Benzalkonium Research Articles

<i>In vitro</i> study of the bactericidal activity for new derivatives of quaternary ammonium salts based on pyridoxine against gram-positive / gram-negative bacteria

BACKGROUND: Preventive care and successful treatment of infectious diseases (including hospital-acquired infections) are among the most important tasks of modern healthcare. Not many effective antiseptics and disinfectants available can solve this problem. Quaternary ammonium salts are currently one of the promising classes of disinfectants; however, their use is limited by the ability of microorganisms to develop resistance to the compounds. Modification of quaternary ammonium salts with substituents of various profiles is a possible way to solve this problem. AIM: To conduct a comparative analysis of the bactericidal activity of two original quaternary ammonium compounds based on pyridoxine in comparison with benzalkonium chloride. MATERIALS AND METHODS: The bactericidal profiles of 0.1 and 0.2% aqueous solutions of original quaternary ammonium salts based on pyridoxine were studied against two widespread pathogens: Staphylococcus aureus and Escherichia coli. Antibacterial activity data were obtained using a standard in vitro test (bactericidal activity test on a metal surface; exposure time of 1, 5, and 15 min). In addition to standard conditions, antibacterial efficacy was studied under protein loading conditions, in which BSA solution was added to the surface. RESULTS: For the studied compounds, the reduction factor (RF, reduction lgCFU of microorganisms) was on average ≥3. Protein loading led to a decrease in efficiency by 1–3 times. An interesting effect of exposure time-dependent specificity reversal to the S. aureus and E. coli was observed. CONCLUSIONS: The results showed the high activity of the studied compounds, which corresponds to the effectiveness criterion of RF ≥3 for commercial compounds used in this field.

Effect of terpene alcohol fragment and type of anion in the pyrrolidinium salts on the physicochemical properties and antibacterial activity

Pyrrolidinium salts containing in the cation chiral substituent derived from three terpene alcohols: (–)-menthol, (–)-borneol, and (+)-fenchol and consisting of six different anions: chloride [Cl]−, tetrafluoroborate [BF4]−, hexafluorophosphate [PF6]−, trifluoromethanesulfonate [OTf]−, bis(trifluoromethylsulfonyl)imide [NTf2]−, bis(pentafluoroethylsulfonyl)imide [NPf2]−, and perfluorobutanesulfonate [C4F9SO3]− were compared in terms of physicochemical properties and antimicrobial activity. The thermal properties including phase transition temperatures, thermal stability, specific rotation have been taken into consideration. Liquid pyrrolidinium salts with [NTf2]− and [NPf2]− anions, which can be classified as chiral ionic liquids, have also been compared in terms of density, dynamic viscosity, surface tension and contact angle on the surfaces of different polarity. The selected pyrrolidinium salts were evaluated for activity against nine bacterial strains using the agar well diffusion method. The zones of inhibition of bacterial growth were determined for pyrrolidinium salts used at different concentrations and depending on the structure of the cation and anion and compared with benzalkonium chloride as a positive control.

HPLC-DAD method for concurrent estimation of netarsudil, latanoprost and benzalkonium chloride: Stability indicating study, impurity separation, assay of ophthalmic preparations and greenness/whiteness valuation

A validated, stability indicating, multiuse and sustainable HPLC-DAD method was developed for simultaneous determination and separation of the ophthalmic ternary mixture of netarsudil (NTS), latanoprost (LTP) and benzalkonium chloride (BZC) in presence of four related compounds and suspected impurities. Effectual liquid chromatographic separation was accomplished by using a Zorbax-SB Phenyl column with gradient elution of a mobile phase consisting of buffer mixture solution of phosphate and sodium pentane sulfonate (pH 3.0) and acetonitrile at flow rate 1.5 mL/min. DAD was tuned at 254 nm for measuring peak area of NTS and 210 nm for LTP and BZC. The proposed procedure showed to be effective in the stability investigation of the cited drugs. The suggested HPLC procedure was validated based on the International Council for Harmonization (ICH) guiding principles. The three analytes were determined within linearity ranges of 1–100 µg/mL, 5–200 µg/mL and 10–200 µg/mL for NTS, LTP and BZC respectively with excellent analytical performance. Assay of several ophthalmic preparations was successfully carried out using the validated method, which was further appraised together with some relevant reported methods in regard to green and white analytical chemistry aspects using AGREE and RGB-12 tools. Very few published analytical records were found for NTS/LTP mixture. After surveying the scientific literature, no documentation was retrieved for a similar inclusive stability-indicating impurity-profiling separative method for the synchronized quantitation of NTS, LTP together with co-formulated preservative BZC.

A Standardized Extract of Green-Cotyledon Small Black Soybean (EYESOY®) Ameliorates Dry Eye Syndrome in an Animal Model

Purpose Dry eye syndrome is a common ocular disease that causes morbidity, high healthcare burden, and decreased quality of life. In this study, we evaluated the beneficial effects of a standardized extract of small black soybean (EYESOY®) in a benzalkonium chloride (BAC)-induced murine model of dry eye. Methods Experimental dry eye was induced by instillation of 0.02% BAC on the right eye of the Sprague-Dawley rats. Saline solution or EYESOY were administered orally every day for 8 weeks. Results EYESOY significantly improved tear volume in the cornea compared with that in the BAC group. Moreover, EYESOY inhibited damage to the corneal epithelial cells and lacrimal glands by suppressing the oxidative and inflammatory responses in a mouse dry eye model. It also increased the goblet cell density and mucin integrity in the conjunctiva. Conclusions Our results suggest that EYESOY has the potential to alleviate dry eye syndrome.

Optimalisation of in vitro sterilisation methods for North Sumatra local garlic (Allium Sativum L.)

Abstract The establishment stage is critical to the success of plant tissue culture. Each plant tissue has unique tissue surface characteristics that interact with various natural microbes. The goal of this study was to find a sterilisation method that is effective at removing contamination while not damaging or inhibiting explant regeneration. In this study, Completely Randomized Design (CRD) factorial with 2 factors was used. The first factor was the disinfectant, namely T1 (Benzalkonium chloride 0.5%), T2 (Nordox 6 g/L 0.6%), and T3 (Clorox 10%). The second factor is the type of media, consisting of M1 (BDS supplemented with 1.8 μM/L 2,4-D and 9.2 μM/L Kinetin), M2 (BDS supplemented with 9 μM/L 2,4-D and 9.2 μM/L Kinetin), M3 (MS supplemented with 9 μM/L 2,4-D and 4.6 μM/L Kinetin), and M4 (MS media supplemented with 1.3 μM/L 2,4-D and 9.2 μM/L Kinetin. The observed parameters were the percentage of contamination, the survival rate, the type of contamination, the percentage of callus growing, weight and diameter. The T2 treatment was the most effective in reducing contamination and had the highest survival rate. T3 treatment resulted in the highest callus regeneration percentage, callus weight, and callus diameter, but also the highest level of contamination.

Innovative multifunctional nanocapsules with antibacterial, perfume, and UV-initiated coating properties

Polymer nanocapsules containing fragrance were fabricated for antibacterial, pleasing scent and UV-coating applications. Poly (2-methacryloyloxy dodecyl dimethyl ammonium chloride-4-allyloxy-2-hydroxybenzophenone)-block-polymethyl methacrylate-iodide (P(QAC12-BP)-b-PMMA-I) was first synthesized by solution iodine transfer polymerization (solution ITP) for use as a polymerizable surfactant in miniemulsion polymerization where benzalkonium chloride (BKC) was used as a cosurfactant. The nanocapsules were prepared using poly(methyl methacrylate–divinylbenzene) (P(MMA–DVB)) as a shell, whereas mangosteen oil (MO) was used as a fragrance core model for aroma. High colloidal stability nanocapsules with a size of about 213 nm were obtained. The nanocapsule surface contained QAC12 segments of 15.10 µmol/g-capsule (UV measurement), giving the high positive charge (+70 mV). An essential oil encapsulated inside the nanocapsule had a high encapsulation efficiency (>90%). The nanocapsules effectively inhibited bacterial growth because of QAC12 and BKC on their surface. The nanocapsules are able to coat the substrate via UV-activated covalent bonds of the BP segment.

Comparative analysis of the effect of drugs lowering intraocular pressure on a primary culture of human corneal epithelium and A549 immortalized cell line

Background. Glaucoma as one of the most common eye diseases can be a comorbid condition of an epithelial corneal defect of various etiologies. Maintaining an optimal level of ophthalmotonus includes the prescription of antiglaucoma drugs, including benzalkonium chloride-preserved drugs.The aim of the study. To compare the effect of antiglaucoma drugs, as well as benzalkonium chloride (BC), on a primary culture of human corneal epithelium and A549 immortalized cell line.Methods. The effect of brimonidine, dorzolamide and timolol (1/100, 1/50, 1/20 and 1/10 dilutions; exposure 24 hours) on a monolayer of a human corneal epithelial primary culture and A549 immortalized cell line was assessed by structural changes in cells (phase-contrast microscopy) and MTT assay data. The cytotoxic effect of BC was studied in concentrations corresponding to its content in these dilutions of the antiglaucoma drug. Using a model of a linear defect in the monolayer of a corneal epithelial primary culture and A549 immortalized cell line, the effects of brimonidine, dorzolamide and timolol (1/100 and 1/20 dilutions; exposure 48 hours) were assessed by cell migration activity.Results. Among drugs (BC-free), dorzolamide (1/50, 1/20 and 1/10 dilutions) causes minor structural changes in human corneal epithelium and A549 immortalized cell line; timolol (1/100, 1/50, 1/20 and 1/10 dilutions) causes minor structural changes in A549 immortalized cell line. Structural changes in both types of cells, a decrease in their metabolic and migration activity occur under the influence of dorzolamide, brimonidine and timolol (BC-preserved) in 1/100, 1/50, 1/20 and 1/10 dilutions. BC at the studied concentrations exhibits a similar effect.Conclusion. The cytotoxic effect of antiglaucoma drugs is caused by the presence of BC in their composition. Despite similar morphofunctional changes in cells, A549 immortalized cell line is more resistant to the effects of drugs than the human corneal epithelial primary culture. When using it as a cellular model, it is advisable to change the experimental conditions (duration of exposure and concentration of the studied drug).

Synthesis, characterization and antimicrobial evaluation of quaternary ammonium compounds from natural oils

Quaternary ammonium salts refer to any class of salt derived from ammonium in which the nitrogen atom is attached to four organic groups covalently, as in benzalkonium chloride (R4N+). Quaternary ammonium compounds were synthesized from Canola oil (Brasssicanapus) and Coconut oil (Cocos nucifera) extracts by reacting the oils with N,N-diethylethylenediamine in the presence of potassium tertiary butoxide as catalyst. Fourier Transform Infrared (FTIR) Spectrometric analyses of the starting materials, the intermediates and the final products were conducted, the results showed a disappearance of the carbonyl (C=O) stretch of an ester (the oil) at 1744cm-1 and appearance of N-H band of an amide at 3433cm-1, which resulted from the quaternization of benzyl chloride with the intermediates for both oils. Other functional groups such as C=C and C-H stretch of aromatic compound, C=O stretch of an amide were also observed.Mass spectrometric analysis of the final products were conducted and results showed the Molecular Ion peak (M+) which is the molecular weights of the products. Vital fragments such as base peaks were observed for both quats, other fragmented radical cations were observed.Antimicrobial activity of the synthesized Quaternary ammonium compounds (QACs) exhibited excellent anti-bacterial activity covering a diameter of 22 mm and 28 mm of E. coli for QACs from Cocos nucifera and Brassic anapus oils respectively as compared to the standard antibiotic (Ampillicin).

Development of Predictive Modeling for Removal of Multispecies Biofilms of Salmonella Enteritidis, Escherichia coli, and Campylobacter jejuni from Poultry Slaughterhouse Surfaces.

Salmonella Enteritidis, Escherichia coli, and Campylobacter jejuni are among the most common foodborne pathogens worldwide, and poultry products are strongly associated with foodborne pathogen outbreaks. These pathogens are capable of producing biofilms on several surfaces used in the food processing industry, including polyethylene and stainless steel. However, studies on multi-species biofilms are rare. Therefore, this study aimed to develop predictive mathematical models to simulate the adhesion and removal of multispecies biofilms. All combinations of microorganisms resulted in biofilm formation with differences in bacterial counts. E. coli showed the greatest ability to adhere to both surfaces, followed by S. Enteritidis and C. jejuni. The incubation time and temperature did not influence adhesion. Biofilm removal was effective with citric acid and benzalkonium chloride but not with rhamnolipid. Among the generated models, 46 presented a significant coefficient of determination (R2), with the highest R2 being 0.88. These results provide support for the poultry industry in creating biofilm control and eradication programs to avoid the risk of contamination of poultry meat.

A Stable Fixed-Dose Combination of Benzalkonium chloride-free Latanoprost and Once-a-day Timolol

Abstract Objective This study outlines the development of a stable fixed dose combination solution formulation of Benzalkonium chloride (BKC)-free latanoprost with once-a-day timolol in a gel-free reservoir (GFR) vehicle. Methods A fixed-dose combination (FDC) formulation of latanoprost and timolol maleate was prepared by mixing polymers, buffers, and ionic preservatives followed by parylene coating of plastic bottles that were used for stability studies. Key findings The FDC formulation was a clear, colorless, slightly viscous solution. The adsorption of latanoprost on the parylene coated plastic bottle surface was reduced. Promoting stability for 36 months. The assay and impurities and other physicochemical quality attributes, such as color, clarity, osmolality, and pH met the required standards of both latanoprost and timolol. The sterility and antimicrobial effectiveness testing (AET) also complied with the United States Pharmacopeia (USP) requirements. Stability was proven for 30 days in simulated in-use conditions. It showed clinically relevant (>2 mm Hg) intraocular pressure (IOP) reduction in a normotensive dog model. It also showed an higher IOP reduction (efficacy) over individual or concomitantly administered drug components and numerically better IOP reduction than the marketed FDC formulation in a conventional vehicle. Faster action was seen within 2-h on first day and recovery took 5 days post treatment cessation. Conclusion A stable FDC formulation in parylene-coated plastic bottles was successfully developed meeting the clinically relevant IOP reduction criteria. Comparable efficacy insptto existing treatment, this FDC is preferable option for patients with conditions such as dry eye and ocular surface disease.

Effects of size on silver nanoparticle stability and inhibition of Vibro parahaemolyticus bacterial cell growth in high chloride media

The stability of silver nanoparticles at average sizes of 10 nm, 30 nm, and 50 nm with polyvinylpyrrolidone stabiliser was evaluated in a medium with high chloride ion concentration. The antibacterial activity of these silver nanoparticles against marine cholera Vibrio parahaemolyticus was studied and compared with ionic Ag+ and a bactericidal agent, Benzalkonium chloride. The results show that the smaller the silver nanoparticles, the higher the stability, and the higher the antibacterial ability, which is closer to the antibacterial ability of the ionic Ag+. These results show the outstanding bactericidal activity of small silver nanoparticles and the potential application of these tiny particles in inhibiting pathogenic bacteria in aquaculture.

Impact of a Novel Antiseptic Lavage Solution on Acute Periprosthetic Joint Infection in Hip and Knee Arthroplasty.

Background: Periprosthetic joint infection (PJI) represents a challenge following hip or knee arthroplasty, demanding immediate intervention to prevent implant failure and systemic issues. Bacterial biofilm development on orthopedic devices worsens PJI severity, resulting in recurrent hospitalizations and significant economic burdens. The objective of this retrospective cohort study is to evaluate the efficacy of this novel antiseptic solution, never previously evaluated in vivo, in managing early post-operative or acute hematogenous PJI following primary hip and knee joint replacements. Methods: The inclusion criteria consist of patients with total hip arthroplasty (THA) or knee arthroplasty diagnosed with acute PJI through preoperative and intraoperative investigations, in accordance with the MSIS ICM 2018 criteria. The minimum required follow-up was 12 months from the cessation of antibiotic therapy. This novel antiseptic lavage solution is composed of ethanol, acetic acid, sodium acetate, benzalkonium chloride and water. Data included demographic characteristics, diagnostic criteria, surgical techniques, post-operative treatment and follow-up outcomes. Results: A total of 39 patients treated with Debridement, Antibiotics Pearls and Retention of the Implant (DAPRI) procedures using this solution between May 2021 and April 2023 were analyzed. At a mean follow-up of 24.6 ± 6.4 months, infection recurrence-free survival rates were 87.2%, with no local allergic reactions or relevant systemic adverse effects detected. Persistent PJI necessitated two-stage revision surgery. Conclusions: This novel antiseptic lavage solution shows promise as an adjunctive tool in the treatment of PJI, demonstrating support in infection control while maintaining a favorable safety profile.

Algorithm for the development of a multicomponent pharmaceutical substance of plant origin with antimicrobial action: from science search to dosage form

Introduction. Despite the proven clinical efficacy of antifungal and anti-inflammatory drugs for the prevention and treatment of seborrheic dermatitis, the search for new targets and the development of new substances with a beneficial effect on the scalp microflora, with a low risk of antimicrobial resistance and adverse effects, are relevant.Aim. Development of the antimicrobial multicomponent pharmaceutical substance of plant origin in stages: from a literature search for promising substances, analysis of their composition by GC-MS, in silico evaluation of the affinity of individual components to pathogenetic targets, selection of the optimal composition of a multicomponent substance based on the results of in vitro research of antimicrobial action and the making of a medical dosage form based on it – a medicinal shampoo for the treatment of seborrheic dermatitis.Materials and methods. Objects of research: tea tree essential oil, 1,8-cineole, α-(-)-bisabolol and the multicomponent substance based on them. Methods: molecular docking (AutoDock version 4.2), prediction of pharmacological activity (Phyto4Health), TLC, GC-MS, study of antimicrobial activity in vitro.Results and discussion. Based on the results of a literature search, 3 promising substances were selected for the development of a multicomponent plant-based substance: tea tree essential oil, 1,8-cineole and α-(-)-bisabolol. Molecular docking predicted the targeted activity of the phytochemicals of tea tree essential oil, 1,8-cineole and α-(-)-bisabolol on the domains of ABC-transporters of microorganisms involved in the pathogenesis of seborrheic dermatitis and justified the possibility of use for therapy. The multicomponent substance has been developed based on tea tree essential oil, 1,8-cineole and α-(-)-bisabolol in a mass ratio of 1 : 1 : 1. The qualitative composition of the substance was assessed by TLC and GC-MS methods, and 15 terpenes were quantitatively identified in its composition with a predominance of terpinen-4-ol (16.98 %), 1,8-cineole (25.63 %) and α-(-)-bisabolol (27.67 %). The synergistic antimicrobial activity of the substance has been established against S. epidermidis, S. aureus, C. albicans and M. furfur in comparison with benzalkonium chloride, ketoconazole and climbazole. The composition of a new medical shampoo based on the investigated substance has been developed, which has a pronounced antifungal effect (more than 99.0 %) against M. furfur without visible suppression of normal microflora. For the novel substance of plant origin and medical shampoo, quality parameters were assessed in accordance with the Russian Pharmacopoeia of XIV edition.Conclusion. A substance of plant origin with synergistic and targeted antimicrobial activity has been developed. It has an interest for further study as a drug and API for new products for the treatment of seborrheic dermatitis.

Disrupted mitochondrial transcription factor A expression promotes mitochondrial dysfunction and enhances ocular surface inflammation by activating the absent in melanoma 2 inflammasome

PurposeSevere dry eye disease causes ocular surface damage, which is highly associated with mitochondrial dysfunction. Mitochondrial transcription factor A (TFAM) is essential for packaging mitochondrial DNA (mtDNA) and is crucial for maintaining mitochondrial function. Herein, we aimed to explore the effect of a decreased TFAM expression on ocular surface damage. MethodsFemale C57BL/6 mice were induced ocular surface injury by topical administrating benzalkonium chloride (BAC). Immortalized human corneal epithelial cells (HCECs) were stimulated by tert-butyl hydroperoxide (t-BHP) to create oxidative stress damage. HCECs with TFAM knockdown were established. RNA sequencing was employed to analyze the whole-genome expression. Mitochondrial changes were measured by transmission electron microscopy, Seahorse metabolic flux analysis, mitochondrial membrane potential, and mtDNA copy number. TFAM expression and inflammatory cytokines were determined using RT-qPCR, immunohistochemistry, immunofluorescence, and immunoblotting. ResultsIn both the corneas of BAC-treated mice and t-BHP-induced HCECs, we observed impaired TFAM expression, accompanied by mitochondrial structure and function defects. TFAM downregulation in HCECs suppressed mitochondrial respiratory capacity, reduced mtDNA content, induced mtDNA leakage into the cytoplasm, and led to inflammation. RNA sequencing revealed the absent in melanoma 2 (AIM2) inflammasome was activated in the corneas of BAC-treated mice. The AIM2 inflammasome activation was confirmed in TFAM knockdown HCECs. TFAM knockdown in t-BHP-stimulated HCECs aggravated mitochondrial dysfunction and the AIM2 inflammasome activation, thereby further triggering the secretion of inflammatory factors such as interleukin (IL) -1β and IL-18. ConclusionsTFAM reduction impaired mitochondrial function, activated AIM2 inflammasome and promoted ocular surface inflammation, revealing an underlying molecular mechanism for ocular surface disorders.

Comparison of aqueous and non-aqueous capillary electrophoresis for the determination of four benzalkonium chloride homologues in compound chemical disinfectants

A new method was established for the simultaneous analysis of four homologous benzalkonium chlorides (dodecyldimethylbenzyl ammonium chloride, tetradecyldimethylbenzyl ammonium chloride, hexadecyldimethylbenzyl ammonium chloride, and octadecyldimethylbenzyl ammonium chloride) in compound chemical disinfectants using non-aqueous capillary electrophoresis (CE) based on a micellar electrokinetic chromatography mode with direct ultraviolet detection. The separation was performed on an uncoated fused quartz capillary with a total length of 60.2 cm and a diameter of 25 μm. The separation buffer consisted of a mixture of methanol/acetonitrile (60:40, v/v) containing 70 mmol/L sodium acetate, 60 mmol/L trifluoroacetic acid and 20 mmol/L sodium dodecyl sulfate. The sample buffer was a methanol solution containing only 2 mmol/L trifluoroacetic acid. The separation voltage was set at 8 kV with a working current of approximately 2.3 μA. The detection wavelength was 214 nm. Under optimal conditions, the limit of detection and limit of quantification for these four benzalkonium chlorides (BACs) were 1.0 mg/L and 5.0 mg/L, respectively. Good linearities were observed in the concentration ranges from 5.0 to 100.0 mg/L, with correlation coefficients above 0.999 for all compounds. The recoveries of these four BACs ranged from 92.5 % to 109.1 % with relative standard deviations below 4.7 %. With the new method, all four BACs could be analyzed in a single injection. In contrast, the aqueous CE method in the National Standard GB/T 26369-2020 only allowed for the simultaneous analysis of the first three homologous. The new method demonstrated the improved peak shape compared to the aqueous CE method and then was successfully applied to the analysis of 19 commercially available samples, such as object table disinfectants, hand sanitizers, and disinfectant wipes, which claimed to contain quaternary ammonium compound. The results obtained using the new method were compared with those of the aqueous CE of the National Standard Method, and no statistically significant differences were observed. The new method is simple in pre-treatment and provides accurate results, making it highly suitable for routine analysis.

A water-soluble preparation for intravenous administration of isorhamnetin and its pharmacokinetics in rats

Flavonoids are considered as health-protecting food constituents. The testing of their biological effects is however hampered by their low oral absorption and complex metabolism. In order to investigate the direct effect(s) of unmetabolized flavonoid, a preparation in a biologically friendly solvent for intravenous administration is needed. Isorhamnetin, a natural flavonoid and a human metabolite of the most frequently tested flavonoid quercetin, has very low water solubility (<3.5 μg/mL). The aim of this study was to improve its solubility to enable intravenous administration and to test its pharmacokinetics in an animal model. By using polyvinylpyrrolidone (PVP10) and benzalkonium chloride, we were able to improve the solubility approximately 600 times to 2.1 mg/mL. This solution was then administered intravenously at a dose of 0.5 mg/kg of isorhamnetin to rats and its pharmacokinetics was analyzed. The pharmacokinetics of isorhamnetin corresponded to two compartmental model with a rapid initial distribution phase (t1/2α: 5.7 ± 4.3 min) and a slower elimination phase (t1/2β: 61 ± 47.5 min). Two sulfate metabolites were also identified. PVP10 and benzalkonium did not modify the properties of isorhamnetin (iron chelation and reduction, and cell penetration) substantially. In conclusion, the novel preparation reported in this study is suitable for future testing of isorhamnetin effects under in vivo conditions.

Comparing the tolerability of preservative-free tafluprost versus preserved latanoprost in the management of glaucoma and ocular hypertension - an observer blinded active-control trial.

Dry eye is a condition related to long-term topical eye therapy. We wish to evaluate the effectiveness and tolerability of preservative free prostaglandin drops versus benzalkonium chloride containing prostaglandin drops in the treatment of glaucoma. Patients undergoing prostaglandin monotherapy underwent a washout period of at least 1 month after which baseline measurements of dry eye severity were taken. Patients were randomised to receive either 0.0015% tafluprost drops or 0.005% latanoprost preserved with 0.02% benzalkonium chloride. Repeat measurements were taken after a 2-month interval. Thirty-five patients completed randomised treatment. No significant difference between groups was found in objective and subjective measurements of dry eye severity. No significant difference was found in measurement of treatment effectiveness. Preservative-free and benzalkonium chloride-containing drops were found to be equally effective in lowering IOP with no significant difference in either subjective or objective measurements of dry eye severity.

Characterization of antibiotic and disinfectant susceptibility in biofilm-forming Acinetobacter baumannii: A focus on environmental isolates.

The clinical role of Acinetobacter baumannii has been highlighted in numerous infectious syndromes with a high mortality rate, due to the high prevalence of multidrug-resistant (MDR) isolates. The treatment and eradication of this pathogen is hindered by biofilm-formation, providing protection from noxious environmental factors and antimicrobials. The aim of this study was to assess the antibiotic susceptibility, antiseptic susceptibility and biofilm-forming capacity using phenotypic methods in environmental A.baumannii isolates. One hundred and fourteen (n = 114) isolates were collected, originating from various environmental sources and geographical regions. Antimicrobial susceptibility testing was carried out using the disk diffusion method, while antiseptic susceptibility was performed using the agar dilution method. Determination of biofilm-forming capacity was carried out using a microtiter-plate based method. Resistance in environmental A. baumannii isolates were highest for ciprofloxacin (64.03%, n = 73), levofloxacin (62.18%, n = 71) and trimethoprim-sulfamethoxazole (61.40%, n = 70), while lowest for colistin (1.75%, n= 2). Efflux pump overexpression was seen in 48.25% of isolates (n = 55), 49.12% (n = 56) were classified as MDR. 6.14% (n = 7), 9.65% (n = 11), 24.65% (n = 28) and 59.65% (n = 68) of isolates were non-biofilm producers, weak, medium, and strong biofilm producers, respectively. No significant differences were observed between non-MDR vs. MDR isolates regarding their distribution of biofilm-producers (P = 0.655). The MIC ranges for the tested antiseptics were as follows: benzalkonium chloride 16-128 μg mL-1, chlorhexidine digluconate 4-128 μg mL-1, formaldehyde 64-256 μg mL-1 and triclosan 2-16 μg mL-1, respectively. The conscientious use of antiseptics, together with periodic surveillance, is essential to curb the spread of these bacteria, and to maintain current infection prevention capabilities.

Effect of Tight Junction-Modulating FCIGRL-Modified Peptides on the Intestinal Absorption of Doxorubicin in Rats.

Doxorubicin is a potent chemotherapy drug, but its oral bioavailability is limited due to its low membrane permeability. Thus, absorption enhancers such as zonula occludens toxin and its six-mer fragment, FCIGRL, have been studied to address this issue. This study aimed to evaluate the effectiveness of four peptides (Pep1, Pep2, Pep3, and Pep4) derived from FCIGRL and investigate the changes in the absorption of doxorubicin, to propose an absorption enhancer for doxorubicin. Pep1 is a modified version of FCIGRL in which the hydroxyl group at the C-terminus is replaced with an amino group. Pep2 is a modified Pep1 in which cysteine is replaced with N3-substituted dipropionic acid. Pep3 and Pep4 are Pep2-modified homodimers. Pharmacokinetic analysis was performed in rats after the intraduodenal administration of doxorubicin solutions containing each FCIGRL-modified peptide and the stabilizer levan or benzalkonium chloride (BC). The results showed that Pep3 and Pep4 administered with levan each significantly increased the intestinal absorption of doxorubicin, as did Pep2 administered with levan/BC. In particular, 10 mg·kg-1 of Pep4 with levan significantly increased the area under the curve (AUC)0-240min of doxorubicin by 2.38-fold (p < 0.01) and the peak concentration (Cmax) by 3.30-fold (p < 0.01) compared to the control solution. The study findings indicate that Pep2, Pep3, and primarily Pep4 are novel absorption enhancers that can open tight junctions for doxorubicin, and the effectiveness of the peptides was directly affected by the presence of levan or levan/BC.

A new G3BP1-GFP reporter system for assessing skin toxicity by real-time monitoring of stress granules in vitro

The skin, the organ with the largest surface area in the body, is the most susceptible to chemical exposure from the external environment. In this study, we aimed to establish an in vitro skin toxicity monitoring system that utilizes the mechanism of stress granule (SG) formation induced by various cellular stresses. In HaCaT cells, a keratinocyte cell line that comprises the human skin, a green fluorescent protein (GFP) was knocked in at the C-terminal genomic locus of Ras GTPase-activating protein-binding protein 1 (G3BP1), a representative component of SGs. The G3BP1-GFP knock-in HaCaT cells and wild-type (WT) HaCaT cells formed SGs containing G3BP1-GFP upon exposure to arsenite and household chemicals, such as bisphenol A (BPA) and benzalkonium chloride (BAC), in real-time. In addition, the exposure of G3BP1-GFP knock-in HaCaT cells to BPA and BAC promoted the phosphorylation of eukaryotic initiation factor 2 alpha and protein kinase R-like endoplasmic reticulum kinase, which are cell signaling factors involved in SG formation, similar to WT HaCaT cells. In conclusion, this novel G3BP1-GFP knock-in human skin cell system can monitor SG formation in real-time and be utilized to assess skin toxicity to various substances.