Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair

Contains fulltext : 169649.pdf (publisher's version ) (Open Access)Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC) can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1) and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was applied to HO-1-luc transgenic mice and HO-1 promoter activity and mRNA expression in skin and several other organs were determined in real-time. In parallel, RIPC was applied directly or 24h prior to excisional wounding in mice to investigate the early and late protective effects of RIPC on cutaneous wound repair, respectively. HO-1 promoter activity was significantly induced on the dorsal side and locally in the kidneys following RIPC treatment. Next, we investigated the origin of this RIPC-induced HO-1 promoter activity and demonstrated increased mRNA in the ligated muscle, heart and kidneys, but not in the skin. RIPC did not change HO-1 mRNA and protein levels in the wound 7 days after cutaneous injury. Both early and late RIPC did not accelerate wound closure nor affect collagen deposition. RIPC induces HO-1 expression in several organs, but not the skin, and did not improve excisional wound repair, suggesting that the skin is insensitive to RIPC-mediated protection

Medical-Grade Honey Kills Antibiotic-Resistant Bacteria and Prevents Amputation in Diabetics with Infected Ulcers: A Prospective Case Series

Diabetic ulcers are at risk of becoming chronic and infected, as diabetics have hampered vascular structures, limiting oxygen and nutrient supply. These wounds can lead to pain, malodor, functional problems, and amputation. The current rise in antibiotic resistance demands for complementary therapies. Medical-grade honey (MGH) forms an attractive option because of its antimicrobial and pro-healing properties. We aim to show the beneficial effects of MGH in infected diabetic ulcers. We present six patients with infected diabetic ulcers, of which some were at risk of (further) amputation. Previous treatments with antibiotics, silver and alginate dressings, surgical closure, and maggot therapy were ineffective; therefore, the treatment was switched to the application of MGH. MGH therapy typically reduced the malodor in a couple of days and controlled infection within 2–3 weeks. MGH also enhanced wound healing by promoting granulation tissue formation, angiogenesis, and re-epithelialization, by decreasing inflammatory and oxidative stress and providing nutrients. Together, wound healing was enhanced, and the patient’s quality of life improved. MGH is safe and cost-effective for treating complicated diabetic wounds with (antibiotic-resistant) infections and at risk of amputation. MGH forms a promising alternative or complementary therapy to replace antibiotics for treating locally infected wounds

Antifungal Activity of a Medical-Grade Honey Formulation against <i>Candida auris</i>

Candida auris is a pathogenic yeast causing outbreaks in intensive care units with high mortality rates. The treatment of C. auris colonization is challenging due to high resistance rates. A potential alternative antifungal treatment is medical-grade honey. In this study the susceptibility of C. auris and other Candida species to the medical-grade honey-based formulation L-Mesitran® Soft was investigated. The medical-grade honey formulation reduced the growth of C. auris and other Candida species in a dose-dependent manner. This inhibition was not only due to the honey component, as treatment with an identical concentration of this component only was less effective and even stimulated the growth of C. albicans and C. glabrata, supporting the interpretation that supplements in the medical-grade honey formulation enhanced the antimicrobial activity. Increasing the concentration of the honey component to 40%, as is also present in an undiluted medical-grade honey formulation, lead to a 1- to 4-log inhibition of all Candida species. Unprocessed local honey reduced the growth of nearly all Candida species more strongly than medical-grade honey. C. auris’ susceptibility to the medical-grade honey formulation did not depend on geographic origin or resistance profile, although the multiresistant isolates tended to be more susceptible. Altogether, medical-grade honey formulation has a strong antifungal activity against C. auris and other Candida species. Future studies should demonstrate whether the treatment of open wounds or skin colonized with C. auris is feasible and effective in the clinical setting

The Use of Medical Grade Honey on Infected Chronic Diabetic Foot Ulcers—A Prospective Case-Control Study

Non-healing wounds are usually colonised and contaminated by different types of bacteria. An alternative to antibiotic treatment in patients with infected wounds with local signs of inflammation may be medical grade honey (MGH). MGH has antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory features. This study aims to evaluate the effect of MGH therapy on infected non-healing wounds, especially for diabetic foot syndrome. Prospective, observational case series (n = 5) of patients with wounds of diabetic foot syndrome are presented. There were five males with an average age of 61.6 years. All wounds were treated with MGH, and the healing trajectory was rigorously and objectively monitored. In all cases, there was a gradual disappearance of odour, pain, and exudation. Moreover, the wound areas significantly reduced within 40 days and there was a decrease in glycated haemoglobin and glycaemia values. All these outcomes resulted in improved quality of life of the patients. Despite bacterial colonisation, antibiotic treatment was not necessary. All wounds were completely healed. MGH has antimicrobial, anti-inflammatory, and antioxidant effects in diabetic foot syndrome wounds, does not increase glycated haemoglobin or glycaemia levels, and thus constitutes an effective alternative to the use of antibiotics in the treatment of locally infected wounds

Antifungal Activity of a Medical-Grade Honey Formulation against Candida auris

Candida auris is a pathogenic yeast causing outbreaks in intensive care units with high mortality rates. The treatment of C. auris colonization is challenging due to high resistance rates. A potential alternative antifungal treatment is medical-grade honey. In this study the susceptibility of C. auris and other Candida species to the medical-grade honey-based formulation L-Mesitran&reg; Soft was investigated. The medical-grade honey formulation reduced the growth of C. auris and other Candida species in a dose-dependent manner. This inhibition was not only due to the honey component, as treatment with an identical concentration of this component only was less effective and even stimulated the growth of C. albicans and C. glabrata, supporting the interpretation that supplements in the medical-grade honey formulation enhanced the antimicrobial activity. Increasing the concentration of the honey component to 40%, as is also present in an undiluted medical-grade honey formulation, lead to a 1- to 4-log inhibition of all Candida species. Unprocessed local honey reduced the growth of nearly all Candida species more strongly than medical-grade honey. C. auris&rsquo; susceptibility to the medical-grade honey formulation did not depend on geographic origin or resistance profile, although the multiresistant isolates tended to be more susceptible. Altogether, medical-grade honey formulation has a strong antifungal activity against C. auris and other Candida species. Future studies should demonstrate whether the treatment of open wounds or skin colonized with C. auris is feasible and effective in the clinical setting

Medical-Grade Honey Outperforms Conventional Treatments for Healing Cold Sores&mdash;A Clinical Study

Cold sores are nasolabial blisters caused by herpes simplex virus (HSV) infections. Novel therapies demonstrating simultaneously antiviral activity and improved wound healing are warranted. The aim of this study was to investigate the efficacy of medical-grade honey (MGH) for treating HSV-induced cold sores. A crossover trial was performed in patients with recurrent cold sores (n = 29). The majority (65.6%) of these patients experience four or more episodes per year, thus forming a valid self-control group. In this study, patients applied an MGH-based formulation (L-Mesitran Soft) on their cold sore at the onset of symptoms (62.1%) or appearing of blister (37.9%) and compared it to their conventional treatments. After complete healing, patients filled in a questionnaire evaluating healing, pain, and itching. The average absolute healing time was 72.4% slower with conventional treatment (10.0 days) compared to MGH (5.8 days). After MGH treatment, 86.2% of all patients experienced faster objective healing (6.9% similar and 6.9% slower) and the subjective healing score was higher in 79.3% of the patients (20.7% similar). If the patients normally experience pain and itching during their cold sores, these levels were lower with MGH therapy compared to conventional treatment in 72.7% and 71.4% of the patients, respectively. Moreover, 100% of the patients prefer MGH treatment over conventional treatment and will use it again on future cold sores. MGH is a promising alternative treatment for cold sores, likely by combining both increased antiviral and wound healing activities while alleviating pain and itching

Synergistic antimicrobial activity of supplemented medical-grade honey against Pseudomonas aeruginosa biofilm formation and eradication

Biofilms hinder wound healing. Medical-grade honey (MGH) is a promising therapy because of its broad-spectrum antimicrobial activity and the lack of risk for resistance. This study investigated the inhibitory and eradicative activity against multidrug-resistant Pseudomonas aeruginosa biofilms by different established MGH-based wound care formulations. Six different natural wound care products (Medihoney, Revamil, Mebo, Melladerm, L-Mesitran Ointment, and L-Mesitran Soft) were tested in vitro. Most of them contain MGH only, whereas some were supplemented. L-Mesitran Soft demonstrated the most potent antimicrobial activity (6.08-log inhibition and 3.18-log eradication). Other formulations ranged between 0.89-log and 4.80-log inhibition and 0.65-log and 1.66-log eradication. Therefore, the contribution of different ingredients of L-Mesitran Soft was investigated in more detail. The activity of the same batch of raw MGH (1.38-log inhibition and 2.35-log eradication), vitamins C and E (0.95-log inhibition and 0.94-log eradication), and all ingredients except MGH (1.69-log inhibition and 0.75-log eradication) clearly support a synergistic activity of components within the L-Mesitran Soft formulation. Several presented clinical cases illustrate its clinical antimicrobial efficacy against Pseudomonas aeruginosa biofilms. In conclusion, MGH is a potent treatment for Pseudomonas biofilms. L-Mesitran Soft has the strongest antimicrobial activity, which is likely due to the synergistic activity mediated by its supplements

Medical-Grade Honey Enhances the Healing of Caesarean Section Wounds and Is Similarly Effective to Antibiotics Combined with Povidone-Iodine in the Prevention of Infections—A Prospective Cohort Study

Caesarean sections (CS) are becoming increasingly popular. The antibiotic resistance crisis and relentless risk of infections, especially in developing countries, demand alternative treatment options. Medical-grade honey (MGH) exerts antimicrobial and healing properties. This study aims to evaluate the effect of MGH treatment on CS wound healing and postoperative complications when compared to conventional treatment (antibiotics in combination with povidone-iodine). In this prospective cohort study, 766 CS patients were included and evenly divided into two groups. The treatment group (n = 383) received an MGH-based formulation (L-Mesitran Soft) and the control group (n = 383) received antibiotics (Amoxicillin) combined with povidone-iodine. The wound healing time and complication rate were determined for both groups, and subsequently, predisposing factors for complications among the baseline characteristics and non-patient-related parameters were determined. The baseline characteristics were similar for both study groups, supporting a homogenous distribution. Postoperative complications were experienced by 19.3% of the patients in the control group and 18.8% in the treatment (MGH) group. The treatment group experienced significantly more superficial pus discharge than the control group, while the latter experienced significantly more deeper pus discharge. BMI, age, duration of hospitalization, anesthesia, and duration of CS could affect the complication risk. MGH significantly enhanced wound healing until day 42. On average, the healing time with MGH was 19.12 ± 7.760 days versus 24.54 ± 8.168 days in the control group. MGH is a potent alternative treatment to antibiotics and povidone-iodine because while the complication risk is similar, MGH has additional benefits. MGH promotes wound healing and does not bear the risk of resistance

Educational Psychology: Advances in learning, cognition and motivation

Mesenchymal stem cell (MSC) administration is a promising adjuvant therapy to treat tissue injury. However, MSC survival after administration is often hampered by oxidative stress at the site of injury. Heme oxygenase (HO) generates the cytoprotective effector molecules biliverdin/bilirubin, carbon monoxide (CO) and iron/ferritin by breaking down heme. Since HO-activity mediates anti-apoptotic, anti-inflammatory, and anti-oxidative effects, we hypothesized that modulation of the HO-system affects MSC survival. Adipose-derived MSCs (ASCs) from wild type (WT) and HO-2 knockout (KO) mice were isolated and characterized with respect to ASC marker expression. In order to analyze potential modulatory effects of the HO-system on ASC survival, WT and HO-2 KO ASCs were pre-treated with HO-activity modulators, or downstream effector molecules biliverdin, bilirubin, and CO before co-exposure of ASCs to a toxic dose of H2O2. Surprisingly, sensitivity to H2O2-mediated cell death was similar in WT and HO-2 KO ASCs. However, pre-induction of HO-1 expression using curcumin increased ASC survival after H2O2 exposure in both WT and HO-2 KO ASCs. Simultaneous inhibition of HO-activity resulted in loss of curcumin-mediated protection. Co-treatment with glutathione precursor N-Acetylcysteine promoted ASC survival. However, co-incubation with HO-effector molecules bilirubin and biliverdin did not rescue from H2O2-mediated cell death, whereas co-exposure to CO-releasing molecules-2 (CORM-2) significantly increased cell survival, independently from HO-2 expression. Summarizing, our results show that curcumin protects via an HO-1 dependent mechanism against H2O2-mediated apoptosis, and likely through the generation of CO. HO-1 pre-induction or administration of CORMs may thus form an attractive strategy to improve MSC therapy