defect gap after fracture revision and stabilization, or through a stab incision into the fracture site. The fibrin matrix was designed to clot in the wound after 60 seconds and to release the nglBMP-2 continuously over several days. RESULTS: Using only fibrin gel, 7% of the rat femoral defect was filled with new formed bone compared with 79% defect filling using 2 microg nglBMP-2 (P=.006). Five and 10 microg nglBMP in fibrin resulted in union of all femoral defects with complete filling of the gap with new bone. Bony bridging and clinical healing was achieved in 7 patients within 24 weeks of administration of nglBMP-2. CONCLUSIONS: Application of nglBMP-2 in a functional matrix can induce bone healing. Controlled release of nglBMP-2 from a fibrin matrix mimics the natural fracture hematoma. CLINICAL RELEVANCE: nglBMP-2/fibrin can successfully replace a cancellous bone autograft in fracture treatment with an associated reduction in graft donor site morbidity and surgical time.

Animals↗
PubMed1981

Incomplete fibrin formation and highly elevated Factor XIII activity in multiple myeloma.

Bleeding is a common complication in patients suffering from multiple myeloma. In some cases a defect in fibrin formation has been suggested as one possible cause of haemorrhagic tendency. As shown in this investigation the defect in fibrin formation, ascertained using PAGE, is due to a lack of alpha-chain polymerization of fibrin monomers in 5/11 patients with IgG myeloma and in 2/5 patients with IgM paraproteinaemia. No disturbed fibrin polymerization could be observed in IgA myeloma (n = 6). Factor XIII concentrations of subunit A and to a lesser extent of subunit S (Laurell technique) were highly elevated in all cases with regular fibrin formation. comparable values were obtained by measuring the transamidase activity of factor XIII by incorporation of 14C-labelled purtrescin into casein. Levels up to 600% of normal could be recorded. In contrast, all patients with a lack of alpha-chain polymerization had a factor XIII activity within the normal range. Addition of factor XIII concentrate to plasma from patients with defective fibrin formation led in 5/8 cases to a partial cross-linking of alpha-monomers. we conclude that in some cases paraproteins can inhibit the factor XIII and prevent its action on fibrin.

Blood Coagulation Tests↗
PubMed2001

Conformational changes upon conversion of fibrinogen into fibrin. The mechanisms of exposure of cryptic sites.

Conformational changes upon conversion of fibrinogen to fibrin result in the exposure of multiple binding sites that provide its interaction with various proteins and cells and, thus, its participation in a number of physiological and pathological processes. Here we focus on conformational changes in the fibrinogen D regions (domains) and alpha C-domains that are directly involved in intermolecular interactions upon fibrin assembly. According to the current view, two alpha C-domains that interact intramolecularly in fibrinogen undergo an intra- to intermolecular switch to form alpha C-polymers in fibrin. The availability of recombinant fragments that correspond to the alpha C-domain made it possible to further clarify this mechanism and to reveal novel cryptic sites in this domain for plasminogen and its activator tPA, whose exposure may play an important role in the regulation of fibrinolysis. To elucidate the mechanism of exposure of cryptic sites in the D regions, we tested the accessibility of their fibrin specific epitopes (A alpha 148-160 and gamma 312-324) that are also involved in binding of plasminogen and tPA, in several fragments derived from fibrinogen (fragment D), and crosslinked fibrin (fragment D-D and its non-covalent complex with the E1 fragment, D-D:E1). Neither D nor D-D bound tPA, plasminogen, or anti-A alpha 148-160 and anti-gamma 312-324 monoclonal antibodies. At the same time both epitopes became accessible in the D-D:E1 complex. Melting of D and D-D revealed that their domains have the same stability while in the D-D:E1 complex they became more stable. These results indicate that upon fibrin assembly, driven primarily by the interaction between complementary binding sites of the E and two D regions, the latter undergo conformational changes that cause the exposure of their cryptic sites. They also suggest that the fibrin specific conformation of the D regions is preserved in the D-D:E1 complex.

Calorimetry, Differential Scanning↗
PubMed2001

Fibrin-mediated plasminogen activation.

Fibrin, but not fibrinogen, enhances the rate of activation of plasminogen by tissue type plasminogen activator (t-PA). Studies with enzymatic and chemical fragments of fibrinogen showed that several sites in fibrinogen are involved in this rate enhancement; these are, A alpha 148-160 (located in CNBr fragment FCB-2), and FCB-5 (a CNBr fragment comprising gamma 312-324), and recently discovered sites in the fibrinogen alpha C domains. All these sites are buried in fibrinogen, but exposed in fibrin and some fibrinogen fragments. For the first two of these, located in the D-domains, this was shown by the fact that monoclonal antibodies against A alpha 148-160 and gamma 312-324 bind to fibrin and rate enhancing fibrin(ogen) fragments, but not to fibrinogen. Direct binding studies indicate that at physiological concentrations plasminogen binds to FCB-2, and t-PA to FCB-5. More detailed studies have demonstrated the importance of residues A alpha-157 and A alpha-152, and that the minimum stretch with rate enhancing properties is A alpha 154-159. The sites in the alpha C domains await further identification. With the recently reported three-dimensional structure of fragments D and D-dimer it is now possible to explain these findings at the molecular level. Molecular calculations and experimental data show that the site A alpha 148-160 in fibrinogen is covered among others by a part of the A alpha chain (A alpha 166-195) that forms an alpha-helix, and by a globular domain formed by the beta-chain. On fibrin formation, the last two may move away, and give access to A alpha 148-160. It is conceivable that in the alpha C domain sites are involved in the early phases of fibrinolysis. The site A alpha 148-160 and that in FCB-5 may be more important at later stages. It is also clear that fibrin polymerization is important. This polymerization has probably several effects: exposure of the rate enhancing sites; mutual positioning of the t-PA and plasminogen binding sites; a concentrating effect of t-PA and plasminogen on the fibrin surface; effects on the kinetic properties of t-PA and plasminogen. These effects together explain the rate enhancement.

Amino Acid Sequence↗
PubMed2005

Fibrin affinity of erythrocyte-coupled tissue-type plasminogen activators endures hemodynamic forces and enhances fibrinolysis in vivo.

Plasminogen activators (PAs; e.g., tissue-type, tPA) coupled to red blood cells (RBCs) display in vivo features useful for thromboprophylaxis: prolonged circulation, minimal extravasation, and preferential lysis of nascent versus preexisting clots. Yet, factors controlling the activity of RBC-bound PAs in vivo are not defined and may not mirror the profile of soluble PAs. We tested the role of RBC/PA binding to fibrin in fibrinolysis. RBC/tPA and RBC/tPA variant with low fibrin affinity (rPA) bound to and lysed plasminogen-containing fibrin clots in vitro comparably. In contrast, when coinjected in mice with fibrin emboli lodging in pulmonary vasculature, only RBC/tPA accumulated in lungs, which resulted in a more extensive fibrinolysis versus RBC/rPA (p < 0.01). Reconciling this apparent divergence between in vitro and in vivo behaviors, RBC/tPA, but not RBC/rPA perfused over fibrin in vitro at physiological shear stress bound to fibrin clots and caused greater fibrinolysis versus RBC/rPA (p < 0.001). These results indicate that because of high fibrin affinity, RBC/tPA binding to clots endures hemodynamic stress, which enhances fibrinolysis. Behavior of RBC/PAs under hemodynamic pressure is an important predictor of their performance in vivo.

Animals↗
PubMed1996

Differential increased survival of staphylococci and limited ultrastructural changes in the core of infected fibrin clots after daptomycin administration.

A possible explanation for the difficulties encountered in curing deep fibrin-embedded infections is that antibiotic diffusion inside the infected fibrin matrix is not homogeneous and is insufficient to neutralize the pathogen. To evaluate this conjecture, the differential pharmacodynamics of daptomycin in fibrin clots infected with methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis was estimated. Daptomycin (20 or 50 mg/kg of body weight) was infused over 30 min. Fibrin clots and blood samples were evaluated from 0.5 to 42 h after the injections. The half-lives of daptomycin in serum and fibrin clot were close to identical after the two doses and averaged 5.4 and 22 h, respectively. The mean areas under the concentration-time curves from 0 to 42 h (AUC0-infinity) for daptomycin concentrations in serum and infected clots were 575 +/- 36.7 and 215 +/- 6.2 micrograms/g/h after administration of 20 mg/kg and 1,089 +/- 39.9 and 326 +/- 16.8 micrograms/g/h after administration of 50 mg/kg. A concentration gradient from the periphery to the core of the clots was observed in many clots up to 18 h after treatment. Mean peak concentrations in the core of the clots reached 60% of the peripheral values (P < 0.05) and were delayed for at least 3 h compared with the peripheral peak concentrations. AUC0-42 h of daptomycin concentration in the periphery and the core of clots were significantly different (P < 0.01). Survival of microorganisms was better in the core than in the periphery, with as much as a 3 log10 CFU/g difference between the center and the surface of the clot. Bacterial examination by transmission electron microscopy also showed noticeable differences in ultrastructural changes between those in the periphery and those in the core of the clots. In conclusion, the pharmacokinetics of daptomycin are significantly different at the periphery and within the core of fibrin clots, which may have led to the higher bacterial survival in the core of clots. Limited diffusion of daptomycin in fibrin, an essential component of the vegetation in bacterial endocarditis, could explain at least in part some of the treatment failures.

Animals↗
PubMed2003

Inhibition of gamma interferon decreases bacterial load in peritonitis by accelerating peritoneal fibrin deposition and tissue repair.

Bowel perforation can lead to significant bacterial spillage, which may then cause septic peritonitis, characterized by a systemic inflammatory response and organ dysfunction. There are several reports that have shown that the development of peritoneal adhesions is dependent on inflammatory cytokine levels and that these adhesions can reduce bacterial spread, possibly by sealing off the cecum in the cecal ligation and puncture (CLP) model of septic peritonitis. There have not, however, been any studies that have utilized a strategy to accelerate tissue repair in order to seal off the injured cecum and reduce bacterial spread as well as ameliorate systemic inflammation. In the present study, we demonstrate that the administration of anti-gamma interferon (IFN-gamma) antibody (1.2 mg/kg of body weight, intravenously) accelerated tissue repair via increased fibrin deposition 12 and 24 h after CLP in rats. This increase in fibrin deposition was associated with peritoneal adhesion 24 h after CLP and a reduction in bacterial load compared to the bacterial load of rats given irrelevant antibody. Plasma fibrin levels, however, were not altered after IFN-gamma antibody administration, suggesting that the inhibition of IFN-gamma activity specifically increased fibrin deposition to the site of injury. Furthermore, plasma interleukin-6, used as a marker of systemic inflammatory response, was reduced in CLP rats given IFN-gamma antibody compared to that found in those given irrelevant antibody. These results suggest that the early inhibition of IFN-gamma activity in the CLP model is beneficial by accelerating fibrin deposition in cecal tissue to prevent bacterial spread and reduce the systemic inflammatory response. Importantly, increased fibrin deposition in the ceca was not associated with increased plasma fibrin whereas the latter may have detrimental effects associated with coagulation disorders.

Animals↗
PubMed1999

Antibiotic-impregnated fibrin glue in ocular surgery: in vitro antibacterial activity.

A strategy to reduce postoperative ocular infections might consist in maintaining a high antibiotic concentration in the eye by using a topical slow-release drug formulation. Fibrin glue is widely used in ocular surgery. Vancomycin, teicoplanin, cephalothin and gentamicin were added to a 500 IU/ml thrombin solution, their concentrations in 1 g fibrin glue being 500 microg for vancomycin and 400 microg for the other drugs. The in vitro antibacterial activity of antibiotic-impregnated fibrin glue was evaluated against a recent clinical isolate of Staphylococcus epidermidis. Moreover the antibiotic elution from fibrin discs in saline was assayed for up to 96 h. Fibrin glue properties were maintained when thrombin was reconstituted with a CaCl2 solution additioned with the antibiotics tested. All antibiotic fibrin mixtures exhibited good antistaphylococcal activity immediately after the preparation. A prolonged inhibition (4 days) of S. epidermidis growth was observed with teicoplanin discs. Gentamicin and teicoplanin levels were higher than those of the other antibiotics. The results suggest that the fibrin glycopeptide and/or gentamicin mixtures can be used, both prophylactically and therapeutically, in ocular surgery.

Cephalothin↗
PubMed1994

Differential lectin binding to the fibrinoid of human full-term placenta: correlation with a fibrin antibody and the PAF-Halmi method.

Placental fibrinoid is thought to contain various glycoproteins originating from cell secretion and tissue degeneration, occasionally merged with fibrin. Information on the characteristics and derivation of the various fibrinoid components, however, is still fragmentary. Therefore, the present histochemical study on acetone-fixed placental tissue sections compared the staining pattern of FITC-conjugated lectins from Ulex europaeus (UEA-I), Bandeiraea simplicifolia (BS-I) and Lycopersicon esculentum (LEA) with the reactivity of a fibrin antibody and a modified paraldehyde-fuchsin stain. Using different color reactions, the latter histological method identified two types of fibrinoid, which correlated well with fibrin-type and matrix-type fibrinoid. Immunohistochemically, fibrin was detected at the intervillous border of the basal plate, in some inner parts and in perivillous fibrinoid. UEA-I bound to endothelial cells and partially to fibrin-type fibrinoid of villi and the basal plate, thus indicating a reaction with immured and disintegrated remnants of endothelial and blood cells. LEA stained fibrin-negative (i.e. matrix-type) fibrinoid homogeneously within the basal plate; the small reactive areas within the perivillous fibrinoid may belong to degenerating trophoblastic residues, because in villi LEA specifically reacted with the syncytiotrophoblast. BS-I heterogeneously labeled matrix-type fibrinoid deposits in the basal plate which surrounded decidual cells and subpopulations of extravillous trophoblast. In cell islands, BS-I also stained fibrinoid surrounding trophoblast cells heterogeneously. The data (1) confirm the existence of two types of placental fibrinoid, fibrin-type and matrix-type fibrinoid, (2) suggest that both types of fibrinoid contain different glycoconjugates, and (3) demonstrate the practical usefulness of the modified paraldehyde-fuchsin method for the identification of the two types of fibrinoid.

Endothelium, Vascular↗
PubMed2004

Thrombin binding to GPIbalpha induces integrin alphaIIbbeta3 dependent platelet adhesion to fibrin in ex vivo flowing whole blood.

We have investigated the role of the thrombin/GPIbalpha interaction in the adhesion of platelets to fibrin in a whole blood ex vivo perfusion model at a shear rate of 280 s(-1). Blood was perfused through parallel-plate chambers containing coverslips coated with cells expressing tissue factor, leading to the generation of thrombin and thus, deposition of fibrin onto the exposed cells. Adhesion of platelets to fibrin and thrombus growth were analyzed. Interestingly, when GPIbalpha was removed from the platelet surface by action of mocarhagin, platelet adhesion on fibrin was inhibited. Furthermore, a monoclonal antibody, VM16d, directed against the thrombin binding site on GPIbalpha also inhibited platelet adhesion on fibrin, showing the importance of the thrombin/GPIbalpha interaction.We then looked at the involvement of alphaIIbbeta3 and showed that platelet adhesion and thrombus growth on fibrin were inhibited by the dodecapeptide, whereas lamifiban only inhibited the growth of the platelet thrombus. These results indicated that binding of thrombin to GPIbalpha induced an intracellular signaling leading to the interaction of the platelet integrin alphaIIbbeta3 with the fibrin-dodecapeptide sequence.

Acetates↗
PubMed2002

Lp(a) particles mold fibrin-binding properties of apo(a) in size-dependent manner: a study with different-length recombinant apo(a), native Lp(a), and monoclonal antibody.

OBJECTIVE: Small-sized apolipoprotein(a) [apo(a)] isoforms with high antifibrinolytic activity are frequently found in cardiovascular diseases, suggesting a role for apo(a) size in atherothrombosis. To test this hypothesis, we sought to characterize the lysine (fibrin)-binding function of isolated apo(a) of variable sizes. METHODS AND RESULTS: Recombinant apo(a) [r-apo(a)] preparations consisting of 10 to 34 kringles and a monoclonal antibody that neutralizes the lysine-binding function were produced and used in parallel with lipoprotein(a) [Lp(a)] particles isolated from plasma in fibrin-binding studies. All r-apo(a) preparations displayed similar affinity and specificity for lysine residues on fibrin regardless of size (K(d) 3.6+/-0.3 nmol/L) and inhibited the binding of plasminogen with a similar intensity (IC50 16.8+/-5.4 nmol/L). In contrast, native Lp(a) particles displayed fibrin affinities that were in inverse relationship with the apo(a) kringle number. Thus, a 15-kringle apo(a) separated from Lp(a) and a 34-kringle r-apo(a) displayed an affinity for fibrin that was higher than that in the corresponding particles (K(d) 2.5 versus 10.5 nmol/L and K(d) 3.8 versus 541 nmol/L, respectively). However, fibrin-binding specificity of the r-apo(a) preparations and the Lp(a) particles was efficiently neutralized (IC50 0.07 and 4 nmol/L) by a monoclonal antibody directed against the lysine-binding function of kringle IV-10. CONCLUSIONS: Our data indicate that fibrin binding is an intrinsic property of apo(a) modulated by the composite structure of the Lp(a) particle.

Antibodies, Monoclonal↗