Fibrin adhesive implant in wound healing repair of dental sockets with topical application of epsilon aminocaproic acid: Histological analysis

The aim of the study was to evaluate wound healing repair of dental sockets after topical application of 5% epsilon-aminocaproic acid (EACA) and the use of fibrin adhesive implant in rats under anticoagulant therapy with warfarin. Sixty Albinus wistar rats were used, divided into three groups of 20. In Group I, the animals were given 0.1 mL/100 mg of 0.9% saline solution per day, beginning 6 days before dental extraction and continuing throughout the experimental period. In Group II, the animals received 0.03 mL of sodium warfarin daily, beginning 6 days before the surgery and continuing until the day of sacrifice; after tooth extractions, the sockets were filled with fibrin adhesive material. In Group III the animals were treated as in Group II, and after extractions, the sockets were irrigated with 5 mL of 5% EACA and filled with the same fibrin adhesive material. All groups presented biological phases of wound healing repair, the differences being evident only in the chronology. The results obtained in Group III were very similar to those of Group I in the last period of wound repair, whereas Group II presented a late chronology compared to the other groups. © 2005 Wiley Periodicals, Inc.

Osseous regeneration in the presence of fibrin adhesive material (Tissucol) and epsilon-aminocaproic acid (EACA).

The effects of Tissucol and Tissucol/EACA on bone healing were evaluated histologically. Experimental defects were made in both tibias of 25 rats. Test materials were placed in defects in right tibias and left tibias served as control. Five animals in each group were killed at 1, 3, 7, 14 and 21 days after surgery. Results showed that: a) Tissucol did not interfere with connective and osseous tissue formation; b) Tissucol allowed new bone formation; c) Tissue residues in Tissucol groups in sections of 21-day specimens did not impair healing; d) Tissucol/EACA was usually completely resorbed and healing was complete 21 days after surgery in the Tissucol/EACA group.

Effects of tissucol™ and epsilon aminocaproic acid in the healing process following dental extraction in dehydrated rats

A histological study was conducted of the alveolar bone healing process following tooth extraction of dehydrated rats after the implantation of fibrin adhesive (TISSUCOL™) associated to previous irrigation of the wound with a 5% epsilon aminocaproic acid solution (EACA). Seventy two rats were used, divided into three groups receiving different treatments after the surgical procedure. In group I, the gingival mucosa was sutured after extraction of the right upper incisor. In groups II and III, chronic dehydration was produced by water deprivation for 9 days (3 days in the preoperative period and 6 days in the postoperative period). In the animals of Group II, after tooth extraction, the gingival mucosa was sutured in the same way as performed in group I. In group III, after extraction, the dental socket was irrigated with 5% EACA, followed by implantation of the fibrin adhesive (TISSUCOL™). The mucosa was sutured in the same way as performed in the other groups. At 3, 7, 15 and 21 postoperative days, the animals were sacrificed in number of 6 for each group. Specimens containing the dental socket were removed and fixed in 10% formalin and decalcified in an equal part formic acid and sodium citrate solution. After routine processing, the specimens were embedded in paraffin for microtomy. We obtained 6 μm semi-serial slices that were stained with hematoxylin and eosin for histological evaluation. The results showed that the water deprivation in the pre- and postoperative periods caused a delay in the alveolar bone healing process. The use of the fibrin adhesive (TISSUCOL™) produced an improvement in the fibrinolytic picture caused by dehydration.

A Randomized Trial of the Topical Effect of Antifibrinolytic Epsilon Aminocaproic Acid on Coronary Artery Bypass Surgery Without Cardiopulmonary Bypass

We assessed the effect of the topical application of epsilon-aminocaproic antifibrinolytic acid (EACA) on the pericardium of patients submitted to coronary artery bypass graft (CABG) without the use of cardiopulmonary bypass (CPB). This is a prospective, randomized, and double-blind study. We evaluated 26 patients with chronic coronary heart disease indicated for CABG without CPB (EACA and placebo groups). The analysis of the postoperative hematological results showed no difference between groups in hemoglobin and hematocrit. There was no difference between the groups regarding the postoperative bleeding through the drains in the first 24 hours, 48 hours, and accumulated loss until removal of drains. The use of EACA in patients undergoing CABG without CPB presented no difference in the reduction of the amount of bleeding and the need for blood transfusions.

A family of textilinin genes, two of which encode proteins with antihaemorrhagic properties

Two peptides, textilinins 1 and 2, isolated from the venom of the Australian common brown snake, Pseudonaja textilis textilis, are effective in preventing blood loss. To further investigate the potential of textilinins as anti-haemorrhagic agents, we cloned cDNAs encoding these proteins. The isolated full-length cDNA (430 bp in size) was shown to code for a 59 amino acid protein, corresponding in size to the native peptide, plus an additional 24 amino acid propeptide. Six such cDNAs were identified, differing in nucleotide sequence in the coding region but with an identical propeptide. All six sequences predicted peptides containing six conserved cysteines common to Kunitz-type serine protease inhibitors. When expressed as glutathione S-transferase (GST) fusion proteins and released by cleavage with thrombin, only those peptides corresponding to textilinin 1 and 2 were active in inhibiting plasmin with K-i values similar to those of their native counterparts and in binding to plasmin less tightly than aprotinin by two orders of magnitude. Similarly, in the mouse tail vein blood loss model only recombinant textilinin 1 and 2 were effective in reducing blood loss. These recombinant textilinins have potential as therapeutic agents for reducing blood loss in humans, obviating the need for reliance on aprotinin, a bovine product with possible risk of transmissible disease, and compromising the fibrinolytic system in a less irreversible manner.

A study of the interaction between Helicobacter pylori and components of the human fibrinolytic system

The interaction of plasminogen, tissue plasminogen activator (t-PA) and urokinase with a clinical strain of Helicobacter pylori was studied. Plasminogen bound to the surface of H. pylori cells in a concentration-dependent manner and could be activated to the enzymatic form, plasmin, by t-PA. Affinity chromatography assays revealed a plasminogen-binding protein of 58.9 kDa in water extracts of surface proteins. Surface-associated plasmin activity, detected with the chromogenic substrate CBS 00.65, was observed only when plasminogen and an exogenous activator were added to the cell suspension. The two physiologic plasminogen activators, t-PA and urokinase, were also shown to bind to and remain active on the surface of bacterial cells. epsilon-Aminocaproic acid caused partial inhibition of t-PA binding, suggesting that the kringle 2 structure of this activator is involved in the interaction with surface receptors. The activation of plasminogen by t-PA, but not urokinase, strongly depended on the presence of cells and a 25-fold enhancer effect on the initial velocity of activation by t-PA compared to urokinase was established. Furthermore, a relationship between cell concentration and the initial velocity of activation was demonstrated. These findings support the concept that plasminogen activation by t-PA on the bacterial surface is a surface-dependent reaction which offers catalytic advantages.

Hydrogen-bonded dimer can mediate supramolecular beta-sheet formation and subsequent amyloid-like fibril formation: a model study

FT-IR data of six terminally blocked tripeptides containing Acp (epsilon-aminocaproic acid) reveals that all of them form supramolecular beta-sheets in the solid state. Single crystal X-ray diffraction studies of two peptides not only support this data but also disclose the fact that the supramolecular beta-sheet formation is initiated via dimer formation. The Scanning Electron Microscopic images of all peptides exhibit amyloid-like fibrils that show green birefringence after binding with Congo red, which is a characteristic feature of many neurodegenerative disease causing amyloid fibrils. (C) 2004 Elsevier Ltd. All rights reserved.

Effects of fibrin adhesive material (Tissucol) on alveolar healing in rats under stress.

The effects of Tissucol on alveolar healing following stress were evaluated histologically, comparing three groups of 28 male albino rats each. Stress was applied and their right upper incisors were extracted. Group A served as an empty control site. In Group B, Tissucol was applied into the alveolar cavity. Group C received local antifibrinolytic treatment (alveolar irrigation with epsilon-aminocaproic acid solution) before implant of Tissucol into the tooth socket. Four animals in each group were killed at 1, 3, 6, 9, 15, 21 and 24 days after surgery. Results showed that: 1) Tissucol did not interfere with connective and osseous tissue formation; 2) Tissucol allowed new bone formation; 3) Tissucol residues in Group B in sections of 24-day specimens did not impair healing; 4) Tissucol was usually completely resorbed and healing was complete 24 days after surgery in Group C.

Surgical and clinical management of a patient with Glanzmann thrombasthenia: A case report

A 6-year-old girl with Glanzmann thrombasthenia presented with caries and periapical lesions in the primary mandibular second molars and moderate gingivitis of the maxillary and mandibular anterior teeth. Dental extraction was recommended, and before every surgical intervention, the patient underwent platelet-concentrate transfusion to prevent hemorrhage. Epsilon aminocaproic acid was administered 6 hours before, and 48 hours after every dental procedure to prevent bleeding. In this case, treatment was effective in the prevention of hemorrhagic complications, during the required dental procedures.

Review of the fibrinolytic system: comparison of different antifibrinolytics used during cardiopulmonary bypass

Antifibrinolytic agents are often used in different clinical situations, especially in cardiac surgery. During several years, aprotinin was the drug of choice because more than antifibrinolytic properties, aprotinin offers a direct effect on kallikrein and inflammatory pathways. In 2008, The Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART) initiated a discussion about real risks associated with aprotinin administration. Tranexamic acid and epsilon-aminocaproic acid appear to be interesting alternatives in our daily practice. The exact mechanism of action, the pharmacokinetic parameters, the efficacy, and the safety profile need to be clarified for lysine analogs. In this review, the different antifibrinolytics will be described with a special interest into the route of work, and recent patents. Current studies about the pharmacokinetic and the pharmacodynamic profile will be described, and finally the benefit-to-risk balance in patients undergoing cardiac surgery with cardiopulmonary bypass will be discussed.

Effects of lactate and acetate on the determination of serum ethyl glucuronide by CZE

The analysis of ethyl glucuronide (EtG), a marker of recent alcohol consumption, in serum with an optimized CZE assay is reported. The method uses a 0.1-mm id fused-silica capillary of 50 cm effective length that is coated with linear polyacrylamide, a pH 4.4 nicotinic acid/epsilon-aminocaproic acid (EACA) BGE, reversed polarity and indirect analyte detection. The assay is based on a 1:1 dilution of serum with deionized water and has LODs for EtG, lactate and acetate of 3.8 x 10(-7) M, 2.60 x 10(-6 )M and 2.18 x 10(-6 )M, respectively. Separation of EtG from endogenous macro- and microcomponents (anionic serum components of high and low concentration, respectively) and its quantification are shown to be possible for a wide range of lactate (stacker) and acetate (destacker) concentrations, macrocomponents that have an impact on the CZE behavior of EtG and that change after intake of ethanol. The assay has been successfully applied to the analysis of EtG, lactate and acetate in (i) sera of volunteers that ingested known amounts of alcohol and (ii) samples of patients that were classified (teetotalers and social drinkers vs. alcohol abusers) via analysis of carbohydrate-deficient transferrin.

Determination of ethyl glucuronide in human serum by capillary zone electrophoresis and an immunoassay

Ethyl glucuronide (EtG) is a marker of recent alcohol consumption. For the optimization of the analysis of EtG by CZE with indirect absorbance detection, the use of capillaries with permanent and dynamic wall coatings, the composition of the BGE, and various sample preparation procedures, including dilution with water, ultrafiltration, protein precipitation, and SPE, were investigated. Two validated screening assays for the determination of EtG in human serum, a CZE-based approach and an enzyme immunoassay (EIA), are described. The CZE assay uses a coated capillary, 2,4-dimethylglutaric acid as an internal standard, and a pH 4.65 BGE comprising 9 mM nicotinic acid, epsilon-aminocaproic acid and 10% v/v ACN. Proteins are removed via precipitation with ACN prior to analysis and the LOQ is 0.50 mg/L. The EIA is based upon commercial reagents which are promoted for the determination of urinary EtG. Krebs-Ringer solution containing 5% BSA is used as a calibration matrix. All samples are ultrafiltered prior to analysis of the ultrafiltrate on a Mira Plus analyzer. Assay calibration ranged between 0 and 2 mg/L and the upper reference limit was determined to be 0.05 mg/L. Both assays proved to be suitable for the analysis of samples from different individuals. For EtG levels above 0.50 mg/L, good agreement was observed for the comparison of the results of the two methods.

Potential antitumoral properties of a new copper complex with santonic acid

A new copper(II) complex of santonic acid [Cu(2)(sant)(4)(H(2)O)(2)]center dot 21/2H(2)O has been prepared and characterized by electronic, vibrational, EPR spectral studies, and stability determinations in solution. The presence of two antiferrromagnetically coupled copper centers in the solid state was detected by EPR. The dinuclear Cu(II) complex crystallizes in the tetragonal P4(3)2(1)2 space group, with a = b = 14.498(3), c = 64.07(1) angstrom. Biological studies indicate that the complex displays interesting potential antitumoral actions. (C) 2008 Elsevier Ltd. All rights reserved.