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Christopher J. Murphy - One of the best experts on this subject based on the ideXlab platform.
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Full‐thickness splinted skin wound Healing models in db/db and heterozygous mice: Implications for wound Healing Impairment
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 2014Co-Authors: Shin Ae Park, Leandro B. C. Teixeira, Vijay Krishna Raghunathan, Jill Covert, Richard R. Dubielzig, Roslyn Rivkah Isseroff, Michael J. Schurr, Nicholas L. Abbott, Jonathan F. Mcanulty, Christopher J. MurphyAbstract:The excisional dorsal full-thickness skin wound model with or without splinting is widely utilized in wound Healing studies using diabetic or normal mice. However, the effects of splinting on dermal wound Healing have not been fully characterized, and there are limited data on the direct comparison of wound parameters in the splinted model between diabetic and normal mice. We compared full-thickness excisional dermal wound Healing in db/db and heterozygous mice by investigating the effects of splinting, semi-occlusive dressing, and poly(ethylene glycol) treatment. Two 8-mm full-thickness wounds were made with or without splinting in db/db and heterozygous mice. Body weights, splint maintenance, wound contraction, wound closure, and histopathological parameters including reepithelialization, wound bed collagen deposition, and inflammation were compared between groups. Our results show that silicone splint application effectively reduced wound contraction in heterozygous and db/db mice. Splinted wounds, as opposed to nonsplinted wounds, exhibited no significant differences in wound closure between heterozygous and db/db mice. Finally, polyethylene glycol and the noncontact dressing had no significant effect on wound Healing in heterozygous or db/db mice. We believe these findings will help investigators in selection of the appropriate wound model and data interpretation with fully defined parameters.
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full thickness splinted skin wound Healing models in db db and heterozygous mice implications for wound Healing Impairment
Wound Repair and Regeneration, 2014Co-Authors: Shin Ae Park, Leandro B. C. Teixeira, Vijay Krishna Raghunathan, Jill Covert, Richard R. Dubielzig, Roslyn Rivkah Isseroff, Michael J. Schurr, Nicholas L. Abbott, Jonathan F. Mcanulty, Christopher J. MurphyAbstract:The excisional dorsal full-thickness skin wound model with or without splinting is widely utilized in wound Healing studies using diabetic or normal mice. However, the effects of splinting on dermal wound Healing have not been fully characterized, and there are limited data on the direct comparison of wound parameters in the splinted model between diabetic and normal mice. We compared full-thickness excisional dermal wound Healing in db/db and heterozygous mice by investigating the effects of splinting, semi-occlusive dressing, and poly(ethylene glycol) treatment. Two 8-mm full-thickness wounds were made with or without splinting in db/db and heterozygous mice. Body weights, splint maintenance, wound contraction, wound closure, and histopathological parameters including reepithelialization, wound bed collagen deposition, and inflammation were compared between groups. Our results show that silicone splint application effectively reduced wound contraction in heterozygous and db/db mice. Splinted wounds, as opposed to nonsplinted wounds, exhibited no significant differences in wound closure between heterozygous and db/db mice. Finally, polyethylene glycol and the noncontact dressing had no significant effect on wound Healing in heterozygous or db/db mice. We believe these findings will help investigators in selection of the appropriate wound model and data interpretation with fully defined parameters.
Dorthe Seidel - One of the best experts on this subject based on the ideXlab platform.
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negative pressure wound therapy vs conventional wound treatment in subcutaneous abdominal wound Healing Impairment the sawhi randomized clinical trial
JAMA Surgery, 2020Co-Authors: Dorthe Seidel, Stephan Diedrich, F Herrle, Henryk Thielemann, Frank Marusch, Rebekka Schirren, Recca Talaulicar, Tobias Gehrig, Nadja Lehwaldtywuschik, M GlanemannAbstract:Importance Negative pressure wound therapy (NPWT) is an established treatment option, but there is no evidence of benefit for subcutaneous abdominal wound Healing Impairment (SAWHI). Objective To evaluate the effectiveness and safety of NPWT for SAWHI after surgery in clinical practice. Design, Setting, and Participants The multicenter, multinational, observer-blinded, randomized clinical SAWHI study enrolled patients between August 2, 2011, and January 31, 2018. The last follow-up date was June 11, 2018. The trial included 34 abdominal surgical departments of hospitals in Germany, Belgium, and the Netherlands, and 539 consecutive, compliant adult patients with SAWHI after surgery without fascia dehiscence were randomly assigned to the treatment arms in a 1:1 ratio stratified by study site and wound size using a centralized web-based tool. A total of 507 study participants (NPWT, 256; CWT, 251) were assessed for the primary end point in the modified intention-to-treat (ITT) population. Interventions Negative pressure wound therapy and conventional wound treatment (CWT). Main Outcomes and Measures The primary outcome was time until wound closure (delayed primary closure or by secondary intention) within 42 days. Safety analysis comprised the adverse events (AEs). Secondary outcomes included wound closure rate, quality of life (SF-36), pain, and patient satisfaction. Results Of the 507 study participants included in the modified ITT population, 287 were men (56.6%) (NPWT, 155 [60.5%] and CWT, 132 [52.6%]) and 220 were women (43.4%) (NPWT, 101 [39.5%] and CWT 119 [47.4%]). The median (IQR) age of the participants was 66 (18) years in the NPWT arm and 66 (20) years in the CWT arm. Mean time to wound closure was significantly shorter in the NPWT arm (36.1 days) than in the CWT arm (39.1 days) (difference, 3.0 days; 95% CI 1.6-4.4;P Conclusions and Relevance Negative pressure wound therapy is an effective treatment option for SAWHI after surgery; however, it causes more wound-related AEs. Trial Registration ClinicalTrials.gov Identifier:NCT01528033
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treatment of subcutaneous abdominal wound Healing Impairment after surgery without fascial dehiscence by vacuum assisted closure sawhi v a c study versus standard conventional wound therapy study protocol for a randomized controlled trial
Trials, 2013Co-Authors: Dorthe Seidel, Rolf Lefering, Edmund NeugebauerAbstract:Background A decision of the Federal Joint Committee Germany in 2008 stated that negative pressure wound therapy is not accepted as a standard therapy for full reimbursement by the health insurance companies in Germany. This decision is based on the final report of the Institute for Quality and Efficiency in Health Care in 2006, which demonstrated through systematic reviews and meta-analysis of previous study projects, that an insufficient state of evidence regarding the use of negative pressure wound therapy for the treatment of acute and chronic wounds exists. Further studies were therefore indicated.
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treatment of subcutaneous abdominal wound Healing Impairment after surgery without fascial dehiscence by vacuum assisted closure sawhi v a c study versus standard conventional wound therapy study protocol for a randomized controlled trial
Trials, 2013Co-Authors: Dorthe Seidel, Rolf Lefering, Edmund NeugebauerAbstract:A decision of the Federal Joint Committee Germany in 2008 stated that negative pressure wound therapy is not accepted as a standard therapy for full reimbursement by the health insurance companies in Germany. This decision is based on the final report of the Institute for Quality and Efficiency in Health Care in 2006, which demonstrated through systematic reviews and meta-analysis of previous study projects, that an insufficient state of evidence regarding the use of negative pressure wound therapy for the treatment of acute and chronic wounds exists. Further studies were therefore indicated. The study is designed as a multinational, multicenter, prospective randomized controlled, adaptive design, clinical superiority trial, with blinded photographic analysis of the primary endpoint. Efficacy and effectiveness of negative pressure wound therapy for wounds in both medical sectors (in- and outpatient care) will be evaluated. The trial compares the treatment outcome of the application of a technical medical device which is based on the principle of negative pressure wound therapy (intervention group) and standard conventional wound therapy (control group) in the treatment of subcutaneous abdominal wounds after surgery. The aim of the SAWHI-VAC® study is to compare the clinical, safety and economic results of both treatment arms. The study project is designed and conducted with the aim of providing solid evidence regarding the efficacy of negative pressure wound therapy. Study results will be provided until the end of 2014 to contribute to the final decision of the Federal Joint Committee Germany regarding the general admission of negative pressure wound therapy as a standard of performance within both medical sectors. Clinical Trials.gov NCT01528033 German Clinical Trials Register DRKS00000648
Ewa K. Stuermer - One of the best experts on this subject based on the ideXlab platform.
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Antimicrobial Hypochlorous Wound Irrigation Solutions Demonstrate Lower Anti-biofilm Efficacy Against Bacterial Biofilm in a Complex in-vitro Human Plasma Biofilm Model (hpBIOM) Than Common Wound Antimicrobials.
Frontiers in microbiology, 2020Co-Authors: Isabell Plattfaut, Julian-dario Rembe, Lioba Franziska Huelsboemer, Manuela Besser, Ewa K. StuermerAbstract: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
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Anti-biofilm activity of antimicrobial hypochlorous wound irrigation solutions compared to common wound antiseptics and bacterial resilience in an innovative in-vitro human plasma biofilm model (hpBIOM)
2020Co-Authors: Julian-dario Rembe, Lioba Franziska Huelsboemer, Manuela Besser, Ewa K. StuermerAbstract:Abstract Background 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 antiseptics. Methods Using an innovative complex in-vitro human plasma biofilm model (hpBIOM), quantitative reduction of P. aeruginosa , S. aureus and MRSA biofilms by three hypochlorous irrigation solutions (two <0.08% and one 0.2% NaClO) were compared to 0.1% octenidine-dihydrochloride/phenoxyethanol (OCT/PE) and 0.04% polyhexanide (PHMB). Efficacy was compared to a non-challenged planktonic approach as well as with increased substance volume over the prolonged treatment course (up to 72h). Qualitative visualisation of biofilms was performed by scanning electron microscopy (SEM). Results Both tested antiseptics (OCT/PE and PHMB) induced significant biofilm reductions within 72h, whereby OCT/PE in an increased volume even managed complete eradication of P. aeruginosa and MRSA biofilms after 72h. The tested hypochlorous wound irrigation solutions however achieved no relevant penetration and eradication of biofilms, despite increased volume and exposure. Only 0.2% NaClO managed a low reduction over prolonged treatment time. Conclusion The results in the here used complex human plasma biofilm model closely mimic the clinical situation of a high challenging environment for antimicrobials to perform in. Under these conditions, the low-dosed hypochlorous wound irrigation solutions are significantly less effective than antiseptics and thus unsuitable for biofilm eradication.
Shin Ae Park - One of the best experts on this subject based on the ideXlab platform.
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Full‐thickness splinted skin wound Healing models in db/db and heterozygous mice: Implications for wound Healing Impairment
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society, 2014Co-Authors: Shin Ae Park, Leandro B. C. Teixeira, Vijay Krishna Raghunathan, Jill Covert, Richard R. Dubielzig, Roslyn Rivkah Isseroff, Michael J. Schurr, Nicholas L. Abbott, Jonathan F. Mcanulty, Christopher J. MurphyAbstract:The excisional dorsal full-thickness skin wound model with or without splinting is widely utilized in wound Healing studies using diabetic or normal mice. However, the effects of splinting on dermal wound Healing have not been fully characterized, and there are limited data on the direct comparison of wound parameters in the splinted model between diabetic and normal mice. We compared full-thickness excisional dermal wound Healing in db/db and heterozygous mice by investigating the effects of splinting, semi-occlusive dressing, and poly(ethylene glycol) treatment. Two 8-mm full-thickness wounds were made with or without splinting in db/db and heterozygous mice. Body weights, splint maintenance, wound contraction, wound closure, and histopathological parameters including reepithelialization, wound bed collagen deposition, and inflammation were compared between groups. Our results show that silicone splint application effectively reduced wound contraction in heterozygous and db/db mice. Splinted wounds, as opposed to nonsplinted wounds, exhibited no significant differences in wound closure between heterozygous and db/db mice. Finally, polyethylene glycol and the noncontact dressing had no significant effect on wound Healing in heterozygous or db/db mice. We believe these findings will help investigators in selection of the appropriate wound model and data interpretation with fully defined parameters.
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full thickness splinted skin wound Healing models in db db and heterozygous mice implications for wound Healing Impairment
Wound Repair and Regeneration, 2014Co-Authors: Shin Ae Park, Leandro B. C. Teixeira, Vijay Krishna Raghunathan, Jill Covert, Richard R. Dubielzig, Roslyn Rivkah Isseroff, Michael J. Schurr, Nicholas L. Abbott, Jonathan F. Mcanulty, Christopher J. MurphyAbstract:The excisional dorsal full-thickness skin wound model with or without splinting is widely utilized in wound Healing studies using diabetic or normal mice. However, the effects of splinting on dermal wound Healing have not been fully characterized, and there are limited data on the direct comparison of wound parameters in the splinted model between diabetic and normal mice. We compared full-thickness excisional dermal wound Healing in db/db and heterozygous mice by investigating the effects of splinting, semi-occlusive dressing, and poly(ethylene glycol) treatment. Two 8-mm full-thickness wounds were made with or without splinting in db/db and heterozygous mice. Body weights, splint maintenance, wound contraction, wound closure, and histopathological parameters including reepithelialization, wound bed collagen deposition, and inflammation were compared between groups. Our results show that silicone splint application effectively reduced wound contraction in heterozygous and db/db mice. Splinted wounds, as opposed to nonsplinted wounds, exhibited no significant differences in wound closure between heterozygous and db/db mice. Finally, polyethylene glycol and the noncontact dressing had no significant effect on wound Healing in heterozygous or db/db mice. We believe these findings will help investigators in selection of the appropriate wound model and data interpretation with fully defined parameters.
Koji Takeuchi - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of gastric ulcerogenic and Healing Impairment effects of bisphosphonates: adverse gastric reactions of bisphosphonate.
Current protocols in toxicology, 2012Co-Authors: Koji Takeuchi, Kikuko AmagaseAbstract:Bisphosphonates (BPPs) were developed as antiresorptive drugs capable of treating diseases related to bone remodeling; however, they have untoward effects including ulceration in the upper gastrointestinal tract and worsen the Healing-Impairment action of nonsteroidal anti-inflammatory drugs, prescribed in patients with arthritis or osteoporosis. We produced ulcers in the antrum by administering BPPs to fasted rats, followed by refeeding, and confirmed their Healing-Impairment action on pre-existing gastric ulcers; the ulcerogenic effect is due to direct mucosal irritation and decrease in the mucosal anti-oxidative system, while the latter effect is due to dysregulation of growth factor expression, such as vascular endothelial growth factor and basic fibroblast growth factor, and angiogenesis in the ulcerated mucosa. In this article, we describe these two animal models for investigating BPP-related adverse reactions, including methods for the induction of antral ulcers and Healing Impairment of gastric ulcers, as well as measurement of pathogenic functional and biochemical changes.
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Current Protocols in Toxicology - Evaluation of gastric ulcerogenic and Healing Impairment effects of bisphosphonates: adverse gastric reactions of bisphosphonate.
Current Protocols in Toxicology, 2012Co-Authors: Koji Takeuchi, Kikuko AmagaseAbstract:Bisphosphonates (BPPs) were developed as antiresorptive drugs capable of treating diseases related to bone remodeling; however, they have untoward effects including ulceration in the upper gastrointestinal tract and worsen the Healing-Impairment action of nonsteroidal anti-inflammatory drugs, prescribed in patients with arthritis or osteoporosis. We produced ulcers in the antrum by administering BPPs to fasted rats, followed by refeeding, and confirmed their Healing-Impairment action on pre-existing gastric ulcers; the ulcerogenic effect is due to direct mucosal irritation and decrease in the mucosal anti-oxidative system, while the latter effect is due to dysregulation of growth factor expression, such as vascular endothelial growth factor and basic fibroblast growth factor, and angiogenesis in the ulcerated mucosa. In this article, we describe these two animal models for investigating BPP-related adverse reactions, including methods for the induction of antral ulcers and Healing Impairment of gastric ulcers, as well as measurement of pathogenic functional and biochemical changes.
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gastric ulcerogenic and Healing Impairment effects of risedronate a nitrogen containing bisphosphonate in rats comparison with alendronate and minodronate
Journal of Physiology and Pharmacology, 2011Co-Authors: Kikuko Amagase, A Inaba, T Senta, Y Ishikawa, K Nukui, T Murakami, Koji TakeuchiAbstract:We examined the mucosal irritating and Healing Impairment effects of risedronate, a nitrogen-containing bisphosphonate (BPP), on rat stomachs, in comparison with those of alendronate and minodronate. Male SD rats were used in the following two studies; 1) the ulcerogenic effects of risedronate, alendronate and minodronate in the antral mucosa, and 2) the Healing Impairment effect of these drugs on gastric ulcers induced by thermocauterization. A single administration of BPPs to fasted rats produced ulcers in the antrum with severe edema and inflammation 3 days after refeeding, although the doses required for this action differed among these BPPs: alendronate >100 mg/kg, risedronate >300 mg/kg, minodronate >10 mg/kg. The generation of antral ulcers induced by these BPPs was accompanied by an increase in myeloperoxidase (MPO) activity and lipid peroxidation as well as a decrease in superoxide dismutase (SOD) activity and glutathione (GSH) content in the mucosa; the extent order of these changes was minodronate >alendronate >risedronate. On the other hand, the Healing of gastric ulcers was significantly delayed by daily administration of alendronate (>30 mg/kg) and minodronate (>10 mg/kg), but not by risedronate, even at 60 mg/kg. Mucosal vascular endothelium-derived growth factor (VEGF) and basic fibroblast growth factor (bFGF) protein expressions were up-regulated after ulceration, in parallel with angiogenesis. Alendronate and minodronate decreased these expressions and angiogenesis, while risedronate had no effect. In conclusion, the gastric adverse effect of risedronate is less potent than alendronate and minodronate. It is assumed that risedronate may be used more safely than other BPPs as an antiresorptive drug in patients.
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Gastric ulcerogenic and Healing Impairment actions of alendronate, a nitrogen-containing bisphosphonate - prophylactic effects of rebamipide.
Current pharmaceutical design, 2011Co-Authors: Koji Takeuchi, S. Kato, Kikuko AmagaseAbstract:Alendronate, a nitrogen containing bisphosphonate (BPP), when given p.o., decreases the transmucosal potential difference by direct irritating action, resulting in non-hemorrhagic lesions in both the corpus and antrum of fasted rats, and after re-feeding produces large ulcers in the antrum with increased vascular permeability and submucosal edema. The pathogenesis of these ulcers may be explained by the Impairment of the mucosal anti-oxidative system and does not involve acid digestion as well as a deficiency of prostaglandins (PGs). Alendronate, although does not affect cyclooxygenase/ PGE2 production in the ulcerated mucosa, but impairs the Healing of gastric ulcers in rats, and this effect may be related to the down-regulation of vascular endothelial growth factor and basic fibroblast growth factor (bFGF), the important growth factors for the vascularization/granulation as well as the suppression of the stimulatory action of epidermal growth factor on the epithelial proliferation/migration. Rebamipide, a mucosal protective and antiulcer drug, does not affect the direct irritating action of alendronate in the gastric mucosa but prevents the alendronate-induced antral ulceration, probably due to anti-oxidative and anti-inflammatory actions. In addition, this agent also antagonizes the Healing Impairment action of alendronate by counteracting the down-regulation of bFGF expression in the ulcerated mucosa. It is assumed that rebamipide is a promising drug that can be used as a prophylactic against the adverse effects of BPPs in the stomach.
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Healing Impairment effect of cyclooxygenase inhibitors on dextran sulfate sodium-induced colitis in rats.
Digestion, 2006Co-Authors: Ryoichi Tsubouchi, S. Kato, Shusaku Hayashi, Yoko Aoi, Hikaru Nishio, Shun Terashima, Shinichi Kato, Koji TakeuchiAbstract:We examined the effects of various cyclooxygenase (COX) inhibitors on the Healing of colonic lesions induced by dextran sulfate sodium (DSS) in the rat. Colonic lesions were induced by 2.5% DSS in the drinking water for 7 days, and then the animals were fed with tap water for subsequent 7 days. Indomethacin (a nonselective COX inhibitor), SC-560 (a selective COX-1 inhibitor), or rofecoxib (a selective COX-2 inhibitor) was given orally twice daily after termination of the DSS treatment. DSS treatment caused severe colonic lesions with a decrease in body weight gain and colon length as well as an increase in myeloperoxidase activity and thiobarbituric acid reactant levels. The severity of colitis gradually reduced, with an improvement of morphological and histological alterations. Daily administration of indomethacin and rofecoxib significantly delayed the Healing of colitis with deleterious influences on histological restitution as well as mucosal inflammation, while SC-560 had no effect. Although COX-1 mRNA was expressed in the colon without much alteration during the test period, the expression of COX-2 was upregulated with a peak on day 3 and decreased thereafter. The mucosal prostaglandin E2 content in the colon showed a biphasic change, in parallel with that of the COX-2 expression. The increased prostaglandin E2 production in the injured mucosa was attenuated by indomethacin and rofecoxib, but not by SC-560. These results suggest that endogenous prostaglandins produced by COX-2 play an important role in the Healing of DSS-induced colonic lesions. Caution should be paid to the use of selective COX-2 inhibitors as well as nonsteroidal anti-inflammatory drugs in patients with colitis.
