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1.
Nat Immunol ; 15(3): 223-30, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24487320

RESUMO

Tyrosine phosphorylation of the adhesion molecule VE-cadherin is assumed to affect endothelial junction integrity. However, it remains unclear whether tyrosine residues of VE-cadherin are required for the induction of vascular permeability and the regulation of leukocyte extravasation in vivo. We found here that knock-in mice expressing a Y685F mutant of VE-cadherin had impaired induction of vascular permeability, but those expressing a Y731F mutant did not. In contrast, mice expressing the Y731F VE-cadherin mutant showed decreased neutrophil-extravasation in cremaster tissue, but those expressing the Y685F mutant did not. Whereas inflammatory mediators induced the phosphorylation of Tyr685 in vivo, Tyr731 showed high baseline phosphorylation. Leukocytes triggered dephosphorylation of Tyr731 via the tyrosine phosphatase SHP-2, which allowed the adaptin AP-2 to bind and initiate endocytosis of VE-cadherin. Thus, Tyr685 and Tyr731 of VE-cadherin distinctly and selectively regulate the induction of vascular permeability or leukocyte extravasation.


Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Permeabilidade Capilar/fisiologia , Quimiotaxia de Leucócito/fisiologia , Células Endoteliais/metabolismo , Animais , Antígenos CD/química , Benzetônio/análogos & derivados , Caderinas/química , Imunofluorescência , Técnicas de Introdução de Genes , Humanos , Immunoblotting , Imunoprecipitação , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Tirosina/metabolismo
2.
Ecotoxicol Environ Saf ; 263: 115268, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37480694

RESUMO

Throughout the coronavirus (COVID-19) pandemic, the sanitizing products benzethonium chloride (BEC) and polyhexamethylene guanidine hydrochloride (PHMG-H) were widely used; however, few studies have investigated their combined toxicity to organisms. In the present study, acute toxicity and genotoxicity of BEC, PHMG-H, and the combination of the two were investigated as endpoints using Daphnia carinata as the model organism. For individual reagents, PHMG-H was found to be more toxic than BEC in terms of both mortality and genotoxicity. DNA damage and survival rate were used as toxicity endpoints. The interaction was evaluated with the concentration addition (CA) model via toxic unit (TU) approach and additive index (AI) method in mixtures at different ratios in TU. Only the binary mixture BEC + PHMG-H at the ratio 1:9 in TU was regarded as synergistic, while all others indicated increased antagonistic effects as the proportion of BEC increased over the PHMG-H concentration. The findings here benefit understanding surrounding precisely how BEC and PHMG-H interact at different mixing ratios, and can assist with the evaluation of risk assessments for binary mixtures in aquatic ecosystems.


Assuntos
COVID-19 , Daphnia , Animais , Benzetônio , Ecossistema , Guanidina/toxicidade
3.
J Appl Microbiol ; 133(6): 3322-3346, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35882500

RESUMO

This review examined 3655 articles on benzalkonium chloride (BKC), benzethonium chloride (BZT) and chloroxylenol (CHO) aiming to understand their impact on antimicrobial resistance. Following the application of inclusion/exclusion criteria, only 230 articles were retained for analysis; 212 concerned BKC, with only 18 for CHO and BZT. Seventy-eight percent of studies used MIC to measure BKC efficacy. Very few studies defined the term 'resistance' and 85% of studies defined 'resistance' as <10-fold increase (40% as low as 2-fold) in MIC. Only a few in vitro studies reported on formulated products and when they did, products performed better. In vitro studies looking at the impact of BKC exposure on bacterial resistance used either a stepwise training protocol or exposure to constant BKC concentrations. In these, BKC exposure resulted in elevated MIC or/and MBC, often associated with efflux, and at time, a change in antibiotic susceptibility profile. The clinical relevance of these findings was, however, neither reported nor addressed. Of note, several studies reported that bacterial strains with an elevated MIC or MBC remained susceptible to the in-use BKC concentration. BKC exposure was shown to reduce bacterial diversity in complex microbial microcosms, although the clinical significance of such a change has not been established. The impact of BKC exposure on the dissemination of resistant genes (notably efflux) remains speculative, although it manifests that clinical, veterinary and food isolates with elevated BKC MIC carried multiple efflux pump genes. The correlation between BKC usage and gene carriage, maintenance and dissemination has also not been established. The lack of clinical interpretation and significance in these studies does not allow to establish with certainty the role of BKC on AMR in practice. The limited literature and BZT and CHO do not allow to conclude that these will impact negatively on emerging bacterial resistance in practice.


Assuntos
Anti-Infecciosos , Compostos de Benzalcônio , Compostos de Benzalcônio/farmacologia , Benzetônio/farmacologia , Antibacterianos/farmacologia , Cloretos , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana
4.
Toxicol Appl Pharmacol ; 431: 115731, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34592322

RESUMO

Benzethonium chloride (BZT) and domiphen bromide (DMP) are widely used as antimicrobials in drugs, vaccines and industry. However, no cardiac safety data has been developed on both compounds. Previously we reported BZT and DMP as high-affinity human ether-a-go-go related gene (HERG) channel inhibitors with unknown proarrhythmic risk. Here, we investigate the cardiotoxicity of BZT and DMP in vitro and in vivo, aiming to improve the safety-in-use of both antimicrobials. In the present study, human iPSC derived cardiomyocytes (hiPSC-CMs) were generated and rabbit models were used to examine the proarrhythmic potential of BZT and DMP. Our results found that BZT and DMP induced time- and dose-dependent decrease in the contractile parameters of hiPSC-CMs, prolonged FPDc (≥ 0.1 µM), caused tachycardia/fibrillation-like oscillation (0.3-1 µM), ultimately progressing to irreversible arrest of beating (≥ 1 µM). The IC50 values of BZT and DMP derived from normalized beat rate were 0.13 µM and 0.10 µM on hiPSC-CMs at 76 days. Moreover, in vivo rabbit ECG data demonstrated that 12.85 mg/kg BZT and 3.85 mg/kg DMP evoked QTc prolongation, noncomplex arrhythmias and ventricular tachycardias. Our findings support the cardiac safety of 0.01 µM BZT/DMP in vitro and the intravenous infusion of 3.85 mg/kg BZT and 1.28 mg/kg DMP in vivo, whereas higher concentrations of both compounds cause mild to moderate cardiotoxicity that should not be neglected during medical and industrial applications.


Assuntos
Anti-Infecciosos/toxicidade , Arritmias Cardíacas/induzido quimicamente , Benzetônio/toxicidade , Canal de Potássio ERG1/antagonistas & inibidores , Frequência Cardíaca/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/toxicidade , Compostos de Amônio Quaternário/toxicidade , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Cardiotoxicidade , Linhagem Celular , Relação Dose-Resposta a Droga , Canal de Potássio ERG1/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Miócitos Cardíacos/metabolismo , Coelhos , Medição de Risco , Fatores de Tempo , Testes de Toxicidade
5.
J Pharmacol Exp Ther ; 373(2): 311-324, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32094294

RESUMO

Treatments for cognitive deficits associated with central nervous system (CNS) disorders such as Alzheimer disease and schizophrenia remain significant unmet medical needs that incur substantial pressure on the health care system. The α7 nicotinic acetylcholine receptor (nAChR) has garnered substantial attention as a target for cognitive deficits based on receptor localization, robust preclinical effects, genetics implicating its involvement in cognitive disorders, and encouraging, albeit mixed, clinical data with α7 nAChR orthosteric agonists. Importantly, previous orthosteric agonists at this receptor suffered from off-target activity, receptor desensitization, and an inverted U-shaped dose-effect curve in preclinical assays that limit their clinical utility. To overcome the challenges with orthosteric agonists, we have identified a novel selective α7 positive allosteric modulator (PAM), BNC375. This compound is selective over related receptors and potentiates acetylcholine-evoked α7 currents with only marginal effect on the receptor desensitization kinetics. In addition, BNC375 enhances long-term potentiation of electrically evoked synaptic responses in rat hippocampal slices and in vivo. Systemic administration of BNC375 reverses scopolamine-induced cognitive deficits in rat novel object recognition and rhesus monkey object retrieval detour (ORD) task over a wide range of exposures, showing no evidence of an inverted U-shaped dose-effect curve. The compound also improves performance in the ORD task in aged African green monkeys. Moreover, ex vivo 13C-NMR analysis indicates that BNC375 treatment can enhance neurotransmitter release in rat medial prefrontal cortex. These findings suggest that α7 nAChR PAMs have multiple advantages over orthosteric α7 nAChR agonists for the treatment of cognitive dysfunction associated with CNS diseases. SIGNIFICANCE STATEMENT: BNC375 is a novel and selective α7 nicotinic acetylcholine receptor (nAChR) positive allosteric modulator (PAM) that potentiates acetylcholine-evoked α7 currents in in vitro assays with little to no effect on the desensitization kinetics. In vivo, BNC375 demonstrated robust procognitive effects in multiple preclinical models across a wide exposure range. These results suggest that α7 nAChR PAMs have therapeutic potential in central nervous system diseases with cognitive impairments.


Assuntos
Benzetônio/farmacologia , Clorobenzenos/farmacologia , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Regulação Alostérica , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cognição/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Macaca mulatta , Masculino , Neurotransmissores/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Escopolamina/farmacologia
6.
Chem Pharm Bull (Tokyo) ; 68(7): 675-678, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612003

RESUMO

The details of the total syntheses of C2'-fluorinated analogs of solamin, an antitumor annonaceous acetogenin, are described. Fluorine was enantioselectively introduced at the C2'-position by organocatalytic α-fluorination of the aldehyde according to a previously reported method. C2'-fluorinated solamin and its C2'-diastereomer were synthesized by the Sonogashira coupling of a tetrahydrofuran fragment and fluorine-containing γ-lactone fragments.


Assuntos
Antineoplásicos/síntese química , Benzetônio/síntese química , Aldeídos/química , Antineoplásicos/química , Benzetônio/química , Flúor/química , Halogenação , Estrutura Molecular
7.
J Wound Care ; 29(Sup10): 18-26, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33048016

RESUMO

OBJECTIVE: Present a treatment protocol to avoid biofilm reformation in hard-to-heal wounds, using a hydrofiber dressing with 1.2% ionic silver, ethylenediaminetetraacetic acid and benzethonium chloride. METHOD: A retrospective, descriptive and analytic study on the use of a treatment protocol, including three case studies. Patient records for hard-to-heal wounds were analysed according to an algorithm for biofilm detection and best-practice recommendations for wound hygiene. RESULTS: The adopted protocol was based on three pillars: identifying clinical signs suggesting biofilm, performing wound hygiene, and applying an antibiofilm dressing. CONCLUSION: Wound healing rates can improve after protocol implementation. Adequate control of local signs of infection and exudate, as well as visual and indirect signs of biofilm, were achieved. All patients progressed well towards wound-size reduction and closure using the hydrofiber dressing.


OBJETIVO: Presentar un protocolo para evitar la reformación de biopelícula en heridas de difícil cicatrización con apósito de hidrofibra reforzada, con plata iónica al 1,2%, potenciado con ácido etilendiaminotetraacético (EDTA) y cloruro de bencetonio. MÉTODO: Estudio retrospectivo, descriptivo y analítico de aplicación de un protocolo de tratamiento, con tres casos de estudio de pacientes tratados en un centro de referencia internacional. Los registros de pacientes con úlceras complejas se analizaron y evaluaron de acuerdo con la inserción en el algoritmo de identificación clínica de biopelículas, y en base a las recomendaciones prácticas para la higiene de heridas. RESULTADOS: El protocolo adoptado se basó en tres pilares: identificación de signos clínicos de sugerencia para la presencia de biopelícula, prácticas de higiene en las heridas, y aplicación de la cobertura de antibiopelícula. CONCLUSIÓN: La capacidad de cicatrización de heridas con este protocolo puede considerarse alta. Los pacientes obtuvieron un adecuado control de todos los signos locales de infección y de exceso de exudado, y la desaparición de los signos visuales e indirectos de biopelícula. Todos presentaron una adecuada progresión, disminución de la superficie de la herida, y cicatrización tras el uso del apósito.


Assuntos
Bandagens , Benzetônio/uso terapêutico , Biofilmes/efeitos dos fármacos , Ácido Edético/uso terapêutico , Prata/uso terapêutico , Cicatrização , Humanos , Estudos Retrospectivos , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/patologia
8.
J Wound Care ; 29(LatAm sup 2): 18-26, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33054618

RESUMO

OBJECTIVE: Present a treatment protocol to avoid biofilm reformation in hard-to-heal wounds, using a hydrofiber dressing with 1.2% ionic silver, ethylenediaminetetraacetic acid and benzethonium chloride. METHOD: A retrospective, descriptive and analytic study on the use of a treatment protocol, including three case studies. Patient records for hard-to-heal wounds were analysed according to an algorithm for biofilm detection and best-practice recommendations for wound hygiene. RESULTS: The adopted protocol was based on three pillars: identifying clinical signs suggesting biofilm, performing wound hygiene, and applying an antibiofilm dressing. CONCLUSION: Wound healing rates can improve after protocol implementation. Adequate control of local signs of infection and exudate, as well as visual and indirect signs of biofilm, were achieved. All patients progressed well towards wound-size reduction and closure using the hydrofiber dressing.


OBJETIVO: Presentar un protocolo para evitar la reformación de biopelícula en heridas de difícil cicatrización con apósito de hidrofibra reforzada, con plata iónica al 1,2%, potenciado con ácido etilendiaminotetraacético (EDTA) y cloruro de bencetonio. MÉTODO: Estudio retrospectivo, descriptivo y analítico de aplicación de un protocolo de tratamiento, con tres casos de estudio de pacientes tratados en un centro de referencia internacional. Los registros de pacientes con úlceras complejas se analizaron y evaluaron de acuerdo con la inserción en el algoritmo de identificación clínica de biopelículas, y en base a las recomendaciones prácticas para la higiene de heridas. RESULTADOS: El protocolo adoptado se basó en tres pilares: identificación de signos clínicos de sugerencia para la presencia de biopelícula, prácticas de higiene en las heridas, y aplicación de la cobertura de antibiopelícula. CONCLUSIÓN: La capacidad de cicatrización de heridas con este protocolo puede considerarse alta. Los pacientes obtuvieron un adecuado control de todos los signos locales de infección y de exceso de exudado, y la desaparición de los signos visuales e indirectos de biopelícula. Todos presentaron una adecuada progresión, disminución de la superficie de la herida, y cicatrización tras el uso del apósito.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Bandagens , Benzetônio/uso terapêutico , Cicatrização/efeitos dos fármacos , Adulto , Idoso de 80 Anos ou mais , Ácido Edético , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Prata , Resultado do Tratamento
9.
Phytopathology ; 109(2): 233-239, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30407880

RESUMO

Xylella fastidiosa infects a wide range of plant hosts and causes Pierce's disease (PD) of grapevines. The type 1 multidrug resistance (MDR) efflux system is essential for pathogenicity and survival of bacterial pathogens in planta. X. fastidiosa, with a single MDR system, is significantly more vulnerable to inhibition by small-molecule treatments than most bacterial pathogens that typically carry redundant MDR systems. A high-throughput cell viability assay using a green fluorescent protein-marked strain of X. fastidiosa Temecula 1 was developed to screen two Prestwick combinatorial small-molecule libraries of drugs and phytochemicals (1,600 chemicals in total) approved by the Food and Drug Administration and European Medicines Agency for cell growth inhibition. The screens revealed 215 chemicals that inhibited bacterial growth by >50% at 50 µM concentrations. Seven chemicals proved to lyse X. fastidiosa cells at 25 µM, including four phytochemicals. Menadione (2-methyl-1,4-naphthoquinone, vitamin K) from the phytochemical library and benzethonium chloride (a topical disinfectant) from the chemical library both showed significant bactericidal activity against X. fastidiosa. Both menadione and benzethonium chloride foliar spray (15 and 5 mM, respectively) and soil drench (5 and 25 mM, respectively) treatments were equally effective in reducing PD symptoms by 54 to 59% and revealed that the effects of both chemical treatments became systemic. However, menadione was phytotoxic when applied as a foliar spray at effective concentrations, causing significant loss of photosynthetic capacity.


Assuntos
Benzetônio/química , Vitamina K 3/química , Vitis , Xylella , Doenças das Plantas
10.
Appl Environ Microbiol ; 84(13)2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29728378

RESUMO

Few studies have been conducted on the susceptibility of bacteria to biocides. A total of 182 methicillin-resistant and -susceptible Staphylococcus aureus isolates collected from healthy or diseased humans and animals in Germany were included in the present study. Sixty-three isolates of animal origin and 119 human isolates were tested for their MICs to eight biocides or heavy metals by the broth microdilution method. The MIC50 and MIC90 values of human and animal isolates were equal or differed by not more than 1 dilution step, and statistical analysis revealed that differences between MICs of human and animal isolates were not significant. However, when taking into account the multilocus sequence type (MLST), a strong tendency (P = 0.054) to higher MICs of silver nitrate was detected for clonal complex 398 (CC398) isolates from humans compared to those from animals. Furthermore, a comparison of MIC values from isolates belonging to different clonal lineages revealed that important human lineages such as CC22 and CC5 exhibited significantly (P < 0.05) higher MICs for the biocides chlorhexidine, benzethonium chloride, and acriflavine than the main animal lineage sequence type 398 (ST398). Isolates with elevated MIC values were tested for the presence of biocide and heavy metal tolerance-mediating genes by PCR assays, and the following genes were detected: mepA (n [no. of isolates containing the gene] = 44), lmrS (n = 36), norA (n = 35), sepA (n = 22), mco (n = 5), czrC (n = 3), smr (n = 2), copA (n = 1), qacA and/or -B (n = 1), qacG (n = 2), and qacJ (n = 1). However, only for some compounds was a correlation between the presence of a biocide tolerance gene and the level of MIC values detected.IMPORTANCE Biocides play an essential role in controlling the growth of microorganisms and the dissemination of nosocomial pathogens. In this study, we determined the susceptibility of methicillin-resistant and -susceptible S. aureus isolates from humans and animals to various biocides and heavy metal ions and analyzed differences in susceptibilities between important clonal lineages. In addition, the presence of biocide or heavy metal tolerance-mediating genes was investigated. We demonstrated that important human lineages such as CC22 and CC5 had significantly higher MIC values for chlorhexidine, benzethonium chloride, and acriflavine than the main farm animal lineage, ST398. In addition, it was shown that for some combinations of biocides and tolerance genes, significantly higher MICs were detected for carriers. These findings provide new insights into S. aureus biocide and heavy metal tolerance.


Assuntos
DNA Bacteriano/isolamento & purificação , Desinfetantes/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Acriflavina/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Benzetônio/farmacologia , Linhagem da Célula/genética , Clorexidina/farmacologia , DNA Bacteriano/genética , Genes Bacterianos , Alemanha , Metais Pesados/metabolismo , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Análise de Sequência de DNA
11.
Zhonghua Nan Ke Xue ; 24(7): 613-617, 2018 07.
Artigo em Zh | MEDLINE | ID: mdl-30173444

RESUMO

Objective: To study the influence of povidone-iodine (PI) versus that of the benzethonium chloride wipe (BCW) on semen collection and semen quality of sperm donors undergoing penile skin disinfection and provide some evidence for the selection of disinfection methods for semen collection. METHODS: We used PI from August to December 2015 and BCWs from January to July 2016 for penile skin disinfection before semen collection, with two samples from each donor, one collected with and the other without penis skin disinfection (the blank control group). After semen collection, we conducted a questionnaire investigation on the influence of the two disinfection methods on semen collection and compared the semen parameters between the two groups of sperm donors. RESULTS: Totally, 185 sperm donors were included in this study, of whom 63 underwent penile skin disinfection with PI and the other 122 with BCWs before semen collection. Statistically significant differences were found between the PI and BCW groups in the adaptability to the disinfectant and rigid disinfection procedures (P <0.05), but not in the other items of the questionnaire (P >0.05). Compared with the sperm donors of the blank control group, those of the PI group showed statistically significant difference in the percentage of progressively motile sperm (PMS) (ï¼»63.02 ± 3.18ï¼½% vs ï¼»61.45 ± 4.78ï¼½%, P<0.05), but not in the abstinence time (ï¼»4.97 ± 1.79ï¼½ vs ï¼»4.7 ± 0.94ï¼½ d, P >0.05), semen volume (ï¼»4.11 ± 1.54ï¼½ vs ï¼»4.15 ± 1.61ï¼½ ml, P >0.05), sperm concentration (ï¼»110 ± 29.6ï¼½ vs ï¼»107.5 ± 31.79ï¼½ ×106/ml, P >0.05), or total sperm count (ï¼»439.10 ± 170.13ï¼½ vs ï¼»434.02 ± 186.91ï¼½ ×106/ejaculate, P >0.05), while those of the BCW group exhibited no remarkable difference in any of the above parameters (P >0.05). Among the samples with abnormal semen quality, significantly fewer were found with abnormal PMS in the BCW than in the PI group (1.64% ï¼»2/122ï¼½ vs 9.68% ï¼»6/62ï¼½, P <0.05). However, there were no significant differences between the PI and BCW groups in the abnormal semen volume, abnormal sperm concentration, or the rate of semen bacterial contamination (P >0.05). CONCLUSIONS: Before semen collection from donors, penile skin disinfection with povidone-iodine may affect both the semen collection process and the quality of donor sperm, while the benzethonium chloride wipe can reduce the influence on the semen collection process and does not affect the semen parameters.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Benzetônio/administração & dosagem , Desinfecção/métodos , Povidona-Iodo/administração & dosagem , Recuperação Espermática , Desinfecção/estatística & dados numéricos , Humanos , Masculino , Pênis , Sêmen , Análise do Sêmen , Pele , Contagem de Espermatozoides , Espermatozoides , Doadores de Tecidos
12.
Eur J Oral Sci ; 125(1): 63-71, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27862353

RESUMO

This study evaluated the stability of resin-dentin interfaces treated with glutaraldehyde-containing agents, and assessed collagen degradation in dentin matrices treated with Gluma. Microtensile bond strength (µTBS) was evaluated 24 h and 6 months after treatment with three desensitizers (Gluma Desensitizer, Gluma Desensitizer Power Gel, and MicroPrime G) and two etch-and-rinse adhesives (Comfort Bond & Desensitizer and iBond TE). Demineralized beams of human dentin were treated with water or Gluma, and the degradation of collagen in these beams was assessed by quantification of the dry mass loss and of the amount of hydroxyproline released from hydrolyzed specimens after 1 or 4 wk. All groups demonstrated significant reduction in µTBS after 6 months, except for Gluma Desensitizer and iBond TE groups, which showed decreases of 7.2% and 10.8%, respectively. The most prevalent failure mode was 'mixed'. Significantly less hydroxyproline was released from Gluma-treated beams than from control beams after 4 wk. Beams treated with Gluma yielded significantly less dry mass loss than did beams in the control group. Collagen cross-linking with glutaraldehyde-containing agents may assist in the stabilization of resin-dentin bonds by reducing the amount of collagen solubilized from dental matrices in the hybrid layer. In turn, this may contribute to the preservation of adhesive interfaces.


Assuntos
Colágeno/efeitos dos fármacos , Materiais Dentários/química , Adesivos Dentinários/química , Dentina/efeitos dos fármacos , Benzetônio/química , Reagentes de Ligações Cruzadas/química , Glutaral/química , Humanos , Hidroxiprolina/metabolismo , Técnicas In Vitro , Metacrilatos/química , Dente Molar , Ácidos Polimetacrílicos/química , Cimentos de Resina/química , Propriedades de Superfície , Resistência à Tração
13.
J Nat Prod ; 79(8): 2039-44, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27533261

RESUMO

An original synthesis of the acetogenin muricadienin, the bioprecursor of solamin, has been developed. The key step in the five-step 41% overall yield synthesis is the catalytic cross-cyclomagnesiation reaction of functionally substituted 1,2-dienes with EtMgBr in the presence of Cp2TiCl2 and magnesium metal. It has been demonstrated for the first time that muricadienin exhibits a moderate in vitro inhibitory activity against topoisomerases I and IIα, key cell cycle enzymes. Using flow cytometry, muricadienin was shown to have high cytotoxicity toward the HEK293 kidney cancer cells (IC50 0.39 µM).


Assuntos
Acetogeninas , Antineoplásicos , Acetogeninas/síntese química , Acetogeninas/química , Acetogeninas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzetônio/química , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Humanos , Estrutura Molecular , Inibidores da Topoisomerase I/farmacologia
14.
Adv Skin Wound Care ; 29(10): 461-8, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27632443

RESUMO

OBJECTIVE: The purpose of this retrospective registry data analysis was to explore the effectiveness of a novel multivalent topical ointment (Terrasil Infection Control Wound Care Ointment; Aspiera Medical, Woonsocket, Rhode Island), containing a patented mineral complex and 0.2% benzethonium chloride in the treatment of nonhealing acute and chronic wounds. DESIGN: Aspiera Medical designed a registry to capture physician experiences and treatment results with Terrasil Infection Control Wound Care Ointment. Physicians were asked to enter deidentified patient data into an online registry. SETTING: Wound clinics in the United States were asked to participate in the registry. PATIENTS: Physicians at 4 wound clinics treated 30 patients (26 of whom completed the treatment) with various chronic wounds that had persisted for an average of 6 months and entered treatment data into the registry. INTERVENTIONS: Patients applied the ointment according to physician orders. Concurrent treatments used by patients included offloading, compression wraps, and dressings, such as collagen and calcium alginate. Patients were treated until complete wound closure or lost to follow-up. MAIN OUTCOME MEASURES: Physicians calculated each patient's percentage wound reduction at each visit. MAIN RESULTS: Thirty patients were entered into the registry. Pretreatment and posttreatment measurements were available for 26 of them. Patients achieved an average surface area reduction of 84% in a mean of 23 days' treatment. CONCLUSION: The antimicrobial and moisturizing ointment studied appears to be effective in promoting wound closure in a variety of acute and chronic wounds. Wounds studied included diabetic foot ulcers, venous leg ulcers, venous stasis ulcers, surgical infections, burns, and insect bites. The results of this registry data analysis will be used to inform planned clinical trials.


Assuntos
Benzetônio/uso terapêutico , Curativos Oclusivos , Sistema de Registros , Úlcera Varicosa/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Doença Crônica , Pé Diabético/diagnóstico , Pé Diabético/tratamento farmacológico , Feminino , Humanos , Úlcera da Perna/diagnóstico , Úlcera da Perna/tratamento farmacológico , Masculino , Pomadas/uso terapêutico , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Úlcera Varicosa/diagnóstico , Cicatrização/fisiologia , Ferimentos e Lesões/diagnóstico
15.
J Wound Care ; 29(LatAm sup 1): 1-12, 2020 01 01.
Artigo em Espanhol | MEDLINE | ID: mdl-31855524

RESUMO

SINOPSIS: Objetivo: Se realizó un estudio prospectivo, observacional, de seguimiento de casos en el servicio de cirugía plástica del hospital El Tunal, Bogotá, Colombia, para evaluar la efectividad de un apósito de hidrofibra reforzada, con plata iónica al 1,2%, potenciado con ácido etilendiaminotetraacético (EDTA) y cloruro de bencetonio en pacientes con heridas de difícil cicatrización. Método: Se incluyeron 23 pacientes con heridas de diferentes etiologías, signos locales de infección, presencia de exudado e indicadores visuales o indirectos de biofilm. Los pacientes fueron divididos en tres grupos: heridas que requerían cicatrización por segunda intención (n=10) (grupo 1), heridas con absceso (n=4) (grupo 2) y heridas en las que se requería preparar el lecho para cobertura quirúrgica (n=9) (grupo 3). El seguimiento de cada caso duró tres meses. Resultados: El grupo 1 demostró una disminución de exudado, infección y signos indirectos de biofilm, así como una reducción significativa de la superficie de la herida con cierre total en ocho de los 10 casos pertenecientes a este grupo. El grupo 2 logró el control de exudado y cierre de la cavidad en un promedio de 21 días. El grupo 3 obtuvo adecuada preparación del lecho de la herida y alcanzó una cobertura quirúrgica en 15 días, en promedio. No se encontraron efectos adversos en los pacientes tratados. Conclusión: Los resultados muestran que el apósito estudiado es efectivo para controlar exudado, infección y signos indirectos de biofilm, así como para disminuir el tamaño de la herida, lograr el cierre de heridas con absceso y preparar el lecho para una cobertura quirúrgica definitiva. ABSTRACT: Objective: A prospective, observational, case-series study evaluated the efficacy of a hydrofiber dressing with ionic silver, ethylenediaminetetraacetic acid and benzethonium chloride in patients with hard-to-heal wounds at El Tunal hospital in Bogota, Colombia. Method: A total of 23 patients with wounds of different aetiologies, local signs of infection, exudate and biofilm were recruited. Patients were divided into three groups: wounds for secondary intention healing (group 1), abscesses (group 2) and wounds for surgical coverage (group 3). Patients were followed up for 3 months. Results: Group 1 showed a reduction in exudate and infection levels, and a decrease in indirect signs of biofilm. There was also a significant reduction in wound surface, with eight out of 10 patients in this group achieving complete wound closure. Group 2 obtained exudate control and wound closure in 21 days, on average. Group 3 demonstrated an adequate wound bed preparation for surgical coverage in 15 days, on average. No side effects were observed. Conclusion: The results showed that the hydrofiber dressing could be effective in controlling exudate and infection levels, and managing the indirect signs of biofilm, as well as reducing the wound surface, achieving wound closure in abscesses and performing wound bed preparation for surgical coverage.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Bandagens , Carboximetilcelulose Sódica/administração & dosagem , Infecção dos Ferimentos/prevenção & controle , Adulto , Benzetônio/administração & dosagem , Ácido Edético/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Prata/administração & dosagem , Resultado do Tratamento , Infecção dos Ferimentos/patologia , Adulto Jovem
16.
Ceska Slov Farm ; 63(3): 123-6, 2014 Jun.
Artigo em Tcheco | MEDLINE | ID: mdl-25115665

RESUMO

This study is focused on the preparation of gels with antimicrobial effects. A quaternary ammonium salt, benzethonium chloride, in a concentration of 0.01-0.5% (w/w) was employed as the drug. The humectant employed was propylene glycol in concentrations of 5% and 10% (w/w). Two types of polymers, chitosan and hydroxyethyl cellulose, in the same concentrations of 2.5% (w/w), were used for gel preparation. Finally the flow properties, rheological parameters and pH values of the gels were evaluated. Based on the obtained results, the samples of the gels prepared on the basis of chitosan and hydroxyethyl cellulose, which have the following optimum composition shown below, were found: 2,5% (w/w) CHIT + 0,5% (w/w) BZCl + 10% (w/w) PG; 2,5% (w/w) HEC + 0,5% (w/w) BZCl + 5% (w/w) PG.


Assuntos
Benzetônio/administração & dosagem , Celulose/análogos & derivados , Química Farmacêutica/métodos , Quitosana/química , Benzetônio/química , Celulose/química , Géis , Polímeros/química , Propilenoglicol/química , Reologia
17.
Ann Clin Biochem ; 61(2): 150-153, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38008911

RESUMO

This case report describes the positive interference of the commonly used skin protective barrier cream used together with urine collection bags on the benzethonium chloride method for urine protein measurements in a 6-month-old female baby, leading to falsely elevated results. The interference was identified by both artificially mixing urine samples with this cream and comparing the results obtained using the benzethonium chloride method with those obtained using the pyrogallol red method.


Assuntos
Benzetônio , Proteinúria , Feminino , Humanos , Lactente
18.
Water Res ; 250: 121024, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38113597

RESUMO

Benzethonium chloride (BZC) is viewed as a promising disinfectant and widely applied in daily life. While studies related to its effect on waste activated sludge (WAS) anaerobic fermentation (AF) were seldom mentioned before. To understand how BZC affects AF of WAS, production of short chain fatty acids (SCFAs), characteristics of WAS as well as microbial community were evaluated during AF. Results manifested a dose-specific relationship of dosages between BZC and SCFAs and the optimum yield arrived at 2441.01 mg COD/L with the addition of 0.030 g/g TSS BZC. Spectral results and protein secondary structure variation indicated that BZC denatured proteins in the solid phase into smaller proteins or amino acids with unstable structures. It was also found that BZC could stimulate the extracellular polymeric substances secretion and reduce the surface tension of WAS, leading to the enhancement of solubilization. Beside, BZC promoted the hydrolysis stage (increased by 7.09 % to 0.030 g/g TSS BZC), but inhibited acetogenesis and methanogenesis stages (decreased by 6.85 % and 14.75 % to 0.030 g/g TSS BZC). The microbial community was also regulated by BZC to facilitate the enrichment of hydrolytic and acidizing microorganisms (i.e. Firmicutes). All these variations caused by BZC were conducive to the accumulation of SCFAs. The findings contributed to investigating the effect of BZC on AF of WAS and provided a new idea for the future study of AF mechanism.


Assuntos
Benzetônio , Esgotos , Fermentação , Anaerobiose , Esgotos/química , Ácidos Graxos Voláteis , Concentração de Íons de Hidrogênio
19.
Pest Manag Sci ; 80(6): 3047-3055, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38319125

RESUMO

BACKGROUND: An urgent need to find new methods for crop protection remains open due to the withdrawal from the market of the most toxic pesticides and increasing consumer awareness. One of the alternatives that can be used in modern agriculture is the use of bifunctional compounds whose actions towards plant protection are wider than those of conventional pesticides. RESULTS: In this study, we present the investigation of the biological efficacy of nine dual-functional salts containing a systemic acquired resistance (SAR)-inducing anion and the benzethonium cation. A significant result of the presented study is the discovery of the SAR induction activity of benzethonium chloride, which was previously reported only as an antimicrobial agent. Moreover, the concept of dual functionality was proven, as the application of presented compounds in a given concentrations resulted both in the control of human and plant bacteria species and induction of SAR. CONCLUSION: The strategy presented in this article shows the capabilities of derivatization of common biologically active compounds into their ionic derivatives to obtain bifunctional salts. This approach may be an example of the design of potential new compounds for modern agriculture. It provides plants with two complementary actions allowing to provide efficient protection to plants, if one mode of action is ineffective. © 2024 Society of Chemical Industry.


Assuntos
Benzetônio , Líquidos Iônicos , Líquidos Iônicos/química , Líquidos Iônicos/farmacologia , Benzetônio/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Cátions/farmacologia , Cátions/química , Proteção de Cultivos/métodos , Bactérias/efeitos dos fármacos
20.
Antimicrob Agents Chemother ; 57(8): 3681-7, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23689719

RESUMO

Candida albicans is the most common etiologic agent of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited and is particularly ineffective against C. albicans biofilms. To address the unmet need for novel antifungals, particularly those active against biofilms, we have screened a small molecule library consisting of 1,200 off-patent drugs already approved by the Food and Drug Administration (FDA), the Prestwick Chemical Library, to identify inhibitors of C. albicans biofilm formation. According to their pharmacological applications that are currently known, we classified these bioactive compounds as antifungal drugs, as antimicrobials/antiseptics, or as miscellaneous drugs, which we considered to be drugs with no previously characterized antifungal activity. Using a 96-well microtiter plate-based high-content screening assay, we identified 38 pharmacologically active agents that inhibit C. albicans biofilm formation. These drugs were subsequently tested for their potency and efficacy against preformed biofilms, and we identified three drugs with novel antifungal activity. Thus, repurposing FDA-approved drugs opens up a valuable new avenue for identification and potentially rapid development of antifungal agents, which are urgently needed.


Assuntos
Antifúngicos/isolamento & purificação , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Ensaios de Triagem em Larga Escala/métodos , Anfotericina B/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Benzetônio/análogos & derivados , Benzetônio/farmacologia , Candida albicans/fisiologia , Dimetil Sulfóxido/química , Desinfetantes/farmacologia , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
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