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.

"Water or not water: That is the question." Analysis of costs and consumption of the operating theaters in a greener perspective.

OBJECTIVE: To compare the amounts of water and plastic used in surgical hand washing with medicated soaps and with alcohol-based products and to compare costs and consumption in a year, based on scheduled surgical activity. METHOD: This retrospective study was carried out at Udine's Gynecology Operating Block from October to November 2022. We estimated the average amount of water with a graduated cylinder and the total cost of water usage based on euros/m3 indicated by the supplier; for each antiseptic agent we collected the data relevant to wash time, amount of water and product used per scrub, number of handscrubs made with every 500 mL bottle and cost of a single bottle. We put data into two hypothetical contexts, namely WHO guidelines and manufacturers' recommendations. Data were subjected to statistical analysis. RESULTS: The daily amount of water using povidone-iodine, chlorhexidine-gluconate and alcohol-based antiseptic agents was 187.6, 140.7 and 0 L/day (P value = 0.001), respectively; A total of 69 000 L/year of water would be saved if alcohol-based products were routinely used. A single unit of an alcohol-based product allows three times as many handscrubs as any other product (P value = 0.001) with consequent reduction in plastic packaging. CONCLUSION: Despite the cost saving being negligible, choosing alcohol-based handrub over medicated soap handrub - on equal antiseptic efficacy grounds - could lead to a significant saving of water and plastic, thus making our operating theaters more environmentally friendly.

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.

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.

Evaluation of Chlorhexidine Concentration on the Skin After Preoperative Surgical Site Preparation in Breast Surgery-A Randomized Controlled Trial.

BACKGROUND: Although there is a rationale supporting that preoperative showering with 2% or 4% chlorhexidine gluconate (CHG) would decrease skin bacterial colonization, there is no consensus that this practice reduces the risk of surgical site infection (SSI). OBJECTIVES: Analyze the skin concentration of CHG after preoperative showering associated with the traditional skin preparation with CHG 4% for breast surgery. METHODS: Randomized controlled trial that included 45 patients, all candidates for augmentation mammaplasty, allocated into three groups (A: no preoperative showering; B: one preoperative showering; C: two preoperative showering with CHG 4%) in a 1:1:1 ratio. Skin swabs collection was performed right before the surgical incision. The samples were, then, sent to spectrophotometry in order to determine the skin concentration of CHG at the beginning of surgery. RESULTS: The age ranged from 18 to 61 years, with a mean of 37 years old. Group C had the lowest median concentration (0.057) followed by group B (0.060) and group A (0.072), however, with no statistical significance. The areola was the place with the lowest median concentration level (0.045), followed by the axilla (0.061) and the inframammary fold (IMF) (0.069). Still, when comparing the distribution of the sites, a statistically significant difference was found only between the axilla and the areola (p = 0.022). CONCLUSION: Preoperative showering with CHG 4% did not increase the concentration of this agent on the skin surface right before the surgical incision. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

What is the benefit of preoperative washing with chlorhexidine gluconate-impregnated cloths on the incidence of surgical site infections? A systematic review and meta-analysis.

OBJECTIVES: While the World Health Organization has recommended preoperative washing with plain or antimicrobial soap for surgical site infection (SSI) prevention, it has not formulated recommendations on use of chlorhexidine gluconate (CHG)-impregnated cloths. The purpose of this systematic review was to evaluate the benefit of preoperative bathing with CHG-cloths on SSI incidence. PATIENTS AND METHODS: Publications were searched on Medline, CENTRAL, Web of Science, Clinical Trial between 01/01/1990 and 30/06/2018. Randomized controlled trials (RCT), quasi-randomized, case-control and cohort studies on patients with surgery (Population) having preoperative bathing with CHG-cloths (Intervention) or antiseptic soap, plain soap, placebo, no washing, no instruction (Comparator) were included. The main outcome was SSI occurrence. The results were synthetized using the Odds-Ratio (OR) and 95% confidence interval [95%CI]. Study quality was assessed using the Cochrane and Newcastle-Ottawa tools and evidence quality with the GRADE method. Statistics were calculated on RevMan5.3. RESULTS: All in all, 1108 publications were identified and 3 were included in the meta-analysis. OR of the 2 cohort studies was 0.25 [95%CI: 0.13-0.50] for use of CHG-cloths the evening and the morning before intervention versus non-compliance with preoperative washing. OR of the RCT was 0.12 [95%CI: 0.02-1.00] for use of CHG-cloths the evening and the morning before intervention versus a shower with antibacterial soap the evening before the intervention. Study quality was moderate. CONCLUSIONS: While the available studies show a benefit for CHG-cloths on SSI occurrence in orthopaedic surgery, there is no comparison with usual practices. Further studies are needed to confirm the benefit of CHG-cloths for preoperative washing.

In vitro antifungal activity of cold atmospheric microwave plasma and synergistic activity against Malassezia pachydermatis when combined with chlorhexidine gluconate.

BACKGROUND: The antifungal efficacy of cold atmospheric microwave plasma (CAMP) against Malassezia pachydermatis has not been to be evaluated. OBJECTIVE: To examine the antifungal effects of CAMP against M. pachydermatis and its synergistic effects with chlorhexidine gluconate (CHX). METHODS: A M. pachydermatis isolate was collected from a dog with otitis externa and Malassezia dermatitis at the Seoul National University Veterinary Medical Teaching Hospital. The antifungal effect was determined by applying CAMP to a M. pachydermatis isolate that was incubated for 3 days at 37°C. After 1, 2, 3 and 5 min of application, the efficacy of the plasma treatment was determined according to the number of colony forming units (CFUs). A mixture consisting of inoculum and CHX was applied to evaluate the synergistic effect of the plasma treatment in the same way. RESULTS: The application of CAMP showed significant antifungal effects against M. pachydermatis. The antifungal effect of CAMP was enhanced by an increased exposure time and output power. The application of CAMP with 0.02% and 0.2% CHX resulted in lower survival rates against M. pachydermatis when compared with its sole application at 1 or 2 min. CONCLUSIONS: The study findings demonstrate that CAMP has a potential as a new antifungal option for M. pachydermatis and has synergistic antifungal effects with CHX in vitro. Clinical applications for CAMP are necessary to assess the antifungal efficacy for patients.

Chlorhexidine gluconate vs povidone-iodine vaginal antisepsis for urogynecologic surgery: a randomized controlled noninferiority trial.

BACKGROUND: Although povidone-iodine (iodine) is the only Food and Drug Administration-approved vaginal antiseptic solution, there is a lack of comparative data evaluating alternatives. Chlorhexidine gluconate is readily accessible, recommended by multiple societies as an alternative for patients with iodine allergy, and preliminary data indicate that it may provide superior antisepsis. OBJECTIVE: This study aimed to compare the effectiveness of chlorhexidine and iodine as presurgical vaginal antiseptic solutions in preventing the most common surgery-associated infection after gynecologic surgery, urinary tract infections. STUDY DESIGN: We conducted a randomized controlled noninferiority trial among women undergoing urogynecologic surgery. The primary outcome measure was symptomatic urinary tract infection within 2 weeks after surgery. The secondary outcomes included culture-proven urinary tract infection at 2 and 6 weeks after surgery, symptomatic urinary tract infections at 6 weeks after surgery, any surgical site infection at 2 weeks after surgery, and patient-reported vaginal irritation after surgery. We required 58 participants per arm to demonstrate noninferiority of chlorhexidine vs iodine (margin of relative risk of <1.5 for the upper limit of 95% confidence interval) between groups for the primary outcome. RESULTS: A total of 119 participants (61 in the chlorhexidine group and 58 in the iodine group) completed the primary outcome and were included in the analyses. There was no difference in the groups' demographic characteristics, medical history, operations performed, or perioperative factors. Chlorhexidine was not inferior to iodine concerning the primary outcome, symptomatic urinary tract infection at 2 weeks after surgery (10% vs 17%; relative risk, 0.6; 95% confidence interval [-∞, 1.3]). Furthermore, chlorhexidine was not inferior to iodine for the secondary urinary tract infection outcomes (culture-proven urinary tract infection at 2 and 6 weeks after surgery and symptomatic urinary tract infection at 6 weeks after surgery). Groups were similar in terms of surgical site infection (overall 3/119 [2.5%]) and presence of any vaginal irritation (4/54 [7.4%], for both groups). CONCLUSION: Chlorhexidine was not inferior to iodine for vaginal antisepsis before urogynecologic surgery concerning urinary tract infection. Given the similar postoperative urinary tract infection rates demonstrated in this study and the lack of difference in vaginal irritation, chlorhexidine seemed to be a safe and reasonable option for vaginal antisepsis before surgical procedures. Additional studies are needed to further examine surgical site infection.

Cytotoxic effect of sodium hypochlorite (Lavanox 0.08%) and chlorhexidine gluconate (Irrisept 0.05%) on human osteoblasts.

PURPOSE: Soft tissue, bone and joint infections are severe complications in orthopedic and traumatological surgery. Lavanox (0.08% NaOCl) and Irrisept (0.05% chlorhexidine gluconate, CHG) are industrially produced antiseptic solutions commonly used in infection treatment. Regarding this clinical indication, the microbicidal effect is often investigated, but toxicity to osteoblasts has rarely been examined. This is important to decide whether these solutions should be used in septic situations in which bone healing must take place. The hypothesis of the present study is that NaOCl and CHG are cytotoxic to osteoblasts even after a short exposure time. METHODS: Human osteoblasts were isolated from donors with osteoarthritis during total knee and hip arthroplasty. Cells were cultivated and treated with both antiseptic solutions for 2, 5 and 10 min in different dilutions. Toxicity was quantified by counting cells, lactate dehydrogenase (LDH) expression, spectrophotometric quantification via XTT assay and FDA/PI fluorescence microscopy. RESULTS: Analyzing viable cells after treatment with both antiseptics showed a significant decrease in viable cells through LDH expression test, XTT assay, fluorescence microscopy and light microscopy, depending on concentration. The time dependence showed a trend to more cell death at longer exposure times, without significance. CONCLUSION: Toxic effects on osteoblasts were shown after treatment with 0.08% NaOCl and 0.05% CHG after an exposure time of 2 min which also was concentration dependent. There was no difference in cytotoxicity between both antiseptics. In conclusion, these antiseptic solutions may be used with caution in situations requiring bone healing. Trial registration number Local ethics committee registration number: 5176-07/16.

Impact of 0.12% Chlorhexidine Gluconate Mouthwash on Peri-Implant Mucositis and Gingivitis After Nonsurgical Treatment: A Multilevel Analysis.

PURPOSE: This study investigated the impact of 0.12% chlorhexidine gluconate mouthwash on dental implants with periimplant mucositis and contralateral teeth with gingivitis at 6 months of follow-up after nonsurgical treatment. MATERIALS AND METHODS: This was a secondary analysis of data from a previous controlled, randomized, double-blinded clinical trial of 30 patients diagnosed with peri-implant mucositis and gingivitis in contralateral teeth, at 6 months following treatment. Patients were randomly assigned into a test group (basic periodontal therapy + 0.12% chlorhexidine mouthwash) or a control group (basic periodontal therapy + placebo). Therapy consisted of an adaptation of the full-mouth scaling and root planing protocol. The clinical parameters of visible Plaque Index, Gingival Bleeding Index, probing depth, bleeding on probing, keratinized mucosa width, and gingival and peri-implant phenotype were evaluated at baseline and at 1, 3, and 6 months posttherapy. Data were analyzed using Poisson multilevel regression analysis with a significance level of .05. RESULTS: The study analyzed 47 implants and contralateral teeth (376 sites) in the test group and 49 implants and contralateral teeth (392 sites) in the control group. No differences were found between the groups at the patient level. At the site level, the teeth and implants presented statistical differences in bleeding on probing, probing depth, and keratinized mucosa width at 3 months for both treatment groups. However, no difference was observed in bleeding on probing in the test group (P = .484) at 6 months, whereas the control group demonstrated increased bleeding on probing (indicating more inflammation) at implant sites than at teeth sites (P = .039). Additionally, implant sites with a thin peri-implant phenotype (P < .001) and located posteriorly (P = .002) presented greater inflammation. CONCLUSION: Use of a 0.12% chlorhexidine mouthwash for 14 days was beneficial for implant sites with peri-implant mucositis, compared to contralateral teeth sites with gingivitis, as indicated by the reduced percentage of teeth with bleeding on probing.

The effectiveness of various gargle formulations and salt water against SARS-CoV-2.

The COVID-19 is difficult to contain due to its high transmissibility rate and a long incubation period of 5 to 14 days. Moreover, more than half of the infected patients were young and asymptomatic. Virus transmission through asymptomatic patients is a major challenge to disease containment. Due to limited treatment options, preventive measures play major role in controlling the disease spread. Gargling with antiseptic formulation may have potential role in eliminating the virus in the throat. Four commercially available mouthwash/gargle formulations were tested for virucidal activity against SARS-CoV-2 in both clean (0.3 g/l BSA) and dirty (0.3 g/l BSA + 3 mL/L human erythrocytes) conditions at time points 30 and 60 s. The virus was isolated and propagated in Vero E6 cells. The cytotoxicity of the products to the Vero E6 was evaluated by kill time assay based on the European Standard EN14476:2013/FprA1:2015 protocol. Virus titres were calculated as 50% tissue culture infectious dose (TCID50/mL) using the Spearman-Karber method. A reduction in virus titer of 4 log10 corresponds to an inactivation of ≥ 99.99%. Formulations with cetylperidinium chloride, chlorhexidine and hexitidine achieved > 4 log10 reduction in viral titres when exposed within 30 s under both clean and dirty conditions. Thymol formulations achieved only 0.5 log10 reduction in viral titres. In addition, salt water was not proven effective. Gargle formulations with cetylperidinium chloride, chlorhexidine and hexetidine have great potential in reducing SAR-CoV-2 at the source of entry into the body, thus minimizing risk of transmission of COVID-19.

Post-Mastectomy Surgical Pocket Irrigation With Triple Antibiotic Solution vs Chlorhexidine Gluconate: A Randomized Controlled Trial Assessing Surgical Site Infections in Immediate Tissue Expander Breast Reconstruction.

BACKGROUND: Post-mastectomy pocket irrigation solution choice is debated and primarily surgeon dependent. We compare triple antibiotic solution (TAS) with 0.05% chlorhexidine gluconate (CHG). OBJECTIVES: The purpose of this study was to determine surgical site infection (SSI) rates after utilizing TAS vs CHG for breast pocket irrigation in immediate tissue expander (TE) breast reconstruction. METHODS: A prospective, blinded, randomized controlled trial was performed in patients (18-81 years old) who underwent bilateral mastectomy with TE reconstruction. In each patient, 1 mastectomy pocket was randomized to TAS and the other to CHG. Both the TE and the pocket were irrigated in the respective solution. The primary outcome was the incidence of SSI. Secondary outcomes were rates of mastectomy flap necrosis, hematoma, and seroma. RESULTS: A total of 88 patients who underwent bilateral immediate breast reconstruction were enrolled. Demographic and operative characteristics were equivalent because each patient served as their own control. Between the TAS and CHG groups, the incidence of SSI did not differ (5 [4.5%] vs 7 [8.0%], P = 0.35), including minor infections (2 [2.3%] vs 1 [1.1%], P = 0.56), major infections (2 [2.3%] vs 6 [6.8%], P = 0.15), and those resulting in explantation (2 [2.3%] vs 5 [4.5%], P = 0.25). Necrosis, hematoma, or seroma formation also did not differ. No patients who developed SSI received radiation. CONCLUSIONS: This study does not demonstrate a statistically significant difference in SSI between TAS and CHG irrigation, though TAS approached statistical significance for lower rates of infectious complications.

Assessment of the cytotoxic effects and chemical composition of the insoluble precipitate formed from sodium hypochlorite and chlorhexidine gluconate.

AIM: To investigate (1) the cytotoxic potential of the brown precipitate (BP) formed with sodium hypochlorite (NaOCl) and chlorhexidine gluconate (CHX), using both a small animal model of Caenorhabditis elegans (C. elegans) and cultured human gingival fibroblasts; and (2) the chemical composition of BP using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). METHODOLOGY: Brown precipitate was obtained by mixing equal volumes of 6% NaOCl and 2% CHX and separating the BP from clear supernatant by centrifugation. The brown precipitate was weighed and solubilized in dimethyl sulfoxide for cytotoxicity experiments. The cytotoxic effect of BP was assessed using C. elegans larvae and primary immortalized human gingival fibroblasts-hTERT (hTERT-hNOF) cells. Various dilutions of BP (25 ng/µL-150 ng/µL), supernatant (0.15% v/v), NaOCl (1:100-1:1000 dilutions of 6% NaOCl) or CHX (1:500-1:1000 dilutions of 2% CHX) along with vehicle control (0.5% v/v ethanol and 0.15% v/v DMSO) or untreated control (growth medium) were tested on C. elegans larvae and hTERT-hNOF cells. Viability was assessed in C. elegans larvae using stereomicroscopy and in hTERT-hNOF cells using dehydrogenase-based colorimetric assay. ToF-SIMS was used to assess the chemical composition of BP in comparison with CHX and para-chloroaniline (PCA). The C. elegans and cell line data were analysed using Log-Rank test and Student's t-test, respectively (p < .05). RESULTS: BP-75 ng/µL and BP-150 ng/µL were significantly more toxic to C. elegans larvae than the untreated, vehicle, supernatant or CHX treatment groups (p < .0001). Similarly, in hTERT-hNOF cells, BP-50 ng/µL, BP-75 ng/µL and BP-150 ng/µL induced significant cytotoxicity within 2 h compared with untreated, vehicle, supernatant and CHX treatments (p < .05). ToF-SIMS analysis of BP revealed ion composition characteristic of both CHX and the carcinogen PCA. CONCLUSIONS: Brown precipitate was toxic in both C. elegans larvae and hTERT-hNOF cells. The ToF-SIMS analysis of BP revealed ions characteristic of CHX and PCA that could account for the toxicities observed in C. elegans larvae and human gingival fibroblasts. Because of the insoluble and toxic nature of BP, consecutive use of CHX and NaOCl irrigants should be avoided in root canal treatment.

Effects of TGF-ß1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells.

We investigated the effectiveness of the transforming growth factor beta-1 (TGF-ß) receptor inhibitor GW788388 on the epithelial to mesenchymal transition (EMT) using human peritoneal mesothelial cells (HPMCs) and examined the effectiveness of GW788388 on the peritoneal membrane using a peritoneal fibrosis mouse model. HPMCs were treated with TGF-ß with or without GW788388. Animal experiments were conducted on male C57/BL6 mice. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. GW788388 was administered by once-daily oral gavage. The morphological change, cell migration, and invasion resulted from TGF-ß treatment, but these changes were attenuated by cotreatment with GW788388. TGF-ß-treated HPMCs decreased the level of the epithelial cell marker and increased the levels of the mesenchymal cell markers. Cotreatment with GW788388 reversed these changes. Phosphorylated Smad2 and Smad3 protein levels were stimulated with TGF-ß and the change was attenuated by cotreatment with GW788388. For the peritoneal fibrosis mice, thickness and collagen deposition of parietal peritoneum was increased, but this change was attenuated by cotreatment with GW788388. GW788388, an orally available potent TGF-ß receptor type 1 inhibitor, effectively attenuated TGF-ß-induced EMT in HPMCs. Cotreatment with GW788388 improved peritoneal thickness and fibrosis, and recovered peritoneal membrane function in a peritoneal fibrosis mouse model.

Efficacy of common antiseptic solutions against clinically relevant microorganisms in biofilm.

AIMS: Periprosthetic joint infections (PJIs) are among the most devastating complications after joint arthroplasty. There is limited evidence on the efficacy of different antiseptic solutions on reducing biofilm burden. The purpose of the present study was to test the efficacy of different antiseptic solutions against clinically relevant microorganisms in biofilm. METHODS: We conducted an in vitro study examining the efficacy of several antiseptic solutions against clinically relevant microorganisms. We tested antiseptic irrigants against nascent (four-hour) and mature (three-day) single-species biofilm created in vitro using a drip-flow reactor model. RESULTS: With regard to irrigant efficacy against biofilms, Povidone-iodine treatment resulted in greater reductions in nascent MRSA biofilms (logarithmic reduction (LR) = 3.12; p < 0.001) compared to other solutions. Bactisure treatment had the greatest reduction of mature Pseudomonas aeruginosa biofilms (LR = 1.94; p = 0.032) and a larger reduction than Vashe or Irrisept for mature Staphylococcus epidermidis biofilms (LR = 2.12; p = 0.025). Pooled data for all biofilms tested resulted in Bactisure and Povidone-iodine with significantly greater reductions compared to Vashe, Prontosan, and Irrisept solutions (p < 0.001). CONCLUSION: Treatment failure in PJI is often due to failure to clear the biofilm; antiseptics are often used as an adjunct to biofilm clearance. We tested irrigants against clinically relevant microorganisms in biofilm in vitro and showed significant differences in efficacy among the different solutions. Further clinical outcome data is necessary to determine whether these solutions can impact PJI outcome in vivo. Cite this article: Bone Joint J 2021;103-B(5):908-915.