RESUMO
Marine long-chain omega-3 polyunsaturated fatty acids (ω3 FA) are involved in numerous cell responses and therefore vital for the mammal organism. Because of the attribution of immunomodulatory effects, a favourable impact on the inflammatory response in chronic wounds and cells involved in wound healing can be suspected. In the experimental setup, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were investigated regarding their impact on metabolic activity, cell proliferation and migration of human keratinocytes (HaCaT) and newborn foreskin fibroblasts (CRL-2522). For simulation of the microenvironment of a chronic wound, human chronic wound fluid (CWF) was used in the experimental setup addressing the in vitro influence of DHA, EPA and CWF on regenerative processes. The results showed a significant increase in the metabolic activity of keratinocytes and fibroblasts after 72 h treatment with DHA and EPA. In contrast, treatment with ω3 FA had no significant positive effect on skin cell proliferation. Both ω3 FA had no influence on in vitro wound closure. CWF demonstrated significantly adverse effects, which ω3 FA were unable to mitigate. It can be concluded that CWF exhibited the expected adverse effect on both skin cell types, especially inhibiting in vitro wound closure. ω3 FAs showed a slightly positive, yet rarely significant effect on human skin cells. Overall, the addition of DHA or EPA showed no relevant benefit for skin cells challenged with human CWF, merely in combination with DHA an initial significant increase in cell metabolism (fibroblasts) and cell proliferation (keratinocytes) could be observed.
Assuntos
Ácidos Graxos Ômega-3 , Animais , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Humanos , Recém-Nascido , Mamíferos , Pele/metabolismo , CicatrizaçãoRESUMO
Background: Sodium hypochlorite (NaClO, SHC)/hypochlorous acid (HClO, HCA) wound irrigation solutions have experienced a renaissance in the prevention and treatment of low-level wound infections. They are attributed with lower cytotoxicity and have therefore gained increasing attention in daily clinical practice. Objectives: To determine the cytotoxicity and antimicrobial efficacy of six NaClO/HClO wound irrigation solutions. Methods: For cytotoxicity evaluation (based on DIN EN 10993-5), human keratinocytes (HaCaT) and human skin fibroblasts (BJ) were used. Staphylococcus aureus and Pseudomonas aeruginosa were used for antimicrobial efficacy evaluation (based on DIN EN 13727). Solutions were evaluated after 1, 5 and 15 min of exposure. Additionally, physicochemical properties (pH and oxidation-reduction potential values) were investigated. Results: Efficacy and cytotoxicity varied significantly between solutions. Generally, increasing antimicrobial activity was associated with decreasing cell viability. Furthermore, a concentration- and time-dependent impact on pathogens and cells was observed: cytotoxic and antimicrobial activity increased with rising NaClO/HClO solution concentrations and extended exposure times. Based on these in vitro evaluations, the following ranking (lowest to highest microbicidal effect and cytotoxic impact) was found: Microdacyn60® (SHC/HCA-M) < Granudacyn® (SHC/HCA-G) < Veriforte™ (SHC/HCA-V) < KerraSol™ (SHC-K) < Lavanox® (SHC-L) ⪠ActiMaris®forte (SHC/SM-A). Conclusions: The presented results indicate that microbicidal effects are almost always associated with certain negative side effects on cell proliferation. Efficacy and biocompatibility of NaClO/HClO solutions depend on their specific formulation and physicochemical properties. The investigations also underline the necessity for exact product- and application-specific efficacy profiles.
Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Desinfetantes/farmacologia , Ácido Hipocloroso/farmacologia , Hipoclorito de Sódio/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/microbiologia , Humanos , Concentração de Íons de Hidrogênio , Queratinócitos/efeitos dos fármacos , Queratinócitos/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Irrigação Terapêutica , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologiaRESUMO
Treating infected acute and/or chronic wounds still represents a major challenge in medical care. Various interactions of antiseptic dressings with wound environments regarding antimicrobial efficacy remain unclear. Therefore, this work aimed to investigate the influence of human acute wound fluid (AWF) on the antimicrobial performance of different antiseptic foam dressings in vitro against typical bacterial wound pathogens. Eight antiseptic polyurethane foam dressings containing either a silver formulation or a polyhexamethylene-biguanide (PHMB) were assessed regarding their antimicrobial potency against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa using a modified time-kill assay based on ISO EN 20743. The antiseptic efficacy was evaluated standardly as well as under the influence of human AWF after 2, 4, 6, and 24 hours. The specific chemical formulation and concentration of the antiseptic substance (ionic or nanocrystalline silver, silver sulfadiazine, PHMB 0.1%/0.5%) embedded within the dressings seemed to play a key role. For certain dressings (two nanocrystalline and one ionic silver dressing), the antimicrobial efficacy was significantly reduced under the influence of AWF compared to unchallenged test series. Unchallenged the efficacy of PHMB was comparable to silver against P. aeruginosa and even significantly superior against S. aureus and E. coli. Challenged with AWF the reduction rates for silver adjusted or even exceeded (P. aeruginosa) those of PHMB. Within a challenging wound environment, especially some silver formulations demonstrated a reduced bacterial reduction. Regarding the presented in vitro results, the biomolecular interactions of antiseptic wound dressings with wound fluid should be part of more extensive investigations, considering varying factors such as bacterial species and wound (micro)environment to develop targeted therapeutic regimes for the individual.
Assuntos
Anti-Infecciosos Locais/farmacologia , Anti-Infecciosos/farmacologia , Bandagens , Poliuretanos/farmacologia , Infecção dos Ferimentos/prevenção & controle , Ferimentos e Lesões/terapia , Doença Aguda , Líquidos Corporais/microbiologia , Drenagem/métodos , Humanos , Técnicas In Vitro , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Sensibilidade e Especificidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificaçãoRESUMO
OBJECTIVE: Vitamins are essential for human health. In terms of local application for wound healing, vitamins' positive effect remains unclear. However, because of the regular appearance of nutritional deficiency in chronic wound patients, a favorable impact of locally applied vitamins can be hypothesized. METHODS: Vitamins B3, B5, B6, B7, B9, B10, B12, and C individually as well as different combinations of B vitamins were investigated regarding their ability to promote proliferation and migration of human skin fibroblasts and keratinocytes. Proliferation assays with and without bacterial challenge, immunocytochemical staining, and scratch assay were used to determine the most effective combination(s). MAIN RESULTS: Some vitamin combinations showed a positive impact on proliferation, especially for keratinocytes after 72 hours. In terms of wound closure, the combinations B9 and B12; B3, B5, B6, and B10; and B3, B5, and B7 improved closure rates by 25% to 30%. The improved closure rates are also reflected by immunocytochemically detected upregulation of the migration marker CXCR4 for several combinations. CONCLUSIONS: Certain combinations of B vitamins demonstrate a positive influence on human keratinocytes and fibroblasts. Vitamins especially promoted fibroblast migration, and a statistically significant induction of keratinocyte proliferation was observed. Therefore, local vitamin application could benefit the physiologic wound healing process.
Assuntos
Ácido Ascórbico/farmacologia , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Complexo Vitamínico B/farmacologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Fibroblastos/fisiologia , Alemanha , Humanos , Técnicas In Vitro , Queratinócitos/fisiologia , Masculino , Sensibilidade e Especificidade , Pele/citologia , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND: Due to demographical changes the number of elderly patients depending on oral anticoagulation is expected to rise. Prolonged bleeding times in case of traumatic injuries represent the drawback of these medications, not only in major trauma, but also in superficial wounds. Therefore, dressings capable of accelerating coagulation onset and shortening bleeding times are desirable for these patients. METHODS: The hemostatic potential and physical properties of different types of superficial wound dressings (standard wound pad, two alginates, chitosan, collagen (Lyostypt(®)), oxidized cellulose, and QuikClot(®)) were assessed in vitro. For this purpose the clotting times of blood under the influence of the named hemostatics from healthy volunteers were compared with Marcumar(®) or ASS(®) treated patients. For that, a newly developed coagulation assay based on spectrophotometric extinction measurements of thrombin activity was used. RESULTS: The fastest coagulation onset was observed for oxidized cellulose (Ø 2.47 min), Lantor alginate-L (Ø 2.50 min) and QuikClot(®) (Ø 3.01 min). Chitosan (Ø 5.32 min) and the collagen Lyostypt(®) (Ø 7.59 min) induced clotting comparatively late. Regarding physical parameters, QuikClot(®) showed the lowest absorption capacity and speed while chitosan and both alginates achieved the highest. While oxidized cellulose displayed the best clotting times, unfortunately it also revealed low absorption capacity. CONCLUSIONS: All tested specimens seem to induce clotting independently from the administered type of oral anticoagulant, providing the possibility to neglect the disadvantage in clotting times arising from anticoagulation on a local basis. QuikClot(®), oxidized cellulose and unexpectedly alginate-L were superior to chitosan and Lyostypt(®). Due to its additional well-known positive effect on wound healing alginate-L should be considered for further investigations.
Assuntos
Bandagens , Hemostáticos , Cicatrização/efeitos dos fármacos , HumanosRESUMO
Gelatin-based hemostats have been used in various surgical fields and showed advantageous effects on central aspects of wound healing when compared to cellulose-based hemostats. Nevertheless, the influence of gelatin-based hemostats on wound healing has not been fully explored yet. Hemostats were applied to fibroblast cell cultures for 5, 30, 60 min, 24 h, 7 and 14 days and measurements were taken at 3, 6, 12, 24 h and 7 or 14 days, respectively. Cell proliferation was quantified after different exposure times and a contraction assay was conducted to measure the extent of the extracellular matrix over time. We further assessed quantitative levels of vascular endothelial growth factor and basic fibroblast growth factor using enzyme-linked immunosorbent assay. Fibroblast counts decreased significantly at 7 and 14 days independent of the application duration (p < 0.001 for 5 min application). The gelatin-based hemostat did not have a negative impact on cell matrix contraction. After application of gelatin-based hemostat, the basic fibroblast growth factor did not change; yet, the vascular endothelial growth factor significantly increased after a prolonged 24 h application time when compared to controls or to a 6 h exposure (p < 0.05). Gelatin-based hemostats did not impair contraction of the extracellular matrix or growth factor production (vascular endothelial growth factor and basic fibroblast growth factor), while cell proliferation diminished at late time points. In conclusion, the gelatin-based material seems to be compatible with central aspects of wound healing. For further clinical assessment, future animal and human studies are necessary.
RESUMO
OBJECTIVE: Ruptured abdominal aortic aneurysm (rAAA) is a critical condition with a high mortality rate. Over the years, endovascular aortic repair (EVAR) has evolved as a viable treatment option in addition to open repair (OR). The primary objective of this study was to compare the safety and efficacy of EVAR and OR for the treatment of rAAA based on a comprehensive analysis of our single-centre 30-year experience. METHODS: Patients treated for rAAA at the Department of Vascular and Endovascular Surgery, University Hospital Düsseldorf, Germany from 1 January 1993 to 31 December 2022 were included. Relevant information was retrieved from archived medical records. Patient survival and surgery-related complications were analysed. RESULTS: None of the patient-specific markers, emergency department-associated parameters, and co-morbidities were associated with patient survival. The 30-day and in-hospital mortality was higher in the OR group vs. in the EVAR group (50% vs. 8.7% and 57.1% vs. 13%, respectively). OR was associated with more frequent occurrence of more severe complications when compared to EVAR. Overall patient survival was 56 ± 5% at 12 months post-surgery (52 ± 6% for OR vs. 73 ± 11% for EVAR, respectively) (p < 0.05). Patients ≥70 years of age showed poorer survival in the OR group, with a 12-month survival of 42 ± 7% vs. 70 ± 10% for patients <70 years of age (p < 0.05). In the EVAR group, this age-related survival advantage was not found (12-month survival: ≥70 years: 67 ± 14%, <70 years: 86 ± 13%). Gender-specific survival was similar regardless of the applied method of care. CONCLUSION: OR was associated with more severe complications in our study. EVAR initially outperformed OR for rAAA regarding patient survival while re-interventions following EVAR negatively affect survival in the long-term. Elderly patients should be treated with EVAR. Gender does not seem to have a significant impact on survival.
RESUMO
OBJECTIVE: The incidence of type B aortic dissection (TBAD) is increasing worldwide; however, the underlying pathomechanisms are not conclusively understood. This study explores the geometric architecture of the aortic arch and supra-aortic branches in TBAD patients as opposed to non-TBAD patients. METHODS: Patient characteristics were retrieved from archived medical records. Computer-assisted tomography (CAT) scans of patients with TBAD and carotid stenosis (CS) from two high-volume centers were analyzed. Various aortic arch parameters and take-off angles of the supra-aortic branches of TBAD patients were measured following centerline normalization in comparison CS patients. A compression index (C-index) was calculated from the para-sagittal, and a torsion index (T-index) was calculated from the para-coronal take-off angles of the supra-aortic branches to analyze aortic arch tortuosity. RESULTS: A total of 199 CAT scans were analyzed, namely, 85 in the TBAD group and 114 in the CS group. The average age was 61.5 ± 13.1 years among the TBAD patients and 71 ± 9.3 years among the CS patients. We found a significantly higher proportion of type III aortic arch configurations in TBAD patients compared with CS patients. Further, the aortic arch angle was steeper in the TBAD group. In the para-sagittal plane, the left subclavian artery (LSA) take-off angle was less steep in TBAD patients. In the para-coronal plane, the left carotid artery (LCA) had a less steep take-off angle, while the LSA had a more obtuse take-off angle in the TBAD group when compared with the CS group. In addition, the inter-vessel distance was increased in TBAD patients. Finally, the T-index was increased, suggesting a significant torsion resulting from the deviating take-off angles of the supra-aortic branches supplying the left half of the body as opposed to the innominate artery (IA) in TBAD patients. CONCLUSIONS: Our results suggest several aortic arch-specific geometric configurations in patients suffering from TBAD that significantly differ from those in CS patients. Further functional studies are needed to verify the pathogenetic relevance of our results and their disease-specific causality. Although our data are not mechanistically explorative, they may serve as a basis for identifying future patients with aortic arch morphology at higher risk for TBAD development and who may benefit from more stringent adjustment of risk factors as a primary prevention concept.
RESUMO
Biofilms are a major problem in hard-to-heal wounds. Moreover, they are composed of different species and are often tolerant to antimicrobial agents. At the same time, interspecific synergy and/or competition occurs when some bacterial species clash. For this reason, the tolerance of two dual-species wound biofilm models of Pseudomonas aeruginosa and Staphylococcus aureus or Enterococcus faecium against antimicrobials and antimicrobial dressings were analyzed quantitatively and by confocal laser scanning microscopy (CLSM). The results were compared to findings with planktonic bacteria. Octenidine-dihydrochloride/phenoxyethanol and polyhexamethylene biguanide (PHMB) irrigation solutions showed a significant, albeit delayed reduction in biofilm bacteria, while the PHMB dressing was not able to induce this effect. However, the cadexomer-iodine dressing caused a sustained reduction in and killed almost all bacteria down to 102 cfu/mL within 6 days compared to the control (1010 cfu/mL). By means of CLSM in untreated human biofilm models, it became evident that P. aeruginosa dominates over E. faecium and S. aureus. Additionally, P. aeruginosa appeared as a vast layer at the bottom of the samples, while S. aureus formed grape-like clusters. In the second model, the distribution was even clearer. Only a few E. faecium were visible, in contrast to the vast layer of P. aeruginosa. It seems that the different species avoid each other and seek their respective niches. These mixed-species biofilm models showed that efficacy and tolerance to antimicrobial substances are nearly species-independent. Their frequent application appears to be important. The bacterial wound biofilm remains a challenge in treatment and requires new, combined therapy options.
RESUMO
Concern about microbial tolerance and resistance to established antimicrobials drives research into alternatives for local antiseptic wound treatment. Precise efficacy profiles are thereby important in the evaluation of potential alternative antimicrobials, and protein interference ("protein error") is a key factor. Here, the antimicrobial efficacy of cetylpyridinium chloride (CPC) and miramistin (MST) was compared to the established antimicrobials octenidine (OCT), povidon-iodine (PVP-I), polyhexamethylene-biguanide (PHMB) and chlorhexidine (CHX). Efficacy was evaluated after 0.5, 1, 3, 5 and 10 min against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecium and Candida albicans using an in vitro quantitative suspension method (based on DIN EN 13727). To investigate protein interference, 0.3% or 3% bovine albumin was used as the challenge. OCT and PVP-I demonstrated a significant efficacy within 0.5 min, regardless of the microbial organism and protein challenge (p < 0.01). CPC and MST showed no inferiority in efficacy, with only MST needing up to 3 min to achieve the same microbial reduction. PHMB and CHX also achieved significant reduction rates over the tested time-course, yet demonstrated a necessity for prolonged exposure (up to 10 min) for comparable reduction. A protein interference was predominantly observed for PHMB against S. aureus, but without statistically significant differences in antimicrobial efficacy between the 0.3% and 3% protein challenges. All other tested agents showed no relevant interference with the presence of protein. CPC and MST proved to be non-inferior to established wound antiseptics agents in vitro. In fact, CPC showed a more efficient reduction than PHMB and CHX despite there being an introduced protein challenge. Both agents demonstrated no significant "protein error" under challenging conditions (3% albumin), posing them as valid potential candidates for alternative antimicrobials in wound management.
RESUMO
Current standards insufficiently acknowledge the influence of the wound micro-environment on the efficacy of antimicrobial agents. To address this, octenidine/phenoxyethanol, polyhexanide, povidone-iodine, and sodium-hypochloride/hypochlorous acid solutions were submitted to standard-based (DIN-EN-13727) or modified peptide-based challenges and compared to a simulated clinical reference using human acute or chronic wound exudate (AWF/CWF). Antimicrobial efficacy against S. aureus and P. aeruginosa was compared using a quantitative suspension method. Agreement between methods were investigated using Bland-Altman (B&A) analysis. Different substances and challenges demonstrated diverging results, depending on class and concentration of agent and challenge. Highly concentrated antiseptics maintained a high efficacy under complex challenges, while especially chlorine-based irrigation solutions showed a remarkably reduced antimicrobial effect. Composition of challenge substance proved more relevant than pure concentration. Therefore, the current standard challenge conditions did not adequately reflect the wound micro-environment with over- or under-estimating antimicrobial efficacy, whilst the modified peptide-challenge showed a higher level of agreement with simulated realistic conditions (AWF/CWF). The results emphasize that a "one-fits-all" approach is not feasible to generalize antimicrobial efficacy, as certain aspects of the complex micro-environment pose a differing influence on varying agents. Based on these results, revision and target focused adaptation of the current standards should be considered.
RESUMO
The treatment of acute and chronic infected wounds with residing biofilm still poses a major challenge in medical care. Interactions of antimicrobial dressings with bacterial load, biofilm matrix and the overall protein-rich wound microenvironment remain insufficiently studied. This analysis aimed to extend the investigation on the efficacy of a variety of antimicrobial dressings using an in vitro biofilm model (lhBIOM) mimicking the specific biofilm-environment in human wounds. Four wound dressings containing polyhexanide (PHMB), octendine di-hydrochloride (OCT), cadexomer-iodine (C-IOD) or ionic silver (AG) were compared regarding their antimicrobial efficacy. Quantitative analysis was performed using a quantitative suspension method, separately assessing remaining microbial counts within the solid biofilm as well as the dressing eluate (representing the absorbed wound exudate). Dressing performance was tested against P. aeruginosa biofilms over the course of 6 days. Scanning electron microscopy (SEM) was used to obtain qualitative visualization on changes in biofilm structure. C-IOD demonstrated superior bacterial reduction. In comparison it was the only dressing achieving a significant reduction of more than 7 log10 steps within 3 days. Neither the OCT- nor the AG-containing dressing exerted a distinct and sustained antimicrobial effect. PHMB achieved a non-significant microbicidal effect (1.71 ± 0.31 log10 steps) at day 1. Over the remaining course (6 days) it demonstrated a significant microbistatic effect compared to OCT, AG and the control. Quantitative results in the dressing eluate correlate with those of the solid biofilm model. Overall, AG- and OCT-containing dressings did not achieve the expected anti-biofilm efficacy, while C-IOD performed best. Chemical interaction with the biofilms extrapolymeric substance (EPS), visualized in the SEM, and dressing configuration (agent concentration and release pattern) are suspected to be responsible. The unexpected low and diverse results of the tested antimicrobial dressings indicate a necessity to rethink non-debridement anti-biofilm therapy. Focussing on the combination of biofilm-disruptive (for EPS structure) and antimicrobial (for residing microorganisms) features, as with C-IOD, using dehydration and iodine, appears reasonably complementary and an optimal solution, as suggested by the here presented in vitro data.
RESUMO
Biofilms pose a relevant factor for wound healing impairment in chronic wounds. With 78% of all chronic wounds being affected by biofilms, research in this area is of high priority, especially since data for evidence-based selection of appropriate antimicrobials and antiseptics is scarce. Therefore, the objective of this study was to evaluate the anti-biofilm efficacy of commercially available hypochlorous wound irrigation solutions compared to established antimicrobials. Using an innovative complex in-vitro human plasma biofilm model (hpBIOM), quantitative reduction of Pseudomonas aeruginosa, Staphylococcus aureus, and Methicillin-resistant S. aureus (MRSA) biofilms by three hypochlorous irrigation solutions [two <0.08% and one 0.2% sodium hypochlorite (NaClO)] was compared to a 0.04% polyhexanide (PHMB) irrigation solution and 0.1% octenidine-dihydrochloride/phenoxyethanol (OCT/PE). Efficacy was compared to a non-challenged planktonic approach, as well as with increased substance volume over a prolonged exposure (up to 72 h). Qualitative visualization of biofilms was performed by scanning electron microscopy (SEM). Both reference agents (OCT/PE and PHMB) induced significant biofilm reductions within 72 h, whereby high volume OCT/PE even managed complete eradication of P. aeruginosa and MRSA biofilms after 72 h. The tested hypochlorous wound irrigation solutions achieved no relevant penetration and eradication of biofilms despite increased volume and exposure. Only 0.2% NaClO managed a low reduction under prolonged exposure. The results demonstrate that low-dosed hypochlorous wound irrigation solutions are significantly less effective than PHMB-based irrigation solution and OCT/PE, thus unsuitable for biofilm eradication on their own. The used complex hpBIOM thereby mimics the highly challenging clinical wound micro-environment, providing a more profound base for future clinical translation.
RESUMO
Zinc as therapeutic agent in skin and wound care has been known for centuries, but its role is controversial and comprehensive investigations in nutrient-deficient environments are lacking. We aimed to provide a broad analysis of different zinc derivatives on proliferation, apoptosis and antimicrobial properties in a simulated nutrient-deficient environment in vitro. Human fibroblasts (CRL2522) and keratinocytes (HaCaT) were treated with a broad concentration range (10 - 0.0001 µg/mL) of zinc-sulfate (ZnSO4), -gluconate (ZnGluc) and -histidine (ZnHis) for 1-6 days under nutrient-deficient media conditions. Cell proliferation was investigated by XTT assay. Targeted analyzes in proliferation (E2F1, PCNA) and apoptosis (TP53) associated genes were performed via qRT-PCR and apoptosis was determined via FACS (annexin V/7-AAD staining). Antimicrobial efficacy was investigated using a quantitative suspension method against S. aureus, P. aeruginosa, E. coli, and C. albicans. The results indicated that 0.1 to 0.001 µg/mL Zn increased cell proliferation in both cell lines. Fibroblasts were more susceptible with significant proliferation peaks on days 2 & 6, and days 1 & 4 for keratinocytes. No relevant changes in gene expression were detected for E2F1 and PCNA nor for TP53. Annexin-V/7-AAD-staining of fibroblasts revealed a small, yet insignificant reduction of apoptosis induction for ZnGluc and ZnSO4. ZnGluc and ZnSO4 (0.1%) achieved high microbial reductions (4-5 log10 reductions) against tested pathogens. ZnGluc and ZnSO4 showed relevant pro-proliferative and antimicrobial, as well as tendential anti-apoptotic features in a simulated nutrient-deficient microenvironment in vitro. This further validates a potential benefit of local zinc treatment in deficient wound microenvironments.
RESUMO
BACKGROUND: Surgical site infection (SSI) describes an infectious complication of surgical wounds. Although SSI is thought to be preventable, it still represents a major cause of morbidity and substantial economic burden on the health system. Wound irrigation (WI) might reduce the level of bacterial contamination, but current data on its role in reducing or preventing SSI is conflicting. Our aim was to investigate the effectiveness of WI with normal saline prior to wound closure for the reduction of SSI in patients undergoing abdominal surgery. METHODS: We conducted a systematic literature search in MEDLINE, EMBASE, and CENTRAL from inception to present, and cross-checked the reference lists of all included primary studies and relevant systematic reviews. (Quasi-) randomized controlled trials (RCTs) investigating the rate of SSI when using normal saline vs. no irrigation prior to wound closure following abdominal surgery were included. Primary outcome was the rate of SSI, secondary outcome the mean length of hospital stay (LOS). RESULTS: Four RCTs including a total of 1194 patients were included for analysis. All studies compared wound irrigation with normal saline with no wound irrigation prior to wound closure. Their risk of bias was moderate. The relative risk of developing a SSI was lower when wound irrigation with normal saline was performed prior to wound closure although the effect was not statistically significant (risk ratio 0.73, 95%-confidence level: 0.37 to 1.43). Similarly, there was no difference in the LOS amongst both intervention arms. CONCLUSION: This systematic review could not identify an advantage for routine irrigation of abdominal wounds with normal saline over no irrigation prior to wound closure in preventing or reducing the rate of SSI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registry number CRD42018082287 .
RESUMO
BACKGROUND: Surgical site infection describes an infectious complication of surgical wounds. This single complication is thought to occur in close to 20% of surgical cases. This complication has been described in all kinds of surgical procedure including minimally invasive procedures. Wound irrigation is frequently used as a means of reducing surgical site infection. However, there is lack of solid evidence to support routine wound irrigation. The aim of this review is to provide evidence for the efficacy of routine wound irrigation with normal saline in preventing surgical site infection. The rate of surgical site infection in cases with and without wound irrigation will be analyzed. METHODS/DESIGN: Systematic literature searches will be conducted to identify all published and unpublished studies. The following databases will be searched for citations from inception to present: MEDLINE (via PubMed), Embase (via Embase), and CENTRAL (via the Cochrane library). The search strategy will be developed by the research team in collaboration with an experienced librarian and checked by a referee according to the Peer Review of Electronic Search Strategies (PRESS) guideline. A draft of the PubMed search strategy could be (irrigation[tiab] OR "Therapeutic Irrigation"[mesh] OR lavage[tiab]) AND (saline[tiab] OR "Sodium Chloride"[mesh] OR sodium chloride[tiab]) NOT ("Comment" [Publication Type] OR "Letter" [Publication Type] OR "Editorial" [Publication Type]). No time limits will be set. The reference lists of eligible articles will be hand searched. Relevant data will be extracted from eligible studies using a previously designed data extraction sheet. Relative risks will be calculated for binary outcomes and mean differences or standardized mean differences, if necessary, for continuous outcomes. For all measures, 95% confidence levels will be calculated. Both arms would be compared with regard to the rate of surgical site infection within 30 days following surgery. We will report the review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. DISCUSSION: This review aims at investigating the value of routine wound irrigation using normal saline in preventing surgical site infection. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42018082287.
Assuntos
Solução Salina , Infecção da Ferida Cirúrgica , Irrigação Terapêutica , Cicatrização , Humanos , Solução Salina/administração & dosagem , Infecção da Ferida Cirúrgica/prevenção & controle , Irrigação Terapêutica/métodos , Metanálise como Assunto , Revisões Sistemáticas como AssuntoRESUMO
In this study, polyaminopropyl biguanide (PAPB) was compared to the molecularly closely related polyhexamethylene biguanide (PHMB) with respect to chemical relationship, antiseptic efficacy and cytotoxicity in vitro. Cytotoxicity for human keratinocytes (HaCaTs) and murine fibroblasts (L929) was determined according to ISO EN 10993-5 for both substances. Antimicrobial efficacy tests were performed via determination of the MBC, quantitative suspension method for substances and investigation of two PAPB- or PHMB-containing dressings against Staphyloccoccus aureus, Escherichia coli and Pseudomonas aeruginosa, according to international standards. Prior mass spectrometry was performed for chemical differentiation of the investigated substances. PHMB showed high toxicity even in low concentrations for both tested cell lines and a high antimicrobial efficacy against S. aureus and E. coli. In the case of PAPB, no or only low cytotoxicity was detected after 72 h, whilst comparable antibacterial features are lacking, as PAPB showed no relevant antimicrobial effects. Even though chemically closely related, PAPB proved to be ineffective in bacterial eradication, whilst PHMB showed a high efficacy. The discovery and establishment of safe and effective alternative antiseptics are important issues for the treatment of infected wounds. In particular, rising bacterial resistances to established agents, as well as ongoing discussions of potential toxic or carcinogenic effects emphasize this necessity. Nevertheless, the presented results highlight that even small changes in the chemical structure of related agents such as PHMB and PAPB can dramatically affect their efficacy and, therefore, need to be carefully distinguished and assessed side by side.
Assuntos
Anti-Infecciosos Locais/farmacologia , Anti-Infecciosos Locais/toxicidade , Biguanidas/farmacologia , Biguanidas/toxicidade , Animais , Anti-Infecciosos Locais/química , Biguanidas/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/fisiologia , Espectrometria de Massas , Camundongos , Viabilidade Microbiana/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
The antimicrobial activity of cetylpyridinium chloride (CPC) and miramistin (MST) solutions at different concentrations (5×10(-5) to 0.4%) and a dressing, containing 0.15% CPC, were tested against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli after 30 (solutions) and 60 min (fleece) incubation, respectively. Furthermore, the cytotoxic effects of CPC and MST were examined in human keratinocyte (HaCaT) and murine fibroblast (L929) cell lines. A dose of 3×10(-3)% CPC or MST was sufficient to entirely eradicate S. aureus after 30 min incubation. To achieve the same effect, higher concentrations were required against E. coli (0.025% CPC; 0.0125% MST) and P. aeruginosa (0.5% CPC; 0.05% MST). The CPC-fleece showed a high antiseptic effect against all three bacterial strains, although it did not completely eliminate P. aeruginosa. Both substances showed a high cytotoxic impact at higher tested concentrations (CPC >3×10(-3)%; MST >8×10(-4)%). CPC showed high antimicrobial potency at low concentrations against S. aureus, accompanied by low cytotoxic (side) effects at these concentrations, whilst the required minimal concentration to eradicate E. coli and P. aeruginosa was shown to be cytotoxic for keratinocytes and fibroblasts. The necessary antibacterial amounts of MST were lower, but also cytotoxic in direct contact with typical human wound cells. With regard to demographic changes and increasing bacterial resistance, new effective antiseptics, such as CPC and MST, incorporated in wound dressings without releasing an active substance could help to improve the treatment and healing rates of chronic wounds.