Polymerization kinetics of n-butyl cyanoacrylate glues used for vascular embolization.

Vascular embolization is a minimally invasive treatment used for the management of vascular malformations and tumors. It is carried out under X-ray by navigating a microcatheter into the targeted blood vessel, through which embolic agents are delivered to occlude the vessels. Cyanoacrylate liquid glues have been widely used for vascular embolization owing to their low viscosity, rapid polymerization/solidification rate, good penetration ability and low tissue toxicity. The objective of this study is to quantitatively investigate the physical properties of two n-butyl cyanoacrylate (nBCA) glues (Glubran 2 and Histoacryl) mixed with an iodized oil (Lipiodol) at various concentrations. We show that an homogeneous solution results from the mixing of the glue and Lipiodol, and that the viscosity, density and interfacial tension of the mixture increase with the proportion in Lipiodol. We have designed a new experimental setup to systemically characterize the polymerization kinetics of a glue mixture upon contact with an ionic solution. We observe that the whole polymerization process includes two phases: an interfacial polymerization that takes place at the interface as soon as the two liquids are in contact with a characteristic time scale of the order of the minute; a volumetric polymerization during which a reaction front propagates within the mixture bulk with a characteristic time scale of the order of tens of minutes. The polymerization rate, front propagation speed and volume reduction increase with the glue concentrations. It is the first time that such comprehensive results are obtained on liquid embolic agents.

Estudo comparativo entre etilcianoacrilato e sutura intradérmica no fechamento de excisões cutâneas / Comparative study of the use of ethyl cyanoacrylate adhesive and intracutaneous suture for cutaneous excision closure

INTRODUÇÃO: As vantagens dos cianoacrilatos em síntese cutânea têm sido sobejamente demonstradas na literatura. Entretanto, esses produtos têm sido subutilizados no Brasil, em decorrência dos elevados custos do octilcianoacrilato. Ademais, a forma mais economicamente acessível, etilcianoacrilato, tem sido pouco estudada como adesivo cutâneo. O objetivo deste estudo foi avaliar a eficiência do etilcianoacrilato na síntese de excisões cutâneas. MÉTODO: Estudo retrospectivo realizado em pacientes portadores de lesões cutâneas superficiais submetidos a excisão elíptica e reparo por fechamento primário. As excisões foram fechadas por meio de suturas profundas relaxadoras e, na superfície da pele, foi utilizado etilcianoacrilato (grupo caso - GCa) ou sutura intradérmica (grupo gontrole - GCo). RESULTADOS: Foram encontrados 33 pacientes portadores de 43 lesões cutâneas (GCa = 20 excisões; GCo = 23 excisões). Cicatrizes inestéticas (GCa = 20 por cento; GCo = 48 por cento), irritação ocular (GCa = 15 por cento; GCo = 0), deiscência (GCa = 5 por cento; GCo = 0), infecção (GCa = 0; GCo = 4,3 por cento) e dermatite de contato (GCa = 0; GCo = 4,3 por cento) foram os problemas encontrados. Os resultados cosméticos foram considerados satisfatórios na maioria das excisões (GCa = 100 por cento, GCO = 95,7 por cento). CONCLUSÕES: O etilcianoacrilato foi adequadamente tolerado neste grupo de estudo, sem induzir necrose, reações alérgicas ou infecções, apresentando diversas vantagens de uso em relação à sutura, incluindo reduzido índice de complicações e grande satisfação dos pacientes.

BACKGROUND: The advantages of cyanoacrylates in cutaneous wound closure have been widely demonstrated in the literature. However, these products have not been widely used in Brazil due to the high costs of octyl cyanoacrylates. Moreover, there have been only a few studies on the most affordable product, ethyl cyanoacrylate, as a cutaneous adhesive. The objective of this study was to evaluate the efficacy of ethyl cyanoacrylate in cutaneous excision repair. METHODS: A retrospective study conducted in patients with superficial skin lesions who underwent elliptical excision and repair by primary closure. The excisions were closed using deep relaxing sutures and either ethyl cyanoacrylate (case group; CaG) or intradermal suture (control group; CoG) on the skin surface. RESULTS: Thirty-three patients were identified with 43 cutaneous lesions (CaG, n = 20; CoG, n = 23). Unsightly scars (CaG = 20 percent; CoG = 48 percent), eye irritation (CaG = 15 percent; CoG = 0), dehiscence (CaG = 5 percent; CoG = 0), infection (CaG = 0; CoG = 4.3 percent), and contact dermatitis (CaG = 0; CoG = 4.3 percent) were the problems observed. The cosmetic results were satisfactory in almost all excisions (CaG = 100 percent; CoG = 95.7 percent). CONCLUSIONS: Ethyl cyanoacrylate was adequately tolerated in this study group, with no necrosis, allergic reactions, or infections. Ethyl cyanoacrylate presented several advantages over suture use, including low complication rates and high patient satisfaction.

Avaliação do etil-2-cianoacrilato (Epiglu®) na síntese de pele: estudo em ratos / Ethyl-2-cyanoacrylate (Epiglu®) evaluation in the skin closure: study in rats

Introdução: O Etil-2-cianoacrilato (ECA) é um adesivo tecidual utilizado por alguns médicos na prática clínica para fechamento de lesões de pele. São substâncias que se autopolimerizam quando em contato com a ferida, formando uma cola forte e flexível. Este trabalho foi realizado visando à avaliação da eficácia e da biocompatibilidade deste polímero (Epiglu®, da empresa Meyer-Haake, Alemanha) na síntese de pele, em modelo experimental. Método: Dez ratos Wistar machos foram submetidos a três incisões longitudinais no dorso. A incisão central foi tratada com suturade pontos simples de nylon 4.0 (grupo controle), a esquerda com sutura subdérmica de nylon 4.0 associado ao ECA, e a direita apenas o ECA. Os animais foram sacrificados nos dias 3, 7, 14, 21 e 30 pós-operatórios. A biocompatibilidade foi avaliada sob observação direta: necrose, inflamação,dermatite de contato, infecção e deiscência; e à microscopia: reação inflamatória, angiogênese, fibroblastos, colágeno, células gigantes e eosinófilos. Resultados: As sínteses realizadas apenas com o ECA apresentaram maior índice de deiscência (p < 0,05). Todos os outros critérios macro e microscópicos avaliados não apresentaram diferenças estatísticas em relação ao controle (p > 0,05). Conclusão: O uso do ECA é uma boa opção de síntese da pele, com boabiocompatibilidade. Atenção deve ser feita às lesões que apresentem algum grau de tensão, onde a associação com a sutura subdérmica torna-se obrigatória.

Background: The Ethyl-2-cyanoacrylate (ECA) is a synthetic tissue adhesive used by some physicians in clinical practice in wound closures. They polymerize rapidly to adhere tightly toproteinaceous surfaces, form a strong and flexible bond. This study was performed to evaluate the efficacy and biocompatibility of this polymer (Epiglu®, of Meyer-Haake company,Germany) in skin wound closures, in rat model. Methods: Ten male Wistar rats were subjected to three incisions which were closed using different treatments. The central incision was treatedwitch Simple suture of nylon 4.0 (control group). Left incision was treated with sub-dermis suture associated with ECA, and right incision only with ECA. Rats were sacrificed on days 3, 7, 14, 21 and 30 after the intervention. The biocompatibility was evaluated due to direct observation: necrosis, inflammation, dermatitis, infection and dehiscence; and microscopy: inflammatory process, angiogenesis, number of fibroblasts, collagen, giants cells and eosynophils. Results: The wound closured only with ECA presented a higher dehiscence level(p < 0.05). It was not observed another macro or microscopic significant difference comparing to the control group (p > 0.05). Conclusion: The use of the ECA is a good option to the skinclosure, with good biocompatibility. Special attention must receive the wounds with some tension, where the association with a sub-dermis suture becomes imperative.

Comparative study of suture and in skin closure of rats / Estudo comparativo entre sutura e cianoacrilatos no fechamento de pele de ratos

PURPOSE: To compare the biocompatibility of ethyl-cyanoacrylate (ECA) and octylcyanoacrylate (OCA) wound closures to sutures in rat skin. METHODS: Twenty-four male Wistar rats were subjected to three incisions which were closed using ECA, OCA or sutures . Rats were divided into four groups which received biopsies on the 3rd, 7th, 14th or 21st post-operative days. Necrosis, inflammation, dermatitis, infection, dehiscence, cicatricial enlargement and costs were examined; the histopathology evaluated was epithelialization, deep openings, foreign substance reaction, residues of synthesis material, fibrosis, inflammation, dehiscence and necrosis. RESULTS: The tissue adhesives presented the largest dehiscence levels, and ECA the lowest cost while the other measures were similar. Regarding histopathology, deep openings were more common with OCA and granulomas were most frequently obtained with ECA. The two tissue adhesives produces less inflammation than the inicial suture from post-operative day 7, while ECA and OCA cause similar inflammatory reactions. ECA did not differ significantly from OCA and sutures on other measures. CONCLUSION: ECA was well tolerated in this study and did not induce necrosis, allergic reactions or infections, presenting several advantages in relation to OCA and sutures, including lower costs and fewer complications.

OBJETIVO: Investigar a biocompatibilidade do etil-cianoacrilato (ECA) em fechamento de pele em ratos comparativamente ao octil-cianoacrilato (OCA) e à sutura. MÉTODOS: Rattus norvegicus albinus (n=24) foram submetidos a três incisões, cada uma fechada por um dos métodos de síntese estudados. Quatro grupos (n=6) foram feitos, conforme o dia pós-operatório (DPO) em que foram eutanasiados: 3DPO, 7DPO,14DPO e 21DPO. Necrose, edema, eritema, dermatite, infecção, deiscência, alargamento cicatricial e custos foram os itens examinados; histopatologicamente avaliou-se epitelização, abertura profunda, reação de corpo estranho, resíduos de material de síntese, fibrose, reação inflamatória, deiscência e necrose. RESULTADOS: Os adesivos apresentaram os maiores níveis de deiscências, e o ECA o custo mais baixo; nos demais itens, não houve diferenças. Histopatologia: A abertura profunda foi mais comum com o OCA; ECA foi o material mais encontrado em granulomas; os adesivos foram mais brandos que a sutura a partir do 7º DPO no quesito inflamação, enquanto que o ECA causou uma reação similar ao OCA; nos outros itens, ECA não apresentou diferença importante em relação ao OCA e à sutura. CONCLUSÃO: O ECA foi bem tolerado neste grupo de estudo, sem induzir necrose, reações alérgicas e infecção, apresentando diversas vantagens de uso em relação ao OCA e à sutura.

Brevibacterium samyangense sp. nov., an actinomycete isolated from a beach sediment.

A novel actinomycete, strain SST-8(T), was isolated from sand sediment of Samyang Beach in Jeju, Korea, and subjected to a polyphasic taxonomic study. The organism, which produced opaque, circular, yellow colonies, with a coryneform morphology, showed the following chemotaxonomic characteristics: meso-diaminopimelic acid as the diamino acid in the peptidoglycan, MK-8(H(2)) as the major menaquinone, phosphatidylglycerol as the only polar lipid, anteiso-C(15 : 0) and anteiso-C(17 : 0) as major fatty acids and a DNA G+C content of 70.7 mol%. The combination of morphological and chemotaxonomic features supported its classification in the genus Brevibacterium. Phylogenetic analyses, based on 16S rRNA gene sequence studies, showed that strain SST-8(T) formed an intermediate branch between the Brevibacterium luteolum/Brevibacterium otitidis and Brevibacterium mcbrellneri/Brevibacterium paucivorans clusters. Sequence similarity calculations based on a neighbour-joining analysis revealed that the closest relatives of strain SST-8(T) were the type strains of B. paucivorans (96.6 %), B. luteolum (96.5 %), B. mcbrellneri (96.3 %), Brevibacterium avium (96.0 %) and B. otitidis (95.9 %). Based on a broad set of phenotypic and genetic data, it was evident that the strain represents a novel species of the genus Brevibacterium. The name Brevibacterium samyangense sp. nov. is proposed, with SST-8(T) (=NRRL B-41420(T)=KCCM 42316(T)) as the type strain.

Shewanella loihica sp. nov., isolated from iron-rich microbial mats in the Pacific Ocean.

A novel marine bacterial strain, PV-4(T), isolated from a microbial mat located at a hydrothermal vent of Loihi Seamount in the Pacific Ocean, has been characterized. This micro-organism is orangey in colour, Gram-negative, polarly flagellated, facultatively anaerobic and psychrotolerant (temperature range, 0-42 degrees C). No growth was observed with nitrate, nitrite, DMSO or thiosulfate as the electron acceptor and lactate as the electron donor. The major fatty acid detected in strain PV-4(T) was iso-C(15 : 0). Strain PV-4(T) had ubiquinones consisting mainly of Q-7 and Q-8, and possessed menaquinone MK-7. The DNA G+C content of the strain was 53.8 mol% and the genome size was about 4.5 Mbp. Phylogenetic analyses based on 16S rRNA gene sequences placed PV-4(T) within the genus Shewanella. PV-4(T) exhibited 16S rRNA gene sequence similarity levels of 99.6 and 97.5 %, respectively, with respect to the type strains of Shewanella aquimarina and Shewanella marisflavi. DNA from strain PV-4(T) showed low mean levels of relatedness to the DNAs of S. aquimarina (50.5 %) and S. marisflavi (8.5 %). On the basis of phylogenetic and phenotypic characteristics, the bacterium was classified in the genus Shewanella within a distinct novel species, for which the name Shewanella loihica sp. nov. is proposed. The type strain is PV-4(T) (=ATCC BAA-1088(T)=DSM 17748(T)).

Brooklawnia cerclae gen. nov., sp. nov., a propionate-forming bacterium isolated from chlorosolvent-contaminated groundwater.

Two novel facultatively anaerobic bacterial strains, BL-34(T) and BL-35, isolated from groundwater contaminated by a mixture of chlorosolvents were characterized using a polyphasic approach. The two strains exhibited essentially identical taxonomic features except for a vitamin B(12) requirement by strain BL-35 for optimal growth. Phylogenetically, the isolates were affiliated with members of the family Propionibacteriaceae and were placed in a phylogenetic branch adjacent to, but distinct from, those of the genera Propionimicrobium, Propionibacterium, Luteococcus, Propioniferax and Tessaracoccus. The cells of the novel strains were Gram-positive, non-motile, non-spore-forming pleomorphic rods. They produced catalase but not oxidase, and nitrate reduction did not occur in peptone/yeast extract/glucose medium. Propionate and acetate were the predominant products of glucose fermentation. Fermentation occurred in the presence of 1,2-dichloroethane and 1,1,2-trichloroethane at concentrations up to at least 9.8 mM. The genomic DNA G+C content was 67.5-67.9 mol%. Menaquinone MK-9(H(4)) was the predominant respiratory quinone and meso-diaminopimelic acid was present in the cell-wall peptidoglycan layer. The major cellular fatty acids were C(15 : 0) and anteiso-C(15 : 0). On the basis of the results obtained in this study, strains BL-34(T) and BL-35 should be classified within a novel taxon, for which the name Brooklawnia cerclae gen. nov., sp. nov. is proposed. The type strain of Brooklawnia cerclae is BL-34(T) (=LMG 23248(T)=NRRL B-41418(T)). An additional strain, BL-35 (=LMG 23249=NRRL B-41419), was also characterized.

Occupational exposure to airborne solvents during nail sculpturing.

This study describes occupational exposure to acrylates and other solvents during nail sculpturing, including comparative measurements of the exposure using four different sculpturing methods: The acrylic method, the UV-gel method, the acrylic powder method and the resin method. Thirty-two nail technicians working in 22 different salons participated in the study. In total, 92 measurements were performed, comprising 70 solvent measurements and 22 measurements of ethyl 2-cyanoacrylate. The solvents most frequently present in all samples were acetone, ethyl acetate, toluene and n-butyl acetate, measured in 96%, 94%, 91% and 81% of the samples, respectively. The study shows that the overall solvent exposure was low, with all measurements calculated as the additive effect (n = 70) below 20% of the OEL (arithmetic mean 0.06 and range 0.01-0.19). No statistically significant difference between sculpturing methods were observed (p = 0.05).

In vitro toxicity test of ethyl 2-cyanoacrylate, a tissue adhesive used in cardiovascular surgery, by fibroblast cell culture method.

BACKGROUND: The aim of this study was to evaluate the cytotoxicity of cyanoacrylate polymers (ethyl 2-cyanoacrylate) by an elution test system. In such systems, the material is extracted with a cell culture medium, which is subsequently added onto cultured cells, resulting in an indirect contact between the biomaterial and cells. METHODS: A cell line commonly utilized for cytotoxicity experiments; L929 mouse fibroblasts were used in this study. The effects of extract dilutions on cells were evaluated by two experiments: (a) The cells were suspended and seeded in a medium containing the extract, followed by a short incubation to observe the effects on cell attachment; (b) cells were seeded in a normal medium. Following cell attachment, this was replaced with a medium containing the extract and long-term effects on cell proliferation were measured. The cytotoxicity was quantified using a cell viability assay, well established for use in the evaluation of cell-biomaterial interactions. RESULTS: These results indicate that, in the test system utilized, a tenfold dilution of the extract results in an approximately 10% decrease in cells; this increases to between 30% and 45% in a 1:1 dilution. When a large number of cells (3000/well) were used, proliferation of cells overcame the cytotoxic effect and consistent results could not be observed. CONCLUSIONS: In this study, the observed outcomes follow a similar trend on cell attachment and proliferation with acute effects (4 hours incubation) of the extracts on the cells, producing slightly higher toxicity. Our findings are parallel with the literature findings.

Resistance and stability of a new method for bonding biological materials using sutures and biological adhesives.

The valve leaflets of cardiac bioprostheses are secured and shaped by sutures which, given their high degree of resistance and poor elasticity, have been implicated in the generation of stresses within the leaflets, contributing to the failure of the bioprostheses. Bioadhesives are bonding materials that have begun to be utilized in surgery, although there is a lack of experience in their use with inert tissues or bioprostheses. Tensile testing is performed until rupture in samples of calf pericardium, a biomaterial employed in the manufacture of bioprosthetic heart valve leaflets. One hundred and thirty-two trials are carried out in three types of samples: intact or control tissue (n = 12); samples transected and glued in an overlapping manner with a cyanoacrylate (n = 60); and samples transected, sewn with a commercially available suture material and reinforced at the suture holes with the same cyanoacrylate (n = 60). Seven days after their preparation, 12 samples from each group, including the controls, are subjected to tensile testing until rupture and the findings are compared. In the stability study, groups of 12 each of the remaining 48 glued and 48 sutured and glued samples underwent tensile testing until rupture on days 30, 60, 90, and 120, after their preparation. The results show that bonding with the adhesive provided a resistance ranging between 1.04 and 1.87 kg, probably insufficient for use in valve leaflets, but also afforded a high degree of elasticity. After 120 days, both the glued and the sutured and glued series show excellent elastic behavior, with no rigidity or hardening of the pericardium. These samples present reversible elongation, or strain, when they surpass their elastic limit at rupture. This finding may be due to a load concentration that is damaging to the pericardium, to the behavior of the tissue as an amorphous material, or perhaps to both circumstances. These results need to be confirmed in future studies as they may be of value in the design and manufacture of cardiac bioprostheses.

Occupational asthma caused by exposure to cyanoacrylate.

BACKGROUND: Exposure to acrylates may give rise to rhinitis and asthma in both industrial and domestic environments. The mechanisms underlying these respiratory conditions caused by acrylates remain largely unknown. METHODS: We studied two assembly operators exposed to cyanoacrylate glue who developed rhinitis and asthma symptoms. The causal relationship of these symptoms to cyanoacrylate glue exposure was investigated by serial peak expiratory flow (PEF) monitoring at work and off work. Moreover, inhalation testing was performed by asking the patients to mimic exposure at work with the cyanoacrylate glue in a 7-m3 challenge chamber. RESULTS: Serial PEF monitoring at work and away from work was consistent with occupational asthma in both patients. The methacholine inhalation test was negative in patient 1 (off work) and showed bronchial hyperresponsiveness in patient 2. After 20-min exposure to cyanoacrylate, the patients had late and progressive asthmatic reactions, respectively, and the methacholine test became positive in patient 1. Induced-sputum samples obtained 3 and 24 h after the cyanoacrylate challenge showed a marked increase in sputum eosinophils. CONCLUSION: Exposure to cyanoacrylate in these patients provoked not only variable airflow limitation and bronchial hyperresponsiveness, but also pronounced eosinophilia in sputum.

[Identification of synthetic adhesives by simultaneous pyrolysis methylation gas chromatography].

At present, pyrolysis gas chromatography (Py-GC) is an effective analytical method for trace synthetic adhesives. Synthetic adhesives are usually composed of polar components. Thus, the polar pyrolysis products are normally difficult to measure by Py-GC due to their partial or complete adsorption in the pyrolysis zone, injection system or capillary column and the accuracy of results is seriously affected. Simultaneous pyrolysis methylation gas chromatography (Py-Me-GC) is a fast analytical method which was developed in recent years for polar compounds. The five synthetic adhesives have been identified by using Py-Me-GC in our study. Analytical conditions were: filament pyrolysis apparatus, flame ionization detector (FID), gas chromatograph, FFAP capillary column (30 m x 0.25 mm i.d.) and a quaternary ammonium salt as methylating agent. Major peaks of the products of pyrolysis were analysed qualitatively by GC/MS and comparisons were also made between the results by Py-Me-GC and those by Py-GC. The information gained from the components of substances by Py-Me-GC is more than that by Py-GC. The method is suitable for identifying synthetic adhesives of trace evidence in forensic science.

Avaliaçäo da infiltraçäo marginal por corante em obturaçöes de canais radiculares preparados para núcleo, em virtude do material de preenchimento ou impermeabilizaçäo do remanescente radicular / Coronal sealing ability of endodontic obturations after post and core preparation with or without temporary filling of the endodontic remaing space

Os dentes tratados endodonticamente e preparados para núcleos podem permanecer na cavidade bucal por períodos variados de tempo até que sejam restaurados proteticamente, sofrendo a influência de vários fatores que podem acarretar falhas no selamento marginal proporcionado pelas restauraçöes provisórias. A perda do selamento coronário permite que ocorra a infiltraçäo de microrganismos através da obturaçäo endodôntica, resultando no insucesso desse tratamento. O objetivo desse trabalho foi avaliar a infiltraçäo marginal por corante em obturaçöes de canais radiculares preparados para núcleos, com ou sem o emprego de um material de preenchimento e outro de impermeabilizaçäo do espaço entre o canal radicular e o remanescente da obturaçäo. Foram utilizados 45 dentes unirradiculares humanos extraídos, que, após o preparo biomecânico, foram obturados e preparados para núcleos, permanecendo apenas 5 mm do material obturador no terço apical. Os dentes foram divididos em três grupos: 1) o espaço deixado entre o material obturador e o selamento cervical foi mantido vazio; 2) esse espaço foi preenchido com hidróxido de cálcio; 3) ese espaço foi impermeabilizado com cianoacrilato. A abertura cervical foi selada com Cavit e os dentes foram armazenados em saliva artificial por sete dias. Em seguida, o selamento cervical foi removido e os dentes foram imersos em corante azul de metileno a 2 por cento durante uma semana. Os dados obtidos foram analisados estatisticamente e os melhores resultados foram verificados nos Grupos 2 e 3 quando comparados ao Grupo 1

Indirect determination of isocyanates by gas chromatography.

A gas chromatographic method was developed to determine the purity of synthesized isocyanate monomers, specifically isocyanatoacrylates, and to determine the isocyanate content of synthesized polymers and prepolymers. The method is a modification of an ASTM procedure in which an isocyanate is allowed to react with excess di-n-butylamine. In the ASTM method, the amount of isocyanate present is calculated indirectly from the amount of unreacted di-n-butylamine, determined by back titration with standard hydrochloric acid. Determination of the excess di-n-butylamine by the gas chromatographic method developed has the advantages of providing better precision and requiring less sample than the titrimetric method. The two methods were compared using phenyl isocyanate as a model test compound. A synthesized monomer, methyl alpha-isocyanatoacrylate, was also analyzed, for comparison by both methods.

Gas chromatographic determination of ethyl 2-cyanoacrylate in the workplace environment.

Low levels of airborne ethyl 2-cyanoacrylate (ECA) were monitored by drawing air through sampling tubes containing Tenax GC. After desorption with acetone, ECA was quantified by gas chromatography using a thermionic specific detector in the nitrogen mode. Polymerised ECA was shown to yield ECA monomer under the conditions of gas chromatographic analysis.