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Introduktion: Sjuksköterskor idag står inför en växande patientgrupp med diabetes, som har svårläkta fotsår. Patienterna finns i alla vårdformer som primärvård, specialistvård och kommunal hälso- och sjukvård. För att patienten ska kunna upprätthålla en god livskvalitet och ett bra socialt liv krävs det en säker och snabb sårläkning. Syfte: Arbetets syfte var att beskriva vad som påverkar sårläkning hos patienter med diabetes och svårläkt fotsår, vid undertrycksbehandling. Metod: Denna litteraturstudie har utgått ifrån Polit och Becks (2012) niostegsmodell. Sökningarna har gjorts i CINAHL och PubMed. Kvalitetsgranskning gjordes som resulterade i tio kvantitativa vetenskapliga artiklar. Artiklarnas resultatdel analyserades och grupperades utifrån syftet och efter gemensamma områden.  Resultat: Resultatet i litteraturstudien delades in i två kategorier: sårstatus och behandlingstid. I resultatet framkom att undertrycksbehandling sågs som mer effektiv behandlingsmetod än konventionell fuktighetsbevarande sårbehandling. Volym och sårdjup minskade mer effektivt vid undertrycksbehandling än med konventionell fuktig sårbehandling. Slutsats: Litteraturstudien visar att undertrycksbehandling kan bidra till snabbare sårläkning hos diabetiker med svårläkt fotsår. Alla studier valde mätvärden som storlek, djup och typ av vävnad för att beskriva sårstatus. Behandlingstiden varierade i studierna. Det visade sig även att det vetenskapliga underlaget var begränsat.

The problems and high medical costs associated with chronic wounds necessitate an economical bioactive wound dressing. A new strategy was investigated to inhibit MMP-9 proteases and to release epidermal growth factor (EGF) to enhance healing. Doxycycline (DOX) and EGF were encapsulated on polyacrylic acid modified polyurethane film (PAA-PU) using Layer-by-Layer (LbL) assembly. The number of bilayers tuned the concentration of DOX and EGF released over time with over 94% bioactivity of EGF retained over 4 days. A simple wound model in which MMP-9 proteases were added to cell culture containing fibroblast cells demonstrated that DOX inhibited the proteases providing a protective environment for the released EGF to stimulate cell migration and proliferation at a faster healing rate. In the presence of DOX, only small amounts of the highly bioactive EGF are sufficient to close the wound. Results show that this is new and promising bioactive dressing for effective wound management.

The problems and high medical costs associated with chronic wounds necessitate an economical bioactive wound dressing. A new strategy was investigated to inhibit MMP-9 proteases and to release epidermal growth factor (EGF) to enhance healing. Doxycycline (DOX) and EGF were encapsulated on polyacrylic acid modified polyurethane film (PAA-PU) using Layer-by-Layer (LbL) assembly. The number of bilayers tuned the concentration of DOX and EGF released over time with over 94% bioactivity of EGF retained over 4 days. A simple wound model in which MMP-9 proteases were added to cell culture containing fibroblast cells demonstrated that DOX inhibited the proteases providing a protective environment for the released EGF to stimulate cell migration and proliferation at a faster healing rate. In the presence of DOX, only small amounts of the highly bioactive EGF are sufficient to close the wound. Results show that this is new and promising bioactive dressing for effective wound management.

Abstract Chronic wounds afflict millions worldwide, incurring significant health care costs and chronic suffering. Clinicians are often unsure about treatment, resulting in poor outcomes. Objective To determine the scope of knowledge possessed by fifth year medical students, general practitioners (GP’s) and surgical registrars, concerning chronic wound management. Design Cross sectional study Methods Deans of eight South African medical schools received letters requesting information regarding time devoted to wound-care training. Knowledge-based questionnaires were distributed to final-year students at two universities, surgical registrars at three universities and general practitioners attending refresher courses. Result. Four medical schools replied, of whom only two offered formal teaching. 162 medical students, 45 GP’s and 47 surgical registrars completed questionnaires. The overall median (25th–75th percentiles) knowledge scores for registrars, GP’s and students were 65%;(55%–70%), 55%;(45%–65%) and 45%;(35%–50%) respectively. Whereas the scores of registrars and GP’s did not differ, the student scores were significantly less. Only 32% of registrars and 18% of GP’s attained scores of 70% or more. 96% considered training to be inadequate. Interest in wound-care was only mild to moderate, with more GP’s than registrars requesting literature. Conclusions Very little, if any training on chronic wounds is offered in South Africa. The levels of knowledge cannot be considered adequate for successful treatment, nor for teaching to undergraduates. This preliminary study cannot reflect the attitudes and knowledge throughout the country; however it is clear that there is a need for improved education about these conditions that have huge clinical and economic consequences.

Hyperbaric Oxygen Therapy (HBOT) is an old technology which has acquired value in chronic wound care. HBOT is known to promote local and systemic healing effects by improving the oxygenation of the wound tissue. The increased tissue oxygenation hastens removal of the bacterial bioburden, which allows resolution of inflammation and facilitates matrix production, cell division, and ultimately wound closure. Staphylococcus aureus is the most frequently isolated organism from Diabetic Foot Infections (DFI). Therefore, our lab chose to use the treatment paradigm of HBOT to initially look at the single species level as to how HBOT affects S. aureus. DFI are primarily polymicrobial, so the responses of bacterial communities to this therapy were also considered. Previous research focused solely on host response to HBOT, but our pilot testing indicates that HBOT also exhibits a bacterial response. Initial testing with S. aureus indicated that HBOT can create growth defects in bacteria in vitro. In preliminary experiments, our lab discovered that bacterial culture on solid medium is greatly altered under the pressure of hyperbaric oxygen. Normal robust growth and pigmentation are seen in S. aureus cultured in ambient conditions. However, when the same strain is cultured under HBOT conditions, there is a marked decrease in pigmentation and colony size. When other species were exposed to HBOT conditions, growth on solid media was significantly diminished. Interestingly, K. pneumoniae is able to grow normally under HBOT conditions. Normal air mixtures at the increased pressure do not have any discernable effect on bacterial growth, and the limiting effects of oxygen are not seen unless used at the increased pressure. In a broth macrodilution MIC assay, various antibiotics show an increase in susceptibility after exposure to HBOT. Lastly, biofilm formation is altered under HBOT conditions, further supporting a bacterial adjustment to HBOT and an altered mode of growth. In order to better understand the effects of a high pressure high oxygen environment on the bacterial bioburden, this study investigates the effects of HBOT on bacterial species comprising a chronic wound. Primary data has suggested that HBOT increases susceptibility of antibiotics, and can alter bacterial transcription to hinder growth of many organisms. We hypothesize that Hyperbaric Oxygen Therapy affects diabetic foot infections by changing the healing process via transcriptional alteration of bacterial species in the wound. Furthermore, we hypothesize that HBOT alters the efficacy of some antibiotics as well as affecting the biofilm capacity of many bacterial species.

Chronic wounds represent an under-acknowledged socioeconomic epidemic, affecting 1.8 million new patients per year and costing the US health care system upwards of $25 billion annually. This substantial cost is rapidly growing due to a disproportionate occurrence in the ever-aging population. Key features associated with age-related impairment of wound healing include limited energy and nutrient exchange, unremitting inflammations, increased reactive oxygen species (ROS), and diminished blood flow. Most chronic wound therapies target specific molecular mechanisms; however, there are often multiple mitigating factors that prevent normal wound closure. This is likely one reason most wound therapies are minimally effective. In the standard American diet, carbohydrates are broken down for fuel (glucose). While fasting, starvation, and calorie or carbohydrate restriction, beta-oxidation of stored fats in the liver produces ketone bodies (primarily acetoacetate (AcAc) and β-hydroxybutyrate (βHB) to serve as energy metabolites for extra-hepatic tissues. In addition to enhancing metabolic physiology, ketone bodies have recently been discovered to have signaling properties that are independent of their function as energy metabolites. Here we present the evidence for a novel method of inducing therapeutic ketosis via exogenous ketone supplementation to promote enhanced ischemic wound healing in young and aged Fischer 344 rats. Preliminary mechanistic studies demonstrated that exogenous ketone supplementation enhanced wound healing via increasing proliferation and migration, decreasing lactate production, and decreasing ROS production as well as affecting inflammatory cytokines and growth factors. We conclude that exogenous ketone supplementation will be an effective, cost efficient, low toxicity therapy to promote enhancement of wound healing in an aged population.

Infection is one of the factors that may contribute to non-healing of chronic wounds; the presence of antibiotic resistant bacteria serves to exacerbate the problem due to limited treatment options. Bacteria utilise several mechanisms to survive exposure to antibiotics, including synthesis of deactivating enzymes, target modification or substitution, changes to membrane permeability, upregulation of efflux pumps and the formation of a biofilm. Quorum sensing is a density-dependent mechanism of bacterial cell to cell communication that can be instrumental in co-ordinating biofilm initiation. Hyperbaric oxygen therapy (HBOT) is an option offered to some patients with chronic wounds, including diabetic foot ulcers. Evidence suggests that HBOT can reduce the incidence of major amputation in these patients. As well as the direct toxicity of increased tissue oxygenation on anaerobic bacteria HBOT may also increase levels of reactive oxygen and nitrogen species in the wound environment. This study aimed to investigate the effects of hyperoxia and oxidative damage on three specific mechanisms of antibiotic resistance: the activity of penicillinase, an antibiotic deactivating enzyme synthesised by bacteria; the activity of quorum sensing signalling molecules (AHLs); and biofilms and their associated bacteria. It also analysed the population dynamics of, primarily, bacteria in diabetic foot ulcers during HBOT, by the use of molecular analysis tools such as PCRDGGE. The presence of fungal species was investigated in wounds prior to HBOT and in two wounds at two points during HBOT. This study found that hydrogen peroxide, hypochlorous acid and peroxynitrite reduced the activity of penicillinase in vitro. Hypochlorous acid reduced the activity of a range of AHLs in vitro but not in vivo. Oxygen concentration did not have any impact on biofilm mass, nor did it significantly affect the ability of an oxidant-generating enzyme to reduce live bacterial cells within a biofilm. The population dynamics of bacterial species identified in all the wounds were complex and did not undergo identifiable changes during HBOT. Fungal species were identified in all wounds prior to HBOT, though different profiles were observed in the two wounds investigated during HBOT. These results suggest that oxidants could play a role in the attenuation of antibiotic resistance in chronic wound bacteria. It is unclear whether HBOT alters the population dynamics of non-healing wound microflora

<p>Electrostatic interaction is a strong force that attracts positively and negatively charged molecules to each other. Such an interaction is formed between positively charged polycationic polymers and negatively charged nucleic acids. In this dissertation, the electrostatic attraction between polycationic polymers and nucleic acids is exploited for applications in oral gene delivery and nucleic acid scavenging. An enhanced nanoparticle for oral gene delivery of a human Factor IX (hFIX) plasmid is developed using the polycationic polysaccharide, chitosan (Ch), in combination with protamine sulfate (PS) to treat hemophilia B. For nucleic acid scavenging purposes, the development of an effective nucleic acid scavenging nanofiber platform is described for dampening hyper-inflammation and reducing the formation of biofilms.</p><p>Non-viral gene therapy may be an attractive alternative to chronic protein replacement therapy. Orally administered non-viral gene vectors have been investigated for more than one decade with little progress made beyond the initial studies. Oral administration has many benefits over intravenous injection including patient compliance and overall cost; however, effective oral gene delivery systems remain elusive. To date, only chitosan carriers have demonstrated successful oral gene delivery due to chitosan’s stability via the oral route. In this study, we increase the transfection efficiency of the chitosan gene carrier by adding protamine sulfate to the nanoparticle formulation. The addition of protamine sulfate to the chitosan nanoparticles results in up to 42x higher in vitro transfection efficiency than chitosan nanoparticles without protamine sulfate. Therapeutic levels of hFIX protein are detected after oral delivery of Ch/PS/phFIX nanoparticles in 5/12 mice in vivo, ranging from 3 -132 ng/mL, as compared to levels below 4 ng/mL in 1/12 mice given Ch/phFIX nanoparticles. These results indicate the protamine sulfate enhances the transfection efficiency of chitosan and should be considered as an effective ternary component for applications in oral gene delivery.</p><p>Dying cells release nucleic acids (NA) and NA-complexes that activate the inflammatory pathways of immune cells. Sustained activation of these pathways contributes to chronic inflammation related to autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. Studies have shown that certain soluble, cationic polymers can scavenge extracellular nucleic acids and inhibit RNA-and DNA-mediated activation of Toll-like receptors (TLRs) and inflammation. In this study, the cationic polymers are incorporated onto insoluble nanofibers, enabling local scavenging of negatively charged pro-inflammatory species such as damage-associated molecular pattern (DAMP) molecules in the extracellular space, reducing cytotoxicity related to unwanted internalization of soluble cationic polymers. In vitro data show that electrospun nanofibers grafted with cationic polymers, termed nucleic acid scavenging nanofibers (NASFs), can scavenge nucleic acid-based agonists of TLR 3 and TLR 9 directly from serum and prevent the production of NF-ĸB, an immune system activating transcription factor while also demonstrating low cytotoxicity. NASFs formed from poly (styrene-alt-maleic anhydride) conjugated with 1.8 kDa branched polyethylenimine (bPEI) resulted in randomly aligned fibers with diameters of 486±9 nm. NASFs effectively eliminate the immune stimulating response of NA based agonists CpG (TLR 9) and poly (I:C) (TLR 3) while not affecting the activation caused by the non-nucleic acid TLR agonist pam3CSK4. Results in a more biologically relevant context of doxorubicin-induced cell death in RAW cells demonstrates that NASFs block ~25-40% of NF-ĸβ response in Ramos-Blue cells treated with RAW extracellular debris, ie DAMPs, following doxorubicin treatment. Together, these data demonstrate that the formation of cationic NASFs by a simple, replicable, modular technique is effective and that such NASFs are capable of modulating localized inflammatory responses. </p><p>An understandable way to clinically apply the NASF is as a wound bandage. Chronic wounds are a serious clinical problem that is attributed to an extended period of inflammation as well as the presence of biofilms. An NASF bandage can potentially have two benefits in the treatment of chronic wounds by reducing the inflammation and preventing biofilm formation. NASF can prevent biofilm formation by reducing the NA present in the wound bed, therefore removing large components of what the bacteria use to develop their biofilm matrix, the extracellular polymeric substance, without which the biofilm cannot develop. The NASF described above is used to show the effect of the nucleic acid scavenging technology on in vitro and in vivo biofilm formation of P. aeruginosa, S. aureus, and S. epidermidis biofilms. The in vitro studies demonstrated that the NASFs were able to significantly reduce the biofilm formation in all three bacterial strains. In vivo studies of the NASF on mouse wounds infected with biofilm show that the NASF retain their functionality and are able to scavenge DNA, RNA, and protein from the wound bed. The NASF remove DNA that are maintaining the inflammatory state of the open wound and contributing to the extracellular polymeric substance (EPS), such as mtDNA, and also removing proteins that are required for bacteria/biofilm formation and maintenance such as chaperonin, ribosomal proteins, succinyl CoA-ligase, and polymerases. However, the NASF are not successful at decreasing the wound healing time because their repeated application and removal disrupts the wound bed and removes proteins required for wound healing such as fibronectin, vibronectin, keratin, and plasminogen. Further optimization of NASF treatment duration and potential combination treatments should be tested to reduce the unwanted side effects of increased wound healing time.</p> / Dissertation

Bakgrund: Distriktssköterskor har en viktig och ansvarsfull roll i omvårdnaden gällande sårvård, och en betydande del av det självständiga arbetet går åt till att behandla patienter med svårläkta sår. Syfte: Att studera hur distriktssköterskor arbetar med svårläkta sår genom att ta del av deras erfarenheter och upplevelser. Vidare var syftet att undersöka varför de handlar som de gör vid olika situationer och vad grundar de sina beslut på. Metod: Studien har en kvalitativ deskriptiv ansats. Ett strategiskt urval gjordes med inklusionskriteriet att informanterna arbetade som distriktssköterskor i primärvården/vårdcentraler i Norduppland. Tio informanter intervjuades och en strukturerad fråge guide användes. Studien analyserades med en kvalitativ manifest innehållsanalys. Resultat: Resultatet i denna studie visar att informanterna anser att praktisk erfarenhet väger tyngre än formell erfarenhet. Den formella erfarenheten anses vara bristfällig när det gäller sårvård, men lång praktisk erfarenhet anses ge högre sårvårdskompetens. Beslut och bedömningar bygger på ”oskrivna riktlinjer”. Alla informanter arbetar på liknande sätt, men utan att lokala riktlinjer finns nedskrivna på vårdcentralerna. Även den centrala upphandlingen av sårvårdsmaterial påverkar beslutet då bedömningen kan leda till att de vill använda ett annat material än de som är upphandlat. Det framkom i studien att informanterna anser att sårläkning främjas allra bäst genom att få patienter delaktig i sin vård. Slutsats: Då distriktssköterskan i sin profession har ett egenansvar samt en skyldighet att hålla sig uppdaterad med ny evidens, så är slutsatsen att behovet och ansvaret behöver belysas. Förslag till vidare forskning är att efter implementerade riktlinjer studera hur de följs. / Background: Nurses have an important and responsible role in the care regarding wound care, and a significant part of the independent work is used to treat patients with chronic wounds. Purpuse: Study how nurse is working with chronic wounds by taking part of their experiences. A further aim was to examine why they act as they do in different situations and what they based their decisions on. Method: The study was a qualitative descriptive approach. A strategic choice was made with that the informants worked as nurses in primary care / medical centers in Northern Uppland. Ten informants interviewed and a structured query guide used. The study was analyzed with a qualitative manifest content analysis. Results: The results of this study show that the practical experience outweighs formal qualification. The formal experience is considered deficient when it comes to wound care, but long practical experience is considered to provide a higher wound care expertise. Decisions and judgments based on "unwritten guidelines". All informants working in a similar way, but without the local guidelines. Although the central procurement of wound care materials affect the decision on which assessment to use. The informants believe that healing is promoted at its best by getting patients involved in their care. Conclusion:The nurse has own responsibility in their profession to keep themselves updated with new evidence. The conclusion is that the need and responsibility has to be clarified. Suggestions for further research are that after the guidelines implemented, study how this are followed.