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Cadexomer-iodine ointment shows stimulation of epidermal regeneration in experimental full-thickness wounds
Abstract
The use of iodine in wound healing is still controversial. Both wound healing-stimulating effects and toxic effects leading to impaired wound healing have been reported. In order to study the direct effects of iodine on wound healing without interference of infectious pathogens, we investigated wound-healing parameters in noninfected experimental full-thickness wounds in the pig. Topical iodine treatment with an ointment consisting of a combination of iodine and cadexomer (modified starch), was compared with cadexomer ointment, the vehicle without iodine, and with treatment with saline. Treatment lasted for 30 days, followed by 30 days of wound assessment. The rate of epithelialization, wound contraction, systemic iodine absorption and several immunohistochemical markers were evaluated. All 36 wounds healed without macroscopic signs of wound infection and reepithelialized within 21 days. During the first 9 days of treatment, wounds treated with cadexomer-iodine ointment showed significantly more epithelialization than the wounds treated with either cadexomer or saline. In addition, the epidermis of wounds treated with cadexomer-iodine ointment had significantly more epithelial cell layers from day 12 to day 30, and these wounds stained for chondroitin sulphate proteoglycans in the newly formed basement membrane zone, which was not observed with the other treatments. No negative effects of cadexomer-iodine ointment on the formation of granulation tissue, neovascularization or wound contraction were observed. During the treatment systemic iodine absorption was physiologically acceptable. These results showed that treatment with cadexomer-iodine-containing ointment had positive effects on epidermal regeneration during the healing of full-thickness wounds in the pig compared with ointment alone or saline treatment.
... 4,[28][29][30] In our study, we used cadexomer iodine, a starch polymer that is safe to use, modulates the inflammatory response, and is active against biofilms. 27,32,34 Some studies 4,27,32,34,35 have also found a positive effect on wound healing, more specifically on epidermal regeneration, with more epithelial cell layers, more rete ridges, and a thicker stratum corneum present in the tissue formed. 35 Another interesting finding in the study reported here was the effect of boric acid on microbial growth, particularly for P aeruginosa. ...
... 27,32,34 Some studies 4,27,32,34,35 have also found a positive effect on wound healing, more specifically on epidermal regeneration, with more epithelial cell layers, more rete ridges, and a thicker stratum corneum present in the tissue formed. 35 Another interesting finding in the study reported here was the effect of boric acid on microbial growth, particularly for P aeruginosa. Indeed, only the boric acid group had MBLs of P aeruginosa that did not differ significantly from those for the cadexomer iodine group during the entire observation period. ...
Objective:
To compare the effect of multiple wound dressings on microbial growth in a perfused equine wound model.
Sample:
Abdominal musculocutaneous flaps from 16 equine cadavers.
Procedures:
8 full-thickness skin wound covered were created in each flap. Tissues were perfused with saline (0.9% NaCl) solution. Wounds were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (106 CFUs), incubated, and covered with a dressing containing activated charcoal, boric acid, cadexomer iodine, calcium alginate, manuka honey, nanoparticle silver, or polyhexamethylene biguanide or with a control (nonadherent gauze) dressing. Muscle biopsy specimens were obtained at baseline (immediately prior to dressing application) and 6, 12, 18, and 24 hours later for mean bacterial load (MBL) determination. The MBLs at each subsequent time point were compared with that at baseline within dressing types, and MBLs at each time point were compared among dressing types.
Results:
MBLs in MRSA-inoculated wounds covered with cadexomer iodine dressings were significantly decreased from baseline at the 6- and 12-hour time points. For P aeruginosa-inoculated wounds, MBLs were significantly increased from baseline in all wounds at various times except for wounds with cadexomer iodine dressings. The MBLs of wounds with cadexomer iodine dressings were lower than all others, although not always significantly different from those for wounds with boric acid, manuka honey, nanoparticle silver, and polyhexamethylene biguanide dressings.
Conclusions and clinical relevance:
In this nonviable perfused wound model, growth of MRSA and P aeruginosa was most effectively reduced or inhibited by cadexomer iodine dressings. These results and the effect of the dressings on wound healing should be confirmed with in vivo studies.
... The beads of polymers in CI are swelled up by the wound exudates and gently discharge integrated iodine, preventing its accumulation and thereby preventing iodine-related complications such as allergic contact dermatitis, systemic acidosis, and so on [4][5][6]. CI ointment showed positive effects on the increased rate of epithelial regeneration, wound contractility, desloughing, formation of granulation tissue, and neovascularization [7]. ...
Several iodine formulations have been used for wound care for ages, but still there exist a number of controversial issues regarding their uses in the present era. Many published studies are available for both povidone iodine (PI) and cadexomer iodine (CI) with conflicting outcomes due to different preparations used and different study types. PI has a broad spectrum of activity including antiseptic properties, anti-inflammatory properties, low cytotoxicity, and good tolerability with the absence of associated resistance. CI is an immobilized iodine molecule in a hydrophilic modified-starch polymer bead with the dual property of cleansing the wound by absorbing the exudate and bactericidal effect by sustained release of iodine molecules over the infected wound. The preparations comprising PI and CI improve wound healing and minimize the bacterial infestation or contamination in various chronic wounds, burns, and ulcers. This review narrates the comparison of CI and PI for the management of wounds in the context of biofilm reduction, wound size reduction, and granulation tissue promotion.
... The area is then painted as earlier with 10% PVP-I solution over the site to be operated on and over whole limb if fracture is in the limb. 13,14 The paint is kept for at least 10 minutes or till it get dried before incision. ...
p class="abstract"> Background: The most common cause or source of infection in operating room is bacteria coming from inadequate cleaning of skin, surrounding environment, from the staff and from patient itself; especially geriatric with low immunity and diabetic patients. Surgical site skin infection complicates an estimated 5% of all surgeries performed in operation theater. Every measure must be taken to reduce the surgical site infection henceforth reducing the cost of treatment and morbidity of the patient. Povidone-iodine seems to be the best and cheap option.
Methods: One hundred and forty two patients who underwent orthopaedic surgery has been studied for the postoperative outcome following pre-surgical skin preparation with 2 step use of povidone iodine (PVP-I). The area to be operated is scrubbed with PVP-I scrub 7.5% and then painted with 10% PVP-I solution on operative area and wide area above and below. The paint is kept for at least 10 min or till it dry and then washed with normal saline or cleaned with sterile gauze soaked in normal saline. All postoperative patients were given intravenous antibiotics for at least 3 days. Dressing was done with PVP-I as per protocol.
Results: It has been found that out of one hundred and forty two patients studied, only 3.52% developed infection. Out of five infected patients, two were female and three with fracture were male patients.
Conclusions: PVP-I is still one of the best anti-microbial preparation widely used in orthopaedic surgery till date. It has broad spectrum anti-microbial activity and do not have any history of developing any resistance to its content.</p
... For PVP-I-L, proliferation and improvement of microcirculation have been demonstrated in in vitro and animal experiments [30,162,163] . In animal models, the application of C-I promotes epithelial cell regeneration and thus wound healing [164,165] . In PAOD (peripheral arterial occlusive disease)-associated ulcers, C-I was tolerated without irritation [166] . ...
Aim: To describe the indication and technique of microbiological wound investigation in treating infected or colonised wounds with or without multi-drug resistant microorganisms (MDROs). The clinical symptoms and criteria of locally or systemically infected wounds are summarized and described. Method: An interdisciplinary consensus of microbiological wound diagnosis was elaborated between representatives of different medical specialities. Moreover, some perspectives on future wound diagnostics were presented. Results: The panel agreed on ten clinical signs, situations and symptoms, which give the indication for further microbiological wound investigation: formation of pus, clinical signs or suspicion of an infection, suspicion or presence of a surgical site infection, localised progredient infection with or without systemic involvement (e.g. joint empyema, phlegmone), gangrene formation and necrotising fasciitis, ulcerative neoplasia, burn wounds with > 15% thermally injured surface area, exacerbation of dermatological disorders, localised wound infection without sign of systemic involvement after 3 days treatment with antiseptics without obvious clinical improvement, and chronic skin lesion with indication to screen for MDROs. The panel agreed that no indication for microbiological investigation is given in acute wounds without signs of infection and uncomplicated superficial wounds. Today, the gold standard for microbiological investigation is processing tissue biopsies in the laboratory. However, in many instances it may be easier and more rapid to perform a wound swab. If swabs are obtained, the Essener circle or the Levine technique shall be applied. Wound swabs, however, are the method of choice in screening for wound colonisation with MDROs. Additionally, information is summarised pertaining to transport and processing of microbiological wound specimens Also, potential applicability of future wound diagnostic methods based on genomic, metabolomic and proteomic approach are discussed. Conclusion: Beside a full understanding of all clinical symptoms and clinical experience of wound experts the correct microbiological wound investigation will be the basis for a succesfull management of infected wounds.
... 7 Polymer-iodine complexes, known as iodophors, are currently in use as antiseptics and in wound care dressings to prevent infection. [8][9][10][11] Povidone iodine (PVP-I) is one of the most widely used iodophors, and in vitro and in vivo studies have long demonstrated that PVP-I is highly effective against a broad spectrum of bacterial wound isolates and even antibiotic-resistant species. [12][13][14][15][16] PVP-I is available in many different formulations including solutions, creams, ointments, sprays, and wound dressings and there is evidence that PVP-I may even improve wound healing. ...
Three-dimensional (3D) printing holds tremendous potential as a tool for patient-specific devices. This proof-of- concept study demonstrated the feasibility, antimicrobial properties, and computed tomography (CT) imaging characteristics of iodine/polyvinyl alcohol (PVA) 3D meshes and stents. Under scanning electron microscopy, cross-linked PVA displays smoother and more compacted filament arrangements. X-ray and transaxial CT images of iodized PVA vascular stents show excellent visibility and significantly higher Hounsfield units of radiopacity than control prints. Three-dimensional PVA prints stabilized by glutaraldehyde cross-linking and loaded with iodine through sublimation significantly suppressed Escherichia coli and Staphylococcus aureus growth in human blood agar disk diffusion assays. It is suggested that PVA 3D printing with iodine represents an important new synthetic platform for generating a wide variety of antimicrobial and high-visibility devices.
... 77 The cadexomer component of this compound causes sloughing of the wound while providing broad-spectrum antimicrobial coverage through sustained release of iodine, thereby accelerating wound healing by increasing epidermal regeneration. 78 Although rare, the main disadvantage of this agent is the potential for systemic absorption and toxicity of iodine, which has limited its use a topical antimicrobial. 79 In addition, Iodosorb and similar products are relatively expensive compared with other agents in the oxidative halide category. ...
Burn wounds disrupt the body's primary defense against invasion and colonization by microorganisms. Topical antimicrobials are one component in burn wound care. These agents suppress microbial growth to advantage skin cells and wound healing. Topical antimicrobials can be divided into 2 superclasses: antiseptics and antibiotics. We review the 4 main classes of topical antiseptics (emulsifiers, acids, oxidizers, and heavy metals) and antiseptic-impregnated dressings in current clinical use and address the mechanisms, as well as the advantages and disadvantages of each antiseptic for burn wound management.
... For PVP-I-L, proliferation and improvement of microcirculation have been demonstrated in in vitro and animal experiments [30,162,163] . In animal models, the application of C-I promotes epithelial cell regeneration and thus wound healing [164,165] . In PAOD (peripheral arterial occlusive disease)-associated ulcers, C-I was tolerated without irritation [166] . ...
Wound antisepsis has undergone a renaissance due to the introduction of highly effective wound-compatible antimicrobial agents and the spread of multidrug-resistant organisms (MDROs). However, a strict indication must be set for the application of these agents. An infected or critically colonized wound must be treated antiseptically. In addition, systemic antibiotic therapy is required in case the infection spreads. If applied preventively, the Wounds-at-Risk Score allows an assessment of the risk for infection and thus appropriateness of the indication. The content of this updated consensus recommendation still largely consists of discussing properties of octenidine dihydrochloride (OCT), polihexanide, and iodophores. The evaluations of hypochlorite, taurolidine, and silver ions have been updated. For critically colonized and infected chronic wounds as well as for burns, polihexanide is classified as the active agent of choice. The combination 0.1% OCT/phenoxyethanol (PE) solution is suitable for acute, contaminated, and traumatic wounds, including MRSA-colonized wounds due to its deep action. For chronic wounds, preparations with 0.05% OCT are preferable. For bite, stab/puncture, and gunshot wounds, polyvinylpyrrolidone (PVP)-iodine is the first choice, while polihexanide and hypochlorite are superior to PVP-iodine for the treatment of contaminated acute and chronic wounds. For the decolonization of wounds colonized or infected with MDROs, the combination of OCT/PE is preferred. For peritoneal rinsing or rinsing of other cavities with a lack of drainage potential as well as the risk of central nervous system exposure, hypochlorite is the superior active agent. Silver-sulfadiazine is classified as dispensable, while dyes, organic mercury compounds, and hydrogen peroxide alone are classified as obsolete. As promising prospects, acetic acid, the combination of negative pressure wound therapy with the instillation of antiseptics (NPWTi), and cold atmospheric plasma are also subjects of this assessment.
... It is popularly incorporated with 0.9% (w/w) iodine to form cadexomer-iodine (CI) ointment for wound healing. Here, cadexomer serves as a carrier for iodine [108]. It swells when applied to the wounds and releases the iodine slowly into them, providing antiseptic properties. ...
Biodegradable polymers are popularly being used in an increasing number of fields in the past few decades. The popularity and favorability of these materials are due to their remarkable properties, enabling a wide range of applications and market requirements to be met. Polymer biodegradable systems are a promising arena of research for targeted and site-specific controlled drug delivery, for developing artificial limbs, 3D porous scaffolds for cellular regeneration or tissue engineering and biosensing applications. Several natural polymers have been identified, blended, functionalized and applied for designing nanoscaffolds and drug carriers as a prerequisite for enumerable bionano technological applications. Apart from these, natural polymers have been well studied and are widely used in material science and industrial fields. The present review explains the prominent features of commonly used natural polymers (polysaccharides and proteins) in various nanomedical applications and reveals the current status of the polymer research in bionanotechnology and science sectors.
... Preclinically, a study of un-inoculated full thickness porcine wounds demonstrated significant benefits of CI on epithelization. 46 Clinically, a review of therapies for venous leg ulcers (VLU) found a lack of treatments with significant, quality evidence to support their use; however, CI was specifically noted for significant evidence of improved VLU healing. 25 It is intriguing to consider CI's superior VLU healing in the context of the superior anti-biofilm action demonstrated here. ...
Examination of clinical samples indicates bacterial biofilms are present in the majority of chronic wounds, and substantial evidence suggests biofilms contribute significantly to delayed healing. Bacteria in biofilms are highly tolerant of antimicrobials, and little data exist to guide the choice of anti-biofilm wound therapy. Cadexomer Iodine (CI) was recently reported to have superior efficacy compared to diverse wound dressings against Pseudomonas aeruginosa biofilms in an ex vivo model. In the current study, the strong performance of CI versus P. aeruginosa biofilm was confirmed using colony and colony drip-flow in vitro wound biofilm models. Similar in vitro efficacy of CI was also demonstrated against mature Staphylococcus aureus biofilms using the same models. Additionally, the rapid kill of mature S. aureus and P. aeruginosa colony biofilms was visualized by confocal microscopy using Live/Dead fluorescent stains. Superior in vitro efficacy of CI versus staphylococcal biofilms was further demonstrated against MRSA using multiple biofilm models with log reduction, Live/Dead, and metabolic endpoints. Comparator antimicrobial dressings, including silver-based dressings used throughout and other active agents used in individual models, elucidated only limited effects against the mature biofilms. Given the promising in vitro activity, CI was tested in an established mouse model of MRSA wound biofilm. CI had significantly greater impact on MRSA biofilm in mouse wounds than silver dressings or mupirocin based on Gram-stained histology sections and quantitative microbiology from biopsy samples (>4 log reduction in CFU/g versus 0.7-1.6, p<0.0001). The superior efficacy for CI in these in vitro and in vivo models suggests CI topical products may represent a better choice to address established bacterial biofilm in chronic wounds. This article is protected by copyright. All rights reserved.
... The cadexomer-iodine formulation seems to be effective in controlling the bacterial burden and is also able to accelerate epithelialization through up-regulation of cytokines and growth factors (Lamme et al., 1998;Ohtani et al., 2007). In addition, cadexomer-iodine may improve the healing of chronic wounds by inhibiting excessive protease activities (Eming et al., 2006). ...
The advantageous biocompatibility and cell proliferative effects of synthetic and natural biomaterials have promoted their broad use in various medical areas, including wound healing. Most synthetic biomaterials show excellent physical properties but are, in general, complicated to fabricate, whereas natural biomaterials normally show no cell toxicity or elicit foreign body responses but show high natural variability. This chapter gives an overview of existent biomaterials used for wound healing purposes, especially the naturally obtained categories such as polysaccharide-based, protein-based, nanofiber-based, and marine biomaterials, which have been investigated in depth in vivo and in clinical studies. The potentials, but also the limitations, of novel biomaterials for wound healing applications are also discussed.
... Such porosity is important for exchange of gases and moisture from the wound to the surroundings. 41,42 It has been observed that complete occlusion of the wounds in the presence of iodine is toxic to the tissue. 43 Thus, a semiocclusive dressing like cryogel containing iodine is appropriate for this purpose. ...
In this study, potential of cryogel bilayer wound dressing and skin regenerating graft for the treatment of surgically created full thickness wound was evaluated. The top layer was composed of polyvinylpyrrolidone-iodine (PVP-I) cryogel and served as the antiseptic layer while the bottom regenerative layer was made using gelatin cryogel. Both components of the bilayer showed typical features of cryogel interconnected macropore network, rapid swelling, high water uptake capacity of about 90%. Both PVP and gelatin cryogel showed high tensile strength of 45 kPa and 10 kPa, respectively. Gelatin cryogel sheets were essentially elastic and could be stretched without any visible deformation. The antiseptic PVP-I layer cryogel sheet showed sustained iodine release and suppressed microbial growth when tested with skin pathogens (zone of inhibition ~2 cm for sheet of 0.9 cm diameter). The gelatin cryogel sheet degraded in vitro in weeks. The gelatin cryogel sheet supported cell infiltration, attachment and proliferation of fibroblasts and keratinocytes. Microparticles loaded with bioactive molecules (mannose-6-phosphate and human fibrinogen) were also incorporated in the gelatin cryogel sheets for their role in enhancing skin regeneration and scar free wound healing. In vivo evaluation of healing capacity of the bilayer cryogel was checked in rabbits by creating full thickness wound defect (diameter 2 cm). Macroscopic and microscopic observation at regular time intervals for 4 weeks demonstrated better and faster skin regeneration in the wound treated with cryogel bilayer as compared to untreated defect and the repair was comparable to commercial skin regeneration scaffold Neuskin®. Complete skin regeneration was observed after 4 weeks of implantation and no sign of inflammatory response. Defects implanted with cryogel having mannose-6-phosphate showed no scar formation, while the wound treated with bilayer incorporated with human fibrinogen microparticles showed early signs of skin regeneration; epidermis formation occurred at two weeks of implantation.
... Studies exploring cadexomer-iodine formulations as a topical application found them to be effective in controlling bacterial load 84 . Subsequent studies in humans and porcine models showed an acceleration of epidermal migration and re-epithelialisation, through upregulation of cytokines like vascular endothelial growth factor (VEGF) 85,86 . Cadexomeriodine was also found to positively affect healing rates in chronic wounds in one small study conducted by Eming and colleagues 87 . ...
Materials used in modern wound dressings have been designed to provide optimum levels of hydration, pH and gas exchange for wound healing. However, materials that provide these properties do not always provide the optimum conditions for cell attachment and growth. Plasma polymerisation is a method by which a thin ‘pin-hole’ free coating can be deposited on the surface of materials, optimising the surface for cell growth whilst leaving the bulk properties unchanged. Plasma polymerised coatings have found use as surfaces for in vitro cell studies and in wound care applications. In this article we will first give a brief introduction to plasma polymerisation. Subsequently the attachment, proliferation and migration of cells involved in wound healing on plasma polymers are reviewed. The attachment of keratinocytes, fibroblasts and endothelial cells to surfaces have been studied in detail. Cell proliferation and, in particular, cell migration have been studied to a lesser extent.
... Several studies have found that CI is an effective debriding and antiseptic agent for chronic wounds, such as venous leg ulcers [60][61][62][63][64][65]. When CI is used as a dressing, it removes pus, debris, and wound exudates from wounds and reduces bacterial counts [66]. ...
Starch has been used as a biomaterial for several applications including tissue engineering scaffolds, substrates for cell seeding, drug delivery systems, bone replacement implants, wound dressings, among others. In this paper, we review the use of starch-based materials for the development of wound dressings. First, we shall cover the basic characteristics of wounds, including a brief discussion of the wound healing process and the different types of dressings available for the treatment of wounds. Then, the general properties of starch as a biomaterial are described with special emphasis on the properties of several modified starches. The different processing routes for the production of starch-based wound dressings are revised in some detail. Starch-based wound dressings under investigation and commercially available products are also reviewed in order to assess the performance of starch as a biomaterial in the healing processes.
... For more product information and a sample "patch" please call: 69 . This group compared cadexomer-iodine with normal saline -12 pigs were allocated to each group, statistical significance was reached (p<0.05). ...
The use of iodine in wound management can be traced back hundreds of years and yet continues to divide and create debate amongst today's clinicians. Is there a place for this agent in either infected or non-infected wounds? The body of evidence and pharmacopeia of iodine-based products available can prove daunting. This review outlines the properties of iodine-based products and seeks to examine the relevant clinical studies in an attempt to provide an evidence-based structure to facilitate the choice of iodine-based product. The authors reviewed both animal and human studies. Over 50 studies have been conducted on the use of iodine in wound care. Analysis of the literature reveals that there does appear to be a place for iodine in wound management, particularly in the presence of infection. However, the literature highlights iodine may cause harm, therefore a sound knowledge of the factors that contribute to the activity of iodine and its potential for cytotoxicity is required for its judicious use.
... In this research, there were no negative effects of iodine cadexomer in relationship to the formation of granulation tissue, neovascularization and wound contraction. These results were similar to those of other authors 15 .showing that epidermal regeneration had positive effects throughout the healing process with its use. ...
To assess vthe action of iodine cadexomer in the healing process of surgical wounds in rats and if cytotoxicity occurs with the systemic absorption of iodine.
Thirty six Wistar rats were used and performed 53 wounds with surgical punch of 6 mm diameter on them. Two lesions were made diametrically opposed on groups with distilled water (GAD) and sodium chloride (GCS); on the right lesions were used bandage with distilled water and on the left ones dressing with sodium chloride. In cadexomer iodine (GCI) group, a punch injury was made only on the left side and the dressing was carried out with cadexomer iodine. The groups were divided in two sub-groups according to the day of death (7 and 14). Microscopically was used H&E staining, through which the inflammation could be observed and also the neovascularization. Staining with Masson trichrome studied fibrosis. TSH and free T4 were used for absorption recognition of iodine, and its toxic potential was performed before death with the animal anesthetized.
Microscopic analysis showed more marked intensity of inflammation in group GAD, subgroup 14 days. Neovascularization showed be discrete in GCS sub-group 14 days. Fibrosis was more pronounced in the group GCI. Comparing the types of treatment, there was statistical significance between groups GCI and GCS (p<0.013). The TSH and T4, showed no difference between the control group and GCI in relation to the absorption of iodine. In evaluating the GCI and control groups, within each treatment, statistical significance was found between them (p<0.001) when compared the days of observation.
Cadexomer iodine had beneficial effects in all phases of the healing process without cytotoxicity due iodine absorption.
... In Europe and North America, as well as Japan, Cadexomeriodine, a commercially available ointment that releases iodine slowly from beads of dextrin and epichlorohydrin, is commonly used in treatments. This preparation is an effective debridement and antiseptic agent for treating chronic, exudative wounds (21)(22)(23), because it removes necrotic tissue, bacterial components and biofilm synthesised by bacteria (24,25), and stimulates epidermal regeneration (26). ...
Selecting an appropriate treatment for a given case of skin wound is crucial for inducing optimal healing. We used an animal model consisting of normal rabbit ears in order to assess the efficacy of treatments for skin wounds with/without a wet dressing, anti-microbial reagent, or topical wound-stimulatory reagents. The degree of healing in each group was evaluated and compared using four histological parameters: (i) degree of reepithelialisation, (ii) amount of granulation tissue formation and (iii) the number of capillary lumens and (iv) fibroblasts in the granulation tissue. Treatment using wet dressings presented an increase in capillary number compared to the open dry wound. Although the retention of PI in wound tissue after application significantly inhibited reepithelialisation (P < 0·05), rinsing povidone-iodine (PI) off with saline after application was comparable in effect to using only a wet dressing. The three topical reagents, namely, basic fibroblast growth factor, prostaglandin E1 and dibutyryl cyclic adenosine monophosphate, significantly improved reepithelialisation (P < 0·05). In conclusion, wounds should be kept hydrated by applying topical reagents. If there are any signs of bacterial infection, PI can be applied if rinsed later with saline in order to minimise its cytotoxic effects.
... Preparations containing PvP-I resulted have also presented milder but significant vascular damage. this is in line with investigations which have demonstrated that the prolonged exposure of human skin to aqueous iodine-solutions may cause irritations or rarely even severe skin reac- tions [5, 17, 20,232425 . Moreover, highly diluted PvP- I-solutions were shown to bear severe cytotoxicity in cell cultures of human skin fibroblasts in vitro [5, 17, 20, 24] . ...
Antiseptics are frequently used for the prophylaxis and treatment of local infections of chronic wounds. Whereas local antiseptics in general have a positive effect on wound healing an uncritical use may impair wound healing due to toxic side effects.
We sought to assess the vascular irritation potential of different antiseptic solutions and ointments commonly used for short and long term application as a measure of tissue toxicity.
The vascular irritation was evaluated by the hen's egg test (HET) on the chorioallantoic membrane (CAM). The effects on the vessels of a mucous membrane were directly assessed by stereomicroscopic observation in vivo.
Severe CAM irritation was observed after short-term applications of 1% octenidin-2HCl (Octenisept), 72% isopropanol (Cutasept), 0.35% chloroxylenol (Dettol) and 10% PVP-I ointment (Betaisodona). Medium irritations were observed for 10% PVP-I solution (Betaisodona), 3% lysosomal PVP-I ointment (Repithel), 1.8% cadexomer-iodine ointment (Iodosorb) and 1% cadexomer-iodine pellets (Iodosorb). Finally, slight irritations were observed for 1% PVP-I solution (Betaisodona), 0.1% polyhexanid plus betain (Prontosan) and 1% silver-sulfadiazine ointment (Flammazine), whereas 0.04% polyhexanid solution (Lavanid), washings from sterile maggots of Lucilia sericata and filtrated enzymes from Clostridium histolyticum (Iruxol-N) showed no effects of irritation. In the long-term approaches, no vascular irritations were found for polyhexanid, washings from Lucilia sericata and enzyme filtrations from Clostridium histolyticum.
The vascular injuries caused by the studied antiseptics are an indirect indicator of their tissue toxicity. Strikingly, even therapeutic substances, which have been regarded as safe in their application for the treatment of chronic wounds in clinical studies, showed severe irritations on the CAM. We suggest that agents with no or low irritation potential on the CAM should be preferred in the clinical practice in order to obtain optimal results.
... CI consists of hydrophilic starch polymer beads that incorporate molecular form iodine. 0.9% CI preparation with macrogol base is widely available (Bianchi, 2001). Upon application to wounds it slowly releases iodine with swelling of polymer beads induced by exudates (Lamme et al., 1998; Zhou et al., 2002). Although PI sugar ointment and CI ointment have been considered to achieve the same clinical results, we have previously reported that PI and CI ointments exhibit different iodine releasing properties, and that their bases distinctly differ in water absorption capacities (Noda et al., 2009). ...
Iodine preparations for external use are recommended for treating pressure ulcers with manifestations of infection and necrosis. These ulcers abundantly produce wound exudates, which could be absorbed by water-soluble base. In this study we aimed to improve the previously reported methodologies for water absorption and new methodologies were developed in Franz diffusion cell with 100kDa molecular weight cut-off (MWCO) membranes. Using these new methodologies water absorbing capacities of existing iodine preparations [povidone-iodine (PI) sugar ointment, iodine-potassium iodide (IKI) gel, cadexomer-iodine (CI) ointment] and another superabsorbent polymer dextranomer paste were evaluated. Water absorption indexes were 7.52, 1.98, 1.44 and 2.90(mg/cm(2)/min(0.5)), respectively. With PI sugar ointment observed amount of water absorbed increased in a linear fashion over time. In contrast, with IKI gel, CI ointment and dextranomer paste observed amount of water absorbed decreased over time. When the observed amount of water absorbed was plotted against square of time, the lines of IKI gel and CI ointment became linear. With dextranomer paste the line became biphasic with 1-folding point. These results suggest that water diffusion into matrix is the rate limiting step in IKI gel, CI ointment and dextranomer paste, and that capacity of absorbing wound exudates could substantially differ among these ointments.
... In summary, we did not observe any significant differences between the three groups and especially between the two treatment groups versus the physiological saline group, which could be interpreted as a great success for both the iodine 3% and the newly developed polihexanidepreserved wound covering gel. Potential toxic effects caused by the applied formulations, including the PVPiodine 3% (the effects of which are controversial in terms of wound healing [11][12][13][14][15] ), were not observed: there was no delayed angiogenesis or increased endothelial damage, measured as oedema formation, amongst the groups. No infection was seen clinically in any of the groups. ...
Daily wound assessment, including dressing changes and the removal of old ointments causes discomfort for the patient. We therefore developed a new thermoreversible and transparent gel formulation that allows for filling wounds of different shapes and depths. The aim of the study was to investigate the effect of a wound covering gel on wound healing and the skin's microcirculation.
Investigations were carried out in a standardized and reproducible wound model (hairless mice SKH1/hr, n = 30). Three groups were studied by intravital fluorescence microscopy: treatment with polihexanide-preserved wound covering gel, a formulation containing 3% povidone (PVP)-iodine, and physiological saline for control. Microcirculatory standard parameters were analysed.
The non-perfused area vanished within 14 days due to angiogenesis. The venular diameter, oedema formation and functional capillary density showed no significant differences between the three groups.
The use of the newly developed wound covering gel has no toxic effects on microcirculation and angiogenesis and reveals no significant differences in the overall assessment of microcirculation compared to the control group and the well-established PVP-iodine. The transparent antibacterial wound covering gel allows for direct wound assessment. Due to its thermoreversible gel formulation it enables good wound contact and easy handling.
... In Europe, North America and Japan a macrogol ointment consisting of CI is available (Bianchi, 2001) (Cadex TM Ointment, Smith & Nephew, Tokyo, Japan ). Upon application the polymer beads in CI are swollen by wound exudates and gradually release incorporated iodine (Lamme et al., 1998; Zhou et al., 2002). These ointments are recommended by the Japanese Society of Pressure Ulcers to treat the pressure ulcers carrying an infection or a necrotic tissue (Ohura, 2005). ...
Topical iodine forms are used for infected and necrotic pressure ulcers. Despite antimicrobial advantages several potential disadvantages were observed with controversial results. To clarify the controversy, the reactivity of povidone-iodine (PI) sugar ointment and cadexomer-iodine (CI) ointment toward biological components was investigated. L-Tyrosine as a component of proteins and egg lecithin as a component of lipid membranes were reacted with forms of iodine. Furthermore, water absorption abilities of ointments were investigated. The reactions of PI sugar ointment and CI ointment with L-tyrosine were reversely dependent on iodine concentrations. CI ointment reacted with lecithin in an iodine concentration dependent manner, while PI sugar ointment reacted with lecithin in an iodine concentration independent steady manner. However, at the clinically relevant iodine concentration (0.1, w/v%) PI sugar ointment reacted efficiently with L-tyrosine and less efficiently with lecithin, while CI ointment reacted efficiently with lecithin and less efficiently with L-tyrosine. Water absorption rate constant was 29.9 mg/cm(2)/min(0.5) for PI sugar ointment and 15.3 for CI ointment. Water absorption capacity per weight over 24 h was 26% forPI sugar ointment and 76% for CI ointment [corrected]. These results suggest that PI sugar ointment and CI ointment have different characteristics for iodine reactivity and water absorption.
The integumentary system consists of the skin, hair, mammary glands, adnexal glands, and toenails. Hair quality may be modified by such environmental factors as day length, temperature, elevation, and general nutrition, but the dominant factor in determining quality is heredity. Parasitic diseases of the skin include mange, pediculosis, and myiasis. Fungal dermatitis is uncommon in camelids, but can occur in both South American Camelids (SACs) and Old World Camels. Overgrowth of the toenail is the most common disorder of the SACs foot. Camelid mastitis occurs in the same forms as seen in dairy cattle, namely, subclinical, peracute, acute and chronic. The goals of the proliferative phase are to form granulation tissue and an epithelial covering over the wound. There is a dearth of veterinary research regarding wound healing in camelids, yet a plethora of literature involving research on small laboratory animals and humans exist.
The capture and safe storage of radioactive iodine (¹²⁹I or ¹³¹I) are of a compelling significance in the generation of nuclear energy and waste storage. Because of their physiochemical properties, Porous Organic Polymers (POPs) are considered to be one of the most sought classes of materials for iodine capture and storage. Herein, we report on the preparation and characterization of two triazine-based, nitrogen-rich, porous organic polymers, NRPOP-1 (SABET = 519 m² g⁻¹) and NRPOP-2 (SABET = 456 m² g⁻¹), by reacting 1,3,5-triazine-2,4,6-triamine or 1,4-bis-(2,4-diamino-1,3,5-triazine)-benzene with thieno[2,3-b]thiophene-2,5-dicarboxaldehyde, respectively, and their use in the capture of volatile iodine. NRPOP-1 and NRPOP-2 showed a high adsorption capacity of iodine vapor with an uptake of up to 317 wt % at 80 °C and 1 bar and adequate recyclability. The NRPOPs were also capable of removing up to 87% of iodine from 300 mg L⁻¹ iodine-cyclohexane solution. Furthermore, the iodine-loaded polymers, I2@NRPOP-1 and I2@NRPOP-2, displayed good antibacterial activity against Micrococcus luteus (ML), Escherichia coli (EC), and Pseudomonas aeruginosa (PSA). The synergic functionality of these novel polymers makes them promising materials to the environment and public health.
On‐site, prehospital care is vital for minimizing the severity of injuries caused by acute burns, especially those of the second‐ and third‐degrees. Burn wounds typically have irregular shapes and depths and cover a large total body area. Due to the severity and complexity of burn wounds, traditional sheet‐like wound dressings are not always suitable. Alternatively, sprayable wound dressings can be used for convenient, quick, and large‐scale dressing changes. They can also prevent infection and secondary trauma depending on their reagent content. Sprayable wound dressings function as a therapeutic barrier that provides moisturization and pain relief, absorbs extrudates, protects against bacterial infections, and acts as a delivery system for small molecules and drugs. This review discusses the recent developments in sprayable hydrogel‐based wound dressings for high‐degree burns. An introduction to burn wound classifications, the ideal burn dressing designs and characteristics, and the current availability of commercial spray‐on burn dressings are presented. To achieve the optimal healing capacities using sprayable wound dressings, researchers are currently focusing on modifying the solution viscosities, propellant systems, and pump nozzle designs for spray formulations. Finally, the use of hydrogel‐based dressings to replace skin graft surgeries for tissue regeneration is discussed.
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Numerous emerging and re-emerging advanced materials have been successful in capturing iodine pollutants that pose an unprecedented global challenge to public health. However, little attention has been paid to the reutilization of the captured iodine. Herein, we report on a pyrrolidone-based polymer capable of reversible iodine capture for reutilization in antibacterial applications. The pyrrolidone-based polymer poly(N-vinyl-2-pyrrolidone-co-vinyl acetate), denoted as P(VAc-NVP), was synthesized facilely via a one-step radical copolymerization strategy, and the synthesis was regulated by step-by-step optimization, specifically by tuning the feed ratio of NVP to VAc. The as-synthesized P(VAc-NVP) copolymer functioned as an adsorbent for iodine in various solutions, including water/ethanol, cyclohexane, and petroleum ether, in addition to having the special capability of releasing iodine in the presence of starch or bacteria. This opens up a new horizon for its functional practical use as a flexible adsorbent to capture iodine for safe disposal. Interestingly, the P(VAc-NVP) copolymer, after adsorbing iodine, showed antibacterial ability against pathogenic bacteria, including Staphylococcus aureus and Escherichia coli, when a series of simulated and practical antibacterial assays were conducted. It is believed that this proposed strategy based on the synergism of iodine capture and antibacterial use should have great potential for environmental remediation and public healthcare.
Purpose:
This study investigated whether the compound of hyaluronic acid (HA)-povidone iodine (PI) has the potential effectiveness to enhance diabetic wound healing.
Materials and methods:
In this study, a dorsal skin defect (area, 6×5 cm) in a streptozotocin-induced diabetes rodent model was used. Seventy male Wistar rats were divided into 7 groups: normal control, diabetic control receiving no treatment, diabetic rat treated with HAL only (lower molecular weight 100 KDa); HAH only (higher molecular weight 1000 KDa); PI only (01%); HAL-PI compound; and HAH-PI compound groups. The wound dressing was changed twice per week. Wound healing progress was assessed once per 3 days post-operatively. Histologic examination was performed with hematoxylin and eosin staining. CD45, Ki-67, prolyl 4-hydroxylase (rPH), and vascular endothelial growth factor (VEGF) were evaluated with immunohistochemical (IHC) staining.
Results:
The results revealed that the wound area was significantly reduced in the HAH-PI treated diabetic rats as compared to the control group (P < 0.001). The HAH-PI group increased the wound healing time as compared to the HAH or PI only, or HAL-PI group. Histological findings revealed significant increase in neo-vessels and suppress inflammatory response in HAH-PI as compared to the control. IHC staining revealed significant increase in the Ki67, rPH and VEGF expressions and suppress the CD45 expression in the HAH-PI treatment group as compared to the other groups.
Conclusion:
Treatment with HAH-PI complex dressing significantly facilitated diabetic wound healing associated with suppressed pro-inflammatory response and increased neovascularization and tissue regeneration.
Myriads of wound-care products are on the market, and making the right choice for a specific wound can be complex, especially because the scientific literature on wound-care products in horses is sparse. To select the best possible dressing, the veterinarian must decide which material is needed to enhance healing. The clinician must then determine if antimicrobial therapy is required. Several antibacterial compounds are available for topical use and are often more effective than systemically administered antibiotics in the management of severe contamination, critical colonization, or infection. To serve the requirements of specific wounds, several combinations of antimicrobial drugs and dressings are available. The wound milieu changes as healing progresses and so do the requirements for dressings. Continued assessment, based on a thorough clinical examination and sound knowledge of the healing process, is indicated, therefore, to maintain an optimal environment for healing.
Topical treatments have been used in wound care for centuries. Many of the treatments, however, have not – or only to a very limited degree – undergone scientific scrutiny. This is especially true for many of the products that are available over the counter. Determining the contents of many of these products can be difficult, and as a rule of thumb, products without a list of ingredients should not be used on wounds. In contrast, effects of wound cleansers and solutions used for irrigation have been investigated in several studies. Although cleansers and antiseptics had, for some years, fallen out of favor due to their detrimental effects on cells cultured in vitro, current best evidence suggests that they may be of benefit if used judiciously. The negative impact on cell cultures has, in many studies, not been replicated when the products were used in vivo. Use of antiseptics on heavily contaminated or infected wounds seems to enhance healing through a reduction of the wound's bioburden.
Objective:
To investigate the effect of a novel topical wound-healing agent, low-concentration povidone-iodine ointment (LPIO) with a hydrophobic white petrolatum-rich base on skin-wound models in rats and rabbits.
Method:
The therapeutic efficacy of topically applied LPIO was compared to that of standard-concentration povidone-iodine ointment (SPIO) and non-treatment control, using a full-thickness skin-wound model in 24 hairless rats and a full-thickness skin-defect model in rabbit earlobes. The animals were kept under standardised conditions at the Central Research Laboratory of Maruishi Pharmaceutical Co. Ltd. (Osaka, Japan). Therapeutic efficacy was evaluated based on macroscopic wound-size reduction, as well as histopathological and immuno-histochemical examinations.
Results:
LPIO enhanced wound healing in rat full-thickness skin ulcers, reducing wound size and inflammation, when compared with that in SPIO and non-treatment control. LPIO also markedly improved wound healing in rabbit earlobe ulcers by significantly improving re-epithelialisation, compared with that in SPIO.
Conclusion:
The results of this study suggest that LPIO is a useful topical therapy for ulcerative lesions.
It is estimated that 2% to 3% of the population aged over 65 suffer or have suffered from venous ulcer. The existence of numerous therapeutic options clearly indicates that an efficient method of leg ulcer treatment has not yet been developed and that the management of this entity poses a major therapeutic challenge. Currently, compression therapy, multicomponent in particular, has proven to be the most efficacious method in the prevention and treatment of venous ulcer. Regular wound toilet and cleaning are important prerequisites for the healing process to start. Various topical agents in the form of creams and ointments containing proteolytic enzymes are used for this purpose; mechanical cleaning is also highly efficient. In case of clinically suspect bacterial colonization, the use of systemic and topical antibiotics is not justified and topical antiseptics should be used instead. A variety of wound dressings that provide a moist medium for ulcer healing are available. Some systemic agents such as flavonoids and pentoxifylline have proved efficient in precipitating ulcer healing if coadministered with compression therapy. Therapeutic options also include hyperbaric oxygen therapy and vacuum assisted therapy. Surgical therapy can be used for ulcer sequels (ulcer covering with a free skin graft) or causes of venous ulcer (varicose veins and insufficient perforators). The desired outcome, i.e. venous ulcer healing, can be achieved by a combination of compression therapy and other methods available.
Hydroxypropyl chitosan biguanide hydrochloride (HPCGH) was synthesized through the method of "amino protection-graft reaction-deprotection", the HPCGH membrane (HPCGH-PVP-M) was then prepared from a mixture of gelatin and polyvinylpyrrolidone (PVP), following that, the iodine membrane (HPCGH-PVP-I2-M) was obtained via the adsorption of iodine in iodine alcohol solution. The properties of HPCGH-PVP-I2-M were characterized by Fourier-transform infrared (FT-IR), 1H-NMR, X-ray diffraction (XRD) as well as thermogravimetric analysis (DTG) studies. The investigation results suggest that HPCGH-PVP-I2-M has a better amorphous structure and a better thermal stability compared to that of HPCGH-PVP-M. Investigations were carried out on the iodine content demonstrating that HPCGH-PVP-M has superior properties for the adsorption of iodine. The iodine release studies in this work showed that HPCGH-PVP-I2-M emitted iodine slowly and kept the iodine for a long time, and that HPCGH-PVP-I2-M had the property of sustained-release iodine, furthermore, the higher the temperature and the higher the iodine content, the faster the release of iodine was. It was also found that the antibacterial activity of HPCGH-PVP-I2-M against E. coli and S. aureus was better than that of HPCGH-PVP-M and that the inhibition zone diameters increased with an increase in the amount of iodine. When the content of iodine was 16.02% and the temperature was 37 °C, the inhibition zone diameters of HPCGH-PVP-I2-M against E. coli and S. aureus were approximately 28 ± 1 mm and 30 ± 1 mm, respectively, hence the significant antibacterial activity. This journal is
Antiseptics have long and commonly been used on wounds to prevent or treat infection. However, citing cytotoxicity data, many authors have advised against their use on open wounds. This article discusses antiseptics and their use on open wounds, as well reviews relevant animal studies and clinical trials examining the effects of commonly used antiseptics, including iodine compounds (povidone iodine and cadexomer iodine), chlorhexidine, hydrogen peroxide, acetic acid, and silver compounds. This article examines their effects on wound healing and reepithelization and their efficacy on reducing bacterial number in wounds and incidence of wound infections. The authors found despite cytotoxicty data, most antiseptics have not been shown to clearly impede healing, especially newer formulations like cadexomer iodine (which speeds healing) and novel silver delivery systems. These compounds appear to be relatively safe and efficient in preventing infection in human wounds. Given this review, the role of antiseptics on wounds and their role in wound care management should be reconsidered.
The chronic wounds represent a public health problem health which the prevalence increases with age, patient health and sedentary lifestyle. Indeed, in the occidental countries, 1.69% of the elderly person aged over 65 years is suffering from leg ulcers . Moreover, the chronic wounds appearance increases for the diabetic patients who suffering neuropathy (diabetic type I and II together) with 2.2%/years of probability to developp a leg ulcer. The infection of the chronic wounds increases with wound healing delay, thus, cares need to be repeated to prevent or fight wound infection until their complete healing. In the case of infected wound, the critical colonization or localized infection can result without adapted treatment to surgery operation in order to prevent systemic infection or death. Nevertheless, the chronic wound represents a favourable site for the rapid developpment of the pathogen agents. The bacterial proliferation can lead to the biofilm formation which increases the bacterial protection against the body\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\'s natural defences and antimicrobial agents. So, the aim of this work is elaborate a medical device as wound dressing for extended broad spectrum antibacterial drug release. The textile device used in this project is a non-woven textile based on polyethylene terephtalate (PET) functionalized with Pad-Dry-Cure method with chitosan (CHT). In the present work, two crosslinking agents are evaluated, genipin (Gpn) and citric acid (CTR), which allows obtaining a CHT network coated at the surface of the textile fibers. Thus, there are ionic functions at the surface of the PET; positive charges when the crosslink agent is Gpn, positive or negative charges in function of the amount of the CTR used in the solution.The ionic charges from the PET functionalized by CHT crosslinked by Gpn (PET-Gpn/CHT), are used to build a multilayer system layer-by layer self-assembly. The polyelectrolytes (PE) used to build this multilayer system by dip-coating are: the CHT, as cationic PE, and cyclodextrin (CD) polymer, as anionic PE (it was developed and studied by the team in previously work). The ability of the CD to form inclusion complex, from the CD polymer included in the multilayer coating, is used in the case of PET-Gpn/CHT to load one antiseptic with broad spectrum, the chlorhexidine (Chx). This Chx loaded multilayer system is optimized and evaluated physic-chemically, biologically and microbiologically. The study is also realized on the functionalized PET-CTR/CHT. This system, anionic or cationic, in function of the quantity of the crosslinking agent used, is loaded respectively by silver (Ag+) or iodide (I3-). A physico-chemical and microbiological evaluation are realized to evaluate their antibacterial efficiency. Finally, the multilayer system is built-up on the anionic PET-CTR/CHT loaded by silver to reduce its release out of the multilayer system. Chemical completed by microbiology tests are realized to verify the influence on the antibacterial activity and the kinetic of the release of the multilayer system
A mixture of hyaluronan and iodine complex KI3 (Hyiodine®) has been developed to support wound healing. In this study, the effect of hyaluronan, KI3, and their combination on progression of wound healing in excision skin wounds in rats was determined.
To evaluate the possible toxic effects of iodine after Hyiodine application for wound healing, iodine systemic absorption from the Hyiodine-treat- ed wounds and its distribution profile were quantitatively described and compared after intravenous iodide administration using 131I as a radiolabel.
Treatment of rats with Hyiodine resulted in an enhancement of wound healing, proved by greater degrees of wound contraction and reduction in mean wound healing time compared to other treated rats on hours 1, 2, 24, and 216. Even if wound therapy with Hyiodine resulted in systemic iodine uptake, the estimated iodine absorbed dose in human therapy is tolerable, and the theoretical risk of its systemic toxic effects is minimal.
A hyaluronan-iodine hydrogel has a great potential for effective treatment of wounds. .
Background: The use of iodine is a controversial issue even though it has been used in wound management for over 150 years. There is a large amount of published literature available for both povidone and cadexomer iodine although the results are often conflicting due to the large array of different preparations used and different study types employed. Objectives: This literature review concentrates on the use of povidone and cadexomer iodine. The review highlights their antimicrobial efficiency, the issue of bacterial resistance, and effects on tissue and cells involved in wound healing. Toxicity and adverse reactions associated with these antimicrobial agents are also considered. Major findings: The literature supports the use of povidone and cadexomer iodine as effective antimicrobial agents that bacteria have not developed resistance to. Other findings noted that povidone and cadexomer iodine should be used with caution and at decreased concentrations in patients with extensive burns and systemic complications such as renal failure, thyroid dysfunction, and other severely immunocompromised patients. Conclusions: The literature supports the use of povidone and cadexomer iodine in wound care for its effects on tissue and cells, especially in newer formulations. Cadexomer iodine has proven to be very effective in chronic wounds while povidone iodine has been noted to be more effective in infected acute wounds. Gaps in the research have been identified as a lack of clear evidence comparing new formulations of povidone iodine to traditional preparations. It is clear that more research evidence is required for clinicians who routinely use these antimicrobial agents in wound management.
Cross‐linked cationic starches N‐(2‐hydroxyl)propyl‐3‐trimethyl ammonium starch chloride (CQS chloride), N‐(2‐hydroxyl)propyl‐3‐trimethyl ammonium starch iodide (CQS iodide), and N‐(2‐hydroxyl)propyl‐3‐trimethyl ammonium starch iodide–iodine (CQS triiodide) with the degree of substitution (DS) according to cationic groups from 0.04 to 0.62, as well as cross‐linked starch–iodine complexes were synthesized and tested as potential antibacterial agents. Cationic starch iodine derivatives were obtained during ion exchange reaction between CQS chloride and iodide or iodide–iodine anions in aqueous solutions. CQSDS≤0.3 chloride can form several types of iodine complexes, such as the blue amylose–iodine inclusion complex and ionic CQS+I−·(I2)m complex (m ≥ 1). The antibacterial activity of modified starches–iodine samples against different pathogenic bacterial cultures and contaminated water microorganisms was evaluated. CQS chloride and CQS iodide were found to be bacteriostatic. A strong antibacterial activity was characteristic of CQS triiodides in which molecular iodine is present in both ionic and inclusion complexes. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
The science of wound care has evolved over the past 20 years. Trends in health care including clinical practice guidelines, evidence‐based practice, and disease‐state management have strengthened the practice of wound management. This article discusses recent strides in this field that may be applicable in orthopaedic nursing. Therapeutic tools discussed include holistic patient assessment, patient health enhancement protocols, therapies and modalities for optimization of the wound bed, and new and developing topical treatments for chronic and acute wounds.
Chronic wounds represent a significant medical burden. Such wounds fail to normally progress through the stages of healing, often complicated by a proinflammatory milieu caused by increased proteinases, hypoxia, and bacterial burden. As a result, several modalities, such as dressings, antimicrobials, growth factors, and human skin substitutes, have been devised in an attempt to correct the chronic wound environment. This review addresses these modalities with a focus on evidence and randomized controlled trials.
Diabetic foot ulcers are the most common lower extremity complications of diabetes. Peripheral neuropathy and peripheral vascular disease are the underlying risk factors for diabetic foot ulcers, subsequently leading to infections and requiring antimicrobial therapy for the management of the disease. Each risk factor is a target for clinical intervention, with the intent to delay or prevent disease progression to amputation. The effective therapy includes interdisciplinary care, which involves optimized pharmacological interventions in concert with other treatments such as debridement strategies and specialized wound dressings. The pharmacological therapy alone cannot lead to successful therapy, and therefore, these supplementary techniques/modalities should not be overlooked. It is therefore the aim of this report to review various pharmacological interventions, specific to the diabetic foot and wound healing, along with incorporation of advanced therapies required to achieve a multifaceted treatment of diabetic foot ulcers and provide basis for superior drugs as well as drug delivery systems.
Les plaies cutanées constituent un motif de consultation majeur en clientèle canine. L auteur présente d abord les principales caractéristiques de la peau des chiens et chats et s attarde sur les particularités ayant des conséquences sur les plaies. Les plaies sont ensuite abordées dans leur grande diversité clinique et étiologique puis leur évolution physiologique est décrite. Les aspects de la cicatrisation sont à la fois étudiés sur un plan microscopique et macroscopique. Après avoir décrit les complications, l auteur présente les principaux facteurs pouvant altérer la cicatrisation, comme les affections pathologiques ou les traitements associés. L auteur aborde enfin le traitement des plaies. Les traitements classiques sont décrits de la réception de l animal à la cicatrisation complète. Les traitements plus récents ou alternatifs sont aussi présentés. Les connaissances sur la cicatrisation continuent d évoluer, l auteur a tenté d en réaliser un bilan complet et actuel.
Osteomyelitis affects up to 32% of full-thickness pressure ulcers and increases treatment costs and the risk of systemic complications. Current diagnosis and treatment practices are variable. A literature and retrospective chart review, using a wound electronic medical record (WEMR), were conducted to develop an evidence-based protocol of care for treatment of osteomyelitis in pressure ulcers and to evaluate outcomes of care. The seven steps in the protocol of care include: 1) acknowledgment of osteomyelitis risk in patients with Stage IV pressure ulcers, 2) clinical evaluation for local or systemic signs of infection upon initial presentation, 3) radiographic evaluation (magnetic resonance imaging or bone scan), 4) surgical debridement to remove all nonviable tissue and/or scarred and infected bone, 5) obtaining pathology reports from sterile bone biopsy and deep microbial cultures, 6) targeted systemic antimicrobial therapy, and 7) tissue reconstruction following resolution of infection. WEMR data review (177 patients) identified 50 patients with osteomyelitis (prevalence 28%). Of those, 41 underwent 87 bone debridements for osteomyelitis. Eight (20%) patients experienced complications elated to treatment. Average time to discharge following debridement was 4.3 +/- 5.7 days and 76% of wounds with more than two consecutive WEMR entries showed a decrease in area at their final visit. The outcomes observed are encouraging and the WEMR facilitates implementation and evaluation of the treatment protocol. Ongoing data acquisition will help assess outcomes and refine the current management protocol and should improve diagnosis and care.
Moist treatment of wounds has been shown to improve epithelialization, however at an increased risk of bacterial infection. In this monocentric, randomized, open, phase II pilot study of polyvinyl pyrrolidone-iodine, a well-established topical antiseptic was tested in a new liposomal complexed form in patients receiving meshed skin grafts after burns or reconstructive procedures. Mesh skin graft sites of 36 patients were dressed either with the new polyvinyl-pyrrolidone-iodine liposome hydrogel formulation (Betasom hydrogel) (n = 21), or chlorhexidine-gauze (n = 15). After the first dressing change, wounds were assessed daily and documented every other day until they were healed. Methods of analysis included clinical assessment, photoplanimetry (rate of epithelialization), impedance measurement (moisture of surface and wound healing quality), patient's assessment of pain and other sensations, and thyroid hormones (T3, T4, and TSH). The rate of epithelialization was improved with Betasom hydrogel compared to chlorhexidine-gauze on day 11 (96.3% vs. 75.9% p = 0.056) and significantly on day 13 (100% vs. 82.3% p = 0.005), respectively. Impedance measurements showed an earlier return to normal values (day 9) in Betasom-hydrogel-treated wounds as opposed to chlorhexidine treatment (day 11). Clinical assessment indicated significantly better antiseptic efficacy (p = 0.002) and wound healing quality (p = 0.004) of Betasom hydrogel. Graft loss occurred at a significantly lower rate in Betasom treatment (n = 1; 5%), than in chlorhexidine treatment (n = 5; 35.7%) (p = 0.001). No relevant adverse events or clinically relevant changes of thyroid hormones were observed with Betasom hydrogel. The rationale of this new polyvinyl pyrrolidone-iodine liposomal formulation was based on the properties of liposomes that provide higher moisture to the wound surface, release PVP-iodine at a low rate, and target the substance more exactly by interaction with the cell surface. These initial clinical results show earlier epithelialization and better healing in wounds treated with polyvinyl pyrrolidone-iodine liposome hydrogel, which combines moisture and antisepsis, compared to wounds treated with a conventional antiseptic chlorhexidine-gauze.
Antiseptic agents, particularly slow-release preparations, are increasingly being used in the management of chronic wounds. One such agent, cadexomer iodine, carries iodine (0.9% weight/weight) immobilized in beads of dextrin and epichlorhydrin and has been demonstrated to be highly effective in promoting healing of exudative wounds. However, there have been no studies directly assessing the potential lack of toxicity of cadexomer iodine on human cutaneous tissues.
To determine if, within a certain concentration range, cadexomer iodine is non-toxic to human cells and cutaneous tissue and to assess histologically human chronic exudative wounds that are being treated with cadexomer iodine.
We examined the effects of varying concentrations of cadexomer iodine on the viability of human fibroblasts in culture (by trypan blue exclusion). The morphology, cellular proliferation capacity (measured by [3H]thymidine uptake), ability to produce alpha 1(I) procollagen chain mRNA, and cell outgrowth from neonatal foreskin explants were also evaluated in human fibroblasts after incubation with various concentrations of cadexomer iodine. Moreover, biopsies of chronic exudative wounds concurrently treated with cadexomer iodine were stained with haematoxylin and eosin or a Gram stain and evaluated microscopically.
At concentrations of up to 0.45%, cadexomer iodine was found to be non-toxic to fibroblasts in vitro; there were no changes in viability, morphology, cellular proliferation, ability to produce collagen, and cell outgrowth from explants. In vivo, skin biopsies of chronic exudative wounds being treated with cadexomer iodine demonstrated no evidence of cell necrosis, displayed re-epithelialization, and revealed bacteria within the cadexomer beads.
These studies demonstrate that cadexomer iodine has definite non-toxic concentration ranges for fibroblasts in vitro, which are consistent with a lack of cellular toxicity in human chronic exudative wounds treated with cadexomer iodine. Cadexomer iodine may also have the additional property of trapping microorganisms.
Venous ulcers affect up to 2.5 million patients per year in the United States. Although not usually fatal, these chronic wounds severely affect patients' quality of life because of impaired mobility and substantial loss of productivity. Although venous ulcers are typically small initially, they are often undertreated, progressing to larger ulcers that are associated with more serious complications requiring more complex treatments. In this report we detail the pathogenesis of venous ulcers together with potential complications, including exudate, erythema, cellulitis, dermatitis, pain, and possible malignancy. The clinician's regimen should always include a wide range of treatment modalities to ensure comprehensive care and effective wound closure. The treatment modalities and specific protocol for venous ulcers are discussed, and include topical dressings, antibiotics, debridement, compression therapy, and cellular therapy. These treatment modalities, in combination with early recognition and regular monitoring using digital photography and planimetry measurements, will ensure rapid healing and minimize complications and cost.
Moist wound treatment improves healing at a possibly increased risk of bacterial infection and many local antiseptics impair healing. A moist treatment modality with efficient antimicrobial activity would be desirable.
In this monocentric, randomized, observer blinded, phase III study, a new hydrosome polyvinyl-pyrrolidone (PVP)-iodine preparation in hydrogel containing iodine in a 3% concentration (Repithel) was investigated for its effect on epithelialization in patients receiving meshed skin grafts. Grafts of 167 patients (donor site defects, burn wounds, or chronic defects) were dressed either with Repithel (n=83) covered with a gauze (Jelonet), or Jelonet-gauze only (n=84) until healing.
Grafts receiving Repithel healed significantly earlier (9.4 days versus 12.4 days; p<0.0001) and faster than controls as measured by neo-epithelialization of mesh holes between days 7 and 11 (91.2+/-22.8% versus 82.3%+/-28.6, p<0.0001). A subgroup analysis showed that the effects on grafted burn wounds (p=0.0042) and chronic defects (p<0.0001) was more significant than on donor sites. Also a higher take rate of grafts (p=0.0053) and a reduced loss of grafts was observed with Repithel treatment (8 grafts versus 20 grafts) (p=0.0063, respectively). Smokers had improved graft take (p=0.0069) and higher rate of epithelialization (p=0.0040) compared to smokers of the control group.
The results demonstrate significant clinical advantages of Repithel. This new local wound healing drug combines antisepsis and wound moisture efficiently resulting in significantly enhanced epithelialization, decreased transplant losses, and significantly improved healing especially in smokers.
Moist wound treatment is a well recognized method for the treatment of aseptic acute and chronic wounds. While the moist environment is beneficial to the woundhealing process, it also increases the risk of bacterial superinfection. We here report on the results of a clinical phase-III-study in which we tested the effect of a new PVP-iodine liposomal hydrogel (Repithel) on split-thickness skin grafts. This formulation optimizes moist wound treatment by improving the cell proliferation rate while preventing wound infection.
The aim of this phase-III-study was to analyse the efficacy and tolerance of Repithel in patients receiving meshed skin grafts.
167 patients with transplantation wounds were either treated with lipid gauze alone (control group) or with lipid gauze and Repithel. In both groups the extent of neoepithelization, the frequency and severity of graft losses and the time until complete wound closure was achieved were determined. Analysis of the re-epithelization was achieved by photoplanimetry. Impedance measurements gave additional information on the regeneration of the epidermal barrier.
Wounds receiving Repithel showed a significantly faster neoepithelisation than wounds which were treated with lipid gauze alone. Treatment with Repithel significantly reduced both the number of graft losses and the size of area lost. The time until wounds were closed completely was significantly shorter in patients receiving Repithel than in controls. The positive effects of Repithel on wound healing were especially observed in smokers, patients with chronic wounds, burns or infected wounds.
Repithel supports healing of meshgraft transplants and reduces the risk of graft loss. Patients who heal poorly benefit particularly from the Repithel treatment.
Although cadexomer iodine is widely used for the treatment of skin ulcers such as decubitus ulcers, the mechanism by which it enhances wound healing is not clear. Recently, it has been demonstrated that macrophages play an important role in wound healing by inducing inflammation and angiogenesis.
We examined the effects of cadexomer and cadexomer iodine on tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) production by macrophages.
Human macrophages were obtained by culturing CD14+ monocytes with macrophage colony stimulating factor (M-CSF) in the presence or absence of cadexomer or cadexomer iodine. The production of cytokines and the expression of mRNA were evaluated by enzyme linked immunosorbent assay (ELISA) of the culture supernatants and by reverse transcriptase polymerase chain reaction (RT-PCR) analysis, respectively. In addition, we examined the tissue concentration of VEGF in the wounds treated with or without cadexomer iodine.
Cadexomer and cadexomer iodine significantly increased the expression of IL-1β, IL-8, TNF-α and VEGF mRNA, while they did not affect that of IL-6, IL-10, IL-12p40 or bFGF mRNA. In addition, they significantly increased the production of IL-1β and TNF-α. Although we could not detect increased production of VEGF in the culture supernatants, the western blot analysis of macrophages demonstrated the increased production of VEGF by the treatment with either cadexomer or cadexomer iodine. The treatment with cadexomer iodine increased the tissue concentration of VEGF in the skin wounds.
These data suggest that cadexomer and cadexomer iodine have beneficial effects on wound healing in addition to those related to their antibacterial activity.
Iodine is an antiseptic that has been used in wound care for more than 150 years. Traditional formulations of iodine had serious limitations that were reduced in later products. Much has been written about iodine and opinions on its clinical efficacy are divided. There have been reviews of the chemical properties of iodine, its antimicrobial activity, human physiology, cytotoxicity and its clinical effectiveness, but few have addressed all these aspects. With the recent development of iodine-containing wound care products and the continued publication of laboratory and clinical studies, it seems timely to reassess the evidence relating to the effectiveness of iodine for treating wounds. This literature review attempts to provide an appropriate chemical and physiological background of the characteristics of iodine in order to provide a sound basis for understanding the available microbiological and clinical data. It will show that understanding the factors that contribute to the activity and potential cytotoxicity of iodine are important in evaluating the clinical evidence. Although definitive studies are needed, the sustained delivery of low doses of free iodine offers the potential to inhibit a broad range of microbial species without selecting for resistant strains or inducing cytotoxic effects.
The topical application of a mixture of sugar and povidone-iodine (PI) has been reported to accelerate the healing of cutaneous wounds and ulcers by promoting reepithelialization and granulation tissue formation, as well as by having an anti-microbial effect. In order to clarify the efficacy of a 70% sugar and 3% PI paste (U-PASTA(SP) on infectious skin ulcers, we made a bacterial infection model using methicillin-resistant Staphylococcus aureus (MRSA) on the skin of diabetic db/db mice, and investigated the effect of the paste on the healing process of wounds. Full-thickness wounds were made on the backs of female diabetic mice, (C57BL/ksJ db/db) and inoculated with S. aureus. SP was applied to the closed wounds for 8 days. The degree of repair was evaluated using three histological parameters: The degree of reepithelialization was given a percentage value of 0-100%; the amount of granulation tissue was quantified by measuring the area of granulation (mm(2)); and the number of capillary lumens in the granulation tissue was counted in the complete wound cross-section at 100x magnification. In addition, the colony-forming units (CFU) of MRSA on the wounds were counted. Continuous MRSA infection in the wounds of db/db mice was demonstrated with macroscopic and histopathological images. Wounding and infection caused by MRSA on the back of the diabetic mice significantly induced delayed reepithelialization, granulation tissue formation with inflammatory cell infiltrate and increased CFU on wounds (P < 0.01, respectively) compared to those of the MRSA-infected normal mice. Application of SP significantly accelerated reepithelialization (P < 0.01) and decreased CFU (P < 0.05) of the ulcers in the MRSA-infected wounds, compared to the non-treated group. Histopathological evaluation and CFU on this animal model revealed no significant difference between Methicilin-sensitive Staphylococcus aureus and MRSA infection. These results indicate that wounding on db/db mice provides a useful animal model of bacterial skin infections, and that SP is an effective topical agent for the treatment of diabetic skin ulcers.
Notwithstanding the progress that has been made in our understanding of wound healing, relatively little is known about the interaction of chronic wounds with materials used in their management. We have been investigating the pro- and antioxidant properties of wound management materials with a view ultimately to determine whether and how these properties contribute to the healing process. Our studies with cadexomer (the modified starch used as an iodine carrier in lodosorb powder, ointment, and in lodoflex paste dressing) have revealed no significant pro- or antioxidant properties. Cadexomer iodine (0.05 – 2% w/v), however, modulated L929 fibroblast proliferation in culture whilst lodosorb powder (1 – 2% w/v) and iodine itself (0.009 – 0.018% w/v) inhibited superoxide generation by latex bead- or phorbol ester-stimulated mouse peritoneal macrophages. These effects on fibroblasts and macrophages we believe both arose through oxidation of intracellular reductants such a NAD(P)H and glutathione by iodine. In investigations of the excipients of lodosorb ointment and lodoflex, no hydrogen atom/electron donation was shown in the DPPH assay by polyethylene glycols and poloxamers but a previously unrecorded antioxidant effect, possibly singlet oxygen-scavenging, was observed. Our results indicate that whilst lodosorb powder may contribute only pro-oxidant effects from the iodine it releases to a wound, the ointment and paste formulations additionally contribute an antioxidant effect that may conceivably enhance energy availability for tissue repair.
In a crossover study designed to judge the efficacy of the topical polymeric starch iodophore, cadexomer iodine, in accelerating the healing of venous stasis ulcers, 75 patients were prospectively randomly assigned to receive either cadexomer iodine or standard treatment. The control treatment consisted of a standard saline wet-to-dry compressive dressing. The patients improved with either treatment: ulcers healed more than twice as rapidly using cadexomer iodine (n = 38) as with standard therapy (n = 37) (P = .0025). Ulcers treated with cadexomer iodine showed trends toward less pain, exudate, pus, and debris, and a more rapid development of granulation tissue. Twelve patients crossed over from control treatment to the use of cadexomer iodine because of a failure to heal, but no patients switched to control therapy from the use of cadexomer iodine (P = .01). Except for occasional mild local burning in wounds treated with cadexomer iodine, no adverse effects were noted with either regimen.
Povidone-iodine ointment is a widely used topical antimicrobial agent in thermally injured patients. In 17 patients with burns ranging from 4 to 85% TBSA this agent was applied to both partial- and full-thickness burns. Peak serum iodine levels in patients treated within 24 hours of injury ranged from 595 to 4,900 $mUg per dL. The amount of iodine absorbed was directly related to the size of the burn. Serum iodine levels continued to rise until the drug was discontinued and remained elevated for as long as 7 days after discontinuance. Iodine excretion was directly related to renal function. The highest serum and lowest urinary iodine levels were present in patients who developed renal failure. Thyroid function was not affected by drug usage. A proven cause-and-effect relationship between the elevated serum iodine attributed to the absorption of povidone-iodine- and metabolic acidosis, hypernatremia, and hyperosmolarity was not established. Close monitoring of the patient's fluid and electrolyte balance is imperative during drug usage. The drug is contraindicated in any patient with impaired renal function. The high serum levels of this inorganic ion imply potential toxicity, but clinical evidence of cell or organ toxicity is as yet undetermined.
Collagenous dermal templates can prevent scarring and wound contraction in the healing of full-thickness defects. In a porcine wound model, full-thickness wounds were substituted by reconstituted and native collagen sponges in combination with autologous split-skin mesh grafts and covered with a semipermeable wound membrane. Native collagen sponges were also linked with either hyaluronic acid, elastin, or fibronectin. Reconstituted collagen matrixes, composed of cross-linked small collagen fibrils, disintegrated within a week and did not contribute to dermal regeneration, whereas native collagen matrixes, composed of intact collagen fibers, disintegrated within 2 weeks and did contribute to dermal regeneration. Addition of extracellular matrix proteins retarded the disintegration to 4 weeks. However, fibronectin-treated matrixes caused aberrant epithelization. When hyaluronic acid was added, matrixes were invaded by more fibroblasts and myofibroblasts. This process correlated with fibrosis and wound contraction. In contrast, the native collagen/elastin matrix reduced the amount of fibroblasts and myofibroblasts. This latter matrix resulted in optimal dermal regeneration and little wound contraction.
We tested different biodegradable matrix materials as dermal substitutes in a porcine wound model. Matrixes were covered with a split-skin mesh graft and protected with a microporous, semipermeable membrane, which prevents blister formation, wound infection and provides ultimate healing conditions. Evaluation parameters were as follows: epithelization, dermal reconstitution, wound contraction, and cosmetic and functional aspect. A microfibrillar matrix of nondenatured collagen gave the best result, with immediate fibroblast ingrowth and epidermal outgrowth. Slight inflammatory reaction and minimal wound contraction were observed. Application of a split-skin mesh graft, in combination with this collagen matrix, generated a thicker dermal layer than did a split-skin mesh graft directly applied on a wound bed. However, the histologic dermal architecture was less optimal than one obtained with a full-thickness punch graft method. Other matrixes caused inflammatory reactions, interfering with epithelization and dermal reconstitution. We conclude that a nondenatured collagen matrix, in combination with a split-skin mesh graft, can provide a substitute dermis in a full-thickness wound. This combination is preferable to a split-skin mesh graft directly applied on the wound bed. With our microporous semipermeable membrane, the combined use of a dermal substitute and a split-skin mesh graft can be applied in a single-stage operation.
Nicht experimentell infizierte standardisierte Verbrennungsverletzungen und solche, die mit einer konstanten Keimzahl eines bestimmtenPseudomonas aeruginosa-Stammes kontaminiert worden waren, wurden unterschiedlich behandelt. Dabei wurden Silbersulfadiazin- und Cefsulodin-Creme sowie Polyvidon-Jod-Salbe eingesetzt. Die Heilverlufe wurden durch Wundflchenbestimmungen kontrolliert. Die nicht experimentell infizierten Wunden zeigten unbehandelt die besten Ergebnisse. Nicht signifikant schlechter waren die Heilverlufe bei den mit Cefsulodin-Creme behandelten Tieren. Die deutlichste Abheilungsverzgerung boten die mit PVP-Jod behandelten Wunden. Pseudomonas-infizierte Brandwunden heilten unter prophylaktisch durchgefhrter Silbersulfadiazin-und Cefsulodin-Behandlung im Vergleich zur Kontrollgruppe signifikant schneller ab. PVP-Jod fhrte auch hierbei zu einer verzgerten Wundheilung.Non-infected standardized burns and those contaminated experimentally with a constant number of organisms of a selectedPseudomonas aeruginosa strain underwent varying forms of treatment with silver sulfadiazine, cefsulodin cream and povidone iodine ointment. Wound healing was controlled by evaluating the wound area. In burns which had not been infected experimentally, healing was best without any treatment. Burns treated with cefsulodin cream showed delayed healing, though this was not significant. The most significant delay, however, was observed in wounds treated with povidone iodine. Wounds infected withPseudomonas healed considerably better than the control group when treated prophylactically with silver sulfadiazine and cefsulodin. However, burns treated with povidone iodine again showed delayed healing.
Species of Proteus, Serratia, and Pseudomonas became resistant to chlorhexidine after five to eight transfers in vitro. Cross-resistance to benzalkonium chloride also was detected. Resistance to povidone-iodine was not encountered. Chlorhexidine resistance was stable after drug-free transfers of Serratia and Pseudomonas but was transitory for Proteus.
Studies were carried out to detect the modifications, if any, on the peri-umbilical flora of six healthy volunteers after two or three daily applications of Hexomedine solution (HEX) and Betadine solution (PVI) repeated for five consecutive days. A standardized scrubbing method was used for bacterial sampling. Surviving bacteria were selected with both selective and non-selective media, and then identified by gas chromatographic fatty acid analysis. Both antiseptics were highly effective, showing both immediate and residual antimicrobial activities. The use of HEX led to a slight increase in Gram-positive cocci and a small decrease in coryneforms, but PVI produced a marked increase in Gram-positive cocci and a sharp decrease in coryneforms. The two antiseptics, however, caused no major alteration in the cutaneous microbial population. Indeed, neither the overgrowth of Gram-negative bacilli nor the emergence of resistant species was observed.
The antibacterial activity of eight antiseptic creams: 1 per cent silver sulphadiazine; 0.2 per cent nitrofurazone; 0.1, 0.5 and 1 per cent chlorhexidine; 2.2 per cent cerium nitrate; 10 per cent povidone iodine; and 1 per cent silver sulphadiazine with 2.2 per cent cerium nitrate were evaluated in vitro. The evaluation included the minimum inhibitory concentration (MIC) against 100 microorganisms isolated from burn patients, the chronology of the bacterial activity against Ps. aeruginosa and Staph. aureus and the penetration strength of the creams through a novel in vitro model contaminated with 17 microorganisms of different species isolated from burn patients. The results revealed that 0.5 per cent or 1 per cent chlorhexidine, 2.2 per cent cerium nitrate, and 1 per cent silver sulphadiazine with 2.2 per cent cerium nitrate were the creams which were effective at the highest dilutions. 0.5 per cent chlorhexidine and 10 per cent povidone iodine had the greater bactericidal activity. Finally, 0.2 per cent nitrofurazone showed greater penetration strength within the eschar model in comparison with the weaker penetration of 0.5 per cent and 1 per cent chlorhexidine and the absence of penetration by the rest of the antibacterial creams.
An in vitro method using a burn eschar 'equivalent' is described to compare the efficacy of several antimicrobial creams. Fragments of lyophilized pigskin were used as 'germ carriers' and after 24 h of treatment the effectiveness of the antimicrobial creams was tested through the evaluation of bacterial recovery both from the surface and from within the 'germ carriers'. The results showed a striking full skin thickness effectiveness of 0.5 per cent chlorhexidine, 10 per cent providone iodine and 2 per cent cerium nitrate in comparison with the weak activity demonstrated by 1 per cent silver sulphadiazine cream.
The efficacy of topical antiseptic therapy for wounds and skin ulcers has been shown to be at the expense of fibroblast and leukocyte function and, in general, wound healing. Specifically, continued fibroblast function after exposure to antiseptics has been correlated to the concentration of the antiseptic. At concentrations that preserve fibroblast function, 0.005% sodium hypochlorite, 0.001% providone-iodine, 0.0025% acetic acid, and 0.003% hydrogen peroxide were tested for their effectiveness against various clinical isolates. Staphylococcus aureus, Escherichia coli, Group D enterococci, Pseudomonas aeruginosa, and Bacteroides fragilis were exposed to the antiseptics and plated in a standard microbiological fashion. The cultures showed that sodium hypochlorite inhibited the growth of all the bacteria (p less than 0.001), whereas povidone-iodine reduced the colonies of S. aureus and acetic acid inhibited P. aeruginosa. Our study suggests that 0.005% sodium hypochlorite can be used as a debriding and topical antibacterial agent for wounds and skin ulcers without inhibiting fibroblast activity essential to normal wound repair.
This report presents the case of a patient who expired 10 hours following and emergent hip-wound debridement where Betadine, a povidone iodine solution, was used to provide continuous postoperative wound irrigation. Toxic manifestations of systemic iodine absorption appeared to cause her demise.
An established wound model in the pig has been modified using a Stomahesive ring to enable study of the effects of fluids used in wound care. Full thickness wounds (up to 9 mm deep) were treated with the substances under test. Each application was held in place with a Stomahesive flange, the inner part of which had been excised as far as the hard plastic ring. All dressings were then covered with OpSite which allowed gaseous exchange whilst retaining treatment fluids and secretions. Wounds were treated immediately and at 2 and 4 days. The experiment was terminated after 7 days and the whole wound, with dressing, was excised for histological examination. The wounds covered with OpSite alone and those treated with sugar paste under Opsite were found to be infilled with granulation tissue over which epidermal migration was taking place. Those wounds which had been packed with gauze, to which had been added one of the following: chlorhexidine gluconate 0.2%, Irgasan 0.2%, povidone iodine 0.8% or EUSOL half-strength, showed delayed healing in that less infilling had taken place over the same time period. This delay could be attributed to the nature of the chemicals used and/or the influence of gauze packing. This delay in the healing of wounds treated with chemical agents was least with EUSOL half-strength and greatest with chlorhexidine. No toxic effects were observed with sugar paste which may be preferable to antiseptics for the management of dirty or infected wounds.
A total of 67 patients with treatment resistant chronic venous ulcers were admitted to hospital for 6 weeks of bed rest and daily dressings. The patients came from a rural area in Poland with poor socioeconomic conditions. They were randomized to treatment with either standard dressings or with cadexomer iodine. After 6 weeks all but four patients had shown a clear reduction of ulcer area; the mean reduction was 54% within the former group and 71% with cadexomer iodine. The latter treatment was significantly more effective than the standard hospital dressings in debriding the ulcer, accelerating healing and reducing pain. Elevation of serum concentrations of protein-bound iodine occurred after treatment with cadexomer iodine in patients with large ulcers, but tests of thyroid function showed no changes associated with the use of cadexomer iodine. It is concluded that cadexomer iodine significantly accelerates the healing of chronic, infected, treatment-resistant, venous ulcers in hospitalized patients.
The improvement in infusion therapy of burn patients in the last decades has led to a marked reduction of the early mortality rate and to an increase in the importance of severe wound infection and septicaemia. For the control of infection, detailed bacteriological monitoring is recommended. The main therapeutic fields for prevention of infection are: immunotherapy, antisepsis, aseptic techniques, and rapid restoration of the destroyed body surface. The most important part of antisepsis in burns is topical treatment. The good bacteriological and clinical results with povidone-iodine (PVP-I), in combination with open treatment are described. A possible disadvantage of this therapy was the extensive iodine resorption. However, no disorders of thyroid function were revealed, and the TRH test indicated no abnormal reactions of the hypothalamus-pituitary axis. The high serum and urine iodine levels returned rapidly to normal after discontinuing the PVP-I application.
A prospective study was conducted to investigate the effect of long term therapy with two iodine-containing mouth rinses on thyroid function. Two groups of subjects were treated daily for 6 months with either a 5% polyvinylpyrrolidone (PVPI)-1.5% H2O2 mixture (Perimed) or a 5% PVPI-water mixture. Thyroid function studies, serum iodine concentrations, and urinary iodine excretion were measured before treatment, at 6-week intervals during the 6-month treatment period, and 3 weeks after the last treatment. There was evidence of significant iodine absorption (elevated serum total iodine and inorganic iodide concentrations and urinary iodine excretion) from daily use of both Perimed and the PVPI-water mixture. Serum T3 and T4 concentrations and the free T4 index did not change. There was a small significant rise in serum TSH concentrations during mouth rinse therapy, but all values remained within the normal range. This small increase in serum TSH is a normal adaptive response to the antithyroid effect of increased iodine intake and accounts for the maintenance of normal serum T4 and T3 concentrations. While daily use of these iodine-containing mouth rinses does result in significant iodine absorption, there is no evidence for the development of thyroid dysfunction during a 6-month course of therapy.
This study has shown that Betadine cream with or without Aserbine is as easy to apply and remove as Betadine ointment plus Aserbine. With Betadine cream there is as good as and in some instances better healing than with Betadine ointment/Aserbine in the topical treatment of burns. However, the addition of a necrolytic cream to Betadine cream does have favourable effects on wound healing and bacterial counts. More importantly, this study suggests that Betadine cream can penetrate the wound more effectively than the Betadine ointment/Aserbine combination but that the addition of a necrolytic cream is still advantageous.
Cadexomer iodine (Iodosorb) is a hydrophilic starch powder containing iodine, which is a suitable dressing for granulating wounds such as venous ulcers. A total of 61 outpatients with chronic venous ulcers participated in a randomised optional crossover trial using cadexomer iodine or a standard dressing for their ulcers. The trial lasted for 24 weeks or until the ulcer had healed. Two patients withdrew during the course of the trial. Both treatments were highly effective, but the epithelium of ulcers dressed with cadexomer iodine grew again significantly faster (p less than 0.001). At the midpoint of the trial (12th week) 13 of 30 patients receiving standard treatment were changed to cadexomer iodine, while only three of 29 receiving cadexomer iodine changed to the standard dressing (p less than 0.02). In most cases ulcers were dressed and rebandaged daily by the patients themselves after instruction and supervision. This may be better than having dressings and bandages applied by professionals less regularly.
Three topical antibiotics and four antiseptics (1% povidone-iodine, 0.25% acetic acid, 3% hydrogen peroxide, and 0.5% sodium hypochlorite) were directly applied to cultured human fibroblasts to quantitatively assess their cytotoxicity. The four antiseptics were found to be cytotoxic; all of the cytotoxic agents except hydrogen peroxide were subsequently found to adversely affect wound healing in an animal model. Comparison of bactericidal and cytotoxic effects of serial dilutions of these four topical agents indicated the cellular toxicity of hydrogen peroxide and acetic acid exceeded their bactericidal potency. Bactericidal noncytotoxic dilutions of povidone-iodine and sodium hypochlorite were identified. These experiments provide evidence that 1% povidone-iodine, 3% hydrogen peroxide, 0.5% sodium hypochlorite, and 0.25% acetic acid are unsuitable for use in wound care. This sequence of experiments could be used to identify bactericidal, noncytotoxic agents prior to their clinical use.
The effects of several antiseptic agents on granulation tissue were studied using rabbit ear chambers as models of the healing wound. This enabled us to study dynamically the action of these agents on the microcirculation of the wound. All the agents tested caused some adverse effect, but in the cases of hypochlorite antiseptics Eusol and Chloramine T, blood flow in the capillary circulation of the granulation tissue ceased and the process of repair was subsequently delayed. A laser Doppler flowmeter was used to measure these changes in local perfusion which reflected the toxic effects seen on microscopy of the ear chamber.
Chronic ingestion of iodide or iodide-generating organic compounds in amounts of ten or more times the daily requirements for hormone biosynthesis leads to iodide goiter in certain subjects. Predisposing factors are uncertain but may involve a damaged thyroid parenchyma; this must, however, be minimal since full recovery of normal thyroid function occurs upon iodide withdrawal in nearly all cases. In certain cases cogoitrogens such as sulfanilamides or antipyrine (phenazone) may contribute.Iodide goiter occurs at all ages and in the fetus may lead to fatal respiratory obstruction. Goiter or myxedema may exist independently but they frequently occur together except in an endemic form (apparently due to seaweed ingestion) in which euthyroid goiter is the rule.The clinical picture is that to be expected from varying degrees of hypothyroidism with or without goiter. Diagnosis is complicated by iodide contamination but the following test results can be expected: BEI or T4, low or normal; total or plasma inorganic iodide, high; urine iodine, high; 131I uptake, any value (depends on plasma iodide) may be high despite high plasma iodide, there is a high absolute iodine uptake and rebound after iodide withdrawal; thyroid 131I half-life, rapid will parallel serum 131I (“iodide” curve); SCN− or ClO4− discharge, positive; autoantibody titers, usually low. Diagnosis requires shrinking of the goiter and return to the euthyroid state within two to six weeks upon iodide withdrawal.It has been necessary to study the mechanism in acute experiments. With increasing single doses of iodide, thyroidal organic iodine formation increases to a maximum following which there is a sharp decrease in the formation of organic iodine. This inhibition is greater with successive steps in hormone synthesis so that MIT:DIT and iodotyrosine:iodothyronine ratios increase. That similar events occur in man is inferred from 131I kinetics and discharge of 131I by ClO4− or SCN- but a direct demonstration has been wanting. It is highly probable that failure to escape from inhibition accounts for or contributes to iodide goiter in man.A number of mechanistic proposals for the iodide effect have been made but have not been proved: (1) inflammatory changes in the parenchyma; (2) a structure-breaking effect of iodide on some crucial enzyme; (3) inhibition of carbohydrate or other intermediary metabolism to limit formation of reduced pyridine nucleotide levels and hence substrate for peroxidases of the thyroid; (4) chemical mechanisms operating via the triiodide equilibrium and/or H2OI+ formation.A second major effect of excess iodide is to inhibit release of organic iodine from the thyroid if the parenchyma is stimulated; however, TSH is not per se required. This action of iodide is generally ascribed to inhibition of thyroglobulin proteolysis but supporting evidence is meager.
Ninety-three patients with treatment-resistant venous ulcers were included in a multicentre randomized trial to compare cadexomer iodine and the standard treatment used in each centre combined with compression bandages, in healing venous ulcers. The mean duration of ulcers before the trial was more than 2 years. With standard treatment the mean ulcer size increased slightly during the 6-week trial whereas with cadexomer iodine the ulcer size was significantly reduced. Cadexomer iodine was more effective than standard treatment for reduction of pain, removal of pus and debris, removal of exudate, stimulation of granulation and reduction of surrounding erythema. Bacterial infection of ulcers increased or did not change during treatment with the standard therapy whereas cadexomer iodine significantly reduced infection with Staphylococcus aureus, Pseudomonas aeruginosa and other pathogenic organisms. A correlation was seen between the time taken to reduce or eliminate infection with Staphylococcus aureus and rate of ulcer healing. Four patients complained of transient pain in the ulcer after application of the cadexomer iodine. It is concluded that cadexomer iodine increased the rate of healing of infected chronic venous ulcers.
The absorption of iodine from iodine-containing PVP preparations and the possibility of iodide being split off from the organic compound were tested in subjects with normal thyroid function after they had used PVP-iodine as mouth-antiseptic (15 subjects), vaginal gel (20 subjects) or liquid soap (20 subjects). Serum I-, T3, T4, TSH and urinary iodide excretion were measured, as an index of thyroid function, before and after the PVP application. Increase in iodine supply was up to 2 mg daily in the test subjects. The overwhelming proportion of the absorbed iodine (greater than 75%) was as organically bound iodine. In none of the subjects was there evidence of developing hyper- or hypothyroidism as a result of the additional iodine supply. Approximate values for the biological half-life and the distribution volume of total iodine in the body were also obtained.
Thirty-four patients with decubitus ulcers were studied in a randomized trial to compare topical cadexomer iodine with the standard decubitus ulcer treatments used in the participating hospitals. There was a significant reduction of ulcer area with both treatments within three weeks; however, eight of 16 patients treated with cadexomer iodine had a reduction of ulcer area of more than 50 per cent, compared with one of 18 patients treated with the standard treatment (P less than 0.01). Twenty-seven patients continued the same treatment for five more weeks, during which time six in the cadexomer iodine group healed, compared with one in the standard treatment group (P less than 0.05). Cadexomer iodine was superior to the standard treatment in removing pus and debris from the ulcer surface and in reducing pain at the ulcer site. It was found to be easy both to apply and to remove from the ulcers and did not stain skin or clothing. Transient smarting during the first hour after application was reported by three patients, and one patient complained of skin irritation. The results show that cadexomer iodine applied daily has a debriding effect on decubitus ulcers and accelerates healing.
Non-infected standardized burns and those contaminated experimentally with a constant number of organisms of a selected Pseudomonas aeruginosa strain underwent varying forms of treatment with silver sulfadiazine, cefsulodin cream and povidone iodine ointment. Wound healing was controlled by evaluating the wound area. In burns which had not been infected experimentally, healing was best without any treatment. Burns treated with cefsulodin cream showed delayed healing, though this was not significant. The most significant delay, however, was observed in wounds treated with povidone iodine. Wounds infected with Pseudomonas healed considerably better than the control group when treated prophylactically with silver sulfadiazine and cefsulodin. However, burns treated with povidone iodine again showed delayed healing.
To determine if application of iodide to vaginal mucosa of pregnant women results in significant iodide absorption or changes in thyroid function, we studied 18 intrapartum women for whose examinations during labor povidone-iodine gel was used as a lubricant and 16 for whose examinations an iodine-free lubricant was used. Both serum inorganic iodine and total serum iodine increased significantly (p less than 0.001) after iodide exposure and fell (p = 0.003) to near baseline within two days. In both groups, serum thyroxine and triiodothyronine fell during labor and delivery; differences between groups were not significant. In the iodine-treated group, however, there was a significant increase in thyroid-stimulating hormone at two days postpartum (p less than 0.001). Iodide applied to vaginal mucosa of pregnant women is absorbed and affects the maternal pituitary-thyroid axis.
Povidone-iodine ointment is a widely used topical antimicrobial agent in thermally injured patients. In 17 patients with burns ranging from 4 to 85% TBSA this agent was applied to both partial- and full-thickness burns. Peak serum iodine levels in patients treated within 24 hours of injury ranged from 595 to 4,900 micrograms per dL. The amount of iodine absorbed was directly related to the size of the burn. Serum iodine levels continued to rise until the drug was discontinued and remained elevated for as long as 7 days after discontinuance. Iodine excretion was directly related to renal function. The highest serum and lowest urinary iodine levels were present in patients who developed renal failure. Thyroid function was not affected by drug usage. A proven cause-and-effect relationship between the elevated serum iodine attributed to the absorption of povidone-iodine and metabolic acidosis, hypernatremia, and hyperosmolarity was not established. Close monitoring of the patient's fluid and electrolyte balance is imperative during drug usage. The drug is contraindicated in any patient with impaired renal function. The high serum levels of this inorganic ion imply potential toxicity, but clinical evidence of cell or organ toxicity is as yet undetermined.
The primary effect sought with most topical wound therapy is antimicrobial. Topical wound agents are thought to promote normal healing by protecting the wound from infection. In this study, we examined the effect of six commonly used topical wound agents (bacitracin, sodium hypochlorite, silver nitrate, silver sulfadiazine, mafenide acetate, and povidone-iodine) on epithelialization and neovascularization in noninfected wounds. For this study, a new wound model was used in which direct visualization and quantification of wound epithelialization and neovascularization were carried out throughout the entire healing process.
We measured the effect which 500 U per g of bacitracin, 0.25 percent of sodium hypochlorite, 0.5 percent silver nitrate, 1 percent silver sulfadiazine, 8.5 percent mafenide acetate, and 10 percent povodione-iodine had on the rate of wound epithelialization and neovascularization. The agents were applied topically to 99 circular full-thickness wounds (2.25 mm diameter, 0.125 mm depth) created on the dorsum of male hairless mouse ears. This model enabled us to visualize and measure directly wound epithelialization and neovascularization repeatedly throughout healing, using intravital video microscopy and computerized digitized planimetry.
Control wounds and wounds treated with silver sulfadiazine (n = 18) and mafenide acetate (n = 14) epithelialized in 7.2 +/- 0.7, 7.1 +/- 0.3, and 7.3 +/- 0.3 days, respectively. This was significantly (p < 0.01) faster than the wounds treated with povidone-iodine (n = 10), sodium hypochlorite, (n = 8), and bacitracin (n = 13). Wounds treated with povidone-iodine epithelialized the slowest (11.8 +/- 0.55 days). Wound neovascularization was completed most rapidly in the groups treated with povidone-iodine and silver sulfadiazine (15.0 +/- 0.4 and 15.3 +/- 0.7 days, respectively). This was significantly (p < 0.05) faster than wounds treated with silver nitrate (n = 15), which neovascularized in 18.4 +/- 0.56 days. One-half of the wounds treated with sodium hypochlorite (eight of 16) did not epithelialize or neovascularize.
The various antimicrobial agents studied in our in vivo model affect wound epithelialization and neovascularization differently. These effects on these two very important aspects of healing should be taken into consideration when indicating a specific agent for treatment of different types of wounds.
Topical treatment of wounds is an important aspect of wound care, although secondary to surgical and systemic care. Dressing materials come in many forms to suit wound types and preferences. No hard evidence exists to place any one approach above another. All wounds deserve individualized attention and care plans. Likewise, a plethora of solutions exist to augment dressing materials in cleansing, antibiosis, and débridement. Traditional agents, including hydrogen peroxide, Dakin's solution, and povidone-iodine, are more tissue toxic than their common usage would indicate. We prefer frequent dressing changes with natural fiber gauze and nontoxic solutions such as saline. The scalpel, curette, and rongeur are, in our experience, much preferred to enzymatic agents when débridement is needed. We encourage scrutiny of commercial products based on clinical merit and effectiveness as documented in the medical literature. Platelet derived growth factors are an effective adjunct to wound healing and are primarily indicated when the condition of patients and their wounds has otherwise been optimized.
There is mounting concern regarding the efficacy of many germicides on the market because officially recognized germicidal tests for various classes of microorganisms vary widely and often lack reproducibility and proper quantitation. We report here a carrier method for simultaneously and quantitatively assessing the efficacy of liquid chemical germicides against a mixture of microorganisms of varying degrees of resistance.
In the test, each small glass cup (10 mm wide x 14 mm long) was contaminated with 10 microliters of a standardized mixture of Staphylococcus aureus, Mycobacterium bovis bacille Calmette-Guérin, Trichophyton mentagrophytes spores, Sabin poliovirus type 1, and Bacillus stearothermophilus spores in 5% fetal bovine serum. The inoculum was dried for 60 minutes under ambient conditions and covered with 60 microliters of the disinfectant under test or a balanced salt solution control for the desired contact time. The carrier was then placed in 2940 microliters of an eluent and the eluates assayed separately for the five microorganisms. Tap water was used to dilute the test product as needed.
Of the 11 products tested, 2% alkaline glutaraldehyde, 0.6% sodium hypochlorite (about 5000 ppm free chlorine), and a 0.4% quarternary ammonium compound containing 23% hydrochloric acid were effective against all five challenge organisms. A hard-surface spray containing 0.1% o-phenylphenol with 79% ethanol was effective against all but bacterial spores; 70% (volume/volume) ethanol alone and povidone-iodine (1% available iodine) were effective against S. aureus, the mycobacterium, and the fungus; a 3% solution of peroxygen compounds was effective only against S. aureus and the poliovirus; 1.5% chlorhexidine gluconate, 0.06% quaternary ammonia compound, and 0.03% o-phenylphenol + 0.03% p-tertiary amylphenol could inactivate nothing but S. aureus; and 3% hydrogen peroxide was ineffective in all tests.
This method shows promise for use with various classes of microorganisms, individually or as mixtures. Its application should enable the classification of germicides according to spectrum of activity.
The relationship between wound healing and cutaneous microbiology is a complex one mediated by the type of wound, its treatment, and the defense mounted by the injured individual. Acute wounds harbor microflora similar to that of noninjured skin. "Dirty" traumatic wounds or chronic wounds with devitalized tissue offer more opportunity for microflora colonization, with the potential for bacterial adherence to the host cells and ultimate invasion into viable tissue or infection. The alterations of these wound environments can be brought on by topical treatments. Occlusive dressings with various moisture vapor transmission rates can provide a wound environment suitable for microflora proliferation. In spite of this increase in numbers of organisms, most wounds do not become infected, as shown by a survey of published trials. Infection requires the proper pathogenic microorganism, its attachment, and subsequent multiplication. To cause an infection, an organism must invade viable tissue and evade the host defense response. The many occlusive dressing types available offer an opportunity to select a wound therapy tailored for the microenvironment most suitable for healing. Wounds can be protected from exogenous microfloral contamination with dressings. Some dressing types, such as hydrocolloid dressings with no moisture vapor transmission, should not be used on chronic wounds suspected of harboring anaerobic organisms. Other typical treatments, such as antiseptics, can injure tissue and make infection more probable, providing devitalized tissue for bacterial adhesion. Povidone-iodine solution has been shown not be efficacious, whereas povidone-iodine cream effectively limits bacteria and infection.(ABSTRACT TRUNCATED AT 250 WORDS)
We report a modified technique of delayed primary wound closure using a wound wick. A rodent model was used to determine its influence on healing. After loose primary closure of two paravertebral incisions on the dorsum of male rats, a 10 cm length of ribbon gauze, soaked in either saline or 1% povidone-iodine, was inserted into the right sided wound. Wicks were soaked daily with the same solution until removal on the third post-operative day. The inclusion of a wick soaked in saline had an early transient effect on healing. A more prolonged impairment of healing was demonstrated in povidone-iodine wicked wounds and their respective controls. These data suggest that povidone-iodine impaired healing not only in the wicked wound, but also inhibited healing in the adjacent unwicked wound which was not directly exposed to the antiseptic. The observed delay in healing in povidone-iodine wicked wounds must however be balanced against its beneficial effect on wound infection rates. We suggest that further evaluation of this method of closure in contaminated wounds is warranted.
Infection is one of the most frequent complications of wound healing despite the use of antibiotics and modern sterile technique; it accounts for considerable patient morbidity, discomfort, and prolonged hospitalization, and it must be avoided to permit proper healing. For this purpose, topical antiseptics have been employed for several years. Among these povidone-iodine formulations (polyvinylpyrrolidone iodine; PVP-I; e.g., Betadine preparations), which consist of a water-soluble complex of elemental iodine and a synthetic polymer, have a broad antimicrobial spectrum, and have not been reported to develop bacterial resistance. Because some reports have suggested that PVP-I may interfere with wound healing, a critical review of studies concerning PVP-I and wound healing was undertaken, with emphasis placed on in vivo models that replicate, as closely as possible, human wound healing. Four forms of PVP-I were evaluated: PVP-I solution, PVP-I skin cleanser/surgical scrub, PVP-I ointment, and PVP-I cream. PVP-I solutions had virtually no deleterious effect on wound healing: application of 10% PVP-I solution to rat, guinea pig, rabbit, or pig wounds did not reduce wound tensile strength or delay re-epithelialization. In three human studies, no significant difference in healing was observed for 1%, 5% or 10% PVP-I solution except for a slight delay during the first 24 hours after the application of 5% PVP-I solution in one study; healing was normal by 72 hours. PVP-I skin cleansers/surgical scrubs contain ammonium nonoxynol-4-sulphate and lauramide DEA which, like all detergents, can cause tissue damage and delay healing. This was substantiated by a guinea pig study in which the detergent component but no the antiseptic produced these effects. In human trials, no damage occurred if cleansing of the wound with PVP-I skin cleansers/surgical scrubs was followed by saline irrigation. These results are consistent with recommendations for promptly rinsing the wound with water to remove the detergent if detergent-containing PVP-I preparations are used for wound care. PVP-I ointment (10%) delayed wound closure inn rats during the fourth through tenth days post-treatment; however, during the next two weeks, healing was accelerated, and by day 24, healing was equal to the controls. No delays occurred when pigs or rabbits were tested. In human wounds, no delays occurred in healing, even when gel-type occlusive dressings were added to the wounds; in fact, bandage-wearing time was shortened in those patients treated with PVP-I ointment. PVP-I cream (5%) was also studied in humans; the cream formulation appeared to decrease healing time. Based on these studies, it can be concluded that povidone-iodine preparations do not have a deleterious effect on wound healing.
We investigated the architecture of the extracellular matrix (ECM) during healing of full-thickness wounds in the pig. Two different treatments, one based on epidermal transplantation (split skin mesh grafts, SP wounds) and one consisting of a combination of epidermal transplantation and a dermal matrix substitute (MA wounds) were compared. The dermal matrix consisted of native bovine collagen coated with elastin hydrolysate. The latter treatment reduced wound contraction and improved tissue regeneration. The expression patterns of fibronectin, von Willebrand factor, laminin, chondroitin sulfate, and elastin, detected by immunohistochemistry, were examined in time and indicated different stages of healing. During the early phase of healing the dermal matrix induced more granulation tissue, a different fibronectin expression pattern, and rapid vascular cell ingrowth (von Willebrand factor). Furthermore, in the MA wounds chondroitin sulfate was detected earlier in the basement membrane and fibronectin staining disappeared more rapidly. During later stages of healing, chondroitin sulfate expression was selective for areas in which ECM remodeling was active; in these specific areas elastin staining reappeared. ECM remodeling and elastin regeneration occurred both in the upper and lower dermis for the MA wounds but only in the upper dermis for the SP wounds. Electron microscopic evaluation of the wounds after 2 weeks showed many myofibroblasts in the SP wounds, whereas in the MA wounds cells associated with the dermal matrix had characteristics of normal fibroblasts. The results suggest that the biodegradable dermal matrix served as a template for dermal tissue regeneration, allowed faster regeneration, and improved the quality of healing in large full-thickness skin defects.
Povidone-iodine cream for topical antisepsis
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Can an-timicrobials be effective without impairing wound healing – evaluation of a cadexomer-iodine ointment
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