DEVELOPMENT OF A NEXT-GENERATION ANTIMICROBIAL WOUND DRESSING

Odgođeno cijeljenje rana zbog infekcije je teret zdravstvenim sustavima, a jednako tako i pacijentu i onome koji skrbi za njega. Bitan čimbenik u nastajanju infekcije i odgođenog cijeljenja je razvoj i prisutnost biofi lma u ranama. Biofi lm je zajednica mikroorganizama, zaštićena izvanstaničnim sluzavim matriksom u rani, koji može tolerirati obranu domaćina i primijenjena antimikrobna sredstva, kao što su antibiotici ili antimikrobne obloge. Rastući broj znanstvenih dokaza upućuje da biofilm već egzistira u većini kroničnih rana, a može biti i prethodnik infekciji dok istodobno uzrokuje odgođeno cijeljenje. In vivo modeli pokazali su da su upala, granulacija i epitelizacija, te procesi normalnog cijeljenja rane narušeni prisustvom biofilma. Izazov u razvoju nove antimikrobne obloge za ranu bio je da standardna antimikrobna sredstva učinimo učinkovitija protiv biofilma, a rješenje je uslijedilo nakon opsežnih istraživanja i ispitivanja biofi lma. Kombinacija metalnog kelatora, površinski aktivne tvari i kontrole pH faktora pokazala je snažnu sinergističku anti-biofi lm akciju u oblozi od karboksimetilceluloze sa 1,2 % ionskog srebra. Ta je učinkovitost testirana i dokazana u kompleksnim in vitro i in vivo modelima rana s biofilmom, a zatim i u klinički kontroliranim studijama, i to u studiji na 42-pacijenta i 113 kliničkih evaluacija. Naknadno ispitivanje nastavljeno je nakon dostupnosti obloge u evaluaciji na 112 slučaja, gdje je obloga pokazala učinkovito kontroliranje eksudata i suspektnog biofi lma na ranama koje teško cijele i pri tome poticanje procesa cijeljenja rana i to nakon prosječno 4 tjedna primjene nove obloge u inače standardnom protokolu njege. To je bilo popraćeno niskim brojem nuspojava. U drugoj procjeni bili su evaluirani i klinički znakovi infekcije i podatci o veličini rane, prije i nakon procjene. Nakon prosječno 5,4 tjedana uporabe obloge, svi su klinički znakovi infekcije bili reducirani, s prosječnom učestalošću od 36 % do 21 %. U prosjeku u 62 % rana postignuta je redukcija veličine, uz smanjenje veličine do 90 % i 10 potpuno zacijeljenih rana. Najnoviji kliničkih dokazi za novu generaciju antimikrobne obloge za ranu potvrđuju njenu sigurnost i učinkovitost u kontroli eksudata, infekcije i biofi lma, a osim toga potvrđuju i zacijeljivanje rana koje dugo i teško ili uopće ne cijele. Znanstvenu potporu za najnoviju tehnologiju i generaciju antimikrobne obloge potvrđuju in vitro i in vivo dokazi, tako da su buduća komparativna i randomizirana klinička ispitivanja neophodna za potpuno razumijevanje kliničke i ekonomske učinkovitosti koju može donijeti ova najnovija tehnologija.Delayed wound healing due to infection is a burden on healthcare systems, and the patient and caregiver alike. An emerging factor in infection and delayed healing is the presence development of biofilm in wounds. Biofilm is communities of microorganisms, protected by an extracellular matrix of slime in the wound, which can tolerate host defences and applied antimicrobials such as antibiotics or antimicrobial dressings. A growing evidence base exists suggesting that biofi lm exists in a majority of chronic wounds, and can be a precursor to infection while causing delayed healing itself. In vivo models have demonstrated that the inflammatory, granulation and epithelialization processes of normal wound healing are impaired by biofi lm presence. The challenge in the development of a new antimicrobial wound dressing was to make standard antimicrobial agents more effective against biofilm, and this was answered following extensive biofilm research and testing. A combination of metal chelator, surfactant and pH control displayed highly synergistic anti-biofi lm action with 1.2% ionic silver in a carboxymethylcellulose dressing. Its effectiveness was challenged and proven in complex in vitro and in vivo wound biofi lm models, followed by clinical safety and performance demonstrations in a 42-patient study and 113 clinical evaluations. Post-market surveillance was conducted on the commercially available dressing, and in a 112-case evaluation, the dressing was shown to effectively manage exudate and suspected biofi lm while shifting diffi cultto-heal wounds onto healing trajectories, after an average of 4 weeks of new dressing use in otherwise standard wound care protocols. This was accompanied by a low frequency of dressing related adverse events. In a second evaluation, clinical signs of infection and wound dimension data, before and after the evaluations, were also available. Following an average of 5.4 weeks of dressing use, all signs of clinical infection were reduced, from an average frequency of 36% to 21%. An average of 62% wound size reduction was achieved, with 90% of wounds reducing in size and 10 wounds healing completely. The new clinical evidence for this next-generation antimicrobial wound dressing suggests it is safe and effective at managing exudate, infection and biofilm, while it can shift established, stubborn wounds onto healing trajectories. The scientific rationale for this new dressing technology is supported by in vitro and in vivo evidence, so now further comparative, randomized and outcome-based clinical studies are required to fully understand the clinical and economic benefits this new dressing technology can bring

Wound Biofilm and Therapeutic Strategies

Since the turn of the millennium, an evolving body of scientific and clinical evidence indicates that biofilm is implicitly linked to delayed wound healing and infection. Currently, wound anti-biofilm strategies rely on non-specific wound bed preparation techniques involving physical debridement and cleansing, and innovative technologies designed to specifically manage biofilm have only just begun to emerge. The first output of anti-biofilm research and product development in wound care show great promise for patients, clinicians and healthcare institutions. The aim of this chapter is to address the current clinical biofilm problem, describe existing and emerging strategies to combat wound biofilm and review the available evidence

Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis

Granulocytes are pivotal regulators of tissue injury. However, the transcriptional mechanisms that regulate granulopoiesis under inflammatory conditions are poorly understood. Here we show that the transcriptional coregulator B cell leukemia/lymphoma 3 (Bcl3) limits granulopoiesis under emergency (i.e., inflammatory) conditions, but not homeostatic conditions. Treatment of mouse myeloid progenitors with G-CSF — serum concentrations of which rise under inflammatory conditions — rapidly increased Bcl3 transcript accumulation in a STAT3-dependent manner. Bcl3-deficient myeloid progenitors demonstrated an enhanced capacity to proliferate and differentiate into granulocytes following G-CSF stimulation, whereas the accumulation of Bcl3 protein attenuated granulopoiesis in an NF-κB p50–dependent manner. In a clinically relevant model of transplant-mediated lung ischemia reperfusion injury, expression of Bcl3 in recipients inhibited emergency granulopoiesis and limited acute graft damage. These data demonstrate a critical role for Bcl3 in regulating emergency granulopoiesis and suggest that targeting the differentiation of myeloid progenitors may be a therapeutic strategy for preventing inflammatory lung injury

Surface Instability in Windblown Sand

We investigate the formation of ripples on the surface of windblown sand based on the one-dimensional model of Nishimori and Ouchi [Phys. Rev. Lett. 71, 197 (1993)], which contains the processes of saltation and grain relaxation. We carry out a nonlinear analysis to determine the propagation speed of the restabilized ripple patterns, and the amplitudes and phases of their first, second, and third harmonics. The agreement between the theory and our numerical simulations is excellent near the onset of instability. We also determine the Eckhaus boundary, outside which the steady ripple patterns are unstable.Comment: 23 pages, 8 figure