Adsorption of an antiseptic in a functionalized fixed-bed: Analysis of breakthrough scenarios and validation of simplistic models defending a novel proposition.

BACKGROUND: Chlorhexidine gluconate (CHG) and cetrimide, which are widely used in various pharmaceutical compositions, are considered potentially hazardous compounds. This combination was largely used during and after Covid 19 pandemic for sanitization. Removal of these two compounds from pharmaceutical waste-water with commercial and functionalized activated carbon in a packed bed column is reported. METHODS: Effects of changes in bed height, flow rate, and initial concentration on the performance of the packed bed are analyzed using Yoon-Nelson, BDST and Thomas models for commercial scale-up operation. The effects of primary design parameters like bed depth and operating parameters like inflow rate and inlet concentration of influent wastewater are studied on the extent of removal of cetrimide and chlorhexidine gluconate. Granular activated carbon (GAC) is functionalized using HF and NH4OH. The extent of enhanced adsorption using the functionalized GAC is demonstrated using breakthrough curves. SIGNIFICANT FINDINGS: K. H. Chu's iconic proposition is validated. Breakthrough time (BT) increases with bed heights and it is less in the case of cetrimide as compared to chlorhexidine gluconate. This shows that cetrimide wins in the competition and occupies the pores much faster than CHG. Mostly, BT-CHG (GAC) < BT-CHG (FAC-HF) < BT-CHG (FAC-NH3) and BT-cetrimide (GAC) < BT-cetrimide (FAC-NH3) < BT-cetrimide (FAC-HF) for a particular bed height. BT-CHG(FAC-HF)BT-cetrimide(FAC-HF)

A Randomized Controlled Trial of Povidone-Iodine Versus Chlorhexidine Gluconate With Isopropyl Alcohol for Preoperative Vaginal Antisepsis.

Many surgeons request use of 10% povidone-iodine (PI) for vaginal antisepsis; however, when PI is contraindicated, some surgeons request use of chlorhexidine gluconate (CHG) instead. The purpose of this randomized controlled trial was to determine any significant differences in self-reported symptoms associated with vaginal antisepsis with either 10% PI scrub or 4% CHG with 4% isopropyl alcohol. The control group comprised 62 participants who underwent vaginal antisepsis with the PI product, and the intervention group comprised 58 participants who underwent vaginal antisepsis with the CHG product. Participants completed surveys immediately before surgery, immediately after surgery, and 48 to 72 hours after surgery. No significant differences were found in the reported vaginal symptoms between the two groups for any survey. One participant in the intervention group reported symptoms consistent with an allergic reaction. Additional studies are needed on the use of CHG for vaginal antisepsis.

Combinatorial effects between aromatic plant compounds and chlorhexidine digluconate against canine otitis-related Staphylococcus spp.

The increasing prevalence of antimicrobial resistance among bacterial pathogens necessitates novel treatment strategies, particularly in veterinary medicine where otitis in dogs is very common in small animals' clinical routines. Considering this challenge, this study explores the efficacy of aromatic plant compounds (APC), including eugenol (EUG), trans-cinnamaldehyde (TC), and geraniol (GER), and their synergistic potential when combined with the antiseptic agent chlorhexidine (CLX), offering insight into alternative therapeutic approaches. The disk diffusion assay revealed differential sensitivity of Staphylococcus spp. strains to the tested compounds, with EUG and GER showing moderate inhibition zones and TC displaying considerably larger inhibition zones. Further analysis through MIC and MBC determinations suggested that EUG required the highest concentrations to inhibit and kill the bacteria, whereas TC and GER were effective at lower concentrations. Combined with CLX, all three plant-derived compounds demonstrated a significant enhancement of antibacterial activity, indicated by reduced MIC values and a predominantly synergistic interaction across the strains tested. GER was the most potent in combination with CLX, presenting the lowest mean FICi values and the highest fold reductions in MIC. This study emphasizes the APC's potential as an adjunct to conventional antimicrobial agents like CLX. The marked synergy observed, especially with GER, suggests that such combinations could be promising alternatives in managing bacterial otitis in dogs, potentially mitigating the impact of antibiotic resistance.

Efficacy of an experimental gaseous ozone-based sterilization method for clear aligners.

OBJECTIVES: To assess effectiveness of an experimental sterilization method based on the exposure of an O3/O2 gas mixture directly inside the packaging for clear aligners. MATERIALS AND METHODS: Fifty samples consisting of pieces of polyethylene terephthalate glycol (PET-G) aligners were contaminated by manual handling and subsequently divided into different groups (n = 30 for exposure to O3/O2 gas at different times, n = 10 for positive control with 2% chlorhexidine digluconate, n = 10 for negative control). The measurement of optical densities (OD) of the initial and final microbial cultures was recorded for all groups. Kruskal-Wallis test was used for differences between groups while Wilcoxon test was used to compare initial and final OD values within groups. Statistical significance was set at P < .05. RESULTS: Comparison within the groups showed statistically significant differences for exposure to the gaseous mixture (72 hours), for positive and negative controls. Other significant differences were found in the multiple comparisons between the application of gaseous ozone (48 hours and 72 hours) and the negative control. CONCLUSIONS: The direct exposure of gaseous ozone on the aligners inside their packaging showed microbicidal capacity at 72 hours, which was equivalent to the positive control with immersion in chlorhexidine digluconate. This innovative sterilization procedure could be considered in the final manufacturing processes of clear aligners to eliminate the potentially pathogenic microorganisms that are deposited on surfaces of these orthodontic devices.

2% chlorhexidine gluconate aqueous versus 2% chlorhexidine gluconate in 70% isopropyl alcohol for skin disinfection prior to percutaneous central venous catheterisation: the ARCTIC randomised controlled feasibility trial.

OBJECTIVE: Catheter-related sepsis (CRS) is a major complication with significant morbidity and mortality. Evidence is lacking regarding the most appropriate antiseptic for skin disinfection before percutaneous central venous catheter (PCVC) insertion in preterm neonates. To inform the feasibility and design of a definitive randomised controlled trial (RCT) of two antiseptic formulations, we conducted the Antiseptic Randomised Controlled Trial for Insertion of Catheters (ARCTIC) feasibility study to assess catheter colonisation, sepsis, and skin morbidity. DESIGN: Feasibility RCT. SETTING: Two UK tertiary-level neonatal intensive care units. PATIENTS: Preterm infants born <34 weeks' gestation scheduled to undergo PCVC insertion. INTERVENTIONS: Skin disinfection with either 2% chlorhexidine gluconate (CHG)-aqueous or 2% CHG-70% isopropyl alcohol (IPA) before PCVC insertion and at removal. PRIMARY OUTCOME: Proportion in the 2% CHG-70% IPA arm with a colonised catheter at removal. MAIN FEASIBILITY OUTCOMES: Rates of: (1) CRS, catheter-associated sepsis (CAS), and CRS/CAS per 1,000 PCVC days; (2) recruitment and retention; (3) data completeness. SAFETY OUTCOMES: Daily skin morbidity scores recorded from catheter insertion until 48 hours post-removal. RESULTS: 116 babies were randomised. Primary outcome incidence was 4.1% (95% confidence interval: 0.9% to 11.5%). Overall catheter colonisation rate was 5.2% (5/97); CRS 2.3/1000 catheter days; CAS 14.8/1000 catheter days. Recruitment, retention and data completeness were good. No major antiseptic-related skin injury was reported. CONCLUSIONS: A definitive comparative efficacy trial is feasible, but the very low catheter colonisation rate would make a large-scale RCT challenging due to the very large sample size required. ARCTIC provides preliminary reassurance supporting potential safe use of 2% CHG-70% IPA and 2% CHG-aqueous in preterm neonates. TRIAL REGISTRATION NUMBER: ISRCTN82571474.

Effect of immersion in disinfectants on the color stability of denture base resins and artificial teeth obtained by 3D printing.

PURPOSE: To evaluate the effect of immersion in disinfecting solutions on the color stability of denture base resins and artificial teeth obtained by 3D printing. MATERIALS AND METHODS: Forty discs (15 × 3 mm) were obtained for each group: Lucitone 550 and Cosmos Denture 3D (denture base resins), Duralay and Cosmos TEMP 3D (artificial teeth resins). The discs were immersed in disinfectant solutions: Corega Tabs, 2% chlorhexidine digluconate, 0.25% sodium hypochlorite, and distilled water. Color measurements were obtained with a spectrophotometer before immersion in disinfectants and after the simulated periods of 6 and 12 months. Data (ΔE00 ) were submitted to mixed three-way ANOVA and Bonferroni post-test. RESULTS: For denture base resins, Cosmos Denture 3D showed greater color change regardless of the solution and immersion time. The immersion time of 6 months influenced the color change of the denture base resins regardless of the disinfectant solution. For the artificial teeth resins, the immersion time of 12 months showed a significant color change when compared to 6 months. Cosmos TEMP 3D showed greater color change for all solutions, except for 0.25% sodium hypochlorite. Duralay resin showed greater color change in 2% chlorhexidine, regardless of immersion time. CONCLUSIONS: For denture base resins, the immersion time significantly changed the color regardless of the solution. For artificial teeth resins, Cosmos TEMP 3D showed greater color changes in all solutions when compared to Duralay, except for 0.25% sodium hypochlorite. Chlorhexidine digluconate significantly changed the color of Duralay.

Endodontic sealers after exposure to chlorhexidine digluconate: An assessment of physicochemical properties.

OBJECTIVES: Final root canal irrigation should ideally maintain the physicochemical stability of root canal sealers. We seek to assess the effect of contact with 2% chlorhexidine digluconate (CHX) on the physicochemical properties of AH Plus, BioRoot™ RCS, and Pulp Canal Sealer (PCS). METHODS: Mixed sealers were placed in cylindrical teflon molds and allowed to set for 1.5x the manufacturers' setting time. Half of the specimens had their free surface in contact with CHX for the first minute of their setting period. Solubility, radiopacity, surface roughness, microhardness and wettability of the sealers were assessed up to 28 days after setting. Elemental analysis of sealer surfaces and their leachates together with pH measurements were also performed. Appropriate parametric and non-parametric analysis with post hoc tests were performed (p < 0.05). RESULTS: Exposure to CHX had no effect on solubility and radiopacity of all sealers. CHX altered the surface roughness of PCS and BioRoot RCS (p < 0.05). Contact with CHX reduced the microhardness of AH Plus and PCS (p < 0.05). AH Plus was more hydrophilic after CHX contact, whereas PCS became more hydrophobic (p < 0.05). AH Plus and PCS surfaces appeared to adsorb CHX as exhibited by chlorine peaks after contact with CHX. Sealer leachates' alkalinity was not affected. CHX increased elution of silicon and zirconium for BioRoot and zinc for PCS leachates. SIGNIFICANCE: In our study, CHX affected sealers' physicochemical properties to various extents. Further studies are needed to confirm the obtained results by investigating various final irrigation strategies and correlating to biological properties.

Effect of Different Disinfecting Agents on Surface Roughness and Color Stability of Heat-cure Acrylic Denture Material: An In Vitro Study.

AIM: The current study aimed to determine the impact of three different disinfectants on the surface roughness and color stability of heat-cure acrylic denture material. MATERIALS AND METHODS: Using a stainless-steel mold, disc-shaped wax patterns with dimensions of 10 mm in diameter and 2 mm thick (in accordance with ADA Specification No. 12) were created and prepared for a total of 75 acrylic samples. Dimensions of all 75 acrylic samples were checked with a digital Vernier caliper. About 25 samples of denture base material were immersed in three different chemical disinfectants: Group I: immersed in chlorhexidine gluconate solution, group II: immersed in sodium hypochlorite solution, and group III: immersed in glutaraldehyde solution. All samples were scrubbed daily for 1 minute with the appropriate disinfectant and submerged for 10 minutes in the same disinfectant. Between disinfection cycles, samples were kept in distilled water at 37°C. Color stability was measured using a reflection spectrophotometer. Surface roughness values were measured by a profilometer at baseline following 15 days and 30 days. RESULTS: After 15 days, the color stability was better in chlorhexidine gluconate solution group (4.88 ± 0.24) than sodium hypochlorite solution (4.74 ± 0.18) and glutaraldehyde solution group (4.46 ± 0.16). The mean surface roughness was less in glutaraldehyde solution group (2.10 ± 0.19), followed by chlorhexidine gluconate solution group (2.48 ± 0.09) and sodium hypochlorite solution group (2.64 ± 0.03). After 30 days, the color stability was significantly better in chlorhexidine gluconate solution group (4.40 ± 0.02), followed by sodium hypochlorite solution (4.06 ± 0.16) and glutaraldehyde solution group (3.87 ± 0.17). The mean surface roughness was significantly lesser in glutaraldehyde solution group (2.41 ± 0.14), followed by chlorhexidine gluconate solution group (2.94 ± 0.08) and sodium hypochlorite solution group (3.02 ± 0.13). CONCLUSION: In conclusion, the color stability was significantly better in chlorhexidine gluconate solution group than sodium hypochlorite solution and glutaraldehyde solution group. But the surface roughness was significantly lesser in the glutaraldehyde solution group, followed by the chlorhexidine gluconate and sodium hypochlorite solution group. CLINICAL SIGNIFICANCE: The maintenance of the prosthesis requires the use of a denture disinfectant; therefore, it is crucial to select one that is effective but would not have a negative impact on the denture base resin's inherent characteristics over time. How to cite this article: Kannaiyan K, Rakshit P, Bhat MPS, et al. Effect of Different Disinfecting Agents on Surface Roughness and Color Stability of Heat-cure Acrylic Denture Material: An In Vitro Study. J Contemp Dent Pract 2023;24(11):891-894.

Aqueous skin antisepsis before surgical fixation of open fractures (Aqueous-PREP): a multiple-period, cluster-randomised, crossover trial.

BACKGROUND: Chlorhexidine skin antisepsis is frequently recommended for most surgical procedures; however, it is unclear if these recommendations should apply to surgery involving traumatic contaminated wounds where povidone-iodine has previously been preferred. We aimed to compare the effect of aqueous 10% povidone-iodine versus aqueous 4% chlorhexidine gluconate on the risk of surgical site infection in patients who required surgery for an open fracture. METHODS: We conducted a multiple-period, cluster-randomised, crossover trial (Aqueous-PREP) at 14 hospitals in Canada, Spain, and the USA. Eligible patients were adults aged 18 years or older with an open extremity fracture treated with a surgical fixation implant. For inclusion, the open fracture required formal surgical debridement within 72 h of the injury. Participating sites were randomly assigned (1:1) to use either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate immediately before surgical incision; sites then alternated between the study interventions every 2 months. Participants, health-care providers, and study personnel were aware of the treatment assignment due to the colour of the solutions. The outcome adjudicators and data analysts were masked to treatment allocation. The primary outcome was surgical site infection, guided by the 2017 US Centers for Disease Control and Prevention National Healthcare Safety Network reporting criteria, which included superficial incisional infection within 30 days or deep incisional or organ space infection within 90 days of surgery. The primary analyses followed the intention-to-treat principle and included all participants in the groups to which they were randomly assigned. This study is registered with ClinicalTrials.gov, NCT03385304. FINDINGS: Between April 8, 2018, and June 8, 2021, 3619 patients were assessed for eligibility and 1683 were enrolled and randomly assigned to povidone-iodine (n=847) or chlorhexidine gluconate (n=836). The trial's adjudication committee determined that 45 participants were ineligible, leaving 1638 participants in the primary analysis, with 828 in the povidone-iodine group and 810 in the chlorhexidine gluconate group (mean age 44·9 years [SD 18·0]; 629 [38%] were female and 1009 [62%] were male). Among 1571 participants in whom the primary outcome was known, a surgical site infection occurred in 59 (7%) of 787 participants in the povidone-iodine group and 58 (7%) of 784 in the chlorhexidine gluconate group (odds ratio 1·11, 95% CI 0·74 to 1·65; p=0·61; risk difference 0·6%, 95% CI -1·4 to 3·4). INTERPRETATION: For patients who require surgical fixation of an open fracture, either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate can be selected for skin antisepsis on the basis of solution availability, patient contraindications, or product cost. These findings might also have implications for antisepsis of other traumatic wounds. FUNDING: US Department of Defense, Canadian Institutes of Health Research, McMaster University Surgical Associates, PSI Foundation.

Pharmaceutical Incompatibility of Lubricating Gel Formulation Reduces Antibacterial Activity of Chlorhexidine Gluconate: In Vitro Study in Northern Thailand.

Chlorhexidine gluconate (CHG) is a cationic disinfectant. The positive charge of CHG molecules binds to phospholipid's negative charge in bacterial cell walls, causing membrane disruption. The in vitro kinetic physical, chemical and biological incompatibilities of nine lubricating gels with 1% w/v CHG were investigated. Five containing anionic thickener, two containing nonionic thickener, and two containing cationic thickener were collected from hospitals in northern Thailand. All the anionic and nonionic lubricating gels significantly reduced (p < 0.05) the CHG amount after 5 min of exposure time from 12.54% to 54.99%, respectively. In contrast, the amount of CHG exposed with cationic lubricating gels was maintained. Antibacterial activity was significantly reduced to a 1.17-4.33 log10 reduction for Staphylococcus aureus ATCC25923 and a 1.07-3.52 log10 reduction for Escherichia coli ATCC25922 after 5 min exposure to all anionic and nonionic lubricating gels. In contrast, the two cationic lubricating gels maintained the antibacterial activity of the CHG solution (5.69 ± 0.14 and 5.45 ± 0.17 log10 reduction). The results suggest that anionic and nonionic thickeners in lubricating gel formulations may neutralize the positive charge and reduce the antibacterial activity of CHG, reducing its effectiveness as a disinfectant.

Evaluation of efficacy of subgingival administration of 1% chlorhexidine gel as an adjunct to scaling and root planing in the treatment of chronic periodontitis - A clinical and microbiological study.

Aim: The aim of the present study was to evaluate the clinical and microbiological effects of subgingival administration of 1% chlorhexidine gel (Chlorhexamed® 1% gel) in patients with chronic periodontitis. Settings and Design: The study was done in a parallel-arm design with a total of 30 patients with 60 sites suffering from chronic periodontitis. The patients were divided into control and experimental groups. Materials and Methods: The clinical parameters recorded were plaque index, gingival index, modified sulcular bleeding index, probing pocket depth and relative attachment level at baseline, 1 month and 3 month. Microbiological colony-forming units were assessed for Porphyromonas gingivalis, Fusobacterium nucleatum and Tannerella forsythia at baseline, 1 week, 1 month and 3 months. The control group received scaling and root planing (SRP) after baseline evaluation; however, the experimental group received the application of Chlorhexamed® gel within 48 hours after SRP. Then, the values obtained were subjected to statistical analysis. Results: Both groups showed significant improvement from the baseline to 3 months in all clinical and microbiological parameters. The experimental group showed better improvement in all parameters. Conclusion: The use of Chlorhexamed® gel has proven to be an efficacious adjunct with SRP in the treatment of chronic periodontitis.

Efficacy of surgical skin preparation with chlorhexidine in alcohol according to the concentration required to prevent surgical site infection: meta-analysis.

BACKGROUND: A combination of chlorhexidine gluconate and alcohol (CHG-alcohol) is recommended for surgical skin preparation to prevent surgical site infection (SSI). Although more than 1 per cent CHG-alcohol is recommended to prevent catheter-related bloodstream infections, there is no consensus regarding the concentration of the CHG compound for the prevention of SSI. METHODS: A systematic review and meta-analysis was performed. Four electronic databases were searched on 5 November 2020. SSI rates were compared between CHG-alcohol and povidone-iodine (PVP-I) according to the concentration of CHG (0.5 per cent, 2.0 per cent, 2.5 per cent, and 4.0 per cent). RESULTS: In total, 106 of 2716 screened articles were retrieved for full-text review. The risk ratios (RRs) of SSI for 0.5 per cent (6 studies) and 2.0 per cent (4 studies) CHG-alcohol were significantly lower than those for PVP-I (RR = 0.71, 95 per cent confidence interval (c.i.) 0.52 to 0.97; RR = 0.52, 95 per cent c.i 0.31 to 0.86 respectively); however, no significant difference was observed in the compounds with a CHG concentration of more than 2.0 per cent. CONCLUSIONS: This meta-analysis is the first study that clarifies the usefulness of an alcohol-based CHG solution with a 0.5 per cent or higher CHG concentration for surgical skin preparation to prevent SSI.

Clinical and Radiographic Success of 2% Chlorhexidine Gluconate with Mineral Trioxide Aggregate in Indirect Pulp Treatment of Primary Molars.

Purpose: To compare the clinical and radiographic success rates of indirect pulp treatment (IPT) in primary molars using mineral trioxide aggregate (MTA) with and without two percent chlorhexidine gluconate (CHX).
Methods: A blinded, randomized, controlled clinical trial was performed in a split-mouth desi gn. Eighty primary molars in 40 subjects from four to eight years of age were randomly allocated so that each subject had one tooth treated with MTA and CHX and the other tooth treated with MTA alone. Study teeth had deep caries without signs and symptoms of pulpal inflammation or necrosis. All teeth were restored with stainless steel crowns. Follow-up was done at 12 months to evaluate the teeth clinically and radiographically.
Results: At the follow-up, one tooth from each group had failed. Upon the clinical and radiographic evaluations, the overall success rate for both groups was 97 percent. No statistically significant difference was found in the success rate between the two groups.
Conclusions: IPT in primary molars using MTA with or without CHX demonstrated satisfactory clinical and radiographic outcomes in a period of 12 months.

Study of post-opening stability of active ingredients in hand sanitizers.

INTRODUCTION: Hand disinfection plays an important role in infection control. Currently, hand sanitizers containing ethanol and chlorhexidine gluconate as active ingredients are widely used. Most of hand sanitizers have a defined expiration date for use. However, there was no rule about the expiration date after opening defined with the evidence. Therefore, we examined the fluctuation of active ingredients and disinfection effect after opening the bottle. METHOD: Twelve hand sanitizers from 44 to 921 days after opening set in different places in the hospital were examined and unopened hand sanitizer used as a control. Chlorhexidine gluconate and ethanol of each samples were measured by high performance liquid chromatography and gas chromatography, respectively. The correlation between the concentration of each ingredient obtained and the number of days after opening, bottle weight, storage temperature and humidity was analyzed. A time-kill test based on ASTM E2315-03 was performed to confirm the actual disinfection effect. RESULTS: It was observed that active ingredients had not been decreased up to 921 days after opening and were not affected by storage conditions after opening. In addition, a decrease of disinfection effect was not observed in any sample. CONCLUSIONS: We found that hand sanitizers do not need to be discard after a number of days have passed because the active ingredients are retained even after opening in it.

Evidence-based review of chlorhexidine gluconate and iodine in the preoperative skin preparation of young infants.

PURPOSE: The preoperative preparation of young infants' skin requires special considerations. Commonly used solutions for preparing the skin preoperatively include chlorhexidine (CHG) and iodine. The Centers for Disease Control and Prevention (CDC) has recommendations for preparing skin for surgery and other invasive procedures for adults, but they do not have recommendations for young infants' skin. The purpose of this evidence-based literature review is to synthesize the literature, compare, and inform healthcare providers about the safety and efficacy of CHG and iodine as preoperative preparation solutions for young infants' skin. For this project young infants is defined as infants less than 48 weeks' postmenstrual age and those born prematurely and less than 28 days old. CONCLUSIONS: We analyze 19 articles that met the inclusion criteria. Three discussion themes emerge: systemic absorption, dermatologic burns, and CHG and iodine efficacy. PRACTICE IMPLICATIONS: We need more research regarding the safety and efficacy of CHG and iodine solutions for preoperative preparation of young infants' skin. Findings suggest the cautious use of CHG and iodine solutions on patients born at or before 28 weeks' postmenstrual age, especially those less than 28 days postnatal age.

Pharmacologic Inhibition of Histone Deacetylase 6 Prevents the Progression of Chlorhexidine Gluconate-Induced Peritoneal Fibrosis by Blockade of M2 Macrophage Polarization.

Peritoneal fibrosis contributes to ultrafiltration failure in peritoneal dialysis (PD) patients and thus restricts the wide application of PD in clinic. Recently we have demonstrated that histone deacetylase 6 (HDAC6) is critically implicated in high glucose peritoneal dialysis fluid (HG-PDF) induced peritoneal fibrosis, however, the precise mechanisms of HDAC6 in peritoneal fibrosis have not been elucidated. Here, we focused on the role and mechanisms of HDAC6 in chlorhexidine gluconate (CG) induced peritoneal fibrosis and discussed the mechanisms involved. We found Tubastatin A (TA), a selective inhibitor of HDAC6, significantly prevented the progression of peritoneal fibrosis, as characterized by reduction of epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) protein deposition. Inhibition of HDAC6 remarkably suppressed the expression of matrix metalloproteinases-2 (MMP2) and MMP-9. Administration of TA also increased the expression of acetylation Histone H3 and acetylation α-tubulin. Moreover, our results revealed that blockade of HDAC6 inhibited alternatively M2 macrophages polarization by suppressing the activation of TGF-ß/Smad3, PI3K/AKT, and STAT3, STAT6 pathways. To give a better understanding of the mechanisms, we further established two cell injured models in Raw264.7 cells by using IL-4 and HG-PDF. Our in vitro experiments illustrated that both IL-4 and HG-PDF could induce M2 macrophage polarization, as demonstrated by upregulation of CD163 and Arginase-1. Inhibition of HDAC6 by TA significantly abrogated M2 macrophage polarization dose-dependently by suppressing TGF-ß/Smad, IL4/STAT6, and PI3K/AKT signaling pathways. Collectively, our study revealed that blockade of HDAC6 by TA could suppress the progression of CG-induced peritoneal fibrosis by blockade of M2 macrophage polarization. Thus, HDAC6 may be a promising target in peritoneal fibrosis treatment.

Microneedle-Mediated Permeation Enhancement of Chlorhexidine Digluconate: Mechanistic Insights Through Imaging Mass Spectrometry.

PURPOSE: Chlorhexidine digluconate (CHG) is a first-line antiseptic agent typically applied to the skin as a topical solution prior to surgery due to its efficacy and safety profile. However, the physiochemical properties of CHG limits its cutaneous permeation, preventing it from reaching potentially pathogenic bacteria residing within deeper skin layers. Thus, the utility of a solid oscillating microneedle system, Dermapen®, and a CHG-hydroxyethylcellulose (HEC) gel were investigated to improve the intradermal delivery of CHG. METHODS: Permeation of CHG from the commercial product, Hibiscrub®, and HEC-CHG gels (containing 1% or 4% CHG w/w) was assessed in intact skin, or skin that had been pre-treated with microneedles of different array numbers, using an Franz diffusion cells and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). RESULTS: Gels containing 1% and 4% CHG resulted in significantly increased depth permeation of CHG compared to Hibiscrub® (4% w/v CHG) when applied to microneedle pre-treated skin, with the effect being more significant with the higher array number. ToF-SIMS analysis indicated that the depth of dermal penetration achieved was sufficient to reach the skin strata that typically harbours pathogenic bacteria, which is currently inaccessible by Hibiscrub®, and showed potential lateral diffusion within the viable epidermis. CONCLUSIONS: This study indicates that HEC-CHG gels applied to microneedle pre-treated skin may be a viable strategy to improve the permeation CHG into the skin. Such enhanced intradermal delivery may be of significant clinical utility for improved skin antisepsis in those at risk of a skin or soft tissue infection following surgical intervention.

Effect of chlorhexidine digluconate on antimicrobial activity, cell viability and physicochemical properties of three endodontic sealers.

OBJECTIVE: Assess the biological and physicochemical properties of AH Plus, BioRoot RCS and Pulp Canal Sealer (PCS) leachates with and without chlorhexidine (CHX). METHODS: The sealers were studied in no contact and 1-minute contact with CHX. For biological properties (antibacterial activity and cytotoxicity), leachates were formed in saline of freshly mixed, 1-, 7- and 28 days set sealers. The antibacterial properties of sealer leachates were investigated for planktonic and biofilm growth of E. faecalis, S. mutans, S.epidermidis and S.aureus. The 3-(4,5 dimethylthiazolyl-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate murine fibroblast cell viability after exposure to the leachates. The physical properties (water uptake, sorption, solubility, porosity, surface characteristics) of sealers and the pH of the immersion liquid (saline or distilled water) were also assessed over a 28-days period. RESULTS: CHX improved the antibacterial properties of the sealer leachates and reduced cell viability for all sealer leachates, except for freshly mixed PCS. BioRoot RCS leachates presented the highest antibacterial properties and cell viability with and without CHX contact. PCS was the material most affected by CHX in terms of physical properties, whereas for AH Plus, solubility was increased. CHX did not affect the physical properties of BioRoot RCS, except for solubility that was decreased. CHX contact did not change sealers' alkalinity in distilled water whereas it increased it for AH Plus and BioRoot RCS in saline. SIGNIFICANCE: CHX improved the antibacterial efficacy of sealer leachates and either compromised or did not affect cell viability. CHX affected to various extent sealers' physicochemical properties.