Benzethonium chloride affects short chain fatty acids produced from anaerobic fermentation of waste activated sludge: Performance, biodegradation and mechanisms.

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.

Critical care echocardiography: barriers, competencies and solutions. A survey of over 600 participants.

INTRODUCTION: Critical care echocardiography (CCE) is at the core of point-of-care ultrasound (POCUS), and although a list of the necessary competencies has been created, most European countries do not have established training programmes to allow intensivists to gain such competencies. To address barriers to the implementation of CCE, we conducted an online European survey, and analysed the current barriers to this with the aim of providing novel, modern solutions to them including environmental considerations. MATERIAL AND METHODS: A 23-item survey was distributed via email with support from the European Society of Intensive Care Medicine, national societies, and social media. Questions focused on bedside CCE prevalence, competencies, and barriers to its implementation. An additional questionnaire was sent to recognised experts in the field of CCE. RESULTS: A total of 644 responses were recorded. Most respondents were anaesthesia and intensive care physicians [79% ( n = 468)], and younger, with 56% in their first five years after specialization ( n = 358). Most respondents [92% ( n = 594)] had access to an ultrasound machine with a cardiac probe, and 97% ( n = 623) reported being able to acquire basic CCE windows. The most common barriers identified by respondents to the implementation of CCE in practice were a lack of sufficient experience/skill [64% ( n = 343)], absence of formal qualifications [46% ( n = 246)] and lack of a mentor [45% ( n = 243)]. Twenty-eight experts responded and identified a lack of allocated time for teaching as a main barrier [60% ( n = 17)]. CONCLUSIONS: We found that bedside CCE is perceived as a crucial skill for intensive care medicine, especially by younger physicians; however, there remain several obstacles to training and implementation. The most important impediments reported by respondents were inadequate training, absence of formal qualifications and difficulties in finding a suitable mentor.

Toxicity of benzethonium chloride and polyhexamethylene guanidine hydrochloride mixtures on Daphnia carinata: synergistic and antagonistic effects at specific ratios.

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.

Deciphering the interaction impacts between antiseptic benzethonium chloride and biofilm nitrification system: Performance, resistance mechanisms and biodegradation.

Benzethonium chloride (BEC) is one of emerging bacteriostatic agents. BEC-bearing wastewater generated during sanitary applications in food and medication is easily combined with other wastewater streams to flow into wastewater treatment plants. This study focused on the long-term (231 days) impacts of BEC on the sequencing moving bed biofilm nitrification system. Nitrification performance was tolerant to low concentration of BEC (≤ 0.2 mg/L), but the nitrite oxidation was severely inhibited when the concentration of BEC was 1.0-2.0 mg/L. Partial nitrification maintained about 140 days with nitrite accumulation ratio over 80%, mainly caused by the inhibition of Nitrospira, Nitrotoga and Comammox. Notably, BEC exposure in the system might cause the co-selection of antibiotic resistance genes (ARGs) and disinfectant resistance genes (DRGs), and the resistance of biofilm system to BEC was strengthened by efflux pumps mechanism (qacEdelta1 and qacH) and antibiotic deactivation mechanism (aadA, aac(6')-Ib and blaTEM). Extracellular polymeric substances secretion and BEC biodegradation were also contributed to the system microorganisms resisting BEC exposure. In addition, Klebsiella, Enterobacter, Citrobacter and Pseudomonas were isolated and identified as BEC degrading bacteria. The metabolites of N,N-dimethylbenzylamine, N-benzylmethylamine and benzoic acid were identified, and the biodegradation pathway of BEC was proposed. This study brought new knowledge about the fate of BEC in biological treatment units and laid a foundation for its elimination from wastewater.

Anti-biofilm effects and healing promotion by silver oxynitrate-based dressings.

Microbial growth within a wound often manifests as biofilms, which can prevent healing and is difficult to eradicate. Novel silver dressings claim to combat wound infection, but anti-biofilm efficacy and effects on healing independent of infection are often unclear. Using in vitro and in vivo S. aureus and P. aeruginosa biofilm models, we report the efficacy of a dressing which produces Ag1+ ions; an Ag1+ dressing containing ethylenediaminetetraacetic acid and benzethonium chloride (Ag1+/EDTA/BC), and a dressing containing silver oxynitrate (Ag Oxysalts) which produces Ag1+, Ag2+ and Ag3+ ions, against wound biofilms, and their effects on healing. Ag1+ dressings had minimal effect on in vitro and murine (C57BL/6j) wound biofilms. In contrast, Ag Oxysalts and Ag1+/EDTA/BC dressings significantly reduced viable bacteria within in vitro biofilms and demonstrated a visible reduction in bacteria and EPS components within murine wound biofilms. The dressings had different effects on the healing of biofilm-infected and uninfected wounds, with Ag Oxysalts dressings having a greater beneficial effect on re-epithelialisation, wound size and inflammation than the control treatment and the other silver dressings. The different physicochemical properties of the silver dressings result in varied effects on wound biofilms and healing which should be considered when selecting dressings to treat biofilm-infected wounds.

Ketamine preservative benzethonium chloride potentiates hippocampal synaptic transmission and binds neurotransmitter receptors and transporters.

Benzethonium chloride (BZT) is an excipient used in numerous products including (R,S)-ketamine (ketamine) drug formulations for human and veterinary use. Emerging evidence indicates BZT is pharmacologically active. BZT may therefore contribute to some of the clinical or preclinical effects observed with ketamine. In the present study, we evaluated: (i) the affinity of BZT for neurotransmitter receptors and transporters, (ii) the effects of BZT on hippocampal synaptic transmission in vitro, and (iii) plasma and brain concentrations of BZT following its intraperitoneal administration to male CD1 mice. Radioligand binding assays determined the affinity of BZT for neurotransmitter targets. Effects of BZT on field excitatory postsynaptic potentials (fEPSPs) were established via electrophysiological recordings from slices collected from male C57BL/6J mice. The binding assays revealed that BZT binds to numerous receptors (e.g., σ2 Ki = 7 nM) and transporters (e.g., dopamine transporter Ki = 545 nM). Bath application of BZT potentiated hippocampal fEPSPs in mouse hippocampal slices with an EC50 of 2.03 nM. Following intraperitoneal administration, BZT was detected in the plasma, but not in the brain of mice. These data highlight that studies measuring peripheral endpoints or directly exposing systems, in vitro, intracerebroventricularly, or intracortically, to BZT-containing formulations should account for the direct effects of BZT. Our findings also suggest that earlier data attributing pharmacological effects to ketamine may be confounded by BZT and that additional investigation into the functional impact of BZT is warranted. This article is part of the Special Issue on 'Ketamine and its Metabolites'.

Ecological Risk Analysis for Benzalkonium Chloride, Benzethonium Chloride, and Chloroxylenol in US Disinfecting and Sanitizing Products.

Use of three topical antiseptic compounds-benzalkonium chloride (BAC), benzethonium chloride (BZT), and chloroxylenol (PCMX)-has recently increased because of the phaseout of other antimicrobial ingredients (such as triclosan) in soaps and other disinfecting and sanitizing products. Further, use of sanitizing products in general increased during the coronavirus (COVID-19) pandemic. We assessed the environmental safety of BAC, BZT, and PCMX based on best available environmental fate and effects data from the scientific literature and privately held sources. The ecological exposure assessment focused on aquatic systems receiving effluent from wastewater-treatment plants (WWTPs) and terrestrial systems receiving land-applied WWTP biosolids. Recent exposure levels were characterized based on environmental monitoring data supplemented by modeling, while future exposures were modeled based on a hypothetical triclosan replacement scenario. Hazard profiles were developed based on acute and chronic studies examining toxicity to aquatic life (fish, invertebrates, algae, vascular plants) and terrestrial endpoints (plants, soil invertebrates, and microbial functions related to soil fertility). Risks to higher trophic levels were not assessed because these compounds are not appreciably bioaccumulative. The risk analysis indicated that neither BZT nor PCMX in any exposure media is likely to cause adverse ecological effects under the exposure scenarios assessed in the present study. Under these scenarios, total BAC exposures are at least three times less than estimated effect thresholds, while margins of safety for freely dissolved BAC are estimated to be greater than an order of magnitude. Because the modeling did not specifically account for COVID-19 pandemic-related usage, further environmental monitoring is anticipated to understand potential changes in environmental exposures as a result of increased antiseptic use. The analysis presented provides a framework to interpret future antiseptic monitoring results, including monitoring parameters and modeling approaches to address bioavailability of the chemicals of interest. Environ Toxicol Chem 2022;41:3095-3115. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Impact of benzalkonium chloride, benzethonium chloride and chloroxylenol on bacterial antimicrobial resistance.

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.

Feeding low-level benzethonium chloride can promote the start-up, fast recovery and long-term stable maintenance of partial nitrification for low-ammonium wastewater.

The establishment of stable partial nitrification (PN) is beneficial to promote the application of anaerobic ammonium oxidation, especially for low-ammonium wastewater. This study demonstrated an innovative approach for achieving PN through feeding low-level benzethonium chloride (BZC). PN was started and maintained for 125 days after the sequential feeding of 0.2 and 1 mg/L BZC for 50 days. The damaged PN recovered rapidly within eight days by feeding 2 mg/L BZC, and it thrived for more than 172 days, indicating that nitrite-oxidizing bacteria did not adapt to BZC. The removal of BZC changed from adsorption to degradation gradually. Increased extracellular polymeric substances secretion and altered protein secondary structures explained sludge granulation during BZC feeding, which may be closely related to long-term stable maintenance of PN. PICRUSt2 revealed the underlying microbial mechanisms in depth. Overall, this research proposed a novel scheme to achieve robust PN treating low-ammonium wastewater through feeding low-level BZC.

Quantification of the actual composition of polymeric nanocapsules: a quality control analysis.

Nanocapsules (NCs) are drug delivery nanosystems that contain an oily core, stabilized by a surfactant, and surrounded by a polymeric shell. The assembling of the components is based on physical and physicochemical forces, and, hence, usually, only a fraction of each component is finally part of the NCs' structure, while the remaining amount might be solubilized or forming micelles in the NCs' suspending medium. Usually, reports on the characterization of nanostructures simply indicate the association efficiency of the loaded drugs instead of their complete final composition. In this work, we have developed a liquid chromatography (LC) mass spectrometry (MS) methodology that allows the quantification of all the components of a series of NCs prepared by different techniques, namely DL-α-tocopherol; D-α-tocopherol polyethylene glycol 1000 succinate; benzethonium; lecithin; hexadecyltrimethylammonium; 1,2-dioleoyl-3-trimethylammoniumpropane; caprylic/capric triglycerides; macrogol 15-hydroxystearate; polysorbate 80; polysialic acid; hyaluronic acid; and polyethylene glycol polyglutamic acid. The LC-MS method was validated in terms of linearity (0.9383 < r2 < 0.9997), quantification limits, and recoveries of the isolated NCs' and waste fractions. The final composition of the isolated NCs was found to strongly depend on their composition and preparation technique. In our view, the rigorous quantification of the exact composition of nanosystems is essential for the progress of nanotechnology. This quantitative analysis will allow researchers to draw more accurate conclusions about the influence of the nanosystems' composition on their biological performance.

Care Perceptions in two ICU Nursing Care Delivery Models: A qualitative-comparative approach.

OBJECTIVES: Analyzed in compared perspective perceptions about nursing care, nurse-patient interaction, and nursing care outcomes in two ICU nursing staff in a high-complexity hospital institution, whose Nursing are Delivery Models (NCDM) are differentiated by the proportion of nurses and nurse assistants (NA) per team and by the assigned tasks and responsibilities. METHODS: Particularist ethnography with adaptation to virtual methodologies. It included the sociodemographic characteristics of 19 nurses and 23 NA, 14 semi-structured interviews, review of patients' clinical records, and a focus group. Coding, categorization, inductive analysis, validation of results with participants were conducted and thematic saturation was achieved. RESULTS: Four themes were identified: i) Professionalized care: a nursing of superior value; ii) senses and feelings of care; iii) nursing workload, generating factors and impacts; and iv) nursing missed care as concrete expression of the nursing workload. CONCLUSIONS: Compared nursing teams perceived nursing care in different ways, since it was experienced based on the assigned responsibilities and the possibilities of interaction with patients. Nursing care in the NCDM of the ICU with prevalence of direct bedside care by nurses with support from NA, it was perceived as holistic, comprehensive, and empathetic; whereas in the ICU with prevalence of delegated care to NA, it was related with administrative leadership and management of the ICU. Regarding the results, the NCDM of the ICU of direct bedside care by nurses showed better performance in patient safety and was closer to the skill level and legal responsibility of the nursing staff.

A Novel Biomarker of Neuronal Glutamate Metabolism in Nonhuman Primates Using Localized 1H-Magnetic Resonance Spectroscopy: Development and Effects of BNC375, an α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator.

BACKGROUND: The development of treatments for cognitive deficits associated with central nervous system disorders is currently a significant medical need. Despite the great need for such therapeutics, a significant challenge in the drug development process is the paucity of robust biomarkers to assess target modulation and guide clinical decisions. We developed a novel, translatable biomarker of neuronal glutamate metabolism, the 13C-glutamate+glutamine (Glx) H3:H4 labeling ratio, in nonhuman primates using localized 1H-magnetic resonance spectroscopy combined with 13C-glucose infusions. METHODS: We began with numerical simulations in an established model of brain glutamate metabolism, showing that the 13C-Glx H3:H4 ratio should be a sensitive biomarker of neuronal tricarboxylic acid cycle activity, a key measure of overall neuronal metabolism. We showed that this biomarker can be measured reliably using a standard 1H-magnetic resonance spectroscopy method (point-resolved spectroscopy sequence/echo time = 20 ms), obviating the need for specialized hardware and pulse sequences typically used with 13C-magnetic resonance spectroscopy, thus improving overall clinical translatability. Finally, we used this biomarker in 8 male rhesus macaques before and after administration of the compound BNC375, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor that enhances glutamate signaling ex vivo and elicits procognitive effects in preclinical species. RESULTS: The 13C-Glx H3:H4 ratios in the monkeys showed that BNC375 increases neuronal metabolism in nonhuman primates in vivo, detectable on an individual basis. CONCLUSIONS: This study demonstrates that the ratio of 13C-Glx H3:H4 labeling is a biomarker that may provide an objective readout of compounds affecting glutamatergic neurotransmission and could improve decision making for the development of therapeutic agents.

Proarrhythmic effects induced by benzethonium chloride and domiphen bromide in vitro and in vivo.

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.

Solvent-free production of thermoplastic lignocellulose from wood pulp by reactive extrusion.

A novel acylation approach suited to rapid bulk thermoplasticization of lignocellulose without solvents was previously demonstrated by the authors in benchtop batch studies. The method relies upon a benzethonium chloride/sulfuric acid functionalizing agent at low concentrations to act as a wetting agent for the wood pulp, similar to an ionic liquid, yet binds to the lignocellulose ester as a flow aid in the final thermoplastic. The present investigation evaluates the approach in a residence time-limited (45-90 s) continuous twin-screw reactor, where intensive mixing and heat were found to yield high acylation. The modified lignocellulose exhibited desired thermoplasticity by being melt moldable without the need for plasticizers and maintained much of the excellent stiffness of cellulose, demonstrating a maximum flexural modulus of 5.4 GPa and tensile modulus of 1.8 GPa. The influence of extrusion conditions on thermoplasticity was examined by a Design of Experiments (DOE) analysis.

Identification and functional validation of FDA-approved positive and negative modulators of the mitochondrial calcium uniporter.

The mitochondrial calcium uniporter (MCU), the highly selective channel responsible for mitochondrial Ca2+ entry, plays important roles in physiology and pathology. However, only few pharmacological compounds directly and selectively modulate its activity. Here, we perform high-throughput screening on a US Food and Drug Administration (FDA)-approved drug library comprising 1,600 compounds to identify molecules modulating mitochondrial Ca2+ uptake. We find amorolfine and benzethonium to be positive and negative MCU modulators, respectively. In agreement with the positive effect of MCU in muscle trophism, amorolfine increases muscle size, and MCU silencing is sufficient to blunt amorolfine-induced hypertrophy. Conversely, in the triple-negative breast cancer cell line MDA-MB-231, benzethonium delays cell growth and migration in an MCU-dependent manner and protects from ceramide-induced apoptosis, in line with the role of mitochondrial Ca2+ uptake in cancer progression. Overall, we identify amorolfine and benzethonium as effective MCU-targeting drugs applicable to a wide array of experimental and disease conditions.

Protocolo de tratamiento de heridas con apósito de hidrofibra reforzada, con plata iónica al 1,2%, potenciado con EDTA y cloruro de bencetonio para evitar la recurrencia de biopelícula.

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.

Protocolo de tratamiento de heridas con apósito de hidrofibra reforzada, con plata iónica al 1,2%, potenciado con EDTA y cloruro de bencetonio para evitar la recurrencia de biopelícula.

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.

Rapid start-up of partial nitrification process using benzethonium chloride-a novel nitrite oxidation inhibitor.

Benzethonium chloride (BZC) is an antibacterial compound with extensive applications in various anti-infective products. However, the feasibility of attaining partial nitrification of municipal wastewater using BZC has not been reported. In this work, BZC was used for the first time to attain partial nitrification. Batch experiments indicated nitrite oxidizing bacteria (NOB) was more vulnerable to BZC than ammonia oxidizing bacteria (AOB). When activated sludge was treated only once with 0.023 g BZC·(g MLSS)-1 for 18 h, partial nitrification was attained at the 29th cycle with NAR of 97.46% and sustained 91 cycles in stability tests. Complimentary DNA sequencing analysis revealed the suppression of Nitrospira was the reason for partial nitrification. Oligotyping analysis indicated AOB could likely resist to BZC by both the species shifts and development of tolerance, while most NOB species could not adapt to BZC. This study revealed the feasibility of BZC as a novel NOB inhibitor.

Syntheses of C2'-Fluorinated Analogs of Solamin.

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.

Synergistic Effect of Benzethonium Chloride Combined with Endoxan against Hepatocellular Carcinoma in Rats through Targeting Apoptosis Signaling Pathway.

Combination therapy has been the trendy of care, particularly in cancer remedy, since it is a rational approach to increase response and tolerability and to diminish resistance. Hence, there is a growing interest in combining anticancer drugs to maximizing efficacy with minimum systemic toxicity through the delivery of lower drug doses. Therefore, in the present study, the value of combination between benzethonium chloride (benzo) and endoxan (endo) as anti-tumor drug sensitization of hepatocellular carcinoma HCC treatment were detected both in vitro and in vivo. Crystal violet test was performed to detect the proliferation of HepG2 cells treated with benzo or/and endo. In addition, the HCC rat model was established by diethylnitrosamine (DEN) administration. The antitumor effect was enhanced with the combined treatment of the two drugs, particularly in the group with benzo and endo. The results confirmed that the HCC condition was developed in response to lower expressions of caspase 3 and P53 which, in turn, was due to the overexpression of Bcl-2, and downregulation of cytochrome C. The treatment with benzo combined with endo caused significant activation of caspase-3 mediated apoptotic signals that could be responsible for its anti-HCC potential. Meantime, benzo combined with endo treatments could reduce the hepatocellular carcinogenesis by reducing the expression of MMP-9. Therefore, benzo and endo treatments may be a hopeful therapeutic drug for HCC. Also, more studies are recommended to feat the idea of this research for medical use.
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