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Wound dressings produced by electrospinning exhibit a fibrous structure close to the one of the extracellular matrix of the skin. In this article, electrospinning was used to fabricate fiber mats based on the well-known biopolymers poly(ɛ-caprolactone) (PCL) and methylcellulose (MC) using benign solvents. The blend fiber mats were cross-linked using Manuka honey and additionally used as a biodegradable platform to deliver bioactive glass particles. It was hypothesized that a dual therapeutic effect can be achieved by combining Manuka honey and bioactive glass. Morphological and chemical examinations confirmed the successful production of submicrometric PCL-MC fiber mats containing Manuka honey and bioactive glass particles. The multifunctional fiber mats exhibited improved wettability and suitable mechanical properties (ultimate tensile strength of 3-5 MPa). By performing dissolution tests using simulated body fluid, the improved bioactivity of the fiber mats by the addition of bioactive glass was confirmed. Additionally, cell biology tests using human dermal fibroblasts and human keratinocytes-like HaCaT cells showed the potential of the fabricated composite fiber mats to be used as wound dressing, specially due to the ability to support wound closure influenced by the presence of bioactive glass. Moreover, based on the results of the antibacterial tests, it is apparent that an optimization of the electrospun fiber mats is required to develop suitable wound dressing for the treatment of infected wounds.

Background Manuka honey (MH) has significant antibiofilm activity in vitro and in vivo against Staphylococcus aureus, methicillin-resistant S aureus (MRSA), and Pseudomonas aeruginosa. This is the first randomized, single-blinded, placebo-controlled phase 1 clinical trial investigating the safety and preliminary efficacy of MH with augmented methylglyoxal (MGO) rinses in recalcitrant chronic rhinosinusitis (CRS). Methods Patients were included after previously undergoing endoscopic sinus surgery and presenting with signs and symptoms of sinus infection with positive bacterial cultures on sinus swabs. Patients were randomized to receive 14 days of twice-daily 16.5% MH + 1.3 mg/mL MGO sinonasal rinses and concurrent 10 days of placebo tablets (MH), or 14 days of twice-daily saline sinonasal rinses and concurrent 10 days of culture-directed antibiotic therapy (CON). Safety observations included the University of Pennsylvania Smell Identification Test (UPSIT) and adverse-event (AE) reporting. Efficacy was assessed comparing microbiology results, Lund-Kennedy scores (LKSs), and symptom scores using the visual analog scale (VAS) and 22-item Sino-Nasal Outcome Test (SNOT-22). Results Twenty-five patients completed the study. MH demonstrated a good safety profile with no major AEs and no changes in UPSIT. Six of 10 (60%) MH patients had a reduction in bacterial culture rate with 1 of 10 of those having negative cultures, compared with 12 of 15 (80%) in the control group with 7 of 15 having negative cultures upon completion of the study. Conclusion This study concludes that twice-daily 16.5% MH augmented with 1.3 mg/mL MGO sinonasal rinses alone for 14 days is safe but not superior to culture-directed oral antibiotics and twice-daily saline rinses.

Manuka honey is an ancient remedy to improve wound healing; however, an effective delivery system is needed to facilitate extended release of honey into wounds. We developed an electrospun dermal regeneration template consisting of a poly (ε-caprolactone) (PCL) scaffold embedded with 1%, 5%, 10%, or 20% manuka honey. In vitro studies demonstrated that honey PCL scaffolds were not toxic to macrophages, and they allowed for macrophage infiltration into the scaffolds. Vascular endothelial growth factor (VEGF), a marker of angiogenesis, was released by macrophages cultured with scaffolds and macrophage/scaffold conditioned media promoted endothelial cell tube formation in an angiogenesis assay. In a full thickness murine wound model, the scaffolds prevented rapid wound contraction. In vivo, cells infiltrated the scaffolds by post-wounding day 7, but the honey scaffolds did not affect collagen deposition at that time. In summary, preliminary studies investigating the effect of honey on tissue repair show that scaffolds prevent rapid wound contraction, allow for cell infiltration, and promote angiogenesis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2620-2628, 2019.

Previous studies have identified honey as an agent in bacterial inhibition and a mediator in lowering the pH at the wound site. Manuka honey (MH), indigenous to New Zealand, contains a Unique Manuka Factor that provides an additional antibacterial agent. While there are many potential benefits to incorporating MH into wounds, there is currently no ideal way to deliver the material to the site of injury. Cryogels are a type of scaffold that possess high porosity, mechanical stability, and a sponge-like consistency. This study uniquely incorporates varying amounts of MH into cryogel scaffolds, utilizing its properties in a sustained release fashion to assist in the overall healing process, while using the cryogel structure as a tissue template. All cryogels were evaluated to determine the effects of MH on porosity, swelling potential, mechanical durability, and cell compatibility. The release of MH was also quantified to evaluate bacterial clearance potential, and the scaffolds were mineralized to replicate native bone. It was determined that a 5% MH silk fibroin cryogel has the potential to inhibit bacterial growth while still maintaining adequate porosity, mechanical properties, and cell infiltration. Such a scaffold would have use in a number of applications, including bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1918-1933, 2018.

This article was published Open Access in Immunity, Inflammation and Disease (online) available at http://dx.doi.org/10.1002/iid3.153

Background Manuka honey (MH) has been shown in vitro to be effective against biofilm-producing bacteria. This study assessed the effectiveness of MH for patients with active chronic rhinosinusitis (CRS) and prior sinus surgery. Methods This prospective single-blinded (clinician only) randomized controlled trial recruited patients with active CRS and prior sinus surgery. Patients received either MH or saline (SAL) sinus irrigations twice daily for 30 days and were offered oral antibiotics and/or oral/topical steroids as indicated. Outcomes were 22-item Sino-Nasal Outcome Test (SNOT-22) change score (primary), culture negativity, and Lund-Kennedy endoscopic change score. Results Forty-two patients were analyzed (MH, n = 20; SAL, n = 22). The SNOT-22 change score achieved a clinically significant improvement in both groups but was similar between MH (median [interquartile range]: −12 [−20, −1]) and SAL (−12.5 [−22, −6]) (p = 0.57). Culture negativity was better on MH (8/19, 42%) compared to SAL (4/21, 19%), nearing statistical significance (p = 0.11). Lund-Kennedy endoscopic change score improved in both groups but was not statistically better on MH (−3 [−5, 0]) compared to SAL (−1 [−2, 0]) (p = 0.20). For patients not receiving oral antibiotics/steroids, culture negativity was statistically better on MH (5/10, 50%) compared to SAL (0/6, 0%) (p = 0.04). MH was well-tolerated. No adverse events were reported. Conclusion In patients with active CRS and prior sinus surgery, both MH and SAL improved outcomes, but there was no statistically significant difference between these groups. However, in the subset that did not receive oral antibiotics/steroids, culture negativity was statistically better on MH, suggesting that MH alone may be effective for acute exacerbations of CRS.

Objective To investigate the effect of 66% Manuka honey gel on the concentrations of transforming growth factor (TGF)-β1 and TGF-β3, bacterial counts and histomorphology during healing of contaminated equine distal limb wounds. Methods In this experimental study of 10 Standardbred horses, five full-thickness skin wounds (2 × 1.5 cm) were created on one metacarpus and six similar wounds were created on the contralateral metacarpus. Wounds were assigned to three groups: non-contaminated control wounds; contaminated control wounds; contaminated wounds treated daily with 1 mL Manuka honey gel topically for 10 days. For the contaminated wounds, faeces were applied for 24 h after wound creation. In five horses wounds were bandaged and in the other five horses wounds were left without a bandage. Biopsies were taken on days 1, 2, 7 and 10 after wounding to evaluate the effects of Manuka honey gel, wound contamination and bandaging on TGF-β1 and TGF-β3 concentrations, aerobic and anaerobic bacterial counts, and histomorphology. Results Manuka honey gel had no significant effect on TGF-β1 and TGF-β3 concentrations or wound bacterial counts. Manuka honey gel decreased wound inflammation (days 7, 10), increased angiogenesis (days 2, 7, 10), increased fibrosis and collagen organisation (day 7) and increased epithelial hyperplasia (days 7, 10). Conclusions Treatment with Manuka honey gel resulted in a more organised granulation tissue bed early in wound repair, which may contribute to enhanced healing of equine distal limb wounds.

Antimicrobial resistance is a problem in human and animal healthcare. Honey may be used for its wound healing properties and antimicrobial effects.To investigate the antimicrobial activity of two commercially available medical grade honeys (MGHs) against Staphylococcus spp. and Pseudomonas spp. isolates.Two formulations, MGH1 (40% w/v honey) and MGH2 (80% w/v Manuka honey), were tested in vitro for minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC) against 11 Staphylococcus and 11 Pseudomonas isolates at low [1.5 × 10MGH2 showed a lower MIC against staphylococci than MGH1, although this was not statistically significant. MGH1 had stronger bactericidal effects against staphylococci than MGH2, although this effect was statistically significant only at the higher bacterial concentration (P 0.01). For Pseudomonas spp., MGH1 had significantly higher antimicrobial activity (both MIC and MBC) than MGH2 against all isolates tested and at both bacterial concentrations (P 0.05).Both MGHs were effective in vitro against common cutaneous pathogens including meticillin-resistant staphylococci and Pseudomonas species. The higher efficacy of the MGH1 formulation against Pseudomonas and its consistent effects against staphylococci, while containing only half of the amount of honey compared to MGH2, invites further investigation of the mechanisms and clinical applications of MGH1.La résistance antimicrobienne est un problème en santé humaine et animale. Le miel pourrait être utilisé pour ses propriétés de cicatrisation et ses effets antimicrobiens.Etudier l'activité antimicrobienne de deux miels médicaux disponibles dans le commerce (MGHs) contre les souches de Staphylococcus spp. et Pseudomonas spp. MATÉRIELS ET MÉTHODES: Deux formulations, MGH1 (miel à 40% w/v) et MGH2 (miel de Manuka à 80% w/v), ont été testées in vitro pour la concentration minimale inhibitrice (MIC) et les concentrations minimales bactéricides (MBC) contre 11 souches de Staphylococcus et 11 Pseudomonas à faibles [1.5 × 10Les deux MGHs étaient efficaces in vitro contre les pathogènes cutanés fréquents incluant les staphylocoques résistant à la méticilline et Pseudomonas. La plus grande efficacité de la formulation de MGH1 contre Pseudomonas et ses effets contre staphylocoques, alors que contenant moitié moins de mile que MGH2, implique la réalisation d'autres études des mécanismes et des applications cliniques de MGH1.INTRODUCCIÓN: la resistencia a los antimicrobianos es un problema en la salud humana y animal. La miel puede usarse por sus propiedades de cicatrización en heridas y por sus efectos antimicrobianos. OBJETIVO: investigar la actividad antimicrobiana de dos mieles de grado médico (MGHs) disponibles comercialmente frente a aislados de Staphylococcus spp. y Pseudomonas spp. MÉTODOS Y MATERIALES: dos formulaciones, MGH1 (40% p/v de miel) y MGH2 (80% p/v de miel de Manuka), se probaron in vitro para detectar concentraciones inhibitorias mínimas (MIC) y concentraciones bactericidas mínimas (MBC) frente a 11 aislados de Staphylococcus y 11 aislados de Pseudomonas a bajas [1,5 × 10Die antimikrobielle Resistenz ist ein Problem bei der Gesundheitsvorsorge des Menschen und der Tiere. Honig könnte aufgrund seiner Wundheilungseigenschaften und antimikrobieller Wirkungsweisen Verwendung finden. ZIEL: Eine Untersuchung der antimikrobiellen Aktivität zweier kommerziell verfügbarer medizinischer Honige (MGHs) im Einsatz gegen Staphylococcus spp. und Pseudomonas spp. Isolate.Zwei Formulierungen, MGH1 (40% w/v Honig) und MGH2 (80% w/v Manukahonig) wurden in vitro auf ihre minimale Hemmstoffkonzentration (MIC) und minimale bakterizide Konzentration (MBC) gegenüber Staphylococcus und 11 Pseudomonas Isolate getestet, wobei niedrige[1,5 x 10MGH2 zeigte eine niedrigere MIC gegenüber Staphylokokken als MGH1, obwohl dieses Ergebnis nicht statistisch signifikant war. MGH1 zeigte eine deutlichere bakterizide Wirkung gegenüber Staphylokokken als MGH2, obwohl dieses Ergebnis nur bei höheren bakteriellen Konzentrationen statistisch signifikant war (P0,01). Bei Pseudomonas spp. zeigte MGH1 eine signifikant höhere antimikrobielle Aktivität (sowohl MIC als auch MBC) als MGH2 gegenüber allen getesteten Isolaten und bei beiden bakteriellen Konzentrationen (P0,05).Beide MGHs waren in vitro gegen übliche Hautpathogene inklusive Methicillin-resistenten Staphylokokken und Pseudomonas Spezies wirksam. Die höhere Wirksamkeit der MGH1 Formulierung gegenüber Pseudomonas und seine konstante Wirkung gegenüber Staphylokokken, obwohl es nur die halbe Menge an Honig im Vergleich zu MGH2 beinhaltete, laden zu weiterer Untersuchung des Mechanismus und der klinischen Anwendung von MGH1 ein.背景: 抗生素耐药性是人类和动物医疗保健中的一个问题。由于蜂蜜具有愈合伤口和抗菌作用,因而值得使用。 目的: 研究现有市售的两种药用级别蜂蜜(MGHs)对葡萄球菌和假单胞菌分离株的抗菌活性。 方法和材料: 两种配方,MGH1 (40% w/v 蜂蜜) 和MGH2 (80% w/v Manuka 蜂蜜),针对11个葡萄球菌和11个假单胞菌分离株,体外测定其最小抑制浓度(MIC)和最小杀菌浓度(MBC),选择培养液的低 [1.5 × 10背景: 抗菌薬耐性は、人間および動物のヘルスケアにおける問題である。蜂蜜は、その創傷治癒特性および抗菌効果のために使用される場合がある。 目的: 本研究の目的は、2つの市販された医療グレードの蜂蜜(MGH)によるブドウ球菌およびシュードモナス属菌株に対する抗菌活性を調査することである。 材料と方法: MGH1(40%w / v蜂蜜)とMGH2(80%w / vのマヌカ蜂蜜)の2製剤に対し、それぞれ感染時の全身および皮膚細菌負荷を表す、低濃度[1.5×104コロニー形成単位(cfu)/ウェル]および高濃度(1.5×106 cfu /ウェル)のブドウ球菌および緑膿菌それぞれ11分離株に対する最小発育阻止濃度(MIC)と最小殺菌濃度(MBC)をin vitroでテストした。 結果: MGH2は、MGH1よりもブドウ球菌に対する低いMICを示したが、統計的に有意ではなかった。 MGH1はMGH2よりブドウ球菌に対して強い殺菌効果があったが、細菌濃度が濃い場合にのみ統計的に有意であった(P0.01)。緑膿菌においては、MGH1は、試験した全分離株および両細菌濃度で、MGH2よりも抗菌活性(MICおよびMBCの両方)が有意に高かった(P0.05)。 結論と臨床的重要性: 両MGHは、メチシリン耐性ブドウ球菌と緑膿菌を含む一般皮膚病原体に対してin vitroで効果的であった。 MGH2と比較し、半量の蜂蜜しか含まない一方で、緑膿菌に対するMGH1製剤の高い効力およびブドウ球菌に対する一貫した効果は、MGH1のメカニズムおよび臨床応用のさらなる調査をもたらす。.A resistência antimicrobiana é um problema na saúde humana e animal. O mel pode ser utilizado por suas propriedades curativas e efeitos antimicrobianos.Investigar a atividade antimicrobiana de dois méis medicinais (MGHs) comercialmente disponíveis contra Staphylococcus spp. e Pseudomonas spp. isolados. MÉTODOS E MATERIAIS: Duas formulações, MGH1 (40% p / v mel) e MGH2 (80% p / v mel Manuka), foram testadas in vitro para concentrações inibitórias mínimas (MIC) e concentrações bactericidas mínimas (MBC) contra 11 Staphylococcus e 11 Pseudomonas isolados em baixas [1,5 × 10O MGH2 mostrou uma MIC menor contra estafilococos do que o MGH1, embora isso não tenha sido estatisticamente significativo. O MGH1 teve efeitos bactericidas mais fortes contra os estafilococos do que o MGH2, embora esse efeito tenha sido estatisticamente significativo apenas na maior concentração bacteriana (P0,01). Para Pseudomonas spp., O MGH1 apresentou atividade antimicrobiana significativamente maior (MIC e MBC) do que o MGH2 contra todos os isolados testados e em ambas as concentrações bacterianas (P0,05). CONCLUSÕES E IMPORTÂNCIA CLÍNICA: Ambas OS MGHs foram eficazes in vitro contra patógenos cutâneos comuns, incluindo estafilococos resistentes à meticilina e espécies de Pseudomonas. A maior eficácia da formulação MGH1 contra Pseudomonas e seus efeitos consistentes contra estafilococos, embora contenha apenas metade da quantidade de mel em comparação com o MGH2, convida a uma investigação mais aprofundada dos mecanismos e aplicações clínicas do MGH1.

ObjectiveTo investigate the effect of activated protein C (APC) on second intention healing of distal limb wounds in horses.MethodsIn this experimental study of eight Standardbred geldings, six full-thickness skin wounds (2x1.5cm) were created on one metacarpus (biopsy limb) and five similar wounds were created on the contralateral metacarpus (photographed limb). Three wounds on the biopsy limb were treated topically with 190 mu g APC on days 1, 3, 6 and 9, while the remaining three wounds were untreated (control). One treated and one control wound were biopsied on days 4, 7 and 11 for histopathology. Wounds on the photographed limb were treated with either 66% Manuka honey gel, a commercial antibiotic ointment (bacitracin-neomycin-polymixin B ointment; BNP) or petrolatum daily throughout healing, treated on days 1,3,6 and 9 with 190 mu g APC or left untreated. These wounds were digitally photographed and the wound area measured on day 1, then weekly until day 49. Overall time to healing was recorded.ResultsThere was no effect of APC on wound size, the rate of healing or the overall time to heal. However, compared with control wounds, histological scoring demonstrated enhanced epithelialisation (day 4) and angiogenesis (day 11). Wound healing variables for wounds treated with APC, Manuka honey gel and control wounds were not different and the variables for wounds treated with BNP and petrolatum demonstrated delayed healing.ConclusionThe improvements in histological scores in APC-treated wounds suggest further study into the effect of APC on second intention wound healing in horses is warranted.

This study investigated the effect of 3 factors (floral source, honeybee species, and postcollection processing) that influence the antibacterial activity, free radical reduction, and other biochemical compositions of different honey types typical of Thailand. Honey samples from 3 honeybee species (Apis mellifera, Apis cerana ,a ndApis dorsata )w ere obtained from 9 floral sources (longan, wild flower, lychee, coffee, sunflower, sesame, bitter bush, para-rubber, and manuka as a control) in different regions of Thailand. These samples were evaluated for both their total and nonperoxide antibacterial activity against 10 human pathogens by agar incorporation technique. Honey samples were further analyzed to evaluate the capacity for free radical-scavenging activity, total phenolic content, and the total flavonoid contents by the 2,2-diphenyl- 1-picrylhydrazyl assay, Folin-Ciocalteu method, and aluminum chloride colorimetric assay, respectively. Furthermore, the volatile organic compounds (VOCs) of Thai honey samples were investigated by headspace solid-phase microextraction and gas chromatography-mass spectrometry analysis. Findings of this study suggest a strong correlation between floral origin and honeybee species on one hand, and differences in %Brix, total acidity, protein content, antimicrobial activities, free radical reduction, phenolic, and flavonoid contents on the other hand. Moreover, VOCs of wild and coffee honey types were remarkably different, depending on the floral source. Both honeys contained characteristics of VOCs, some of which are involved in antibacterial and antioxidant activities.

In addition to the generic properties of honey, manuka honey has a nonperoxide antimicrobial activity largely attributed to methylglyoxal. Commercially, manuka honey is graded against a standard antiseptic, phenol, to provide a measure of antimicrobial activity referred to as the unique manuka factor (UMF). The higher the UMF, the greater the antimicrobial activity. However, more recently, there is evidence that manuka honey can also modulate the initial inflammatory response through activation of toll-like receptor 4 on monocytes to enhance production of cytokines important in tissue repair and regeneration. Recent studies investigating the effects of manuka honey on second intention healing of lower limb wounds in horses have shown that wounds treated with UMF 20 manuka honey retracted less and healed faster than untreated wounds. Using this wound healing model, the primary effects of manuka honey appeared to be associated with the modulation of the initial inflammatory reaction rather than its antimicrobial effects. Based on the current knowledge, treatment with manuka honey should be instituted as soon as possible after injury. Where bacterial contamination is substantial, manuka honey with a UMF ≥15 should be used. While bandages will improve the contact between the honey and the wound and may be indicated in the early stages of wound healing, prolonged bandaging may lead to the production of excessive granulation tissue. If topical treatment without a bandage is to be used, more honey is not necessarily better. Using a thin film combined with regular application, contact times may be optimised. Application 2–3 times daily to open wounds may improve efficacy. Manuka honey should be applied for at least 21 days after wounding but there may be beneficial effects if it is applied until wound healing is almost complete.

1. Majtan J, Majtan V. Is manuka honey the best type of honey for wound care? Journal of Hospital Infection. 2010 Mar; 74(3): 305-306 2. Robson V, Dodd S, Thomas S. Standardized antibacterial honey (Medihoney) with standard therapy in wound care: randomized clinical trial. J Adv Nurs. 2009 Mar; 65(3): 565-75 3. Thamboo A, Philpott C et al. Single-blind study of manuka honey in allergic fungal rhinosinusitis. J Otolaryngol Head Neck Surg. 2011 Jun; 40(3):238-43 4. Biswal BM, Zakaria A & Ahmad NM. Topical application of honey in the management of radiation mucositis: a preliminary study. Support Care Cancer. 2003; 11:242-248 5. Thamboo A, Philpott C et al. Single-blind study of manuka honey in allergic fungal rhinosinusitis. J Otolaryngol Head Neck Surg. 2011 Jun; 40(3):238-43 6. Butler,G., Al Ghamdi, A., Salom, K., Al-Waili. Honey and microbial infections: a review supporting the use of honey for microbial control. J Med Food. 2011;14(10): 1079-1096 7. Robson V, Cooper RA & Ehsan ME. Honey in wound management following ENT surgery. Primary Intention. 2007 Nov; 15(4): 176-180 8. Flynn M, Breitholtz F, Halvarsson G, Rosengren A, Sadeghi A. (2008, Dec). Classifying skin reactions at the BAHA® implant site. Acknowledgements: The authors would like to thank the members of the University of Arizona Department of Otolaryngology and the University of Arizona School of Medicine for their opinions and suggestions for this work. Author Contact: eafaucett@oto.arizona.edu Table 1. Skin Reaction Characteristics Figure 1. Medihoney ®

Leptospermum scoparium (Mānuka) is the source of nectar for Unique Mānuka Factor (UMF) honey. The chemical component of interest to this study is dihydroxyacetone (DHA). DHA is the precursor for the chemical methylglyoxyl which is the main chemical responsiblefortheUMFactivityinManukahoney.ScreeningcommerciallybredplantsforincreasedDHAsynthesisinL. scoparium is a critical factor in growing the Manuka Honey industry in New Zealand. FT-Raman spectroscopy, in combination with principal component analysis and partial least squares regression analysis, was investigated as an analytical tool for building a screening model for DHA in the nectar of L. scoparium. Leaf samples of seven cultivars of the species L. scoparium were collected in an attempt to correlate metabolic factors in the plant with DHA synthesis in the nectar. Leaf material was analysed using Fourier transform-ramanspectroscopy (FT-Raman). The DHA levels in nectarsamples of the samecultivars were measured using standard LC-MS methods. This study showed that the application of multivariate analysis of FT-Raman spectra from leaf material is a useful tool to screen for DHA potential inL. scoparium. The PLS regression shows that we can screen for DHA concentrations in the range of 3300–7600mg/kg plus or minus 20% standard error and can distinguish low medium and high DHA synthesis in the group of plants studied. The model for predicting DHA concentrations is influenced by a significant contribution from the spectral variance due to beta-carotene and other highly scattering compounds that are not directly correlated with UMF. Copyright © 2014 John Wiley & Sons, Ltd. Additional supporting information may be found in the online version of this article at the publisher’s web site.

Summary This work was undertaken to assess the effects of high-pressure processing on brown pigment formation, antibacterial activity and hydroxymethylfurfural (HMF) content in Manuka honey. The honey was subjected to different pressures (200400 MPa) at ambient temperatures (25-33 "C) and with moderate temperatures (53-74 "C) for holding times (10-30 min). The brown pigment formation in high-pressuretreated sample showed a significant increase (0.16-0.17, P 0.05). Thus, high-pressure processing has no adverse effect on the honey quality because it can control HMF concentration during process. Increasing brown pigment formation is associated with the enhancement of antibacterial activity.

Background Bacterial biofilms are thought to contribute to recalcitrance in chronic rhinosinusitis (CRS) patients. Manuka honey (MH) and its active component methylglyoxal (MGO) have demonstrated antibiofilm activity in vitro. This study evaluated the safety and efficacy of these agents in an in vivo model. Methods To assess safety, ovine frontal sinuses were flushed twice daily for 14 days. In each sheep, 1 sinus was flushed with a panel of MGO concentrations ranging from 0.5 to 7.2 mg/mL alone and flushed with a panel of with 16.5% wt/vol MH enriched with MGO at the same range of concentrations (0.5–7.2 mg/mL; designated MH/MGO). Contralateral sinuses were flushed with saline control. Tissue morphology was assessed histologically and with scanning electron microscopy. Efficacy was tested by developing Staphylococcus aureus biofilms in sheep sinuses. Twice-daily irrigation for 5 days was commenced with either saline, MGO (0.5–3.6 mg/mL) alone, or MH/MGO (with 0.5–3.6 mg/mL MGO). Biofilm biomass was compared between the groups (n = 4) using LIVE/DEAD BacLight staining and confocal scanning laser microscopy. Results The results of the safety assessment, for normal sinuses treated with MGO alone or with MH/MGO (≤1.8 mg/mL) showed normal pseudostratified epithelium and cilia structure; however, higher concentrations caused cilia denudation and squamous metaplasia. As for efficacy, when compared to saline flush, treatment with MH/MGO at 0.9 mg/mL (0.608 ± 0.110 vs 0.316 ± 0.197 μm3/μm2, respectively; p = 0.015) and 1.8 mg/mL (0.676 ± 0.079 vs 0.114 ± 0.033 μm3/μm2, respectively; p = 0.001) significantly reduced biofilm biomass. Conclusion Sinus irrigation with MH/MGO at MGO concentrations between 0.9 and 1.8 mg/mL is both safe to mucosa and efficacious against S. aureus biofilm. MH/MGO irrigation could represent a viable treatment option for recalcitrant CRS.

Objectives To compare the effects of manuka honey and manuka honey gel on second intention healing of noncontaminated distal limb wounds and those contaminated with feces. Study Design Experimental study. Animals Standardbred horses (n = 10). Methods Five full-thickness wounds (2 x 2 cm) were created on both metacarpi. Wounds on 1 forelimb were covered with horse feces for 24 hours. Wounds on the contralateral limb were left uncontaminated. Wounds were assigned to the following 5 different treatments: manuka honey, manuka honey gel or gel applied for 12 days, manuka honey gel applied throughout healing and untreated control. Wound area was measured on day 1 then weekly until day 42 and time to complete healing was recorded. Results Wounds treated with manuka honey gel throughout healing healed faster than all other wounds (P < .05). Wounds treated with manuka honey and manuka honey gel for 12 days healed faster than gel control and untreated control wounds (P < .05). Wounds treated with manuka honey and manuka honey gel for 12days and throughout healing were smaller than gel control and untreated control wounds until day 35 (P < .05). Wounds contaminated with feces had greater retraction for 7 days, but healed faster than noncontaminated wounds (P < .05). Conclusions Treatment of wounds with manuka honey and manuka honey gel reduced wound retraction and overall healing time compared with gel and untreated control wounds.

Recently renewed interest in the therapeutic properties of honey has led to the search for new antimicrobial honeys. This study was undertaken to assess the antimicrobial activity and composition of a locally produced Portobello honey (PBH) on three bacteria known to infect wounds. Manuka honey (MH) was used for comparative purposes. Broth culture and agar disc diffusion assays were used to investigate the antimicrobial properties of honey. The honeys were tested at four concentrations: 75%, 50%, 10% and 1% (v/v) and compared with an untreated control. The composition of honey was determined by measuring: polyphenol content by Folin Ciocalteau method, antioxidant capacity by ferric ion reducing power assay, hydrogen peroxide (H2 O2 ) by catalase test, pH and sugar content by pH strips and refractometer, respectively. Both honeys at 75% and 50% inhibited the majority of the three bacteria tested. 10% PBH exhibited antimicrobial activity to the lesser extent than 10% MH. The difference was very significant (p ≤ 0.001). Both honeys were acidic with pH 4, and both produced H2 O2 . The sugar content of PBH was higher than MH, but the difference was not significant. The MH had significantly higher levels of the polyphenols and antioxidant activity than PBH.

In this study, we investigate the effect of manuka honey‐impregnated dressings (MHID) on the healing of neuropathic diabetic foot ulcers (NDFU). A total of 63 Caucasians, type 2 diabetic patients followed up in the diabetic foot outpatient clinic comprised the study population. Patients were randomised in two groups as follows: group I patients were treated with MHID and group II patients were treated with conventional dressings (CD). The patients were followed up on a weekly basis for 16 weeks. Mean healing time was 31 ± 4 days in group I versus 43 ± 3 days in group II (P < 0·05). In group I patients 78·13% of ulcers became sterile during the first week versus 35·5% in group II patients; the corresponding percentages for weeks 2, 4 and 6 were 15·62% versus 38·7%, 6·25% versus 12·9% and 0% versus 12·9% respectively. The percent of ulcers healed did not differ significantly between groups (97% for MHID and 90% for CD). MHID represent an effective treatment for NDFU leading to a significant reduction in the time of healing and rapid disinfection of ulcers.

Summary Aim: To evaluate the evidence on the impact of different debridement techniques on healing and their efficacy in the treatment of leg ulcers. Methods: Web-based search (PubMed) for trials investigating surgical, enzymatic, autolytic, osmotic, ultrasound-assisted, and biosurgical wound debridement on leg ulcers with regard to healing and efficacy. Results: Both surgical and hydrosurgical methods proved to be effective debridement techniques. For conventional surgical debridement, a significantly greater reduction of the wound surface area and a higher healing rate were reported. Studies on autolytic, osmotic, and enzymatic wound debridement showed effective debridement for krill enzymes, dextranomer and manuka honey. Only for manuka honey was there a significantly greater reduction of the wound surface area compared to standard treatment. One study comparing fibrinolysin/DNAse with placebo and one comparing autolytic with enzymatic debridement showed no significant differences between the respective techniques. Trials on ultrasound-assisted wound debridement reported a positive impact on healing. A significant wound surface area reduction was demonstrated in one of them. Maggot therapy led to effective debridement. The largest trial showed no significantly improved healing. Conclusions: Further studies are needed to strengthen the evidence for a significant impact of wound debridement on the healing of leg ulcers.

Objectives/Hypothesis: Low pH, hydrogen peroxide generation, and the hyperosmolarity mechanisms of antimicrobial action are ubiquitous for all honeys. In addition, manuka honey has been shown to contain high concentrations of methylglyoxal (MGO), contributing the relatively superior antimicrobial activity of manuka honey compared to non-MGO honeys. In high concentrations, manuka honey is effective in killing Staphylococcusaureus biofilms in vitro. Lower concentrations of honey, however, are desirable for clinical use as a topical rinse in chronic rhinosinusitis in order to maximize the tolerability and practicality of the delivery technique. This study, therefore, was designed to evaluate the contribution of MGO to the biofilm-cidal activity of manuka honey, and furthermore determine whether the antibiofilm activity of low-dose honey can be augmented by the addition of exogenous MGO. Study Design: In vitro microbiology experiment. Methods: Five S.aureus strains (four clinical isolates and one reference strain) were incubated to form biofilms using a previously established in vitro dynamic peg model. First, the biofilm-cidal activities of 1) manuka honey (790 mg/kg MGO), 2) non-MGO honey supplemented with 790 mg/kg MGO, and 3) MGO-only solutions were assessed. Second, the experiment was repeated using honey solutions supplemented with sufficient MGO to achieve concentrations exceeding those seen in commercially available manuka honey preparations. Results: All honey solutions containing a MGO concentration of 0.53 mg/mL or greater demonstrated biofilm-cidal activity; equivalent activity was achieved with ≥1.05 mg/mL MGO solution. Conclusions: MGO is only partially responsible for the antibiofilm activity of manuka honey. Infusion of MGO-negative honey with MGO, however, achieves similar cidality to the equivalent MGO-rich manuka honey.

Carbon isotope analyses (delta(13)C) of some New Zealand Manuka honeys show that they often fail the internationally recognised Association of Official Analytical Chemists sugar test (AOAC method 998.12) which detects added C(4) sugar, although these honeys are from unadulterated sources. Failure of these high value products is detrimental to the New Zealand honey industry, not only in lost export revenue, but also in brand and market reputation damage. The standard AOAC test compares the carbon isotope value of the whole honey and corresponding protein isolated from the same honey. Differences between whole honey and protein delta(13)C values should not be greater than +1.0 per thousand, as it indicates the possibility of adulteration with syrups or sugars from C(4) plants such as high fructose corn syrup or cane sugar.We have determined that during the standard AOAC method, pollen and other insoluble components are isolated with the flocculated protein. These non-protein components have isotope values which are considerably different from those of the pure protein, and can shift the apparent delta(13)C value of protein further away from the delta(13)C value of the whole honey, giving a false positive result for added C(4) sugar. To eliminate a false positive C(4) sugar test for Manuka honey, prior removal of pollen and other insoluble material from the honey is necessary to ensure that only the pure protein is isolated. This will enable a true comparison between whole honey and protein delta(13)C isotopes. Furthermore, we strongly suggest this modification to the AOAC method be universally adopted for all honey C(4) sugar tests.

Summary A spectrophotometric bioassay was used to screen selected food ingredients intended for development of functional foods designed to influence the growth of gut bacteria. Dose–response profiles displaying Dgrowth, the magnitude of deviation from growth of controls, were generated for probiotics Lactobacillus reuteri, Lactobacillus rhamnosus, Bifidobacterium lactis and pathogens Escherichia coli, Salmonella Typhimurium and Staphylococcus aureus. Ingredients were manuka honey UMF� 20+(dose-dependently increased probiotics and decreased pathogens); bee pollen (biphasic growth effects against all); Rosehips and BroccoSprouts � (increased all dose-dependently); blackcurrant oil (little effect) and propolis (inhibited all strains). Ingredients were also bioassayed in pairs to assess desirable or undesirable synergistic interactions. Observed synergies included manuka honey (predominantly desirable); rosehips or BroccoSprouts� (desirable and undesirable); blackcurrant oil (desirable) and propolis (tended towards synergies reinforcing its antimicrobial effects), collectively revealing a complex web of interactions which varied by ingredient and bacterial strain. Manuka honey was particularly effective at influencing gut bacteria. The surprising frequency of undesirable synergistic interactions illustrates the importance of pre-testing potential ingredient combinations intended for use in functional foods.

Objective. Comparison of desloughing efficacy after four weeks and healing outcomes after 12 weeks in sloughy venous leg ulcers treated with Manuka honey (Woundcare 18+) vs. standard hydrogel therapy (IntraSite Gel). Background. Expert opinion suggests that Manuka honey is effective as a desloughing agent but clinical evidence in the form of a randomised controlled trial is not available. There is a paucity of research which uses Manuka honey in venous ulcers. Design. Prospective, multicentre, open label randomised controlled trial. Method. Randomisation was via remote telephone. One hundred and eight patients with venous leg ulcers having ≥50% wound area covered in slough, not taking antibiotics or immunosuppressant therapy were recruited from vascular centres, acute and community care hospitals and leg ulcer clinics. The efficacy of WoundCare 18+ to deslough the wounds after four weeks and its impact on healing after 12 weeks when compared with IntraSite Gel control was determined. Treatment was applied weekly for four weeks and follow-up was made at week 12. Results. At week 4, mean % reduction in slough was 67% WoundCare 18+ vs. 52·9% IntraSite Gel (p = 0·054). Mean wound area covered in slough reduced to 29% and 43%, respectively (p = 0·065). Median reduction in wound size was 34% vs. 13% (p = 0·001). At 12 weeks, 44% vs. 33% healed (p = 0·037). Wounds having >50% reduction in slough had greater probability of healing at week 12 (95% confidence interval 1·12, 9·7; risk ratio 3·3; p = 0·029). Infection developed in 6 of the WoundCare 18+ group vs. 12 in the IntraSite Gel group. Conclusion. The WoundCare 18+ group had increased incidence of healing, effective desloughing and a lower incidence of infection than the control. Manuka honey has therapeutic value and further research is required to examine its use in other wound aetiologies. Relevance to clinical practice. This study confirms that Manuka honey may be considered by clinicians for use in sloughy venous ulcers. Additionally, effective desloughing significantly improves healing outcomes.

Apitherapy has become the focus of attention as a form of folk and preventive medicine for treating certain conditions and diseases as well as promoting overall health and well-being. In apitherapy, honey is the therapeutic agent used for dressing surgical wounds, burns or skin ulcers, as well as for dyspepsia, peptic ulcer, etc., because of its antioxidant activity. Therefore, it is important to determine the antioxidants in honey by analytical techniques. In the present study, the antioxidant activities of honeys from different floral sources were investigated by electron spin resonance (1,1-diphenyl-2-picrylhydrazyl (DPPH) and H2O2/NaOH/DMSO scavenging systems), liquid chromatography with coulometric array detection (LC-ED), and liquid chromatography with electrospray mass spectrometry (LC-MS). The antioxidant activities of some unifloral honeys (acacia, Chinese milk vetch, buckwheat and manuka) were evaluated using the radical scavenging systems. It was shown that DPPH radical scavenging activity was significantly different among the honeys, with buckwheat and manuka honeys having significantly higher scavenging activity than acacia honey. In addition, only manuka honey had specific scavenging activity for superoxide anion radicals. The compound responsible for this activity in manuka honey was identified by LC-ED and LC-MS. Careful examination of the LC-ED chromatographic patterns of manuka and other honey samples revealed a distinct peak in the chromatogram of manuka honey to be methyl syringate (MSYR). The radical scavenging activity of MSYR was specific for superoxide anion radicals, similar to the case of manuka honey. Copyright © 2005 Society of Chemical Industry

cope Manuka honey, which shows strong non-peroxide-dependent antibacterial activity, contains unique components, such as methyl syringate 4-O-β-D-gentiobioside (leptosperin) and its aglycone, methyl syringate (MSYR). To determine the potential for biological activity evoked by the ingestion of leptosperin and MSYR, we investigated the absorption and metabolism of these components in manuka honey. Methods and results The incubation of MSYR with liver microsomes or S9 fractions in vitro resulted in the formation of MSYR-glucuronide (MSYR-GA), MSYR-sulfate (MSYR-S), and syringic acid as metabolites. Then, manuka honey (15 g) was fed to healthy human volunteers. MSYR-GA, MSYR-S, and MSYR were detected in both plasma and urine. Within plasma, their levels were highest within 0.5 h to 1 h post-ingestion, and most metabolites disappeared within 3 h. In conjunction with the disappearances, a significant amount of metabolites along with trace leptosperin was excreted in urine within 4 h. To elucidate the detailed metabolisms of leptosperin and MSYR, each compound was separately administered to mice. In each case, MSYR-GA, MSYR-S, and MSYR were detected in both plasma and urine. Conclusion This study shows the major molecular pathway for leptosperin and MSYR metabolism and could facilitate an understanding of biological functions of manuka honey post ingestion. This article is protected by copyright. All rights reserved

The first synthesis of leptosin (I) starting from D-glucose in eight linear steps is presented.

Both honey and sugar are used with good effect as dressings for wounds and ulcers. The good control of infection is attributed to the high osmolarity, but honey can have additional antibacterial activity because of its content of hydrogen peroxide and unidentified substances from certain floral sources. Manuka honey is known to have a high level of the latter. Seven major wound-infecting species of bacteria were studied to compare their sensitivity to the non-peroxide antibacterial activity of manuka honey and to a honey in which the antibacterial activity was primarily due to hydrogen peroxide. Honeys with activity in the middle of the normal range were used. A comparison of the median response of the various species of bacteria showed no significant difference between the two types of activity overall, but marked differences between the two types of activity in the rank order of sensitivity of the seven bacterial species. The non-peroxide antibacterial activity of manuka honey at a honey concentration of 1.8% (v/v) completely inhibited the growth of Staphylococcus aureus during incubation for 8 h. The growth of all seven species was completely inhibited by both types of honey at concentrations below 11% (v/v).