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1.
Iran J Med Sci ; 49(2): 130-133, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38356484

RESUMO

Bronchopleural fistula (BPF), a sinus tract between the bronchial system and the pleural space, is associated with COVID-19 and can lead to pneumothorax, which increases the mortality rate. Due to the analytical status of COVID-19 patients, sealing the BPF necessitates the least minimal invasive treatment. Herein, we demonstrated a technique of sealing post-COVID-19 BPF with direct injection of cyanoacrylate glue under the guidance of a computed tomography scan. Following glue injection, the BPF was completely sealed in all four patients. In conclusion, in COVID-19 patients with small and distal BPF, percutaneous glue injection is recommended for BPF closure.


Assuntos
Fístula Brônquica , COVID-19 , Doenças Pleurais , Humanos , Cianoacrilatos/farmacologia , Cianoacrilatos/uso terapêutico , COVID-19/complicações , Fístula Brônquica/terapia , Doenças Pleurais/terapia , Tomografia Computadorizada por Raios X
2.
Pest Manag Sci ; 79(12): 4977-4989, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37540764

RESUMO

BACKGROUND: Myosin plays a crucial role in cellular processes, while its dysfunction can lead to organismal malfunction. Phenamacril (PHA), a highly species-specific and non-competitive inhibitor of myosin I (FgMyoI) from Fusarium graminearum, has been identified as an effective fungicide for controlling plant diseases caused by partial Fusarium pathogens, such as wheat scab and rice bakanae. However, the molecular basis of its action is still unclear. RESULTS: This study used multiple computational approaches first to elucidate the allosteric inhibition mechanism of FgMyoI by PHA at the atomistic level. The results indicated the increase of adenosine triphosphate (ATP) binding affinity upon PHA binding, which might impede the release of hydrolysis products. Furthermore, simulations revealed a broadened outer cleft and a significantly more flexible interface for actin binding, accompanied by a decrease in signaling transduction from the catalytic center to the actin-binding interface. These various effects might work together to disrupt the actomyosin cycle and hinder the ability of motor to generate force. Our experimental results further confirmed that PHA reduces the enzymatic activity of myosin and its binding with actin. CONCLUSION: Therefore, our findings demonstrated that PHA might suppress the function of myosin through a synergistic mechanism, providing new insights into myosin allostery and offering new avenues for drug/fungicide discovery targeting myosin. © 2023 Society of Chemical Industry.


Assuntos
Fungicidas Industriais , Fungicidas Industriais/farmacologia , Actinas , Miosinas/química , Cianoacrilatos/farmacologia
3.
Plant Dis ; 107(12): 3843-3850, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37272042

RESUMO

Fusarium pseudograminearum is the dominant pathogen causing Fusarium crown rot (FCR) of wheat. Phenamacril is a 2-cyanoacrylate fungicide, having a control effect on diseases caused by Fusarium spp. The objective of this study was to investigate the inhibitory effect of phenamacril on F. pseudograminearum and its control efficacy against FCR. The results showed that phenamacril had a strong inhibitory effect on the mycelial growth of F. pseudograminearum, EC50 values of phenamacril to 63 tested strains were in the range of 0.0998 to 0.5672 µg/ml, and the average EC50 value was 0.3403 ± 0.0872 µg/ml and could be used as the baseline sensitivity of F. pseudograminearum to phenamacril. Phenamacril reduced the germination rate of conidia of F. pseudograminearum, and the EC50 value was 5.0273 to 26.4814 µg/ml. In addition, we found that phenamacril had a teratogenic effect on conidia and blastotubules, which increased the ratio of conidial germination from the middle cells and showed high efficacy on the sporulation quantity of F. pseudograminearum with an EC50 value in the range of 0.0770 to 0.1064 µg/ml. There was no significant correlation between the sensitivity of F. pseudograminearum to phenamacril and its sensitivity to fludioxonil, carbendazim, tebuconazole, and kresoxim-methyl. In vitro and greenhouse assays showed that the treatment with 0.125 µl of active ingredient per gram recorded the best control effect on wheat crown rot, reaching 87.8 and 77.3%, respectively. In two experimental sites in Luoyang, phenamacril also had great control effect against FCR, reaching 83.9%. It was proven that phenamacril has a superior control effect against FCR. This study has laid a foundation for the study of the mechanism of action of phenamacril against F. pseudograminearum and provided a theoretical basis for the application of phenamacril to control FCR.


Assuntos
Fusarium , Triticum , Doenças das Plantas/prevenção & controle , Cianoacrilatos/farmacologia , Crescimento e Desenvolvimento
4.
J Mater Chem B ; 11(20): 4548-4555, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37161694

RESUMO

Varicose veins in legs are common in clinics. Currently, medical adhesive-based, minimally invasive endovenous occlusion is used to treat them. However, the most common cyanoacrylate medical adhesives do not perform well when used under blood/wet conditions. In particular, poor adhesion, short curing time, and high heat release greatly limit their clinical use. In this paper, we demonstrate the use of a composite system composed of butyl-cyanoacrylate, triethyl citrate, and nanosilica that exhibits a blood/wet-adhesion capability to serve as a new sealing glue. Hydrophobic triethyl citrate groups displace boundary waters while also protecting cyanoacrylate monomers from undergoing rapid polymerization. Nanosilica increases viscosity, which contributes to in situ extrusion molding and retention. An optimal formulation, FAL-006, exhibited good physical and chemical properties in vitro. The performed additional safety assays indicated that FAL-006 has good biocompatibility. The closure efficiency of FAL-006 in vivo was evaluated in both a rat abdominal aortic closure model and in a sheep lower limb venous closure model. Taken together, these results indicate that FAL-006 exhibits promising potential for use in clinical applications. Furthermore, this study provides a new strategy for designing underwater adhesive agents for additional clinical applications, and a strategy for constructing other biomaterials needed for use under wet conditions.


Assuntos
Varizes , Animais , Ratos , Cianoacrilatos/farmacologia , Cianoacrilatos/uso terapêutico , Varizes/tratamento farmacológico , Varizes/cirurgia , Embucrilato/uso terapêutico , Adesivos/farmacologia , Adesivos/uso terapêutico
5.
Dent Mater J ; 41(5): 757-766, 2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-35793940

RESUMO

The important factors contributing to the effectiveness of fluoride varnish are the amount of fluoride ion release and the retention time of the varnish on the tooth surface. Commercial fluoride varnishes are susceptible to mechanical removal; therefore, patients are informed to avoid eating or performing oral hygiene for at least 12-24 h, which results in patient inconvenience. However, cyanoacrylate-based fluoride varnish would not have these disadvantages. This study compared the daily fluoride ion release, abrasion resistance to brushing, and toxicity to human gingival fibroblasts (hGFs) between a newly-developed cyanoacrylate-based fluoride varnish and conventional fluoride varnish (Duraphat varnish). The results demonstrated that the cyanoacrylate varnish had a significantly higher fluoride release for 9 days after application, higher abrasion resistance to brushing, and slightly less toxicity to hGFs compared with Duraphat varnish. This novel cyanoacrylate varnish could be an alternative fluoride varnish for preventing dental caries.


Assuntos
Cárie Dentária , Fluoretos Tópicos , Cariostáticos , Cianoacrilatos/farmacologia , Cárie Dentária/prevenção & controle , Fibroblastos , Fluoretos/farmacologia , Fluoretos Tópicos/farmacologia , Fator de Crescimento de Hepatócito , Humanos , Fluoreto de Sódio
6.
Environ Pollut ; 304: 119240, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35367504

RESUMO

The fungal species Fusarium can cause devastating disease in agricultural crops. Phenamacril is an extremely specific cyanoacrylate fungicide and a strobilurine analog that has excellent efficacy against Fusarium. To date, information on the mechanisms involved in the uptake, accumulation, and metabolism of phenamacril in plants is scarce. In this study, lettuce and radish were chosen as model plants for a comparative analysis of the absorption, accumulation, and metabolic characteristics of phenamacril from a polluted environment. We determined the total amount of phenamacril in the plant-water system by measuring the concentrations in the solution and plant tissues at frequent intervals over the exposure period. Phenamacril was readily taken up by the plant roots with average root concentration factor ranges of 60.8-172.7 and 16.4-26.9 mL/g for lettuce and radish, respectively. However, it showed limited root-to-shoot translocation. The lettuce roots had a 2.8-12.4-fold higher phenamacril content than the shoots; whereas the radish plants demonstrated the opposite, with the shoots having 1.5 to 10.0 times more phenamacril than the roots. By the end of the exposure period, the mass losses from the plant-water systems reached 72.0% and 66.3% for phenamacril in lettuce and radish, respectively, suggesting evidence of phenamacril biotransformation. Further analysis confirmed that phenamacril was metabolized via hydroxylation, hydrolysis of esters, demethylation, and desaturation reactions, and formed multiple transformation products. This study furthers our understanding of the fate of phenamacril when it passes from the environment to plants and provides an important reference for its scientific use and risk assessment.


Assuntos
Fungicidas Industriais , Raphanus , Produtos Agrícolas , Cianoacrilatos/metabolismo , Cianoacrilatos/farmacologia , Fungicidas Industriais/metabolismo , Raízes de Plantas/metabolismo , Raphanus/metabolismo , Água/metabolismo
7.
Clin Oral Investig ; 26(6): 4499-4507, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35217903

RESUMO

OBJECTIVES: The aim of this study was to analyze the biomechanical characteristics of a novel cyanoacrylate-based tissue adhesive (CTA) for soft-tissue closure of the (non-) tooth-bearing alveolar process and around dental implants. MATERIALS AND METHODS: Halves of porcine mandibles (n = 21) were randomly divided into three experimental intraoral wound closure groups (A-C) with three different mucoperiosteal flap types (F1-3, n = 7 each): F1, crestal incision between the last incisor and the canine with a mesial and distal vestibular relief; F2, crestal double-T-shaped incision and dental implant placement between the canine and the first premolar; and F3, trapezoidal incision on the second premolar. F1-3 were respectively closed using (A) monofil non-resorbable sutures, (B) CTA, and (C) a combination of both. Tensile strength (TS) and elasticity (E) measurements were performed for biomechanical analysis. RESULTS: In F1, CTA showed a significantly reduced TS compared to A (p < 0.001) and C (p < 0.01). In F2, an increased TS of C compared to A (p < 0.01) and B (p < 0.001) was found. Here, E was significantly increased in C compared to B (p < 0.02). In F3, TS was significantly decreased in B compared to A (p < 0.01) and C (p < 0.001). The E in group C was significantly increased compared to B (p < 0.01). CONCLUSIONS: Different biomechanical characteristics between CTA and sutures were found. CTA could be a possible alternative to sutures for intraoral wound closure in special conditions. CLINICAL RELEVANCE: A combination of both, suturing and CTA, could be a promising option in critical soft-tissue wounds requiring high functional stability and elasticity.


Assuntos
Cianoacrilatos , Adesivos Teciduais , Animais , Cianoacrilatos/farmacologia , Técnicas de Sutura , Suturas , Suínos , Adesivos Teciduais/farmacologia , Cicatrização
8.
J Biomed Mater Res B Appl Biomater ; 110(3): 660-667, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34596966

RESUMO

Cerebral spinal fluid (CSF) leakage is a major postoperative complication requiring surgical intervention, resulting in prolonged healing and higher costs. Biocompatible polymers, such as cyanoacrylates, are currently used as tissue adhesives for closing surgical defects and incisions. Coupling these polymers with nanofiber technology shows promising results for generating nanofibers used in wound care, tissue engineering, and drug delivery. Fiber membranes formed by electrospinning of n-octyl-2-cyanoacrylate (NOCA) are investigated for in situ dural closures after neurosurgery to improve the quality of the closure and prevent post-surgical CSF leaks. Electrospun NOCA fiber membranes showed significantly higher sealing capabilities of defects in human dura, with an average burst pressure of 149 mmHg, compared with that of an FDA-approved common dural sealant that had an average burst pressure of 37 mmHg. In this study, microfabrication of NOCA fibers demonstrates a promising technique for dural repairs.


Assuntos
Adesivos Teciduais , Vazamento de Líquido Cefalorraquidiano/prevenção & controle , Vazamento de Líquido Cefalorraquidiano/cirurgia , Cianoacrilatos/farmacologia , Dura-Máter/cirurgia , Humanos , Polímeros , Adesivos Teciduais/farmacologia
9.
J Mater Sci Mater Med ; 32(9): 98, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34406492

RESUMO

To analyze the hemostatic, Dsurgical wounds in donor and recipient areas of free gingival grafts (FGG). Five databases (PubMed, Scopus, Science Direct, Cochrane and Web of Science) were searched up to March 2021 (PROSPERO CRD42019134497). The focus of the study (cyanoacrylate) was combined with the condition (periodontal surgery OR free gingival graft OR free soft tissue graft OR autografts), and outcome (healing OR epithelialization OR pain OR analgesia OR bleeding OR hemostasis OR hemostatic). Studies reporting cyanoacrylate isolated or associated with another substance in FGG stabilization and closure were investigated and assessed for the quality and risk of bias through the Cochrane Manual. Six studies with 323 participants were included. Evaluation of the quality and risk of bias highlighted a low risk for four articles, intermediate for one and unclear for another. The use of cyanoacrylate associated or not with the hemostatic sponge or the platelet-rich fibrin was more effective in healing (three studies), analgesia (four studies), and hemostasis in one study (p < 0.05). However, groups with the association in cyanoacrylate showed superior healing, and analgesic action to the isolated cyanoacrylate group. In addition, two studies demonstrated that cyanoacrylate use reduces surgery duration, one study showed that it reduces postoperative sensibility, and another present hemostatic effect (p < 0.05). There is scarce literature for the use of cyanoacrylate in FGG wounds indicates that it can promote a minor inflammatory response, reduce operation time, does not interfere with healing, relieves postoperative discomfort, and suggests the possibility immediate hemostasis. Its use presents an alternative to suturing in FGG surgeries. But, the limited number of cases and the relative heterogeneity of the included studies suggest caution in generalizing the indication. CLINICAL RELEVANCE: Cyanoacrylate seems to present analgesic effects and less pain when applied to wound closure and covering donor and recipient areas reducing the need for postoperative analgesic medication; and has a healing effect in the closure of the donor area on the palate. In addition, it can reduce bleeding time after surgery, and prevents late bleeding during the first postsurgical week. Scientific justification: To evaluate the hemostatic, analgesic and healing actions of cyanoacrylate compared to the suture thread and other agents when used to close surgical wounds from periodontal free gingival graft surgical wounds in both the donor and recipient areas of the graft. MAIN FINDINGS: The use of cyanoacrylate individually or in association with wound dressing agents presents analgesic effects because the patient reports less pain experienced when cyanoacrylate is applied to the wound closure and covering, thereby reducing the need for postoperative analgesic medication. In addition, a healing effect is observed in the closure of the donor area on the palate; as well as it seems to present hemostatic effects, reducing the bleeding time after surgery, and preventing late bleeding during the first postsurgical week. PRACTICAL IMPLICATIONS: Dentists may cautiously apply cyanoacrylate after periodontal surgeries for free gingival graft in both the donor and recipient areas of the graft. However, they must consider the limitations of the surgery, tension-free positioning, the patient's dyscrasia and postoperative care, constituting a set of predictors for adequate clinical decision-making. Widespread use of such material for all patients and surgical configurations may not be recommended.


Assuntos
Analgésicos/farmacologia , Cianoacrilatos/farmacologia , Gengiva/transplante , Procedimentos de Cirurgia Plástica , Reepitelização/efeitos dos fármacos , Ferida Cirúrgica , Bandagens , Viés , Hemostasia , Hemostáticos/farmacologia , Humanos , Palato/cirurgia , Fibrina Rica em Plaquetas , Risco , Cicatrização
11.
Macromol Biosci ; 21(10): e2100143, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34268867

RESUMO

Cyanoacrylate glues are a renowned synthetic tissue sealant that cures rapidly through polymerization at room temperature, felicitating medical glues to treat skin wounds and surgical openings. Despite a wide range of cyanoacrylates available, only 2-octyl cyanoacrylates (OCA) provides the best biocompatibility. In this study, the polymerization and adhesive properties of 2-octyl cyanoacrylates (OCA) are explored in the presence of a highly biocompatible and biochemically inert polymer, poly(ethylene glycol) polyhedral oligomeric silsesquioxane (PEG-POSS). The effect of PEG-POSS on the polymerization of OCA is examined on a plastic surface and over pig skin. A peel-test is performed to evaluate the strength of OCA adhesive properties between two pieces of pig skin samples. Additionally, thin films of OCA are prepared using different fillers and evaluated for tear test. The results reveal that when applied on the plastic or pig skin, PEG-POSS initiated polymerization in OCA yields a high molecular weight OCA polymer with much better adhesive properties compared to commercially available cyanoacrylate adhesives. The relative change in the molecular weights of OCA compared to commercially available cyanoacrylate bioadhesives such as Dermaflex is much higher. The pig skin peeling test shows that OCA needs higher peeling force than Dermaflex.


Assuntos
Adesivos , Adesivos Teciduais , Adesivos/química , Adesivos/farmacologia , Animais , Cianoacrilatos/química , Cianoacrilatos/farmacologia , Polimerização , Polímeros/química , Polímeros/farmacologia , Suínos , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia
12.
Mol Cell Endocrinol ; 535: 111398, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34274446

RESUMO

BACKGROUND: The mechanochemical enzyme dynamin mediates endocytosis and regulates neuroendocrine cell exocytosis. Enteroendocrine L cells co-secrete the anorectic gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) postprandially and is a potential therapeutic target for metabolic diseases. In the present study, we aimed to determine if dynamin is implicated in human L cell secretion. METHODS: Western blot was performed on the murine L cell line GLUTag. Static incubation of human colonic mucosae with activators and inhibitors of dynamin was carried out. GLP-1 and PYY contents of the secretion supernatants were assayed using ELISA. RESULTS AND CONCLUSION: s: Both dynamin I and II are expressed in GLUTag cells. The dynamin activator Ryngo 1-23 evoked significant GLP-1 and PYY release from human colonic mucosae while the dynamin inhibitor Dynole 3-42 significantly inhibited release triggered by known L cell secretagogues. Thus, the cell signaling regulator dynamin is able to bi-directionally regulate L cell hormone secretion in the human gut and may represent a novel target for gastrointestinal-targeted metabolic drug development.


Assuntos
Dinamina II/metabolismo , Dinamina I/metabolismo , Células Enteroendócrinas/citologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Mucosa Intestinal/citologia , Peptídeo YY/metabolismo , Adulto , Idoso , Animais , Células Cultivadas , Meios de Cultura/química , Cianoacrilatos/farmacologia , Células Enteroendócrinas/efeitos dos fármacos , Células Enteroendócrinas/metabolismo , Feminino , Humanos , Indóis/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Células L , Masculino , Camundongos , Pessoa de Meia-Idade , Tirfostinas/farmacologia
13.
Antiviral Res ; 192: 105102, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34082057

RESUMO

As one of the principal etiological agents of hand, foot, and mouth disease (HFMD), enterovirus 71 (EV71) is associated with severe neurological complications or fatal diseases, while without effective medications thus far. Here we applied dually activated Michael acceptor to develop a series of reversible covalent compounds for EV71 3C protease (3Cpro), a promising antiviral drug target that plays an essential role during viral replication by cleaving the precursor polyprotein, inhibiting host protein synthesis, and evading innate immunity. Among them, cyanoacrylate and Boc-protected cyanoarylamide derivatives (SLQ-4 and SLQ-5) showed effective antiviral activity against EV71. The two inhibitors exhibited broad antiviral effects, acting on RD, 293T, and Vero cell lines, as well as on EV71 A, B, C, CVA16, and CVB3 viral strains. We further determined the binding pockets between the two inhibitors and 3Cpro based on docking studies. These results, together with our previous studies, provide evidence to elucidate the mechanism of action of these two reversible covalent inhibitors and contribute to the development of clinically effective medicines to treat EV71 infections.


Assuntos
Proteases Virais 3C/antagonistas & inibidores , Antivirais/farmacologia , Enterovirus Humano A/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Proteases Virais 3C/química , Acrilamidas/química , Acrilamidas/farmacologia , Animais , Antivirais/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cianoacrilatos/química , Cianoacrilatos/farmacologia , Enterovirus/classificação , Enterovirus/efeitos dos fármacos , Infecções por Enterovirus/virologia , Humanos , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Replicação Viral/efeitos dos fármacos
14.
Sci Rep ; 11(1): 8546, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879808

RESUMO

Open-globe injuries have poor visual outcomes and have increased in frequency. The current standard of care is inadequate, and a therapeutic is needed to stabilize the injury until an ophthalmic specialist is reached. Unfortunately, current models or test platforms for open-globe injuries are insufficient. Here, we develop and characterize an open-globe injury model using an anterior segment organ-culture platform that allows therapeutic assessment for up to 72 h post-injury. Anterior segments maintained in organ culture were kept at physiological intraocular pressure throughout, and puncture injuries were created using a novel pneumatic-powered system. This system can create high-speed, military-relevant injuries up to 4.5 mm in diameter through the cornea. From intraocular pressure readings, we confirmed a loss of pressure across the 72 h after open-globe injury. Proof-of-concept studies with a Dermabond tissue adhesive were performed to show how this model system could track therapeutic performance for 72 h. Overall, the organ-culture platform was found to be a suitable next step towards modeling open-globe injuries and assessing wound closure over the critical 72 h post-injury. With improved models such as this, novel biomaterial therapeutics development can be accelerated, improving care, and, thus, improving the prognosis for the patients.


Assuntos
Cianoacrilatos/farmacologia , Ferimentos Oculares Penetrantes/terapia , Olho/patologia , Pressão Intraocular/fisiologia , Técnicas de Cultura de Órgãos/métodos , Acuidade Visual/fisiologia , Animais , Olho/efeitos dos fármacos , Ferimentos Oculares Penetrantes/patologia , Modelos Teóricos , Suínos , Adesivos Teciduais/farmacologia
15.
Dermatol Surg ; 47(3): 381-384, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625155

RESUMO

BACKGROUND: As minimally invasive techniques were issued, endovenous thermal ablations have emerged. However, the thermal-associated complication has been reported in the treatment of small saphenous vein (SSV) insufficiency, such as sural nerve injury. Recently introduced cyanoacrylate closure (CAC) is a nonthermal modality, so this thermal-associated complication can be avoided. OBJECTIVE: This retrospective study analyzed the feasibility, safety, and 2-year results of CAC for treating SSV insufficiency, particularly the incidence of sural nerve injury. MATERIALS AND METHODS: One hundred sixty-three SSV insufficiencies in 128 patients were treated with CAC were reviewed. Pain, venous severity, and quality of life (QoL) scores were evaluated. Postoperative duplex scanning also evaluated anatomical and clinical success rates. RESULTS: The mean patient age was 56.8 years. The initial technical success rate was 100%. The occlusion rate after 2 years was 96.3%. Pain, venous severity, and QoL scores were improved significantly from 2.4 to 0.0, 4.39 to 0.47, and 11.95 to 2.69, respectively, before and 2 years after CAC. No major complications were observed, such as sural nerve injury. CONCLUSION: Cyanoacrylate closure for the ablation of SSV insufficiency could be a great alternative to endothermal ablation with an excellent success rate and shorter procedure time.


Assuntos
Cianoacrilatos/farmacologia , Veia Safena , Insuficiência Venosa/tratamento farmacológico , Estudos de Viabilidade , Seguimentos , Humanos , Qualidade de Vida , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
16.
Nat Commun ; 11(1): 6211, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277497

RESUMO

Intensive chemotherapy for acute leukemia can usually induce complete remission, but fails in many patients to eradicate the leukemia stem cells responsible for relapse. There is accumulating evidence that these relapse-inducing cells are maintained and protected by signals provided by the microenvironment. Thus, inhibition of niche signals is a proposed strategy to target leukemia stem cells but this requires knowledge of the critical signals and may be subject to compensatory mechanisms. Signals from the niche require receptor-mediated endocytosis, a generic process dependent on the Dynamin family of large GTPases. Here, we show that Dynole 34-2, a potent inhibitor of Dynamin GTPase activity, can block transduction of key signalling pathways and overcome chemoresistance of leukemia stem cells. Our results provide a significant conceptual advance in therapeutic strategies for acute leukemia that may be applicable to other malignancies in which signals from the niche are involved in disease progression and chemoresistance.


Assuntos
Cianoacrilatos/farmacologia , Dinaminas/antagonistas & inibidores , Endocitose/efeitos dos fármacos , Indóis/farmacologia , Leucemia Mieloide/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Doença Aguda , Animais , Linhagem Celular Tumoral , Dinaminas/metabolismo , Humanos , Leucemia Mieloide/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Camundongos Transgênicos , Células-Tronco Neoplásicas/efeitos dos fármacos , Nicho de Células-Tronco/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
17.
Acta Orthop Traumatol Turc ; 54(3): 330-336, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32544069

RESUMO

OBJECTIVE: The aim of this study was to compare the outcomes of primary nerve repair using either ethyl-cyanoacrylate or conventional microsuture technique in a rat peripheral nerve injury model. METHODS: In this study, a total of 30 Wistar Albino rats weighing between 220 and 275 g were used. The rats were randomly divided into three groups (10 in each), including one control (group 1) and two experimental groups (group 2, conventional microsuture repair; group 3, cyanoacrylate repair). In each group, the sciatic nerve was identified and transected. No further intervention was performed in group 1. The nerve was repaired using the epineural technique with a 10/0 atraumatic nylon in group 2 and synthetic cyanoacrylate adhesive in group 3. At the fifth postoperative week, needle electromyography (EMG) was performed to measure distal latency, combined muscle action potential (CMAP), and motor nerve conduction velocity (MNCV). Following the EMG recordings, animals were euthanized. Nerve samples were collected to evaluate vacuolar degeneration, fibrosis, and foreign body reaction histopathologically. RESULTS: In the EMG analysis, mean distal latency was significantly shorter in group 1 (0.85±0.09 ms) than in groups 2 (1.17±0.25 ms) (p=0.0052) and 3 (1.14±0.14 ms) (p=0.0026) while no significant differences existed between groups 2 and 3 (p>0.9999). The mean CMAP was greater in group 1 (10.5±0.35 mV) than in groups 2 (2.86±1.28 mV) (p=0.011) and 3 (2.16±1.34 mV) (p=0.0002), but there was no significant difference between groups 2 and 3 (p>0.9999). The mean MNCV was 53.5±5.95, 39.62±7.31, and 39.84±4.73 mm/sec in groups 1, 2, and 3, respectively. There was a significant difference between groups 1 and 2 (p=0.0052) and between 1 and 3 (p=0.0026), but not between 2 and 3 (p>0.9999). In the histopathological evaluation, the mean vacuolar degeneration score was 0, 2.12, and 1.88 in groups 1, 2, and 3, respectively. No obvious difference was observed between groups 2 and 3 (p=0.743). The mean fibrosis score was 0, 1.62, and 1.77 in groups 1, 2, and 3, respectively. There was no significant difference between groups 2 and 3 (p=0.888). The mean foreign body reaction score was 0, 2.5, and 2.44 in groups 1, 2, and 3, respectively. No difference was present between groups 2 and 3 (p=0.743). CONCLUSION: Primary nerve repair using the cyanoacrylate adhesive may provide similar electrophysiological and histopathological results as compared to the conventional microsuture repair.


Assuntos
Cianoacrilatos/farmacologia , Procedimentos Neurocirúrgicos/métodos , Traumatismos dos Nervos Periféricos/cirurgia , Nervo Isquiático , Procedimentos Cirúrgicos sem Sutura/métodos , Animais , Eletromiografia/métodos , Masculino , Regeneração Nervosa , Traumatismos dos Nervos Periféricos/diagnóstico , Ratos , Ratos Wistar , Nervo Isquiático/lesões , Nervo Isquiático/cirurgia , Técnicas de Sutura , Adesivos Teciduais/farmacologia , Resultado do Tratamento
18.
PLoS One ; 15(6): e0235568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32598376

RESUMO

Filamentous fungi belonging to the genus Fusarium are notorious plant-pathogens that infect, damage and contaminate a wide variety of important crops. Phenamacril is the first member of a novel class of single-site acting cyanoacrylate fungicides which has proven highly effective against important members of the genus Fusarium. However, the recent emergence of field-resistant strains exhibiting qualitative resistance poses a major obstacle for the continued use of phenamacril. In this study, we synthesized novel cyanoacrylate compounds based on the phenamacril-scaffold to test their growth-inhibitory potential against wild-type Fusarium and phenamacril-resistant strains. Our findings show that most chemical modifications to the phenamacril-scaffold are associated with almost complete loss of fungicidal activity and in vitro inhibition of myosin motor domain ATPase activity.


Assuntos
Cianoacrilatos/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Fusarium/crescimento & desenvolvimento , Fusarium/efeitos dos fármacos
19.
Mater Sci Eng C Mater Biol Appl ; 111: 110796, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32279807

RESUMO

Tissue adhesives have emerged as an effective method for wound closure and hemostasis in recent decades, due to their ability to bond tissues together, preventing separation from one tissue to another. However, existing tissue adhesives still have several limitations. Tremendous efforts have been invested into developing new tissue adhesives by improving upon existing adhesives through different strategies. Therefore, highlighting and analyzing these design strategies are essential for developing the next generation of advanced adhesives. To this end, we reviewed the available strategies for modifying traditional adhesives (including cyanoacrylate glues, fibrin sealants and BioGlue), as well as design of emerging adhesives (including gelatin sealants, methacrylated sealants and bioinspired adhesives), focusing on their structures, adhesive mechanisms, advantages, limitations, and current applications. The bioinspired adhesives have numerous advantages over traditional adhesives, which will be a wise direction for achieving tissue adhesives with superior properties.


Assuntos
Adesivos Teciduais/síntese química , Adesivos Teciduais/farmacologia , Animais , Cianoacrilatos/farmacologia , Adesivo Tecidual de Fibrina/farmacologia , Hemostasia/efeitos dos fármacos , Humanos , Cicatrização/efeitos dos fármacos
20.
J Craniofac Surg ; 31(4): e334-e337, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32176002

RESUMO

OBJECTIVE: To enable tongue incisions to be repaired more easily, rapidly, and practically, particularly in pediatric patients by using 2-octyl cyanoacrylate (OCA) tissue adhesive. METHODS: A single linear incision was made on the midline dorsal part of the tongue. Twenty-four rats were randomly divided into the four groups: Group 1 (n = 6), OCA healing at day 5; group 2 (n = 6), OCA healing at day 21; group 3 (n = 6), Vicryl healing at day 5; group 4 (n = 6), Vicryl healing at day 21. In groups 1 and 2, OCA was applied to the incision site. The incisions of the rats in groups 3 and 4 were closed using Vicryl sutures. Histopathological examination was compared between and within the groups at day 5 and 21. RESULTS: The operation duration was significantly shorter with OCA than with Vicryl sutures(P < 0.001). Regarding the histopathological results, there were no differences between group 1 and group 3 in epithelial regeneration, inflammation, fibroblastic activity, edema, presence of giant cells, fibrin deposition, ulceration, abscess formation, and granulation tissue. However, moderate infiltration of acute inflammatory cells was significantly more frequent in group 1 than in group 3. At day 5, the incidence of moderate foreign body residue was significantly higher in group 1 than in group 3. No difference was observed between group 2 and group 4 at day 21 (P > 0.05). CONCLUSION: OCA is a practical, rapid, and effective method for repairing tongue lacerations. Although infiltration by inflammatory cells and foreign bodies increased in the early period, the long-term results of OCA were indistinguishable from those of suturing.


Assuntos
Cianoacrilatos/farmacologia , Lacerações/patologia , Lesões dos Tecidos Moles/patologia , Suturas , Língua/patologia , Animais , Feminino , Lacerações/tratamento farmacológico , Lacerações/cirurgia , Procedimentos Neurocirúrgicos , Ratos , Ratos Sprague-Dawley , Lesões dos Tecidos Moles/tratamento farmacológico , Lesões dos Tecidos Moles/cirurgia , Língua/cirurgia
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