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PubMed2002

A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula.

PURPOSE: Fibrin glue is a novel treatment for anal fistulas and possesses many advantages in the treatment of difficult high fistulas. Fibrin glue treatment is simple and repeatable; failure does not compromise further treatment options; and sphincter function is preserved. We aimed to compare the outcomes of patients with low and high anal fistulas randomly assigned to either fibrin glue or conventional treatment. METHODS: Patients with simple fistulas (low fistulas) and complex fistulas (high, Crohn's, and low fistulas with compromised sphincters) were randomly assigned to either fibrin glue or conventional treatment (fistulotomy or loose seton insertion with or without subsequent advancement flap). Patients with rectovaginal fistulas and anal fistulas associated with chronic cavities, acute sepsis, and side branches were excluded. The primary end point was fistula healing. Secondary end points were complications, changes in preoperative continence score, changes in maximum resting and squeeze pressure, satisfaction scores, and pain scores and time off work (simple fistulas only). RESULTS: Patients in the fibrin glue and conventional treatment arms were well matched for gender, median age, duration of fistula symptoms, and follow-up. Fibrin glue healed three (50 percent) of six and fistulotomy seven (100 percent) of seven simple fistulas (difference, 50 percent; confidence interval, 10 to 90 percent; P= 0.06, Fisher's exact probability test). There was no change in baseline incontinence score, maximum resting pressures, or squeeze pressures between the study arms. Return to work was quicker in the glue arm, but pain scores were similar and satisfaction scores higher in the fistulotomy group. Fibrin glue healed 9 (69 percent) of 13 and conventional treatment 2 (13 percent) of 16 complex fistulas (difference, 56 percent; 95 percent confidence interval, 25.9 to 86.1 percent; P= 0.003, Fisher's exact probability test). There was no change in baseline incontinence score, maximum resting pressures, or squeeze pressures in either study arm. Satisfaction scores were higher in the fibrin glue group. CONCLUSIONS: No advantage was found for fibrin glue over fistulotomy for simple fistulas, but fibrin glue healed more complex fistulas than conventional treatment and with higher patient satisfaction.

Adult↗

PubMed1995

Comparative study of biological glues: cryoprecipitate glue, two-component fibrin sealant, and "French" glue.

BACKGROUND: Although biological glues have been used clinically in cardiovascular operations, there are no comprehensive comparative studies to help clinicians select one glue over another. In this study we determined the efficacy in controlling suture line and surface bleeding and the biophysical properties of cryoprecipitate glue, two-component fibrin sealant, and "French" glue containing gelatin-resorcinol-formaldehyde-glutaraldehyde (GRFG). METHODS: Twenty-four dogs underwent a standardized atriotomy and aortotomy; the incisions were closed with interrupted 3-0 polypropylene sutures placed 3 mm apart. All dogs had a 3- by 3-cm area of the anterior wall of the right ventricle abraded until bleeding occurred. The animals were randomly allocated into four groups: in group 1 (n = 6) bleeding from the suture lines and from the epicardium was treated with cryoprecipitate glue; in group 2 (n = 6) bleeding was treated with two-component fibrin sealant; group 3 (n = 6) was treated with GRFG glue; group 4 (n = 6) was the untreated control group. The glues were also evaluated with regard to histomorphology, tensile strength, and virology. RESULTS: The cryoprecipitate glue and the two-component fibrin sealant glue were equally effective in controlling bleeding from the aortic and atrial suture lines. Although the GRFG glue slowed bleeding significantly at both sites compared to baseline, it did not provide total control. The control group required additional sutures to control bleeding. The cryoprecipitate glue and the two-component fibrin sealant provided a satisfactory clot in 3 to 4 seconds on the epicardium, whereas the GRFG glue generated a poor clot. There were minimal adhesions in the subpericardial space in the cryoprecipitate and the two-component fibrin sealant groups, whereas moderate-to-dense adhesions were present in the GRFG glue group at 6 weeks. The two-component fibrin sealant was completely reabsorbed by 10 days, but cryoprecipitate and GRFG glues were still present. On histologic examination, both fibrin glues exhibited minimal tissue reaction; in contrast, extensive fibroblastic proliferation was caused by the GRFG glue. The two-component and GRFG glues had outstanding adhesive property; in contrast, the cryoprecipitate glue did not show any adhesive power. The GRFG glue had a significantly greater tensile strength than the two-component fibrin sealant. Random samples from both cryoprecipitate and the two-component fibrin glue were free of hepatitis and retrovirus. CONCLUSIONS: The GRFG glue should be used as a tissue reinforcer; the two-component fibrin sealer is preferable when hemostatic action must be accompanied with mechanical barrier; and finally, the cryoprecipitate glue can be used when hemostatic action is the only requirement.

Animals↗

PubMed1992

The effect of fibrin glue on intraperitoneal contamination in rats treated with systemic antibiotics.

Intraperitoneal fibrin sealant lowers septic mortality in a rat model of peritoneal contamination (2 x 10(6) organism inoculum) at the cost of increased late intraabdominal abscesses. This study utilized parenteral antimicrobials to determine if the protective effect of intraperitoneal fibrin could be achieved without increasing the late abscess formation rate. One hundred and fifty-five rats were divided into four groups. Gelatin capsules containing various dilutions of feces (10(10) CFU/ml) and barium sulfate were placed into the abdomen in all groups. Group I controls had no antibiotics or fibrin. In group II, the capsule was surrounded by a solution of cryoprecipitate, thrombin, and calcium (fibrin "glue"). Groups III (no fibrin, antibiotics) and IV (fibrin, antibiotics) received a broad-spectrum cephalosporin intramuscularly postoperatively and then daily. Surviving rats were sacrificed on the tenth postoperative day. At a moderate volume of fecal inoculum (0.3 ml), fibrin reduced mortality from 100% in the control group to 0% in treated animals (P less than 0.001) that did not receive antibiotics. Abscesses formed in 10% of the surviving fibrin-treated rats which were implanted with 0.1 ml of inoculum. In the 0.2 and 0.3 ml inoculum groups substantially more abscesses occurred (75 and 70%, respectively). The protective effect of fibrin was not manifested in the antibiotic-treated rats since no deaths occurred in either group. At higher and lower inoculum doses, no significant differences between fibrin and control groups were observed in mortality or abscess formation, whether or not antibiotics were given.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗

PubMed1995

Effects of fibrin on the secretion of plasminogen activator inhibitor-1 from endothelial cells and on protein kinase C.

We previously demonstrated that cultured human umbilical vein endothelial cells (HUVECs) overlaid with a fibrin clot induced a slight increase in tissue-type plasminogen activator (t-PA) secretion and marked reduction in plasminogen activator inhibitor-1 (PAI-1) secretion. In this study, the intracellular signal transduction after fibrin stimulation was further investigated by analyzing cyclic AMP (cAMP) and protein kinase C (PK-C). When HUVECs were stimulated by fibrin clots, t-PA mRNA increased to 130% but PAI-1 mRNA decreased to 42%. These changes concurred with the data on the protein levels of t-PA and PAI-1 as previously reported. The effect of fibrin on t-PA production in HUVECs was not significantly altered after the elevation of cAMP by either forskolin or dibutyryl cAMP. Furthermore, an effect of fibrin on t-PA production did not appear when the cells were treated by phorbol 12-myristate 13-acetate (PMA) or 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). The suppressive effect of fibrin on PAI-1 secretion from HUVECs was not altered by elevation of cAMP. Regarding the activation of PK-C by PMA, PAI-1 secretion was enhanced, but was suppressed by fibrin stimulation. H-7 suppressed PAI-1 secretion and further stimulation by fibrin almost completely abolished PAI-1 secretion. These changes were well associated with mRNA levels of t-PA and PAI-1. These results suggested that fibrin on HUVECs preferably down-regulates PK-C resulting in a decrease of PAI-1 in both the protein and mRNA levels and that effect of fibrin on t-PA secretion is neither involved in PK-C nor cAMP pathway.

Cells, Cultured↗

PubMed1985

Crosslinking of soluble fibrin and fibrinogen.

Monomeric 125I-desAA-fibrin and 125I-desAABB-fibrin were prepared by treating 125I-fibrinogen with thrombin. Preactivated factor XIII was added to 125I-fibrin/131I-fibrinogen mixtures, and after incubation for 2 and 6 hours, samples were investigated by SDS polyacrylamide gel electrophoresis under reducing conditions. The electrophoresis pattern showed a gamma-gamma band containing both 125I-fibrin and 131I-fibrinogen. These experiments indicate that a fibrin molecule polymerizes with a fibrinogen molecule in a similar way as a fibrin molecule polymerizes to a second fibrin molecule. This type of polymerization results in conformational changes of the molecules involved thus enabling FXIIIa for specific crosslinking reaction. The polymerization of fibrin and fibrinogen molecules as well as the crosslinking of fibrin to fibrinogen molecules seem to represent a mechanism for interrupting the process of further fibrin polymerization.

Blood Coagulation↗

PubMedDate not supplied

A fibrin matrix modulates the proliferation, hormone secretion and morphologic differentiation of cultured human placental trophoblast.

Term placental trophoblast epithelialize fibrin deposits attached to villi in vitro and trophoblast cultured on a fibrin matrix form an epithelial bilayer typical of the trophoblast layer on term villi. We compared the morphology of cells grown on fibrin with cells grown on substrates of type IV collagen, laminin, type I collagen, or Matrigel. We also used autoradiography, hormone assays, electron microscopy, and immunofluorescence to determine what functional activities were influenced by trophoblast-fibrin interactions. Cultured cellular trophoblast from term placentae differentiated to form syncytial trophoblast and to secrete estrogen, progesterone, and hCG in the presence or absence of matrices. Trophoblast proliferation was lower in cells grown on matrices and was inversely related to cell height after 24 h in culture. Cells grown on fibrin remained the tallest and had the lowest labelling index. Cells grown for 72 h on fibrin had the most dilated rough endoplasmic reticulum but the lowest media hormone levels. Only cells grown on a fibrin matrix formed a basal lamina-like structure at the trophoblast-substrate interface, and only a fibrin matrix facilitated trophoblast to form an epithelial bilayer in culture. However, this histology was not accompanied by a change in the amount of syncytial trophoblast formed by the cells grown on fibrin. The results suggest that a fibrin matrix uniquely modulates the trophoblast phenotype, away from the secretion of placental specific products like hCG in favour of a repair-oriented phenotype that forms basement membrane and a trophoblast bilayer.

Cell Differentiation↗

PubMed2006

Preparation of hybrid scaffold from fibrin and biodegradable polymer fiber.

A biodegradable hybrid scaffold was prepared from fibrin and poly(glycolic acid) (PGA) fiber. Mixed fibrinogen and thrombin solution homogeneously dispersed in the presence of various amounts (0, 1.5, 3.0, and 6.0mg) of PGA fiber was freeze-dried to obtain fibrin sponges with or without PGA fiber incorporation. By scanning electron microscopy observation, the fibrin sponges had an interconnected pore structure, irrespective of the amount of PGA fiber incorporated. PGA fiber incorporation enabled the fibrin sponges to significantly enhance their compression strength. In vitro cell culture studies revealed that the number of L929 fibroblasts initially attached was significantly larger for any fibrin sponge with PGA fiber incorporation than for the fibrin sponge without PGA fiber. The shrinkage of sponges after cell seeding was suppressed by fiber incorporation. It is possible that the shrinkage suppression of sponges maintains their intraspace, resulting in the superior cell attachment of a sponge with PGA fiber incorporation. After subcutaneous implantation into the backs of mice, the residual volume of a fibrin sponge with PGA fiber incorporation was significant compared with that of a fibrin sponge without PGA fiber. Larger number of cells infiltrated deep inside the fibrin sponges with PGA fiber incorporation implanted subcutaneously. It is concluded that the fibrin sponge reinforced by fiber incorporation is a promising three-dimensional scaffold of cells for tissue engineering.

Absorbable Implants↗

PubMed2005

Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(L-lactide-co-glycolide) nanospheres and fibrin gel.

Controlled long-term delivery of basic fibroblast growth factor (bFGF) could be used as an angiogenesis therapy. In this study, novel heparin-conjugated poly(L-lactide-co-glycolide) (PLGA) nanospheres (HCPNs) were developed for long-term, zero-order delivery of bFGF. HCPNs were prepared by using a coupling reaction between amino-terminated PLGA nanospheres and heparin in the presence of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. The amount of heparin conjugated to the PLGA nanospheres was increased up to 29-fold by using nanospheres made from lower molecular weight PLGA, or star-shaped PLGA, as compared to nanospheres made from higher molecular weight PLGA, or linear PLGA. The release of bFGF from HCPNs was sustained for 3 weeks with no initial burst release. The bFGF release period was increased to more than 4 weeks using a delivery system of HCPNs suspended in fibrin gel. The release was nearly zero order. The rate of bFGF release from HCPNs in fibrin gel was controlled by the fibrinogen concentration in the fibrin gel. As the fibrinogen concentration increased, the bFGF release rate decreased. The bioactivity of bFGF released from HCPNs in fibrin gel was assessed using human umbilical vein endothelial cell (HUVEC) culture. bFGF released from HCPNs in fibrin gel exhibited HUVEC growth for 15 days, similar to that of cultures to which bFGF in free form was added daily, suggesting that the delivery system of HCPNs in fibrin gel can release bFGF in a bioactive form for a long period. The therapeutic potential of bFGF delivery using HCPNs in fibrin gel was investigated in a mouse limb ischemia model. Immunohistological analysis of mouse ischemic limbs indicated that the microvessel density was much higher in the ischemic limbs treated with bFGF delivery using HCPNs in fibrin gel than in the ischemic limbs treated with daily injections of bFGF or with bFGF delivery using fibrin gel. This study shows that a bFGF delivery system using HCPNs in fibrin gel exhibits controllable, long-term, zero-order release of bFGF and potentiates the angiogenic efficacy of bFGF administration.

Animals↗

PubMed2004

Controlled release of neurotrophin-3 from fibrin gels for spinal cord injury.

The goal of this work was to assess the feasibility of using affinity-based delivery systems to release neurotrophin-3 (NT-3) in a controlled manner from fibrin gels as a therapy for spinal cord injury. A heparin-based delivery system (HBDS) was used to immobilize NT-3 within fibrin gels via non-covalent interactions to slow diffusion-based release of NT-3, thus allowing cell-activated degradation of fibrin to mediate release. The HBDS consists of three components: immobilized linker peptide, heparin and NT-3. The linker peptide contained a Factor XIIIa substrate and was covalently cross-linked to fibrin during polymerization. This immobilized linker peptide sequesters heparin within fibrin gels, and sequestered heparin binds NT-3, preventing its diffusion. Mathematical modeling was performed to examine the effect of heparin concentration on the fraction of NT-3 initially bound to fibrin. In vitro release studies confirmed that heparin concentration modulates diffusion-based release of NT-3. Fibrin gels containing the HBDS and NT-3 stimulated neural outgrowth from chick dorsal root ganglia by up to 54% versus unmodified fibrin, demonstrating that the NT-3 released is biologically active. In a preliminary in vivo study, fibrin gels containing the HBDS and NT-3 showed increased neural fiber density in spinal cord lesions versus unmodified fibrin at 9 days.

Animals↗

PubMed2006

Perivenous application of fibrin glue as external support enhanced adventitial adenovirus transfection in rabbit model.

BACKGROUND: Placement of an external support has been reported to prevent intimal hyperplasia of vein grafts. However, it's application limited by potential complications. Peri-adventitial gene delivery is a promising alternative therapy to reduce intimal hyperplasia, but it is limited by low and transient levels of gene transfection. To get more effective inhibition of intimal hyperplasia and to avoid the limitations associated with these two approaches, a study was undertaken to investigate whether mixing adenovirus with fibrin glue may increase the level and prolong the time period of gene expression. METHODS: Right jugular vein to common carotid artery interposition grafting was performed in 36 male New Zealand white rabbits (2.5-3.0 kg) and the animals were divided into four groups: control group (n = 6); fibrin glue group (n = 6); Ad-GAL group (n = 12); fibrin glue/Ad-GAL group (n = 12). Commercially available fibrin glue and adenovirus expressing the gene for beta-galactosidase (Ad-GAL) was applied separately or in mixing around vein grafts. At 7th day and 14th day after implantation, the grafts were harvested to evaluate transfection rate. At 28th day the grafts were harvested for morphometric analysis. RESULTS: Compared with weak staining in 2.1 +/- 0.5% in Ad-GAL alone grafts, a high level of beta-Galactosidase staining was evident in 13.2 +/- 4.6% in fibrin glue/Ad-GAL grafts at 7th day (P < 0.001). At 14th day, almost no staining (0%) was detected in Ad-GAL alone grafts. However, there was still a relative high level staining (6.3 +/- 3.8%) in fibrin glue/Ad-GAL grafts (P < 0.001 versus Ad-GAL alone group). At 28th day, a statistically significantly decrease in neointimal area (0.68 +/- 0.06 mm(2)versus 1.00 +/- 0.08 mm(2), P < 0.05) was shown in fibrin glue grafts compared with unsupported vein grafts (control group). The same statistically significantly difference was also existed in fibrin glue/Ad-GAL group and unsupported group in neointimal area (0.66 +/- 0.07 mm(2), P < 0.05). CONCLUSIONS: A novel method of adventitial gene delivery using fibrin glue as external support is proposed. Fibrin glue may be an ideal candidate for controlled release delivery that would facilitate adventitial gene transfer.

Adenoviridae↗

PubMed2005

Subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma.

PURPOSE: To evaluate the efficacy of subconjunctival carboplatin in fibrin sealant in the treatment of transgenic murine retinoblastoma. DESIGN: Experimental study using LHbeta-Tag transgenic mice in a randomized controlled trial. PARTICIPANTS AND CONTROLS: Thirty-three 10-week-old LHbeta-Tag transgenic mice: 22 carboplatin-treated animals and 11 control animals. METHODS: Three groups of 11 mice were treated with a single, 30 microl injection of fibrin sealant in the subconjunctival space of 1 eye; the opposite eye was left untreated as an internal control. Group 1 (low-dose group) received 37.5 mg/ml calculated concentration of carboplatin in fibrin sealant (0.66 mg measured total dose). Group 2 (high-dose group) received 75 mg/ml calculated concentration of carboplatin in fibrin sealant (1.23 mg measured total dose). Group 3 (control group) received fibrin sealant only. Mice were killed on day 22 after treatment. Eyes were serially sectioned, and retinal tumor burden was quantified by histopathologic analysis. For statistical analysis of treatment effects, eyes were divided into 6 groups: low-dose group, sealant-treated eyes; low-dose group, untreated eyes; high-dose group, sealant-treated eyes; high-dose group, untreated eyes; control group, sealant-treated eyes; and control group, untreated eyes. MAIN OUTCOME MEASURES: Main outcome measure was mean tumor burden per level per eye in each experimental group. RESULTS: The best therapeutic results were obtained in eyes treated with low-dose carboplatin in fibrin sealant, where no histopathologic evidence of toxicity was observed, and 6 of 11 eyes had zero tumor burden. Tumor burden in the remaining 5 eyes in this group was minimal (4 eyes) or moderate (1 eye) compared with mean control values. Mean tumor burden in this group was significantly smaller than mean tumor burden in untreated eyes from the same mice (P<0.004), sealant-treated eyes in the control group (P<0.004), and untreated eyes in the control group (P<0.002). Although a similar reduction in mean tumor burden was observed in eyes treated with high-dose carboplatin in fibrin sealant, 5 of 10 eyes analyzed in this group also demonstrated histopathologic evidence of severe toxicity. CONCLUSIONS: Subconjunctival carboplatin in fibrin sealant is effective in the treatment of transgenic murine retinoblastoma. A single injection of low-dose carboplatin in fibrin sealant was sufficient to induce complete or near-complete intraocular tumor regression in 10 of 11 eyes (91%), with no associated histologic evidence of toxicity. These results suggest that subconjunctival carboplatin in fibrin sealant provides sustained release and could have clinical use in the treatment of intraocular retinoblastoma.

Animals↗

PubMed2005

Fibrin enhances differentiation, but not apoptosis, and limits hypoxic injury of cultured term human trophoblasts.

We hypothesized that fibrin enhances apoptosis and modulates differentiation of trophoblast in vitro. Cytotrophoblasts isolated from normal term human placentas were cultured < or =72 h in DMEM-10%-FBS on a fibrin matrix in standard or hypoxic conditions. Trophoblasts were cultured on plastic (control), type I collagen (matrix control), or dishes with fibrinogen, fibrin degradation products (FDP), thrombin, plasma fibronectin or cellular fibronectin. Apoptosis was determined by western analysis of the cleavage products of poly-ADP-ribose polymerase and cytokeratin 18 and caspase 3 activity. Cell cycle regulation was quantified by expression of proliferating cell nuclear antigen (PCNA) and p27 protein. Differentiation was determined by media level of hCG and hPL. Compared to the two controls, fibrin matrix had no effect on trophoblast apoptosis or total cell death in standard conditions. Neither fibrin nor collagen altered expression of PCNA or p27. In contrast, fibrin significantly increased the secretion of both hCG and hPL. Fibrin, but not FDP, thrombin or fibronectins, promoted hormonal differentiation. Fibrin limited the impact of a < or =8h of hypoxia on trophoblast hormone release but did not avert the effects of 24h of low oxygen and did not alter apoptosis in hypoxic trophoblast. We conclude that fibrin provides an environment conducive for trophoblast re-epithelialization of the surface of villi, where injury is marked by fibrin deposition.

Apoptosis↗

PubMed1990

Risk factors for postvitrectomy fibrin formation.

We prospectively studied 194 patients undergoing vitrectomy between July 1988 and April 1989 to determine the incidence of postvitrectomy intraocular fibrin formation and the association of a variety of preoperative and intraoperative variables with the formation of severe postvitrectomy fibrin. Overall, 62 (32%) patients developed postvitrectomy fibrin; 25 (13%) had mild fibrin formation, 13 (6.5%) had moderate fibrin formation, and 24 (12.4%) had severe fibrin formation. By logistic multivariate analysis, preoperative factors that were independently predictive of severe fibrin formation included severe flare (P = .004), the presence of a previously placed scleral buckle (P = .001), and poor preoperative visual acuity (P = .007). Anterior epiretinal membrane dissection was the only intraoperative factor that was independently associated with an increased fibrin risk (P = .0003). A risk score derived from the multivariate analysis effectively categorized patients according to their likelihood of developing severe postvitrectomy fibrin. Results of this study may be useful in designing prophylactic interventions to decrease postvitrectomy fibrin formation.

Adult↗

PubMed1979

Fibrin in fibroblast cultures--a metabolic study as a contribution to inflammation and tissue repair.

Embryonic rat fibroblasts were cultured in the presence of fibrin under fibrinolytic and fibrinostatic conditions both in proliferating and confluent stages. The proliferation rate, glucose consumption, glycosaminoglycan contents and distribution pattern were determined. Additionally the influence on rat fibroblast cultures of fibrinogen and its splitting products were reinvestigated. Basing on the experimental results and a literature survey the role of fibrin in chronic inflammation was emphasized. Experimental results: 1. First step of tissue injury was simulated by formation of fibrin above a confluent fibroblast monolayer. The small degree of fibrinolysis with the cultures was sufficient to prevent all metabolic changes except a decrease of sulfate incorporation (immediately reversibly injury). Inhibition of fibrinolysis resulted in a decrease of proliferation and HA contents additionally, but in an increase of total GAG concentration and SO4-GAG. This behaviour continued during the beginning of cell proliferation. 2. The following step of fibrin contraction, improvement of nutrient supply, and cell proliferation was artificially achieved by growing non-confluent cells on the preformed fibrin network. Fibrin enhanced the cell proliferation, total GAG concentration, HA, and the turnover of SO4-GAG (sulfate incorporation). In rapidly proliferating cultures no influence of anti-fibrinolytic agents was observed. 3. On the preformed, partially contracted fibrin the cells grew to confluence: a) Without inhibition of the fibrinolysis, the parameters of the fibrin-free controls were obtained; repair seems to be completed. b) When fibrinolysis was inhibited the cells continued proliferating apparently with a tendency of enhanced HA and decreased SO4-GAG (a stage of "chronic inflammation"). 4. Purified fibrin fractions as well as the supernatant of fibrin containing fibrinopeptides were shown to advance cell proliferation.

4-Aminobenzoic Acid↗

PubMed1998

Osteogenic response of the rabbit femur to a hydroxyapatite thermal decomposition product-fibrin glue mixture.

The effect of fibrin glue on the hardening process of hydroxyapatite thermal decomposition product (HATDP) was investigated in vitro. To study, in vivo, the effect of fibrin glue on osteogenesis, a mixture of HATDP with fibrin glue was injected into the left femurs of 20 rabbits, and HATDP without fibrin glue was injected into the right femurs. New bone formation was observed in the area of direct contact with the fibrin-containing mixture in the metaphysis at 2 weeks after injection in two of four femurs, but not in the fibrin-free group. At 4 weeks after injection, new bone formed a bridge between the mixture and the cortical bone in three of the four specimens. A parameter of osteogenesis (the affinity index) was calculated at 4, 12 and 24 weeks after injection. It was respectively 0.14+/-0.02, 0.49+/-0.12 and 0.44+/-0.05 for the fibrin-containing mixture, and 0.14+/-0.062, 0.44+/-0.15 and 0.49+/-0.04 for the control. A comparable but significant increase in the average affinity index was noted over 12 weeks in both the fibrin-containing and the fibrin-free HATDP. These findings indicate that fibrin glue accelerated the hardening of HATDP but did not inhibit the process of osteogenesis.

Animals↗

PubMed1992

Apolipoprotein(a) and plasminogen interactions with fibrin: a study with recombinant apolipoprotein(a) and isolated plasminogen fragments.

Lipoprotein(a) [Lp(a)], but not low-density lipoprotein (LDL), was previously shown to impair the generation of fibrin-bound plasmin [Rouy et al. (1991) Arterioscler. Thromb. 11, 629-638] by a mechanism involving binding of Lp(a) to fibrin. It was therefore suggested that the binding was mediated by apolipoprotein(a) [apo(a)], a glycoprotein absent from LDL which has a high degree of homology with plasminogen, the precursor of the fibrinolytic enzyme plasmin. Here we have evaluated this hypothesis by performing comparative fibrin binding studies using a recombinant form of apo(a) containing 17 copies of the apo(a) domain resembling kringle 4 of plasminogen, native Lp(a), and Glu-plasminogen (Glu1-Asn791). Attempts were also made to identify the kringle domains involved in such interactions using isolated elastase-derived plasminogen fragments. The binding experiments were performed using a well-characterized model of an intact and of a plasmin-digested fibrin surface as described by Fleury and Anglés-Cano [(1991) Biochemistry 30, 7630-7638]. Binding of r-apo(a) to the fibrin surfaces was of high affinity (Kd = 26 +/- 8.4 nM for intact fibrin and 7.7 +/- 4.6 nM for plasmin-degraded fibrin) and obeyed the Langmuir equation for adsorption at interfaces. The binding to both surfaces was inhibited by the lysine analogue AMCHA and was completely abolished upon treatment of the degraded surface with carboxypeptidase B, indicating that r-apo(a) binds to both the intrachain lysines of intact fibrin and the carboxy-terminal lysines of degraded fibrin. As expected from these results, both r-apo(a) and native Lp(a) inhibited the binding of Glu-plasminogen to the fibrin surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗

PubMed1997

Crosslinking kinetics of the human transglutaminase, factor XIII[A2], acting on fibrin gels and gamma-chain peptides.

Factor XIII is the terminal enzyme of the coagulation cascade which serves to rapidly crosslink the adjacent gamma-chain C-termini of fibrin clots. In vivo, this process is initiated by the proteolytic action of thrombin which simultaneously converts both soluble fibrinogen to fibrin and activates zymogen FXIII; fibrin then spontaneously polymerizes to form a gel which activated FXIII stabilizes through crosslinking. Due to the kinetic complexity and the difficulty of investigating gel phase reactions, methods employing pre-activation of recombinant human Factor XIII (rFXIII[A'2]) were developed to effectively decouple these reactions. By utilizing these methods, the kinetic parameters of gamma-chain crosslinking in fibrin gels could be determined by both initial rate and integrated rate techniques under physiologically relevant conditions. The crosslinking of the gamma-chain of fibrin gels could be described by apparent Michaelis kinetics with K(m)(app) = 6.2 microM, kcat = 1872 min-1, and Ksp = 302 min-1 microM-1 for a fibrin gamma-chain monomer of M(r) = 170000 Da. In contrast, both the crosslinking rates of alpha-chains within fibrin gels (Ksp = 0.38 min-1 microM-1: Bishop et al. (1993)) and the crosslinking of a soluble synthetic peptide containing the unique gamma-chain fibrin crosslinking site (Ksp = 0.030 min-1 microM-1) could not be shown to saturate and gave apparent first-order rates with respect to rFXIII[A'2]. These observations coupled with the large differences in the turnover rates (approximately 10(4)) suggest two likely mechanisms for FXIII[A'2]-substrate interactions: (1) random (or independent) binding of non- or weakly interacting substrate pairs imposes a high entropic barrier (i. e., delta Gbinding) to the formation of a productive catalytic complex, e.g., for soluble gamma-chain peptides and the flexible alpha-chains within fibrin, and (2) binding to an oriented substrate pair effectively lowers the entropic barrier to formation of a Michaelis complex and thus greatly enhances the rate of catalysis, e.g., for gamma-chain pairs within the fibrin fibrils.

Amino Acid Sequence↗

PubMed1998

Fibrin sealing in peptic ulcer bleeding: the fate of the clot.

BACKGROUND AND STUDY AIMS: The injection of fibrin tissue glue is a promising endoscopic method for hemostasis of peptic ulcer bleeding. So far, no clinical study has focused on the ulcer healing process after endoscopic fibrin injection. PATIENTS AND METHODS: A morphological study was performed on all resection specimens from patients operated on between 1 January 1994 and 31 December 1996 for gastroduodenal ulcer bleeding with prior endoscopic injection of fibrin glue. The fibrin clot was characterized histologically for its size, location and aspect. RESULTS: Of 227 patients endoscopically treated with a double-lumen needle, 20 underwent resection. The interval between fibrin injection and resection ranged from 6 hours to 9 days. In 15 patients the ulcer was identified in the resection specimen. No fibrin remnants were detectable in three, sparse fibrin deposits were seen in eight and large amounts of fibrin were noted in the submucosa or subserosa in four specimens. With increasing time, the clot was gradually organized by phagocytes and angio-fibroblasts and was finally replaced by endogenous granulation tissue. An exuberant or tissue-destructive reaction did not appear. CONCLUSIONS: In this study, endoscopic fibrin sealing of bleeding ulcers resulted in appearance of a bland fibroblast-rich granulation tissue. The depth of fibrin glue injection is difficult to standardize with the aid of double-lumen needles.

Duodenum↗