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Although garlic has been used in Chinese traditional medicine for its medical properties for thousands of years, investigations into its mode of action are relatively recent. The purpose of this study was to evaluate the in vitro anti-fungal efficacy of the active principle of garlic, pure allicin and polybutylcyanoacrylate (PBCA) nanoparticles (NPs) loaded with allicin. Pure allicin was prepared by reacting synthetic alliin with a stabilized process of the garlic enzyme alliinase. PBCA NPs were prepared by emulsion polymerization method and pure allicin was wrapped into it. The in vitro efficacy of pure allicin and PBCA-allicin NPs to Candida albicans, Cryputococcus neoformans, Trichophyton rubum, Microsporum gypseum, M. canis and Epidermophyton floccosum was examined and evaluated by MIC and MFC. The MIC of PBCA-allicin NPs to C. albicans (2.93 x 10(-2)mg/ml), T. rubum (1.46 x 10(-2)mg/ml) and E. floccosum (1.46 x 10(-2)mg/ml) was significantly lower than that of pure allicin (5.86 x 10(-2)mg/ml, 2.93 x 10(-2)mg/ml, 2.93 x 10(-2)mg/ml, respectively); accordingly, the MFC of PBCA-allicin NPs to C. albicans (5.86 x 10(-2)mg/ml), T. rubum (2.93 x 10(-2)mg/ml), E. floccosum (2.93 x 10(-2)mg/ml) and M. canis (2.93 x 10(-2)mg/ml) also decreased dramatically. These favourable results indicated that pure allicin has stronger in vitro anti-fungal efficacy to six tested fungi than alliinase and alliin. Moreover, it has improved significantly after pure allicin being wrapped into PBCA NP, which may be due to the NP's good prolonged release effect and nano-scale dimensions.

Objective: To test a new hypothesis that the glue/contrast admixture used for embolisation reduces the dose delivered to AVMs using an experimental model., Method: A model was created using a block of "solid water" (6 x 5 x 2 cm) with twelve wells of different depths. Different concentrations of the glue admixture (Enbucrilate + Lipiodol) were used. The model was irradiated using a 5MV beam with a clinical LINAC system and the dose was checked upstream and downstream. Dose was measured using Kodak XV film, a Vidar 16 bit film scanner and software for therapeutic film dosimetry measurements (RIT software)., Results: The radiation dose varied with the distance beyond the glue solid water interface. For distances of 0, 2 and 5 mm to the film, the mean reduction was 13.65% (SD = 2.94), 6.87% (SD = 1.95) and 1.75% (SD = 1.14), respectively. There was also correlation with the Lipiodol concentration in the mixture. The maximum reductions for 80, 50 and 20% Lipiodol concentrations were 16.1% (SD = 1.32), 14.85% (SD = 0.98) and 10% (SD = 1.21), respectively. There was no correlation between the glue depth and the dose delivered., Conclusion: The hypothesis that the glue mixture used for embolisation reduces the radiation dose delivered was experimentally confirmed with this study.

Purpose: To compare the bacteriostatic effects, corneal cytotoxicity, and ability to seal corneal incisions among fibrin glue and 2 commercially available cyanoacrylate derivatives: N-butyl cyanoacrylate and methoxypropyl cyanoacrylate., Methods: The bacteriostatic activities of these tissue glues were verified by measuring the zones of bacterial growth inhibition surrounding the adhesive droplets on agar plates inoculated with Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, or Mycobacterium chelonae. Corneal cytotoxicity was tested by a direct contact method by using cultured bovine corneal epithelial cells, keratocytes, and corneal endothelial cells challenged with droplets of adhesives. Each of the cells was treated with droplets of adhesives. The ability to seal corneal incisions was verified by calculating the maximum intraocular pressure resistant to leakage of rabbit corneal stab wounds sealed with tissue adhesives., Results: Methoxypropyl cyanoacrylate and N-butyl cyanoacrylate showed bacteriostatic effects against S. aureus, S. pneumoniae, and M. chelonae but not P. aeruginosa and E. coli. In contrast, fibrin glue had no such effects against either Gram-positive or -negative bacteria (P < 0.01). Methoxypropyl cyanoacrylate showed the highest levels of corneal cytotoxicity, followed by N-butyl cyanoacrylate. Fibrin glue, however, showed minimal cytotoxicity (P < 0.01). Methoxypropyl cyanoacrylate and N-butyl cyanoacrylate also displayed a greater ability to seal corneal incisions than that of fibrin glue (P < 0.01)., Conclusions: The bacteriostatic effects, corneal cytotoxicity, and ability to seal corneal incisions differed among the 3 compounds tested. These different properties should be considered when choosing tissue adhesives during corneal surgery.

Conclusion: The compound gelatin-resorcin-formaldehyde (GRF) was a better stabilizing material for cartilage grafts in rabbits than butyl-2-cyanoacrylate. GRF was also better than the suture when comparing fixation of cartilage to the periosteum and inflammatory reaction., Objective: Cartilage grafting is an interesting option for refinements on rhinoplasties. The objective of this study was to compare butyl-2-cyanoacrylate to GRF and suture to determine the efficacy of these methods in restraining grafted cartilage in rabbits., Materials and Methods: Fifteen male adult New Zealand rabbits underwent surgery with the aim of collecting six auricular cartilage grafts from each animal. Two of these grafts in each animal were glued together with butyl-2-cyanoacrylate, two were glued together with compound GRF, and two were sewn together with nylon suture. These sandwich grafts were then glued or sutured to the periosteum of the glabella. After 2, 6, and 12 weeks, groups of five animals were sacrificed and histological analysis for inflammation was performed. Cartilage graft migration, adhesion, and deformities of the grafts were also evaluated., Results: There was less migration of the cartilages glued with GRF than with cyanoacrylate and suture. GRF showed statistically less inflammatory reaction and angiogenesis than the other two methods. The three methods showed a tendency to decrease of fibrosis, inflammation, and angiogenesis as weeks passed. There was no detachment or deformity in the cartilage sandwiches sutured to the glabella's periostium. The majority of detached and deformed cartilages were those glued with cyanoacrylate. The number of detached cartilages was directly related to the number of deformed cartilages. The data were statistically significant (p<0.05).

Alkyl 2-cyano-3-methylthio-3-phosphonylacrylates were synthesized by the reaction of alkyl 2-cyano-3,3-dimethylthioacrylates with dialkyl phosphites. The structures of the new compounds were characterized by elemental analyses, IR, 1H-, 13C- and 31P-NMR spectral data. These compounds were tested in vitro against pathogenic fungi, namely, Fusarium graminearum, Cytospora mandshurica and Fusarium oxysporum. Amongst all compounds, 2d and 2t were found to be effective against the tested fungi at 50 microg/mL. A half-leaf method was used to determine the in vivo protective, inactivation and curative efficacies of the title products against tobacco mosaic virus (TMV). Title compounds 2a and 2b were found to possess good in vivo curative, protection and inactivation effects against TMV with inhibitory rates at 500 mg/L of 60.0, 89.4 and 56.5 and 64.2, 84.2 and 61.2 %, respectively. To the best of our knowledge, this is the first report on the antiviral and antifungal activity of alkyl 2-cyano-3-methylthio-3-phosphonylacrylates.

The standard treatment of zygomatic bone fractures is fixation by microplates or miniplates and screws today. It is very difficult to place plates and screws into thin bones or small bone fragments especially in the facial bones and bones adjacent to important structures. Cyanoacrylate is used as a hemostatic agent, an embolic agent, in retinal tears, in corneal ulcers, in fixation of mandibular osteotomies and in craniofacial surgery. N-2-Butyl cyanoacrylate is a form of cyanoacrylate which is bioabsorbable and biocompatible. It is easily applied to the tissues. We aimed to determine the effect of N-2-butyl cyanoacrylate in the fixation of displaced zygomatic bone fractures. We examined the histotoxicity and the effects on healing and foreign body reaction of N-2-butyl cyanoacrylate. Eight New Zealand white rabbits underwent zygomatic osteotomies bilaterally. The fractures on left sides of the rabbits were determined as study site and right sides as control site. Knight and North classification of zygomatic bone fractures were used and group 4 fractures were made bilaterally. Open reduction of fractures was performed bilaterally and N-2-butyl cyanoacrylate was applied only on left sides. No fixation was made on right sides representing the control group. Postoperatively in the first, second, third and fourth weeks, two rabbits were sacrificed and the fracture sites were examined macroscopically and histopathologically. In the glued study group, fixation was obtained in all cases whereas in the control group, all the fractures were seen to be displaced. Tissue reaction was similar in the study and the control groups.

Background: The purpose of this animal study was to find out whether sutureless anastomoses using N-butyl-2-cyanoacrylate were effective in the suppression of neointimal hyperplasia or not., Material and Methods: Ten male adult mongrel dogs were used in this animal study. The animals were randomly divided into a control group (n = 5) and a study group (n = 5). The study group underwent sutureless anastomoses using N-buthyl-2-cyanoacrylate adhesive. Infrarenal aortoaortic graft was interposed using polytetrafluoroethylene., Results: In the study group, the mean intimal thickness at the proximal anastomosis was 27.4 +/- 1.94 microm and 27.4 +/- 1.51 microm at the distal anastomosis. In the control group, the mean intimal thickness was 138.4 +/- 5.02 mum at the proximal anastomosis and 67.6 +/- 6.42 microm at the distal anastomosis. Intimal thickness at the proximal and distal anastomoses in the control group was significantly (p < 0.001) greater than in the study group. Also, perianastomotic inflammation was more obvious in the control group compared to the study group (p < 0.01)., Conclusion: Sutureless anastomoses using with N-butyl-2-cyanoacrylate adhesive might be a good alternative to conventional suture technique., (Copyright 2007 S. Karger AG, Basel.)

Effect of size of nanoscaled polybutylcyanoacrylate (PBCA) and methylmethacrylate-sulfopropylmethacrylate (MMA-SPM) on the permeability of zidovudine (AZT) and lamivudine (3TC) across the blood-brain barrier (BBB) was investigated. Also, influence of alcohol on the permeability of AZT and 3TC incorporated with the two polymeric nanoparticles (NPs) was examined. The loading efficiency and the permeability of AZT and 3TC decreased with an increase in the particle size of the two carriers. By employing PBCA NPs, the BBB permeability of AZT and that of 3TC became, respectively, 8-20 and 10-18 folds. Application of MMA-SPM NPs leaded to about 100% increase in the BBB permeability of the two drugs. In the presence of 0.5% ethanol, 4-12% enhancement in the BBB permeability of the two drugs was obtained in the current carrier-mediated system.

Background: Most duodenal injuries are managed with primary repair, but the degree of duodenal-wall injury may threaten the integrity of the primary repair. Therefore, we evaluated whether the primary repair site could be reinforced with histoacryl glue (HAG) or HAG with an expanded polytetrafluoroethylene (ePTFE) mesh., Methods: Grade 3 duodenal injury in the second portion of the rat duodenum was chosen as a standard trauma model. Thirty-three male rats were divided into sham (n = 3), 2-layer primary repair (n = 10), 1-layer primary repair plus HAG application (n = 10) and ePTFE attached with HAG over the 1-layer primary repair site (n = 10) groups. Ten-day survival, adhesion grades and histological assessment were taken as outcome measures., Results: A significant survival advantage was identified in the group that had an ePTFE graft attached with HAG over a 1-layer repair when compared with the group that had a 2-layer primary repair. Adhesion grades were found to be particularly increased in the group that had an ePTFE graft attached with HAG over the primary repair site, moderately increased in the primary repair plus HAG application group and lower in the 2-layer primary repair group. ePTFE graft application was found to be beneficial to coverage of the HAG-dependent empty spaces in the serosal layer., Conclusions: A primary repair site after duodenal trauma or a difficult duodenal stump can be reinforced with the application of HAG or ePTFE graft implantation with HAG.

Objective: To assess the histopathological vascular changes after injection of N-butyl-2-cyanoacrylate into the vessels of adult rabbits., Methods: The animals used were 42 pure-blood New Zealand white rabbits weighing 2-3 kg. 0.2 mL cyanoacrylate with lipiodol was injected into the external jugular vein and femoral artery of each rabbit. Tissue specimens were obtained for histopathological study at 3 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 2 months and 3 months after injection., Results: The vessels were obliterated immediately after the injection. The main manifestation of histopathology at 3 days to 2 weeks was an acute inflammatory reaction; this progressed to subacute vasculitis at 3 weeks and a chronic granulomatous foreign body reaction developed at 4 weeks. The glue mass essentially disappeared in 2-3 months, replaced by fibrotic tissue with partial vascular recanalization. At 3 weeks after injection, the elastic fibrils of the arterial wall proliferated distinctly, resulting in narrowing of the lumen with subsequent obliteration, whereas the venous wall still showed inflammation and necrosis without hyperplasia of elastic fibrils. Extrusion of glue was observed over 1-3 months in both arteries and veins and was obvious in the latter., Conclusions: The histopathological changes after injection of N-butyl-2-cyanoacrylate were similar in the arteries and the veins with the exception of hyperplasia of elastic fibrils in the arterial wall and inflammation and necrosis in the venous wall at 2-3 weeks. Glue extrusion was seen in both arteries and veins.

Objective: To evaluate the biocompatibility of polybutylcyanoacrylate nanoparticles (PBCA-NP) manufactured by emulsion polymerization technique., Methods: MTT assay was performed for evaluation of the cytotoxicity of PBCA-NP (e.g. cell proliferation and hemolytic test) experiments of long-term subcutaneous implantation and implantation in the muscular tissues of PBCA-NP was conducted in rabbits to observe the inflammatory reactions due to the implantation., Results: No obvious cytotoxicity or hemolytic reactions were observed (with the hemolytic rate at different concentrations of PBCA-NP(5%). Three months after PBCA-NP implantation, obvious lymphocyte infiltration was not observed in the tissues around the implants which underwent gradual degradation., Conclusion: PBCA-NP possesses good biocompatibility.

Short-chained cyanoacrylates have been used for many years for topical skin closure. Toxic effects in cell culture of a new long-chained octyl-2-cyanoacrylate tissue adhesive are compared with those of short-chained ethyl-2- and butyl-2-cyanoacrylates. Two cellular tests were used: the agar overlay test and the MTT test. An in vitro test using copper plates coated with the three types of cyanoacrylates serves for evaluating the stability of polymerized skin adhesives. Bilateral neck skin incisions in Goettingen miniature pigs were glued on one side with Dermabond. On the other side, conventional sutures were applied. After the pigs were killed, the resulting skin samples were tested for the tensile strength of their wound stability. Samples of pig dermis were exemplarily and histomorphologically characterized. A clinical examination after submandibular lymph node dissection should examine the application in humans. Cell culture tests were used to show the toxic effects of the three cyanoacrylates. In a copper test, octyl-2-cyanoacrylate was more stabile than ethyl- and butyl-cyanoacrylates. Breaking strength was 30% lower 28 days after operation with the new product than with sutures. In electron microscopy, octyl-2-cyanoacrylate showed no disadvantages with regard to tissue regeneration and no histotoxicity. For plastic surgery, this new topical skin adhesive is a real alternative with attractive results, as compared with conventional suture.

Objective: [corrected] To make a comparison between mitoxantrone (DHAQ) and liver targeting drug delivery system mitoxantrone-polybutylcyanoacrylate-nanosphere (DHAQ-PBCA-NS) in respect to their antitumor activity against experimental liver tumor H22 in mice., Methods: Drugs were given intravenously on the 1st, 5th, 9th day after planting tumor respectively. Weight of tumor in mouse was determined and the results were compared with those of mitoxantrone (DHAQ)., Results: There was relationship of dose-effect for both DHAQ and DHAQ-PBCA-NS, and the median effective dose (ED50) of DHAQ and DHAQ-PBCA-NS was 1.04 mg/kg and 0.34 mg/kg respectively. The lethal dose to 50% of the population (LD50) of DHAQ and DHAQ-PBCA-NS i.v. in mice with the same administration schedule was 3.670 mg/kg and 4.225 mg/kg respectively. Therefore, the calculated value of therapeutic index was 3.53 for DHAQ and 12.43 for DHAQ-PBCA-NS. In addition, the antitumor activity of both drugs with different treatment schedules was reported. The results showed: the earlier the mice were treated, the higher the antitumor activity of the two drugs were seen. However, DHAQ-PBCA-NS presented higher activity than DHAQ did, when the same treatment schedule was followed., Conclusion: The results demonstrated that the antitumor activity of DHAQ-PBCA-NS is much higher than that of DHAQ, and DHAQ-PBCA-NS is possessed of liver targeting property.

Background and Purpose: Liquid embolic agents may have potential as a therapeutic option to reconstruct a defective vessel wall. We evaluated the feasibility of transarterial glue embolization in surgically constructed carotid artery aneurysms., Methods: Reconstruction of arterial wall defects with use of glue casts was performed in 16 surgically constructed aneurysms of carotid arteries in rabbits. Via the transfemoral route, glue was injected without balloon protection through a microcatheter into the aneurysmal sac with (n = 8) and without (n = 8) a framework of coils. To identify safe and effective methods, four concentrations (28%, 33%, 40%, 50%) of glue-iodized oil mixtures were used in four aneurysms each. Immediate (n = 16) and 2-month follow-up (n = 10) postembolization angiograms were obtained to evaluate the residual aneurysmal sac and the carotid artery patency., Results: Continuous column injection of glue was possible in all aneurysms, without fragmented migration of the injected glue cast. Catheter sticking or breakage did not occur during catheter retrieval. Glue embolization without a framework of coils (n = 8) resulted in complete obliteration of the aneurysmal sac in five aneurysms and incomplete obliteration with a small residual lumen in three. Two aneurysms resulted in carotid occlusion after catheter removal. A follow-up angiogram (n = 4) showed decreased residual lumen in two aneurysms, no change in the complete aneurysm occlusion in one, and carotid occlusion in one. Glue embolization with a coil framework (n = 8) resulted in complete obliteration of the aneurysmal sac in six aneurysms and incomplete obliteration with a small residual lumen in two. A small amount of spillage occurred in one owing to the improper position of the microcatheter caused by a difficult neck angle to the parent artery. Follow-up angiograms (n = 6) showed decreased residual lumen in one of two aneurysms and no change of the complete occlusion in five of six aneurysms., Conclusion: Effective glue embolization into the aneurysmal sac is technically feasible. Microcatheter position within the aneurysm, concentration of glue, and direction of the aneurysmal neck angle all must be considered. With a coil framework, glue injection was more complete, without deformity or spillage of the glue from the aneurysm.

The phagocytic activity of peritoneal exudate cells (PECs) harvested from peritoneal cavity of mice after a single intraperitoneal (i.p.) treatment with poly(butylcyanoacrylate) nanoparticles (PBCN) and their probable metabolites [poly(cyanoacrylic acid) (PCAA) and n-butanol] was investigated in an in vitro phagocytic assay. Polymer suspension of PBCN was given as a single i.p. injection at doses of 200 and 10 mgkg(-1), 3, 18, 72 and 120 h before the performance of the phagocytic assay. PCAA and n-butanol were given at the same manner at doses of 126.8 and 96.8 mgkg(-1), respectively (equivalent to a dose of 200 mgkg(-1) of intact PBCN after enzyme hydrolysis) 3, 18 and 120 h before the test performance. The phagocytic assay was performed in vitro in tubes with sheep red blood cells (SRBC). Phagocytic index (percentage of PECs ingested more than 3 sheep erythrocytes), phagocytic number, and ingestion capacity (number of erythrocytes ingested per cell) were the parameters used for evaluation of the phagocytic activity. The alterations of phagocytic activity of the PECs observed were strongly time- and dose-dependent. Administration of all tested compounds shortly before the test performance resulted in a considerable decrease in the capability of PECs to ingest SRBC. The alterations of phagocytic activity decreased when the time between the treatment of mice and the phagocytic assay is on the increase. The dose of 200 mgkg(-1) of PBCN administered 120 h before the phagocytic assay led to the significant increase of the phagocytic index of PECs. The phagocytic function of assayed PECs was temporary impeded and 5 days were completely enough for their restoration.

Despite the fact that cyanoacrylates, a group of rapidly polymerizing adhesives, are used widely in general surgery, neuroradiology, otolaryngology, and plastic surgery, scientific data on histopathological changes resulting from the deposition of -butyl-2-cyanoacrylate (NBCA), a new-generation cyanoacrylate derivative, in human tissues is based largely on experimental observations in animals and sporadic postmortem studies in humans. The authors report the consecutive pathological findings of a patient who underwent surgery for facial hemangioma after percutaneous injection of NBCA for devascularization of a lesion, and underwent additional surgery 1 and 6 months after the initial operation for the removal of the residual NBCA cast from the injection site. Acute inflammatory findings after injection of NBCA and the development of a chronic granulomatous foreign body reaction support the histological findings of experimental animal studies and postmortem examinations on humans. Additionally, their findings support the proposed hypothetical sequence of events for the recanalization of cyanoacrylate-embolized vascular structures.

Poly(butylcyanoacrylate) nanoparticles were produced by emulsion polymerisation and used either uncoated or overcoated with polysorbate 80 (Tween 80). [3H]-dalargin bound to nanoparticles overcoated with polysorbate 80 or in the form of saline solution was injected into mice and the brain concentrations of radioactivity determined. Statistically significant, three-fold higher brain concentrations with the nanoparticle preparations were obtained after 45 minutes, the time of greatest pharmacological response assessed as analgesia in previous experiments. In addition the brain inulin spaces in rats and the uptake of fluoresceine isothiocyanate labelled nanoparticles in immortalised rat cerebral endothelial cells, (RBE4) were measured. The inulin spaces after i.v. injection of polysorbate 80-coated nanoparticles were significantly increased by 1% compared to controls. This is interpreted as indicating that there is no large scale opening of the tight junctions of the brain endothelium by the polysorbate 80-coated nanoparticles. In in vitro experiments endocytic uptake of fluorescent nanoparticles by RBE4 cells was only observed after polysorbate 80-overcoating, not with uncoated particles. These results further support the hypothesis that the mechanism of blood-brain barrier transport of drugs by polysorbate 80-coated nanoparticles is one of endocytosis followed by possible transcytosis. The experiments were conducted in several laboratories as part of an EEC/INTAS collaborative program. For various procedural and regulatory reasons this necessitated the use of both rats and mice as experimental animals. The brain endothelial cell line used for the in vitro studies is the rat RBE4.

Background and Purpose: Standard tissue staining using the lipid dye Oil-Red-O has been previously applied to stain vessel specimens, which were embolized with a mixture of n-butyl 2-cyanoacrylate (NBCA) and oil (Lipiodol). That technique, however, results in nonspecific and nonquantitative staining that does not provide the necessary differentiation between NBCA and Lipiodol. We present an innovative staining procedure that quantifies NBCA within treated tissues., Methods: An arteriovenous malformation (AVM) model in swine was used to evaluate the polymerization characteristics of various ratios of Lipiodol/NBCA/glacial acetic acid (GAA) mixtures. To determine the depth of NBCA penetration within the AVM model and to characterize the polymerization patterns of various mixtures within the vessel, histologic cross- and longitudinal sections were prepared for microscopy. These paraffin-embedded tissue sections were stained with a europium aryl-beta-diketone complex (TEC) to improve differentiation between NBCA and Lipiodol. Quantification of NBCA and Lipiodol within the lumen of rete cross-sections was accomplished using image analysis software to determine percent luminal area occluded by embolization., Results: Upon application of TEC, intense europium fluorescence was seen when the tissue samples were excited by low-power UV light (excitation at 365 nm; emission at 614 nm). The area of europium intensity within the lumen corresponded to NBCA concentration, and addition of GAA aided the NBCA distribution throughout the lumen without affecting fluorescence intensity. It was seen that NBCA could be easily differentiated from Lipiodol and that quantification could be readily performed on these sections because of the improved differentiation. For the case of a 50:50 (vol. %) mixture with an added 20 microL of GAA, luminal area distribution of Lipiodol, NBCA, and blood products was 42.6 +/- 3.5%, 33.8 +/- 5.7%, and 23.7 +/-2.7%, respectively., Conclusion: The rare earth metal europium, when added as a fluorescent chelate compound to histologic tissue sections, allowed for differentiation between NBCA and Lipiodol with good detail. These results have facilitated further characterization of NBCA polymerization for the use of AVM embolization.

Polybutylcyanoacrylate nanoparticles (PBCN) and their metabolites (polycyanoacrylic acid--PCAA, and n-butanol) were compared with respect to their effects on the primary immune response of mice to sheep red blood cells (SRBC). PCAA was synthetized via a Knoevenagel reaction. Antibody production (hemagglutinins) and E-rosette-forming cells (E-RFC) were used to document the induction of antigen-specific immune response to SRBC in all immunized mice. PBCN showed a time- and dose-dependent effect on the immune response, both humoral and cellular. The inductive phase of immune response was affected preferably. The high dose of PBCN (200 mg kg(-1)) tended to suppress the immune response. This was expressed more in mice treated before antigenic stimulation. Lower dose (10 mgkg(-1)) stimulated the immune response. A significant difference was found in the effects of PBCN and their metabolites on the immune response. PCAA and n-butanol administered at doses equivalent (after lysosomal hydrolysis) to the doses applied of intact PBCN did not impair significantly the immune response. A clear time dependence and dose dependence were not observed. The study led to the hypothesis that the greater suppressive effect of PBCN, relative to either PCAA or n-butanol, or a mixture of them, is probably due to the blocking of the immunopresenting function of macrophages instead of some toxicity towards the immunocompetent cells.

Butyl-2-cyanoacrylate is an easily applied, bioresorbable, noninfective glue that may provide an alternative to conventional craniofacial fixation techniques. Recent studies have demonstrated that the healing and strength of glue fixation of bone fragments in the craniofacial skeleton is equivalent to that of plate and screw fixation. We sought to determine if this glue could also provide strength and healing in a more stressed environment, that of the mandible. Fourteen New Zealand White rabbits underwent mandibular osteotomies at the angle. The osteotomy was fixed with either a microplate (n = 4) or glue (n = 10). Mandibles were assessed 10 weeks postoperatively and classified according to bone healing, condylar morphology, and dental morphology. Callus and nonunion were more prevalent in the glued group, whereas condylar resorption was similar in both experimental groups. Despite the poor bony healing in the glued group, the teeth did not decay but modified their standard form to meet the demands of the anatomic deformity. Butyl-2-cyanoacrylate does not offer the biomechanical stability afforded by plates and screws in bone subject to large forces.

Bilateral palmar and plantar digital neurectomies were completed in 10 horses (a total of 80 neurectomies) using one of three methods: (1) simple transection (guillotine method); (2) epineural capping; (3) n-butyl cyanoacrylate injected into the epineural sheath to act as a nerve sealant. Horses were regularly evaluated clinically for tenderness in and around the surgical site, as well as skin sensation at the coronary band in the heel region, during the 12-week course of the study. None of the surgical sites exhibited any signs of drainage or infection. Horses were then euthanatized, the nerve stumps were dissected from surrounding tissues, and the length and width of the tissue mass that had formed on the end of the nerve was recorded. Longitudinal and transverse sections of the nerve endings were examined histologically for numbers of proliferating axon sprouts (neuroma formation); whether the axons had penetrated the epineurium; degree of Schwann cell proliferation; degree of chronic inflammation; extent of foreign body reaction; extent of retrograde degeneration of the nerve bundles; and amount of fibrovascular proliferation. The proportion of legs exhibiting tenderness or heel sensation did not differ significantly between the three different treatments at any of the six different times they were examined. There was no difference between the three treatments in the length or width of the fibrous tissue scar on the ends of the nerves or in the number of sprouting axons from the ends of the nerves. Of 80 nerves examined, only two nerves were not confined to the epineurium.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the effects of closing lacerations with suture or cyanoacrylate tissue adhesive on staphylococcal counts in inoculated guinea pig lacerations. Wounds closed with adhesive alone had lower counts than wounds containing suture material (P < 0.05). The results of a time-kill study were consistent with a bacteriostatic adhesive effect of the adhesive against Staphylococcus aureus.

The success of every intestinal surgical procedure primarily depends on correct technical execution of the intestinal sutures. Despite the continuing improvements in intestinal synthesis techniques and the introduction of mechanical staplers, the risk of anastomotic dehiscence remains a major concern. For high-risk anastomoses, defined as those performed under critical conditions, n-butyl-2-cyanoacrylate tissue adhesive allows for quick sealing of the two stumps and supports the physiological wound-healing process. Furthermore, no experimental or clinical studies have shown that this glue has any carcinogenic or mutagenic properties. Thus, we believe that n-butyl-2-cyanoacrylate will be extremely useful for intestinal anastomoses with a high risk of dehiscence.

In this study, the antibacterial and cytotoxic effects of a synthetic tissue adhesive called n-butyl-2-cyanoacrylate (Histoacryl) which provide rapid healing in incision in oral surgical procedures were investigated. The antibacterial effects of Histoacryl were tested by using standard reference strains of Streptococcus pyogenes, Streptococcus mitis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus grown in Mueller-Hinton media (sheep blood supplemented Mueller-Hinton for streptococcus strains) by diffusion technique. The cytotoxic effects were also researched on continuous Vero and primary gingival fibroblast cell cultures by using agar overlay method. In these methods, the inhibition zones produced by Histoacryl were evaluated. As a result, Histoacryl was found to have antibacterial effect on the tested bacteria and produce cytotoxic and cytopathic effects on the tested cell cultures.

Polybutylcyanoacrylate (PBCA) nanoparticles were prepared and loaded with mitoxantrone, a highly effective anticancer drug. The proportion of mitoxantrone bound to the particles was analysed to be about 15 per cent of the initial drug concentration with the incorporation method and about 8 per cent with the adsorption method. Selected nanoparticle formulations were tested in leukaemia- or melanoma-bearing mice after intravenous injection. Efficacy and toxicity of mitoxantrone nanoparticles were compared with a drug solution and with a mitoxantrone-liposome formulation (small unilamellar vesicles with a negative surface charge). Furthermore, influence of an additional coating surfactant, poloxamine 1508, which has been shown to change body distribution of other polymeric nanoparticles, was investigated. It was shown that PBCA nanoparticles and liposomes influenced the efficacy of mitoxantrone in cancer therapy differently: liposomes prolonged survival time in P388 leukaemia, whereas nanoparticles led to a significant tumour volume reduction at the B16 melanoma. Neither nanoparticles nor liposomes were able to reduce the toxic side-effects caused by mitoxantrone, namely leucocytopenia. A slight additional influence of the coating surfactant was observed with only one preparation.

The purpose of the present study was to assess by in vitro means the effect of poly (methylmethacrylate) nanoparticles and poly (butylcyanoacrylate) nanoparticles on transdermal drug delivery. Methanol and octanol were chosen as test permeants. In order to distinguish between thermodynamic effect and those due to biological consequences, two different membranes were employed, i.e., full thickness hairless mouse skin and silicone elastomer sheeting (175 microns). It is evident that poly (methylmethacrylate) nanoparticles and poly (butylcyanoacrylate) nanoparticles increase the permeability of methanol through hairless mouse skin by a factor of 1.2-2. The permeability of lipophilic octanol is either unaffected by nanoparticles or decreases as a function of nanoparticle concentration depending on the lipophilicity of the polymer material.

The effect of the cyanoacrylate tissue adhesive Histoacryl on new bone formation was studied in rats. Experimental heterotopic new bone formation was induced by implanting pieces of demineralized allogeneic bone matrix (DABM) in the abdominal wall of 10 growing Sprague-Dawley rats. This produces cartilage formation within and around the implants after 10 days, followed by enchondral ossification and the formation of an ossicle with remodelling bone and bone marrow after three weeks. Prior to implantation, the DABM-implants were treated with increasing amounts of the tissue adhesive n-Butyl-2-cyanoacrylate-monomer (Histoacryl). New bone formation was quantified at three weeks by assay of the ash content of the implants as a measure of net bone formation, by 45calcium uptake prior to sacrifice, and by histology. Treatment of DABM with the cyanoacrylate caused an intense inflammatory process with a foreign body reaction, and abolished bone induction and new bone formation. Tissue adhesives should be used with caution in fracture surgery since they inhibit new bone formation, cause a foreign body reaction, and may impede fracture healing.

We examined the clinical and histopathologic effects of the instillation of two surgical adhesives in the corneal stroma of rabbits. The adhesives examined in this study included a butyl-2-cyanoacrylate (CA) and a combination of a mussel-derived polyphenolic protein (MAP) with an enzyme polymerizer (COX). In this study, either one of the adhesives or balanced saline solution (as a control) was instilled directly into the corneal stroma following the surgical creation of a perilimbal intralamellar pocket. Animals were examined on a regular basis for a 60-day period following instillation and, at predetermined time points, sacrificed for histopathologic evaluation. The group of animals that received intracorneal instillations of CA consistently manifested early and progressive stromal neovascularization of the affected corneas. Histopathologic examination confirmed the progressive neovascularization, as well as a noticeable inflammatory response surrounding the adhesive. In contrast, instillation of the MAP-COX adhesive produced neovascular and inflammatory responses that were later in onset and milder in degree than those observed with CA. In this experimental model, the MAP-COX adhesive appeared to be better tolerated than did the CA.

It is dealt with the effects of various butycyano-acrylate type surgical adhesives on gram-positive and gram-negative bacterial species. The experimental results show a growth-inhibiting effect on gram-positive germs. Gram-negative germs are not affected. The growth inhibition produced by SO2-containing adhesives is greater than that caused by SO2-free ones. As compared to Histoacryl blue, the Fimomed variants showed a broader spectrum. Furthermore, it was stated that the adhesive exerts its growth-inhibiting effect not only in the monomeric, but also in the polymeric state. A relationship between the gram-behaviour and the antimicrobic effect of the adhesive is taken into consideration.