Antiseptic efficacy of two mouth rinses in the oral cavity to identify a suitable rinsing solution in radiation- or chemotherapy induced mucositis.

OBJECTIVES: Oral mucositis caused by intensive cancer chemotherapy or radiotherapy frequently results in pronounced damage of the oral mucosa leading to painful oral hygiene. To support oral care, antimicrobial effective mouth rinses may be used. Thus, the efficacy of a hypochlorite-based mouth rinse (Granudacyn®), assumed to be highly biocompatible because of the compounds being part of the natural pathogen defense, as possible antiseptic agent in case of oral mucositis was compared to that of an octenidine based antiseptic mouth rinse (Octenidol® md). MATERIALS AND METHODS: The study was conducted as monocentric, controlled, randomized, blind cross over comparative study on 20 volunteers. As a proof of principle, we performed the study on orally healthy subjects and not cancer patients. The efficacy was determined as reduction of colony forming units (cfu) on buccal mucosa as well as in saliva. After mouth rinsing for 30 s, samples were taken after 1 min, 15 min, 30 and 60 min. The lg-reduction was calculated as difference between lg-values of cfu pre- and post-treatment. RESULTS: Both antiseptic mouth rinses induced a significant reduction of cfu on buccal mucosa and in saliva 1 min after mouth rinsing. The effect persisted up to 60 min. The octenidine based rinse was significantly superior to the hypochlorite-based rinse up to the last sample 60 min after rinsing. However, the known cytotoxicity of octenidine argues against its application. CONCLUSION: Within the limits of this study, due to its antiseptic efficacy, the hypochlorite-based rinse Granudacyn® can be regarded appropriate to support the oral hygiene in patients with a sensitive oral mucosa during an aggressive cancer chemotherapy and radiation treatment in case of oral mucositis.

The antifibrotic effects of naringin in a hypochlorous acid (HOCl)-induced mouse model of skin fibrosis.

OBJECTIVES: Fibrosis is a chronic inflammation caused by the loss of innate compensational mechanisms. Naringin (NR) is a flavonoid with antineoplastic and anti-inflammatory effects. Here, we aimed to investigate the antifibrotic effects of NR and underlying mechanisms in a Hypochlorous acid (HOCl)-induced mouse model of skin fibrosis. MATERIALS AND METHODS: A total of 24 six-week-old female BALB/c mice were randomly allocated into five groups: HOCl, Sham, PBS, HOCl + NR and DMSO and selected skin regions were treated for 6 weeks, until sacrifice. The histopathologic and collagenesis of skin resections were analyzed using H&E and PR staining. The mRNA levels of COL1, COL3 and αSMA genes were quantified. Serum samples were also used to evaluate TGF-ß levels and LDH activity. RESULTS: HOCl could increase the relative collagen content, while NR administration on HOCl-treated biopsies decreased collagenesis. COL1, COL3 and αSMA mRNA levels were significantly increased among HOCl-treated skin samples, while NR treatment could decrease these mRNA levels of genes to the extent equal to the levels in the Sham group. Similarly, Naringin-treated samples could decrease TGF-ß levels. CONCLUSIONS: We demonstrated that Naringin could exert protective effects against fibrotic complications of HOCL in skin tissue in vivo, by reducing the collagenesis and decreasing the levels of fibrosis-associated genes.

The effectiveness of the information-motivation model and domestic brushing with a hypochlorite-based formula on peri-implant mucositis: A randomized clinical study.

OBJECTIVE: Management of mucositis is essential for the long-term maintenance of dental implants. This study determined the efficacy, in terms of clinical parameters, of an adjunctive domiciliary agent paired with non-surgical periodontal therapy (NSPT) for patients with peri-implant mucositis. MATERIALS AND METHODS: Patients involved in a periodontal maintenance program were randomly distributed to the domestic use of a chlorhexidine toothpaste and mouthwash (control) or a hypochlorite-based formula brushing solution (test) after diagnosis of peri-implant mucositis. A modified approach towards NSPTwas performed after 10 days of domestic use of the assigned maintenance product in both groups. Clinical and patient-related outcomes were recorded during a 90-day follow-up period. RESULTS: Forty patients completed the three-month study (20 patients per group). Both groups showed relevant clinical and patient outcome improvements after the NSPT (T2) and between T1 and T2 (p < 0 0.01), except for PPD. For the test group, the clinical improvement was significantly greater than that for the control group at the seventh-day evaluation (T1 ) in the gingival index (0-3) and FMBS (%). Favorable outcomes were maintained during the entire follow-up period. CONCLUSION: The present study showed that the modified NSPT paired with the domestic use of nitradine-based formula helps resolve peri-implant mucositis and that nitradine might represent an alternative to chlorhexidine in these cases. CLINICAL RELEVANCE: The gold standard for nonsurgical maintenance is full-mouth disinfection. A previous decontamination of the oral cavity with chlorhexidine or nitradine domiciliary for 10 days could reduce plaque and inflammation, resulting in a painless operative session. This protocol may help reduce airborne contamination and the risk of cross-infection, and during the pandemic, the protocol is safer for clinicians. In the same clinical cases, nitradine may be more efficient than chlorhexidine, and the former has no side effects such as discolouration.

Preliminary Outcomes of Hypochlorous Acid as an Adjunct for Pocket Irrigation in Revision Aesthetic Breast Surgery.

BACKGROUND: Capsular contracture is a challenging problem for plastic surgeons despite advances in surgical technique. Breast pocket irrigation decreases bacterial bioburden. Studies have shown that hypochlorous acid (HOCl; PhaseOne Health, Nashville, TN) effectively penetrates and disrupts biofilms; however, there are limited clinical data regarding this irrigation in breast augmentation. OBJECTIVES: The aim of this study was to investigate the effects of HOCl pocket irrigation in revision breast augmentation by evaluating rates of capsular contracture recurrence, infection, and allergic reactions. METHODS: We performed an institutional review board-approved retrospective chart review of revision breast augmentation cases for Baker grade III/IV capsular contractures in which pockets were irrigated with HOCl. Data were obtained from 3 board-certified plastic surgeons. RESULTS: The study included 135 breasts in 71 patients, who ranged in age from 27 to 77 years (mean, 53.7 years). Follow-up ranged from 12 to 41 months (mean, 20.2 months). Postoperatively, there were 2 unilateral Baker grade III/IV recurrences at 13 months and 1 bilateral Baker grade II recurrence at 3 months. There were no infections or allergic reactions. The overall Baker grade III/IV capsular contracture recurrence rate was 0% at 12 months and 1.5% at 15 months. CONCLUSIONS: Breast pocket irrigation decreases bioburden, which may influence capsular contracture recurrence. We evaluated 3 varied applications of HOCl in revision aesthetic breast surgery and found a low capsular contracture recurrence rate and no adverse reactions. We plan to report our findings with HOCl in primary breast augmentation in the future, and other studies are being conducted on the efficacy of HOCl in aesthetic surgery.

Topical stabilized hypochlorous acid: The future gold standard for wound care and scar management in dermatologic and plastic surgery procedures.

BACKGROUND: Hypochlorous acid (HOCl), a naturally occurring molecule produced by the immune system, is highly active against bacterial, viral, and fungal microorganisms. Moreover, HOCl is active against biofilm and increases oxygenation of the wound site to improve healing. Natural HOCl is unstable; through technology, it can be stabilized into an effective topical antiseptic agent. AIM: This paper focuses on the use of topical stabilized HOCl in wound and scar management for pre-, peri-, and postprocedures-including its ability to reduce the occurrence hypertrophic scars and keloids. The role of the product in other skin conditions is beyond the scope of this article. METHODS: A panel comprising clinicians with experience in cosmetic and surgical procedures met late 2018 to discuss literature search results and their own current clinical experience regarding topical stabilized HOCl. The panel of key opinion leaders in dermatology and plastic surgery defined key insights and consensus statements on the direction of use for the product. RESULTS: Topical stabilized HOCl provides an optimal wound healing environment and, when combined with silicone, may be ideal for reducing scarring. Additionally, in contrast to chlorhexidine, HOCl, used as an antiseptic skin preparation, raises no concerns of ocular- or ototoxicity. CONCLUSIONS: For wound care and scar management, topical stabilized HOCl conveys powerful microbicidal and antibiofilm properties, in addition to potency as a topical wound healing agent. It may offer physicians an alternative to other less desirable wound care measures.

Binding of myeloperoxidase to the extracellular matrix of smooth muscle cells and subsequent matrix modification.

The extracellular matrix (ECM) of tissues is susceptible to modification by inflammation-associated oxidants. Considerable data support a role for hypochlorous acid (HOCl), generated by the leukocyte-derived heme-protein myeloperoxidase (MPO) in these changes. HOCl can modify isolated ECM proteins and cell-derived matrix, with this resulting in decreased cell adhesion, modulated proliferation and gene expression, and phenotypic changes. Whether this arises from free HOCl, or via site-specific reactions is unresolved. Here we examine the mechanisms of MPO-mediated changes to human coronary smooth muscle cell ECM. MPO is shown to co-localize with matrix fibronectin as detected by confocal microscopy, and bound active MPO can initiate ECM modification, as detected by decreased antibody recognition of fibronectin, versican and type IV collagen, and formation of protein carbonyls and HOCl-mediated damage. These changes are recapitulated by a glucose/glucose oxidase/MPO system where low continuous fluxes of H2O2 are generated. HOCl-induced modifications enhance MPO binding to ECM proteins as detected by ELISA and MPO activity measurements. These data demonstrate that MPO-generated HOCl induces ECM modification by interacting with ECM proteins in a site-specific manner, and generates alterations that increase MPO adhesion. This is proposed to give rise to an increasing cycle of alterations that contribute to tissue damage.

DR1440 is a potential iron efflux protein involved in maintenance of iron homeostasis and resistance of Deinococcus radiodurans to oxidative stress.

Iron acquisition by bacteria is well studied, but iron export from bacteria is less understood. Herein, we identified dr1440 with a P-type ATPase motif as a potential exporter of iron from Deinococcus radiodurans, a bacterium known for its extreme resistance to radiation and oxidants. The DR1440 was located in cell membrane as demonstrated by fluorescence labelling analysis. Mutation of dr1440 resulted in cellular accumulation of iron ions, and expression level of dr1440 was up-regulated significantly under iron ion or hydrogen peroxide stress in the wild-type strain, implicating DR1440 as a potential iron efflux protein. The dr1440 mutant displayed higher sensitivity to iron ions and oxidative stresses including hydrogen peroxide, hypochlorous acid, and gamma-ray irradiation compared with the wild-type strain. The high amount of iron in the mutant strain resulted in severe protein carbonylation, suggesting that DR1440 might contribute to intracellular protein protection against reactive oxygen species (ROS) generated from ferrous ion-mediated Fenton-reaction. Mutations of S297A and C299A led to intracellular accumulation of iron, indicating that S297 and C299 might be important functional residues of DR1440. Thus, DR1440 is a potential iron efflux protein involved in iron homeostasis and oxidative stress-resistance of D. radiodurans.

Fatigue Resistance of Nickel-titanium Instruments Exposed to High-concentration Hypochlorite.

INTRODUCTION: The purpose of this study was to introduce a new fatigue test model that simulates the clinical situation for evaluating the corrosion effect of 5.25% sodium hypochlorite (NaOCl) on nickel-titanium (NiTi) files and to evaluate the effect of 3 different temperatures (22°C, 37°C, and 60°C) on the cyclic fatigue of these files. METHODS: Three NiTi files (size 25/.04), K3 (SybronEndo, Orange, CA), K3XF (SybronEndo), and Vortex (Dentsply Tulsa Dental Specialties, Tulsa, OK), were subjected to cyclic fatigue tests inside a novel artificial ceramic canal with a curvature of 60° and a 5-mm radius. A 19-mm-long file segment from the tip was introduced into the canal and immersed in water or 5.25% NaOCl at 3 different temperatures, and the number of revolutions to fracture (Nf) was recorded. The fracture surface of all fragments was examined by a scanning electron microscope. Data were analyzed using univariate analysis of variance with the significance level at 0.05. RESULTS: The Nf of Vortex files was the highest followed by K3XF and K3 (P < .05) at all conditions. The Nf of all files was highest at 22°C and lowest at 60°C (P < .05). However, no difference in Nf was detected in Vortex files between 22°C and 37°C. The Nf of all files in 5.25% NaOCl was shorter than that in water although there was no statistically significant difference. No pitting or crevice corrosion was observed on the fracture surface. CONCLUSIONS: NaOCl, 5.25%, does not significantly affect the fatigue behavior of NiTi files. The fatigue resistance should be tested under specific temperature conditions. The austenite finish temperature of a file is important in determining the fracture risk at body temperature.

Personal protective equipment solution for UK military medical personnel working in an Ebola virus disease treatment unit in Sierra Leone.

The combination of personal protective equipment (PPE) together with donning and doffing protocols was designed to protect British and Canadian military medical personnel in the Kerry Town Ebola Treatment Unit (ETU) in Sierra Leone. The PPE solution was selected to protect medical staff from infectious risks, notably Ebola virus, and chemical (hypochlorite) exposure. PPE maximized dexterity, enabled personnel to work in hot temperatures for periods of up to 2h, protected mucosal membranes when doffing outer layers, and minimized potential contamination of the doffing area with infectious material by reducing the requirement to spray PPE with hypochlorite. The ETU was equipped to allow medical personnel to provide a higher level of care than witnessed in many existing ETUs. This assured personnel working as part of the international response that they would receive as close to Western treatment standards as possible if they were to contract Ebola virus disease (EVD). PPE also enabled clinical interventions that are not seen routinely in West African EVD treatment regimens, whilst providing a robust protective barrier. Competency in using PPE was developed during a nine-day pre-deployment training programme. This allowed over 60 clinical personnel per deployment to practice skills in PPE in a simulated ETU and in classrooms. Overall, the training provided: (i) an evidence base underpinning the PPE solution chosen; (ii) skills in donning and doffing of PPE; (iii) personnel confidence in the selected PPE; and (iv) quantifiable testing of each individual's capability to don PPE, perform tasks and doff PPE safely.

Topical Approaches to Improve Surgical Outcomes and Wound Healing: A Review of Efficacy and Safety.

Surgical procedures are an important piece of a dermatologist's daily practice. Therefore, the optimization of post-surgical wound healing is an area of utmost importance and interest. Although low risk, one notable barrier to proper wound healing is surgical site infection.

In an attempt to mitigate this risk and improve surgical outcomes, multiple topical products continue to be used both pre- and postprocedure. Traditionally, this includes both topical antibiotics and antiseptics. However, these products are not without consequence.

The overuse of topical antibiotics as prophylaxis for infection has contributed to increased bacterial resistance, and in fact is no longer recommended by the American Academy of Dermatology in clean post surgical wounds. Topical antiseptics, including chlorhexidine and povidone-iodine, can have a cytotoxic effect on keratinocytes and may actually impede wound healing as a result. In addition, chlorhexidine in particular can produce both otologic and ocular toxic effects when used on the face. Emerging products, such as hypochlorous acid, may be a potential alternative to the more commonly used agents, as it has effective antimicrobial actions and minimal adverse effects. Therefore, the purpose of this review is to highlight several topical products used to optimize post-surgical wound healing and discuss both their efficacy and safety.

J Drugs Dermatol. 2017;16(3):209-212.

Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding.

OBJECTIVE: Endothelial cell (EC) damage in systemic sclerosis (SSc) is reflected by the shedding of microparticles (MPs). The aim of this study was to show that inhibiting MP release using pantethine or by inactivating ATP-binding cassette transporter A1 (ABCA1) ameliorates murine SSc. METHODS: First, the effects of pantethine on MP shedding and on basal oxidative and nitrosative stresses in ECs and fibroblasts were determined in vitro. The effects of pantethine were then tested in vivo. SSc was induced in BALB/c mice by daily intradermal injection of HOCl. Mice were simultaneously treated daily with pantethine by oral gavage. RESULTS: In vitro, pantethine inhibited MP shedding from tumor necrosis factor-stimulated ECs and abrogated MP-induced oxidative and nitrosative stresses in ECs and fibroblasts. Ex vivo, pantethine also restored redox homeostasis in fibroblasts from mice with SSc. In vivo, mice with SSc displayed skin and lung fibrosis associated with increased levels of circulating MPs and markers of oxidative and endothelial stress, which were normalized by administration of pantethine or inactivation of ABCA1. CONCLUSION: Pantethine is a well-tolerated molecule that represents a potential treatment of human SSc.

Effects of indoor swimming pools on the nasal cytology of pool workers.

OBJECTIVE: We aimed to evaluate the relationship between swimming pool pollutants and allergic rhinitis in swimming pool workers. MATERIALS AND METHODS: Twenty-seven indoor pool workers (group 1) and 49 control subjects (group 2) were enrolled in the study. A skin prick test was performed and a nasal smear was obtained from each subject to evaluate rhinitis. RESULTS: When the groups were compared in terms of epithelial cells, group 1 had significantly more epithelial cells than group 2. When the groups were compared with regard to eosinophils, group 1 had significantly more eosinophils than group 2. The skin prick test results for both groups were not significantly different. CONCLUSION: Indoor pool workers showed severe symptoms of rhinitis and eosinophilic nasal cytology, likely due to chlorine. Nasal cytology is an easy-to-administer diagnostic test and can be used to follow up rhinitis in indoor pool workers, along with nasal endoscopy, a detailed clinical history and a skin prick test.

Crucial role of transient receptor potential ankyrin 1 and mast cells in induction of nonallergic airway hyperreactivity in mice.

RATIONALE: Airway hyperreactivity (AHR) is a key feature of bronchial asthma, and inhalation of irritants may facilitate development of nonallergic AHR. Swimmers exposed to hypochlorite (ClO(-))-containing water show a higher risk of developing AHR. We developed a mouse model in which instillation of ClO(-) before ovalbumin (OVA) induces AHR without bronchial inflammatory cells. OBJECTIVES: To investigate the mechanisms of ClO(-)-OVA-induced nonallergic AHR. METHODS: The involvement of the transient receptor potential ankyrin (TRPA)1 channel was checked in vivo by the use of TRPA1(-/-) mice and in vitro by Ca(2+) imaging experiments. The role of substance P (SP) was investigated by pretreating animals with the receptor antagonist RP67580, by replacing ClO(-) with SP in vivo, and by immunofluorescent staining of large airways of exposed mice. The role of mast cells was evaluated by exposing mast cell-deficient Kit(Wh)/Kit(Wsh) mice to ClO(-)-OVA with or without mast cell reconstitution. MEASUREMENTS AND MAIN RESULTS: ClO(-)-OVA did not induce AHR in TRPA1(-/-) mice, and ClO(-) generates a Ca(2+) influx in TRPA1-transfected cells. Pretreatment with RP67580 reduces ClO(-)-OVA-induced AHR, although no increased SP expression was shown in the airways. SP-OVA exposure resulted in the same AHR as induced by ClO(-)-OVA. Kit(Wsh)/Kit(Wsh) mice did not develop AHR in response to ClO(-)-OVA unless they were reconstituted with bone marrow-derived mast cells. CONCLUSIONS: Induction of AHR by exposure to ClO(-)-OVA depends on a neuroimmune interaction that involves TRPA1-dependent stimulation of sensory neurons and mast cell activation.

Intracellular glutathione protects human monocyte-derived macrophages from hypochlorite damage.

AIMS: Macrophages must function in an inflammatory environment of high oxidative stress due to the production of various oxidants. Hypochlorous acid (HOCl) is a potent cytotoxic agent generated by neutrophils and macrophages within inflammatory sites. This study determines whether glutathione is the key factors governing macrophage resistance to HOCl. MAIN METHODS: Human monocyte derived macrophages (HMDM) were differentiated from human monocytes prepared from human blood. The HMDM cells were exposed to micromolar concentrations of HOCl and the timing of the cell viability loss was measured. Cellular oxidative damage was measured by loss of glutathione, cellular ATP, tyrosine oxidation, and inactivation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). KEY FINDINGS: HOCl causes a rapid loss in HMDM cell viability above threshold concentrations. The cell death occurred within 10 min of treatment with the morphological characteristics of necrosis. The HOCl caused the extensive cellular protein oxidation with the loss of tyrosine residue and inactivation of GAPDH, which was accompanied with the loss of cellular ATP. This cellular damage was only observed after the loss of intracellular GSH from the cell. Removal of intracellular GSH with diethyl maleate (DEM) increased the cells' sensitivity to HOCl damage while protecting the intracellular GSH pool with the antioxidant 7,8-dihydroneopterin prevented the HOCl mediated viability loss. Variations in the HOCl LD(50) for inducing cell death were strongly correlated with initial intracellular GSH levels. SIGNIFICANCE: In HMDM cells scavenging of HOCl by intracellular glutathione is sufficient to protect against oxidative loss of key metabolic functions within the cells.

The organotelluride catalyst (PHTE)2NQ prevents HOCl-induced systemic sclerosis in mouse.

Systemic sclerosis (SSc) is a connective tissue disorder characterized by skin and visceral fibrosis, microvascular damage, and autoimmunity. HOCl-induced mouse SSc is a murine model that mimics the main features of the human disease, especially the activation and hyperproliferation rate of skin fibroblasts. We demonstrate here the efficiency of a tellurium-based catalyst 2,3-bis(phenyltellanyl)naphthoquinone ((PHTE)(2)NQ) in the treatment of murine SSc, through its selective cytotoxic effects on activated SSc skin fibroblasts. SSc mice treated with (PHTE)(2)NQ displayed a significant decrease in lung and skin fibrosis and in alpha-smooth muscle actin (α-SMA) expression in the skin compared with untreated mouse SSc animals. Serum concentrations of advanced oxidation protein products, nitrate, and anti-DNA topoisomerase I autoantibodies were increased in SSc mice, but were significantly reduced in SSc mice treated with (PHTE)(2)NQ. To assess the mechanism of action of (PHTE)(2)NQ, the cytotoxic effect of (PHTE)(2)NQ was compared in normal fibroblasts and in mouse SSc skin fibroblasts. ROS production is higher in mouse SSc fibroblasts than in normal fibroblasts, and was still increased by (PHTE)(2)NQ to reach a lethal threshold and kill mouse SSc fibroblasts. Therefore, the effectiveness of (PHTE)(2)NQ in the treatment of mouse SSc seems to be linked to the selective pro-oxidative and cytotoxic effects of (PHTE)(2)NQ on hyperproliferative fibroblasts.

Higher hypochlorous acid scavenging activity of ethyl pyruvate compared to its sodium salt.

Although a number of studies have focused on the higher ethyl pyruvate antioxidative activity than its sodium salt under various stress conditions, and the greater protective properties of the ester form have been suggested as the effect of better cell membrane penetration, the molecular mechanism has remained unclear. The aim of the present study was therefore to compare the antioxidative activities of sodium and ethyl pyruvate under in vitro conditions by using a liver homogenate as the model for cell membrane transport deletion. The potential effect of ethanol was also evaluated, and hypochlorous acid was used as an oxidant. Our data indicate the concentration-dependent scavenging potency of both sodium and ethyl pyruvate, with the ester having higher activity. This effect was not related to the presence of ethanol. Better protection of the liver homogenate by ethyl pyruvate was also apparent, despite the fact that cell membrane transport was omitted.

Chlorogenic acid protects paraoxonase 1 activity in high density lipoprotein from inactivation caused by physiological concentrations of hypochlorite.

We hypothesized that chlorogenic acids, the main phenolics in coffee, many fruits and Ilex paraguariensis extracts, protect paraoxonase 1 activity in HDL from inactivation by chlorination at concentrations of HOCl (50 microM) and chlorogenic acid (2-10 microM) compatible with those found in humans. When human HDL was incubated in the presence of HOCl/OCl-, a concentration dependent loss of activity was apparent. Of interest, 5 caffeoylquinic acid at 5 micromol/L affords more than 60% protection of the activity reaching 100% at 25 micromol/L. This compound and the plant sources that are rich in them may be protectors of paraoxonase 1 activity.