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Sample records for accelerated ulcer healing

  1. Accelerated Ulcer Healing and Resistance to Ulcer Recurrence with Gastroprotectants in Rat Model of Acetic Acid-induced Gastric Ulcer

    PubMed Central

    Young Oh, Tae; Ok Ahn, Byung; Jung Jang, Eun; Sang Park, Joo; Jong Park, Sang; Wook Baik, Hyun; Hahm, Ki-Baik

    2008-01-01

    Quality of ulcer healing (QOUH) is defined as ideal ulcer healing featuring with the fine granular ulcer scar, high functional restoration and the resistance to recurrence. This study was designed to compare the rates of QOUH achievement in rat gastric ulcer model between acid suppressant treated group and gastroprotectant treated group accompanied with elucidations of molecular mechanisms. Serosal injection of acetic acids for generating gastric ulcer and intraperitoneal (ip) injection of recombinant interleukin 1-beta (IL-1β) for recurring healed ulcer was done in SD rats. The 72 rats were divided into three groups according to treatment as follows; Group I, no further treatment, Group II, 8 weeks treatment of omeprazole, and Group III, 8 weeks of gastroprotectant treatment. IL-1β was administered for ulcer recurrence after 28 weeks of acetic acid injection. At four weeks after gastric ulcerogenesis, 58.3% (7/12) of active gastric ulcer were converted to healing stage in Group III, but 16.7% (2/12) in Group II and none in Group I, for which significant levels of epidermal growth factor, mucin, and pS2/trefoil peptide1 were contributive to these accelerated healings of Group III. ip injections of rIL-1β (200 µg/kg) at 28 weeks after acetic acid injection led to 100% of ulcer recurrence in Group I and 75.0% in Group II, but only 16.7% of Group III rats showed ulcer recurrence. Significantly attenuated levels of inflammatory cytokines including IL-2, transforming growth factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), nitrotyrosine were responsible for the resistance to ulcer recurrence in Group III. Conclusively, gastroprotectant might be prerequisite in order to achieve ideal QOUH through significant inductions of remodeling. PMID:18545642

  2. Collagen scaffolds loaded with collagen-binding NGF-beta accelerate ulcer healing.

    PubMed

    Sun, Wenjie; Lin, Hang; Chen, Bing; Zhao, Wenxue; Zhao, Yannan; Xiao, Zhifeng; Dai, Jianwu

    2010-03-01

    Studies have shown that exogenous nerve growth factor (NGF) accelerates ulcer healing, but the inefficient growth factor delivery system limits its clinical application. In this report, we found that the native human NGF-beta fused with a collagen-binding domain (CBD) could form a collagen-based NGF targeting delivery system, and the CBD-fused NGF-beta could bind to collagen membranes efficiently. Using the rabbit dermal ischemic ulcer model, we have found that this targeting delivery system maintains a higher concentration and stronger bioactivity of NGF-beta on the collagen membranes by promoting peripheral nerve growth. Furthermore, it enhances the rate of ulcer healing through accelerating the re-epithelialization of dermal ulcer wounds and the formation of capillary lumens within the newly formed tissue area. Thus, collagen membranes loaded with collagen-targeting human NGF-beta accelerate ulcer healing efficiently.

  3. Histomorphological characteristics of accelerated healing of acetate ulcers under the effect of glyprolines.

    PubMed

    Trufanova, A V; Baglikova, K E; Bakaeva, Z V; Samonina, G E; Guseva, A A

    2007-08-01

    Glyprolines (PGP, GPG, GPGP, PGPGP, and GPGPGP) modulated histomorphological characteristics of acetate ulcers. They accelerated healing of acetate ulcers, promote complete differentiation of the surface epithelium and glands in the gastric mucosa, contributed to the appearance of a considerable number of fibroblasts at the site of the regenerating mucosa, and significantly decreased the count of macrophages.

  4. [Semax and some glyproline peptides accelerate the healing of acetic ulcers in rats].

    PubMed

    Zhuĭkova, S E; Badmaeva, K E; Samonina, G E; Plesskaia, L G

    2003-01-01

    Previously we showed that peptides PGP, PG, GP and semax have protective anti-ulcer properties using different models of ulcerogenesis. Semax (MEHFPGP) is a nootropic analogue of adrenocorticotropin 4-7 stabilized by PGP in the C-terminal region. In this study we examined the impact of these peptides on the development and healing of acetic ulcers in rats. The histomorphological and dynamical characteristics of acetic ulcers are most similar to human chronic ulcers. All the peptides were shown to accelerate the process of ulcer cicatrisation in a varying degree (GP semax PG PGP). The dynamics of structural changes in the place of ulcer formation investigated with the use of cytohistological control demonstrated that their anti-ulcer effects can be related to their ability to accelerate ulcer clarification from necrotic tissues and to activate the process of cicatrisation and epithelization. PGP and GP were also shown to reduce the inflammation in the ulcer zone on the fifth day after acetic acid application.

  5. Administration of obestatin accelerates the healing of chronic gastric ulcers in rats

    PubMed Central

    Dembiński, Artur; Warzecha, Zygmunt; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Ptak-Belowska, Agata; Kuwahara, Atsukasu; Kato, Ikuo

    2011-01-01

    Summary Background Previous studies have shown that administration of obestatin exhibits a protective effect in the pancreas, attenuating the development of acute pancreatitis. The aim of the present study was to investigate the influence of obestatin administration on the healing of chronic gastric ulcers. Material/Methods Chronic gastric ulcers were induced in rats by 100% acetic acid applied to the serosal surface of the gastric wall. Obestatin was given twice a day intraperitoneally at the dose of 4, 8 or 16 nmol/kg/dose for 6 days. Six days after induction of ulcers, rats were anesthetized and the stomach was exposed for measurement of gastric blood flow and ulcer area. Biopsy samples from the gastric mucosa were taken for determination of mucosal DNA synthesis and for measurement of gastric expression of mRNA for interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Results Induction of gastric ulcers alone increased mucosal blood flow and tissue expression of mRNA for TNF-α and IL-1β, whereas gastric mucosal DNA synthesis was reduced. In rats with gastric ulcers, administration of obestatin increased gastric mucosal blood flow, accelerated the healing rate of these ulcers and partly reversed the gastric ulcer-induced reduction in gastric mucosal DNA synthesis. These results were associated with a reduction in gastric mucosal expression of pro-inflammatory IL-1β and TNF-α. Conclusions Treatment with obestatin increases gastric mucosal blood flow and cell proliferation, leading to acceleration of healing of gastric ulcers. These effects are associated with a reduction in mucosal expression of pro-inflammatory IL-1β and TNF-α. PMID:21804455

  6. A mutein of human basic fibroblast growth factor TGP-580 accelerates colonic ulcer healing by stimulating angiogenesis in the ulcer bed in rats.

    PubMed

    Satoh, H; Szabo, S

    2015-10-01

    Previously, we reported that TGP-580, a mutein of human basic fibroblast growth factor (bFGF), accelerated the healing of gastric and duodenal ulcers in rats. In the present study, we examined the effect of TGP-580 on the healing of colonic ulcers. In male Sprague Dawley rats, ulcers were induced in the colon 6 cm from the anus by enema of 50 μl of 3% N-ethylmaleimide, a sulfhydryl alkylator. The lesions were examined under a dissecting microscope (x10). The concentration of bFGF in the ulcerated colon was measured by enzyme immunoassay, and both the distribution of bFGF and the density of microvessels in the ulcer bed were examined by immunohistochemical staining. The content of bFGF in the ulcerated colon was markedly increased associated with ulcer healing, and ulcer healing was significantly delayed by intravenous administration of a monoclonal antibody for bFGF (MAb 3H3) once daily for 10 days. In the ulcer bed, many cells such as fibroblasts, vascular endothelial cells and macrophages were positively stained with bFGF antiserum. TGP-580, human bFGF or dexamethasone was given intracolonally twice daily for 10 days, starting the day after ulcer induction. TGP-580 (0.2 - 20 μg/ml, 200 μl/rat) dose-dependently accelerated ulcer healing, and its effect was more than 10 times stronger than that of human bFGF. Density (μm/0.01 mm(2)) of microvessels in the ulcer bed was significantly increased by treatment with TGP-580, and there was a good correlation between the density of microvessels and the decrease of ulcerated area (R(2) = 0.633). On the other hand dexamethasone (20 μg/ml) inhibited angiogenesis in the ulcer bed and delayed ulcer healing. These results suggest that angiogenesis in the ulcer bed plays an important role in ulcer healing, and that bFGF mutein TGP-580 accelerated colonic ulcer healing, at least in part, by stimulating angiogenesis, whereas glucocorticoids may delay the healing by inhibiting angiogenesis.

  7. Potential use of blood bank platelet concentrates to accelerate wound healing of diabetic ulcers.

    PubMed

    Han, Seung-Kyu; Kim, Deok-Woo; Jeong, Seong-Ho; Hong, Yong-Taek; Woo, Hong-Suh; Kim, Woo-Kyung; Gottrup, Finn

    2007-11-01

    Many clinical trials have shown the effectiveness of platelet releasates on diabetic wound healing, but large volumes of blood must be aspirated from patients and a platelet separator is required. This study was undertaken to investigate the potential of blood bank platelet concentrate (BBPC) for accelerating diabetic wound healing. Platelet-derived growth factor-BB (PDGF-BB) contents in BBPC were determined by enzyme-linked immunosorbent assay in vitro, and the in vivo study involved comparing extents of wound healing in BBPC-treated and control groups using diabetic mouse wound models. In the in vitro study, 5.2 +/- 1.2 pg of PDGF-BB was found to be released by 1 million platelets in fresh BBPC, and adding thrombin to BBPC significantly increased the levels of PDGF-BB released. Our in vivo study in diabetic mice revealed that BBPC treatment greatly accelerated wound healing. Our results suggest that BBPC has potential to accelerate the healing of diabetic ulcers.

  8. [Influence of honey, royal jelly and propolis on accelerating acetate healing of experimental gastric ulcers in rats].

    PubMed

    Belostotskiĭ, N I; Kas'ianenko, V I; Dubtsova, E A; Lazebnik, L B

    2009-01-01

    This study examines gastric acetic ulcer healing in the rat after administration of honey, royal jelly and propolis into the stomach. Chronic gastric ulcers were induced in male Wistar rats by the application of 100% acetic acid to the serosal surface of the stomach on 60 sec. Bee-keeping products were administrated into the stomach from 2nd to 7th day after acetic ulcer induction. On 7th day animals were killed, and ulcer area was measured in mm2. In gastric juice pH and activity of pepsin were measured. The healing of acetic ulcers is accelerated with the administration of honey, royal jelly or propolis during six days. The largest healing effect was demonstrated with propolis and royal jelly, smaller one with the honey. It was revealed decrease of stomach acid secretion in the rats, which have received bee-keeping products versus the rats of control group.

  9. Acceleration of wound healing in gastric ulcers by local injection of neutralising antibody to transforming growth factor beta 1.

    PubMed Central

    Ernst, H; Konturek, P; Hahn, E G; Brzozowski, T; Konturek, S J

    1996-01-01

    BACKGROUND: Application of neutralising antibodies (NAs) to transforming growth factor beta 1 (TGF beta 1) improves wound healing in experimental glomerulonephritis and dermal incision wounds. TGF beta 1 has been detected in the stomach, but despite the fact that this cytokine plays a central part in wound healing no information is available to determine if modulation of the TGF beta 1 profile influences the healing of gastric ulcers. This study examines gastric ulcer healing in the rat after local injection of NAs to TGF beta 1. METHOD: Chronic gastric ulcers were induced in Wistar rats by the application of 100% acetic acid to the serosal surface of the stomach. Immediately after ulcer induction and on day 2, NAs to TGF beta 1 (50 micrograms), TGF beta 1 (50 ng), saline or control antibodies (IgG; 50 micrograms) were locally injected into the subserosa. Controls received no subserosal injections. Animals were killed on day 5 or 11, the ulcer area was measured planimetrically, sections were embedded in paraffin wax, and stained with trichrome or haematoxylin and eosin. Depth of residual ulcer was assessed on day 11 by a scale of 0-3, the percentage of connective tissue was determined by a semiquantitative matrix score and granulocytes and macrophages in the ulcer bed were also assessed. RESULTS: The application of NAs to TGF beta 1 led to a significant acceleration of gastric ulcer healing on day 11 (0.6 (SD 0.8) v 3.7 (SD 2.6) mm2), a reduction in macrophages (23.7 (SD 22.6) v 38 (26) per 40 x power field) and granulocytes (8.5 (SD 5.6) v 20 (10) per 40 x power field), fewer histological residual ulcers (mean 1 (SD 0.9) v 2 (1.1)), a reduced matrix score, and a regenerative healing pattern. Excessive scarring was seen in the TGF beta 1 treated group. CONCLUSION: Further treatment of gastric ulcers may induce a new treatment modality by local injection of NA to TGF beta 1 in an attempt to accelerate and improve ulcer healing. Images Figure 2 Figure 3 PMID:8991853

  10. The Probiotic Mixture VSL#3 Accelerates Gastric Ulcer Healing by Stimulating Vascular Endothelial Growth Factor

    PubMed Central

    Dharmani, Poonam; De Simone, Claudio; Chadee, Kris

    2013-01-01

    Studies assessing the effect and mechanism of probiotics on diseases of the upper gastrointestinal tract (GI) including gastric ulcers are limited despite extensive work and promising results of this therapeutic option for other GI diseases. In this study, we investigated the mechanisms by which the probiotic mixture VSL#3 (a mixture of eight probiotic bacteria including Lactobacilli, Bifidobacteria and Streptococcus species) heals acetic acid induced gastric ulcer in rats. VSL#3 was administered orally at low (6×109 bacteria) or high (1.2×1010 bacteria) dosages from day 3 after ulcer induction for 14 consecutive days. VSL#3 treatments significantly enhanced gastric ulcer healing in a dose-dependent manner. To assess the mechanism(s) whereby VSL#3 exerted its protective effects, we quantified the gene expression of several pro-inflammatory cytokines, protein and expression of stomach mucin-Muc5ac, regulatory cytokine-IL-10, COX-2 and various growth factors. Of all the components examined, only expression and protein production of VEGF was increased 332-fold on day 7 in the ulcerated tissues of animals treated with VSL#3. Predictably, animals treated with VEGF neutralizing antibody significantly delayed gastric ulcer healing in VSL#3 treated animals. This is the first report to demonstrate high efficacy of the probiotic mixture VSL#3 in enhancing gastric ulcer healing. Probiotic efficacy was effective at higher concentrations of VSL#3 by specifically increasing the expression and production of angiogenesis promoting growth factors, primarily VEGF. PMID:23484048

  11. The use of low output laser therapy to accelerate healing of diabetic foot ulcers: a randomized prospective controlled trial

    NASA Astrophysics Data System (ADS)

    Naidu, S. V. L. G.; Subapriya, S.; Yeoh, C. N.; Soosai, S.; Shalini, V.; Harwant, S.

    2005-11-01

    The aim of this study was to assess the effects of low output laser therapy as an adjuvant treatment in grade 1 diabetic foot ulcers. Methods: Sixteen patients were randomly divided equally into two groups. Group A had daily dressing only, while group B had low output laser therapy instituted five days a week in addition to daily dressing. Serial measurement of the ulcer was done weekly using digital photography and analyzed. Results: The rate of healing in group A was 10.42 mm2/week, and in group B was 66.14mm2/week. The difference in the rate of healing was statistically significant, p<0.05. Conclusion: Laser therapy as an adjuvant treatment accelerates diabetic ulcer healing by six times in a six week period.

  12. Ghrelin accelerates the healing of cysteamine-induced duodenal ulcers in rats

    PubMed Central

    Warzecha, Zygmunt; Ceranowicz, Dagmara; Dembiński, Artur; Ceranowicz, Piotr; Cieszkowski, Jakub; Kuwahara, Atsukazu; Kato, Ikuo; Dembiński, Marcin; Konturek, Peter C.

    2012-01-01

    Summary Background Previous studies have shown that administration of ghrelin exhibits protective and therapeutic effects in the gut. The aim of the present investigation was to examine the influence of ghrelin administration on the course of cysteamine-induced duodenal ulcers, as well as effects on mucosal production of oxygen free radicals and duodenal antioxidant defense. Material/Methods Duodenal ulcers were induced in male Wistar rats by cysteamine administered intragastrically at the dose of 200 mg/kg in 1 ml of saline, 3 times at 4-h intervals. Starting 24 h after the first dose of cysteamine, rats were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 4, 8 or 16 nmol/kg/dose. Seven days after administration of the first dose of cysteamine, the study was terminated. Results Induction of ulcers by cysteamine was accompanied by a reduction in duodenal blood flow, mucosal DNA synthesis and mucosal activity of superoxide dismutase (SOD); whereas mucosal concentration of interleukin-1β and malonyldialdehyde (MDA – an index of lipid peroxidation) were increased. Treatment with ghrelin increased healing rate of duodenal ulcers and enhanced duodenal blood flow, mucosal DNA synthesis and mucosal activity of SOD, and reduced mucosal concentration of interleukin-1β and MDA. Conclusions Treatment with ghrelin increases the healing rate of duodenal ulcers and this effect is related, at least in part, to improvement of duodenal mucosal blood flow, mucosal cell proliferation and antioxidant defense, as well as being related to reduction in mucosal oxidative stress and inflammatory response. PMID:22534700

  13. Yogurt containing Lactobacillus gasseri OLL 2716 (LG21 yogurt) accelerated the healing of acetic acid-induced gastric ulcer in rats.

    PubMed

    Uchida, Masayuki; Shimizu, Kimiko; Kurakazu, Keiko

    2010-01-01

    We have reported that LG21 yogurt containing Lactobacillus gasseri OLL 2716 (LG21 yogurt) inhibits the formation of HCl-induced acute gastric lesions through the generation of prostaglandin E₂. This study aimed to determine the role of viable Lactobacillus in the healing of acetic acid-induced chronic gastric ulcer. LG21 yogurt or γ-ray radiated LG21 yogurt was administered orally twice a day for 10 d at a dose of 5 ml/kg. LG21 yogurt significantly accelerated the healing of the ulcer, but γ-ray radiated LG21 yogurt did not. However, both yogurts significantly inhibited HCl-induced gastric erosive lesions and enhanced the generation of gastric mucosal prostaglandin E₂. From the above results, it was found that viable bacteria are needed to accelerate the healing of chronic gastric ulcer, but not to inhibit gastric lesions.

  14. Application of platelet-rich plasma accelerates the wound healing process in acute and chronic ulcers through rapid migration and upregulation of cyclin A and CDK4 in HaCaT cells.

    PubMed

    Kim, Sung-Ae; Ryu, Han-Won; Lee, Kyu-Suk; Cho, Jae-We

    2013-02-01

    Application of autologous platelet-rich plasma (PRP) has been used for chronic wound healing. The aim of this study was to evaluate the effect of PRP on the wound healing processes of both acute and chronic ulcers and the underlying molecular mechanisms involved. We treated 16 patients affected by various acute and chronic ulcers with PRP. We performed molecular studies of cell proliferation, migration assays, immunoblotting and chloramphenicol acetyltransferase (CAT) assays in PRP-treated HaCaT keratinocyte cells. PRP treatment induced increased rates of cell proliferation and cell migration of HaCaT cells. In addition, the expression of cyclin A and cyclin dependent kinase (CDK) 4 proteins was markedly increased with a low concentration (0.5%) of PRP treatment in HaCaT cells. In 11 patients with chronic ulcers, including stasis ulcers, diabetic ulcers, venous leg ulcers, livedoid vasculitis, claw foot and traumatic ulcers, 9 patients showed 90-100% epithelization after 15.18 days. In 5 patients with acute ulcers, such as dehiscence, open wound and burn wound, 80-100% epithelization was achieved between 4 to 20 days. Topical application of PRP to acute and chronic skin ulcers significantly accelerated the epithelization process, likely through upregulation of the cell cycle regulatory proteins cyclin A and CDK4.

  15. Adenosine accelerates the healing of diabetic ischemic ulcers by improving autophagy of endothelial progenitor cells grown on a biomaterial

    PubMed Central

    Chen, Wen; Wu, Yangxiao; Li, Li; Yang, Mingcan; Shen, Lei; Liu, Ge; Tan, Ju; Zeng, Wen; Zhu, Chuhong

    2015-01-01

    Endothelial progenitor cells (EPCs) seeded on biomaterials can effectively promote diabetic ischemic wound healing. However, the function of transplanted EPCs is negatively affected by a high-glucose and ischemic microenvironment. Our experiments showed that EPC autophagy was inhibited and mitochondrial membrane potential (MMP) was increased in diabetic patients, while adenosine treatment decreased the energy requirements and increased the autophagy levels of EPCs. In animal experiments, we transplanted a biomaterial seeded with EPCs onto the surface of diabetic wounds and found that adenosine-stimulated EPCs effectively promoted wound healing. Increased microvascular genesis and survival of the transplanted cells were also observed in the adenosine-stimulated groups. Interestingly, our study showed that adenosine increased the autophagy of the transplanted EPCs seeded onto the biomaterial and maintained EPC survival at 48 and 96 hours. Moreover, we observed that adenosine induced EPC differentiation through increasing the level of autophagy. In conclusion, our study indicated that adenosine-stimulated EPCs seeded onto a biomaterial significantly improved wound healing in diabetic mice; mechanistically, adenosine might maintain EPC survival and differentiation by increasing high glucose-inhibited EPC autophagy and maintaining cellular energy metabolism. PMID:26108983

  16. Adipose Stem Cells as Alternatives for Bone Marrow Mesenchymal Stem Cells in Oral Ulcer Healing

    PubMed Central

    Aziz Aly, Lobna Abdel; Menoufy, Hala El-; Ragae, Alyaa; Rashed, Laila Ahmed; Sabry, Dina

    2012-01-01

    Background and Objectives Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. Methods and Results Oral ulcers were induced by topical application of formocresol in the oral cavity of dogs. Transplantation of undifferentiated GFP-labeled Autologous Bone Marrow Stem Cell (BMSCs), Adipose Derived Stem Cell (ADSCs) or vehicle (saline) was injected around the ulcer in each group. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) was detected in MSCs by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Expression of VEGF and collagen genes was detected in biopsies from all ulcers. Results: MSCs expressed mRNA for VEGF MSCs transplantation significantly accelerated oral ulcer healing compared with controls. There was increased expression of both collagen and VEGF genes in MSCs-treated ulcers compared to controls. Conclusions MSCs transplantation may help to accelerate oral ulcer healing, possibly through the induction of angiogenesis by VEGF together with increased intracellular matrix formation as detected by increased collagen gene expression. This body of work has provided evidence supporting clinical applications of adipose-derived cells in safety and efficacy trials as an alternative for bone marrow mesenchymal stem cells in oral ulcer healing. PMID:24298363

  17. Enhancement in gastric mucosal EGF and PDGF receptor expression with ulcer healing by sulglycotide.

    PubMed

    Piotrowski, J; Majka, J; Sano, S; Nowak, P; Murty, V L; Slomiany, A; Slomiany, B L

    1995-07-01

    1. The effect of an antiulcer agent, sulglycotide, on mucosal expression of EGF and PDGF receptors with chronic ulcer healing was investigated. 2. Rats with experimentally-induced gastric ulcers were treated twice daily for 14 consecutive days, either with sulglycotide at 200 mg/kg or vehicle, and at different stages of treatment used for quantitation of gastric mucosal EGF and PDGF receptors. 3. The ulcer healing was accompanied by an increase in mucosal expression of both types of receptors. A 1.8-fold increase in EGF and 3.1-fold increase in PDGF receptors occurred by the 4th day following the development of ulcer and reached a maximum of 2.4-3.9-fold increase by the 10-14th day. 4. Treatment with sulglycotide caused accelerated ulcer healing accompanied by a significant enhancement in the receptors expression. A 2.3- and 3.6-fold increase in EGF and PDGF receptor expression occurred by the 4th day of sulglycotide treatment, reaching a 5.5- and 5.6-fold respective increase by the 10th day when the ulcer essentially healed. 5. The results attest to the ability of sulglycotide to stimulate the gastric mucosal proliferative activities associated with ulcer healing.

  18. Recurrent and other new foot ulcers after healed plantar forefoot diabetic ulcer.

    PubMed

    Örneholm, Hedvig; Apelqvist, Jan; Larsson, Jan; Eneroth, Magnus

    2017-04-01

    Diabetic foot ulcer is a serious complication in patients with diabetes. In most outcome studies of this condition, there is a combination of various types of ulcer and ulcer locations. Plantar ulcers are usually localized to the forefoot, and constitute a quarter of all diabetic foot ulcers. There are a limited number of studies regarding development of new ulcers following healing of a plantar forefoot ulcer, and there are no uniform definitions of recurrent and other new ulcers. The aim of this study was to evaluate the outcome of a large cohort of consecutively treated patients with diabetes mellitus and a healed planter forefoot ulcer (n=617) with regard to development, characteristics, and outcome of recurrent and other new ulcers. Patients were followed consecutively and prospectively with a two-year follow-up, according to a pre-set protocol. Out of 617 patients, 250 (41%) did not develop any new ulcer, 262 (42%) developed a new ulcer, 87 (14%) died and 18 (3%) were lost at two years following healing of a plantar forefoot ulcer. Thirty-four per cent developed other new ulcers (112 on the same foot and 99 on the contralateral foot), whereas 51 patients (8%) developed a recurrent ulcer (at the same site and foot). Of the patients who died within two years, 30 patients had developed other new ulcers. The risk of a recurrent ulcer in patients with diabetes and a healed plantar forefoot ulcer was only eight per cent within two years, whereas other new ulcers, on the same foot or on the contralateral foot, was seen in 4 out of 10 patients indicating the need for further preventive measures and surveillance in these patients. We suggest a concise definition for new ulcer to be used in future research. This article is protected by copyright. All rights reserved.

  19. Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system.

    PubMed

    da Silva, Luisa Mota; Allemand, Alexandra; Mendes, Daniel Augusto G B; Dos Santos, Ana Cristina; André, Eunice; de Souza, Lauro Mera; Cipriani, Thales Ricardo; Dartora, Nessana; Marques, Maria Consuelo Andrade; Baggio, Cristiane Hatsuko; Werner, Maria Fernanda

    2013-01-01

    We evaluate the curative efficacy of the ethanolic extract (EET) of roots from Arctium lappa (bardana) in healing of chronic gastric ulcers induced by 80% acetic acid in rats and additionally studies the possible mechanisms underlying this action. Oral administration of EET (1, 3, 10 and 30mg/kg) reduced the gastric lesion area in 29.2%, 41.4%, 59.3% and 38.5%, respectively, and at 10mg/kg promoted significant regeneration of the gastric mucosa, which was confirmed by proliferating cell nuclear antigen immunohistochemistry. EET (10mg/kg) treatment did not increase the gastric mucus content but restored the superoxide dismutase activity, prevented the reduction of glutathione levels, reduced lipid hydroperoxides levels, inhibited the myeloperoxidase activity and reduced the microvascular permeability. In addition, EET reduced the free radical generation and increased scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in vitro. Furthermore, intraduodenal EET (10 and 30mg/kg) decreased volume and acidity of gastric secretion. Total phenolic compounds were high in EET (Folin-Ciocalteau assay) and the analysis by liquid chromatography-mass spectrometry revealed that the main compounds present in EET were a serie of hydroxycinnamoylquinic acid isomers. In conclusion, these data reveal that EET promotes regeneration of damaged gastric mucosa, probably through its antisecretory and antioxidative mechanisms.

  20. Preparation of hydrogel by radiation for the healing of diabetic ulcer

    NASA Astrophysics Data System (ADS)

    Nho, Young-Chang; Park, Jong-Seok; Lim, Youn-Mook

    2014-01-01

    Honey has been used in wound care for thousands of years. The major advantage of honey in wound care is the high osmotic activity, which accelerates the debridement of necrotic tissue and procures an antibacterial effect. It has been reported that the ancient Greeks and Romans used honey as a topical antiseptic for sores and skin ulcers. The aims of this study were to evaluate the antibacterial activities and the healing effect for diabetic ulcers from carboxymethyl cellulose (CMC) hydrogel involving honey.

  1. Anti-ulcer and ulcer healing potentials of Musa sapientum peel extract in the laboratory rodents

    PubMed Central

    Onasanwo, Samuel Adetunji; Emikpe, Benjamin Obukowho; Ajah, Austin Azubuike; Elufioye, Taiwo Olayemi

    2013-01-01

    Background: This study investigated the anti-ulcer and ulcer healing potentials of the methanol extract of Musa sapientum peel in the laboratory rats. Materials and Methods: Methanol extract of the peels on Musa sapientum (MEMS) was evaluated for its anti-ulcer using alcohol-induced, aspirin-induced, and pyloric ligation-induced models, and for its ulcer healing employing acetic acid-induced ulcer models in rats. Results: The findings from this experiment showed that MEMS (50, 100 and 200 mg/kg, b.w.) anti-ulcer and ulcer healing activity (P ≤ 0.05) is dose-dependent. Also, MEMS exhibited healing of the ulcer base in all the treated groups when compared with the control group. Conclusion: The outcomes of this experiment revealed that the anti-ulcer effect of MEMS may be due to its anti-secretory and cyto-protective activity. The healing of the ulcer base might not be unconnected with basic fibroblast growth factors responsible for epithelial regeneration. PMID:23900937

  2. Swift and Complete Healing of Digital Ulcers after Macitentan Treatment

    PubMed Central

    2016-01-01

    Digital ulcers are a burdensome and painful condition with sparse options of treatment. We report the case of a 78-year-old female patient with limited cutaneous systemic sclerosis that sequentially developed digital ulcers. After the appearance of digital ulcers in the soles of her feet she was successfully treated with bosentan. The report of two new digital ulcers in her hands 9 months later alongside with elevated transaminase levels led to a switch to macitentan treatment. A swift and complete healing of both digital ulcers was observed after 3 months, with the restoration of normal biochemical values. PMID:27994906

  3. Healing Properties of Some Indian Medicinal Plants against Indomethacin-Induced Gastric Ulceration of Rats

    PubMed Central

    Bhattacharya, Sayanti; Chaudhuri, Susri R.; Chattopadhyay, Subrata; Bandyopadhyay, Sandip K.

    2007-01-01

    The healing activity of the ethanol extracts of Piper betel, Emblica officinalis, Terminalia bellerica, and Terminalia chebula against the indomethacin-induced stomach ulceration has been studied and compared with that of misoprostol. Compared to autohealing, all the drugs accelerated the healing process, albeit to different extents. The relative healing activities of the extracts was P. betel>E. officinalis>T. bellerica~T. chebula, that correlated well with their in vivo antioxidant and mucin augmenting activities. The excellent healing activity of the extracts of P. betel and E. officinalis indicated a major role of mucin protection and regeneration in the healing of nonsteroidal anti-inflammatory drugs mediated stomach ulceration. PMID:18193104

  4. Gastric ulcer healing with tripotassium dicitrato bismuthate and subsequent relapse.

    PubMed

    Sutton, D R

    1982-07-01

    Fifty patients with endoscopically proven gastric ulcers completed a one month double-blind randomised trial of tripotassium dicitrato bismuthate (TBD) (DeNol) compared with an identical placebo. Ulcer healing occurred in 18 (72%) of the 25 patients given TDB and in nine (36%) of the patients given placebo. The TDB group experienced significantly less pain than the placebo group. During a follow-up of 29 patients with healed ulcers for up to 44 months, relapse occurred in 13 (45%). It was highest in the first three months (27%) and had risen to 41% at two years.

  5. Clinical markers of slow healing and relapsing gastric ulcer.

    PubMed Central

    Battaglia, G; Di Mario, F; Piccoli, A; Vianello, F; Farinati, F; Naccarato, R

    1987-01-01

    The aim of the study was to identify the clinical markers useful in characterising slow healing and relapsing gastric ulcer patients. Ninety nine subjects entered the short term and 79 the long term study (12 months). The following parameters were taken into account: therapy, sex, age, smoking habit, alcohol consumption, analgesic intake, peptic ulcer family history and onset of the disease. Results of the studies were analysed by means of chi 2 test and logistic regression, both in stepwise and in specifying models. Cigarette smoking was found to be the most important risk factor of non-healing (p = 0.04). In women with late onset of the disease, cigarette smoking identified the gastric ulcer subjects at higher risk of non-healing with a predictive probability of 0.4679. Age under 50 years was found to be the most important risk factor of relapsing throughout the entire 12 month follow up period (p = 0.025). In those under 50 years, cigarette smoking and negative peptic ulcer family history in combination, identified the gastric ulcer subjects at higher risk of relapsing, the predicted probability being 0.6027. It is concluded that cigarette smoking is the most important risk factor for non-healing and those who relapse under the age of 50. The possibility of singling out categories of patients more prone not to heal and to relapse suggests new strategies in the management of gastric ulcer disease. PMID:3557191

  6. Modulation of inflammation by Cicaderma ointment accelerates skin wound healing.

    PubMed

    Morin, Christophe; Roumegous, Audrey; Carpentier, Gilles; Barbier-Chassefière, Véronique; Garrigue-Antar, Laure; Caredda, Stéphane; Courty, José

    2012-10-01

    Skin wound healing is a natural and intricate process that takes place after injury, involving different sequential phases such as hemostasis, inflammatory phase, proliferative phase, and remodeling that are associated with complex biochemical events. The interruption or failure of wound healing leads to chronic nonhealing wounds or fibrosis-associated diseases constituting a major health problem where, unfortunately, medicines are not very effective. The objective of this study was to evaluate the capacity of Cicaderma ointment (Boiron, Lyon, France) to accelerate ulcer closure without fibrosis and investigate wound healing dynamic processes. We used a necrotic ulcer model in mice induced by intradermal doxorubicin injection, and after 11 days, when the ulcer area was maximal, we applied Vaseline petroleum jelly or Cicaderma every 2 days. Topical application of Cicaderma allowed a rapid recovery of mature epidermal structure, a more compact and organized dermis and collagen bundles compared with the Vaseline group. Furthermore, the expression of numerous cytokines/molecules in the ulcer was increased 11 days after doxorubicin injection compared with healthy skin. Cicaderma rapidly reduced the level of proinflammatory cytokines, mainly tumor necrosis factor (TNF)-α and others of the TNF pathway, which can be correlated to a decrease of polymorphonuclear recruitment. It is noteworthy that the modulation of inflammation through TNF-α, macrophage inflammatory protein-1α, interleukin (IL)-12, IL-4, and macrophage-colony-stimulating factor was maintained 9 days after the first ointment application, facilitating the wound closure without affecting angiogenesis. These cytokines seem to be potential targets for therapeutic approaches in chronic wounds. Our results confirm the use of Cicaderma for accelerating skin wound healing and open new avenues for sequential treatments to improve healing.

  7. Does social support impact on venous ulcer healing or recurrence?

    PubMed

    Brown, Annemarie

    2008-03-01

    Much of the leg ulcer literature focuses on clinical assessment and management of chronic venous leg ulceration in order to achieve healing. Chronic venous leg ulceration, however, should be classed as a chronic or long-term condition, defined as a condition,'that is currently not curable and therefore can only be managed', although it is not generally acknowledged as such. There is an extensive body of literature which focuses on the psychosocial issues that impact negatively on the quality of life of patients with long-term conditions, such as diabetes or arthritis. These include the emotional impact of pain, social support, coping mechanisms and response to stress and treatment adherence. Health care professionals are becoming increasingly aware of the impact psychosocial issues may have on wound healing in general, but particularly, in chronic venous leg ulceration and prevention of recurrence. This article reviews the current literature on the role of social support and its impact on venous ulcer healing/recurrence and concludes that health professionals caring for patients with chronic venous ulceration need to consider alternative outcome intervention measures for patients for whom healing may not be a realistic option.

  8. Impaired gastric ulcer healing in diabetic mice: role of methylglyoxal.

    PubMed

    Naito, Y; Takagi, T; Oya-Ito, T; Okada, H; Suzuki, T; Hirata, I; Hirai, M; Uchiyama, K; Handa, O; Uchida, K; Yoshikawa, T

    2009-12-01

    Methylglyoxal is a reactive dicarbonyl compound produced from cellular glycolytic intermediates that reacts non-enzymatically with proteins to form products such as argpyrimidine at arginine residue. The aim of the present study was to investigate the role of methylglyoxal in the delayed healing of gastric ulcer in diabetes, and to identify the methylglyoxal-modified proteins as a target molecule of this modification. Using male C57BL/6 mice, diabetes was induced by a single i.p. injection of streptozotocin and gastric ulcers were produced by the focal application of 40% of acetic acid to the serosal surface of the stomach. In order to evaluate the effect of OPB-9195, an inhibitor of methylglyoxal modification, on gastric ulcer healing, mice were given orally OPB-9195 (30 mg/kg) twice daily for 14 days, one week before and after the injection of streptozotocin. The area of gastric ulcer on day 7 was significantly increased in diabetic mice compared to non-diabetic mice, indicating delayed ulcer healing. This increase in ulcer area in diabetic mice was significantly reversed by the treatment with OPB-9195 without affecting blood glucose levels. Proteomics analysis showed the methylglyoxal-modification of peroxiredoxin 6 proteins in the diabetic gastric mucosa around gastric ulcer, and this modification was markedly inhibited by the treatment with OPB-9195. In conclusion, the present study suggests a link of increased methylglyoxal modification of proteins including peroxiredoxin 6 to the delayed gastric ulcer healing in diabetes, and also shows the therapeutic potential of the inhibitor of methylglyoxal modification for the treatment of diabetic gastric ulcers.

  9. Healing ulcers and preventing their recurrences in the diabetic foot

    PubMed Central

    Sabapathy, S. Raja; Periasamy, Madhu

    2016-01-01

    Fifteen percent of people with diabetes develop an ulcer in the course of their lifetime. Eighty-five percent of the major amputations in diabetes mellitus are preceded by an ulcer. Management of ulcers and preventing their recurrence is important for the quality of life of the individual and reducing the cost of care of treatment. The main causative factors of ulceration are neuropathy, vasculopathy and limited joint mobility. Altered bio-mechanics due to the deformities secondary to neuropathy and limited joint mobility leads to focal points of increased pressure, which compromises circulation leading to ulcers. Ulcer management must not only address the healing of ulcers but also should correct the altered bio-mechanics to reduce the focal pressure points and prevent recurrence. An analysis of 700 patients presenting with foot problems to the Diabetic Clinic of Ganga Hospital led to the stratification of these patients into four classes of incremental severity. Class 1 – the foot at risk, Class 2 – superficial ulcers without infection, Class 3 – the crippled foot and Class 4 – the critical foot. Almost 77.5% presented in either Class 3 or 4 with complicated foot ulcers requiring major reconstruction or amputation. Class 1 foot can be managed conservatively with foot care and appropriate foot wear. Class 2 in addition to measures for ulcer healing would need surgery to correct the altered bio-mechanics to prevent the recurrence. The procedures called surgical offloading would depend on the site of the ulcer and would need an in-depth clinical study of the foot. Class 3 would need major reconstructive procedures and Class 4 would need amputation since it may be life-threatening. As clinicians, our main efforts must be focused towards identifying patients in Class 1 and offer advice on foot care and Class 2 where appropriate surgical offloading procedure would help preserve the foot. PMID:28216809

  10. Sustained compression and healing of chronic venous ulcers.

    PubMed Central

    Blair, S. D.; Wright, D. D.; Backhouse, C. M.; Riddle, E.; McCollum, C. N.

    1988-01-01

    STUDY OBJECTIVE--Comparison of four layer bandage system with traditional adhesive plaster bandaging in terms of (a) compression achieved and (b) healing of venous ulcers. DESIGN--Part of larger randomised trial of five different dressings. SETTING--Outpatient venous ulcer clinic in university hospital. PATIENTS--(a) Pressure exerted by both bandage systems was measured in the same 20 patients. (b) Healing with the four layer bandage was assessed in 148 legs in 126 consecutive patients (mean age 71 (SE 2); range 30-96) with chronic venous ulcers that had resisted treatment with traditional bandaging for a mean of 27.2 (SE 8) months. INTERVENTIONS--(a) Four layer bandage system or traditional adhesive plaster bandaging for pressure studies; (b) four layer bandaging applied weekly for studies of healing. END POINTS--(a) Comparison of pressures achieved at the ankle for up to one week; (b) complete healing within 12 weeks. MEASUREMENTS AND MAIN RESULTS--(a) Four layer bandage produced higher initial pressures at the ankle of 42.5 (SE 1) mm Hg compared with 29.8 (1.8) for the adhesive plaster (p less than 0.001; 95% confidence interval 18.5 to 6.9). Pressure was maintained for one week with the four layer bandage but fell to 10.4 (3.5) mm Hg at 24 hours with adhesive plaster bandaging. (b) After weekly bandaging with the four layer bandage 110 of 48 venous ulcers had healed completely within 12 (mean 6.3 (0.4)) weeks. CONCLUSION--Sustained compression of over 40 mm Hg achieved with a multilayer bandage results in rapid healing of chronic venous ulcers that have failed to heal in many months of compression at lower pressures with more conventional bandages. PMID:3144330

  11. Improving venous ulcer healing: designing and reporting randomised controlled trials.

    PubMed

    Weller, Carolina D; McNeil, John; Evans, Sue; Reid, Christopher

    2010-02-01

    The randomised controlled trial (RCT) is often considered the gold standard for judging the benefits of treatments. The application of randomised controlled clinical trials to treatments of venous ulcer healing has lagged behind that of other areas of medicine. To interpret the results of an RCT, readers must understand a variety of aspects of their design, analysis and interpretation. Venous ulcer disease has a high prevalence and has a significant socioeconomic impact in most parts of the world. The management of venous ulcers causes a considerable strain on the health system and is likely to worsen in future. The multi-layer high compression system is described as the current gold standard for treating venous ulcers. A recent meta-analysis of bandaging systems found that multi-layer compression bandages appeared to be superior to single-layer bandages in promoting venous ulcer healing. However, it was noted that many of the studies had small sample sizes and the quality of research in the area was poor. The consolidating standards of reporting trials (CONSORT) statement can help clinicians to discern high-quality studies from ones of poorer quality. This paper discusses how CONSORT can help clinicians and researchers to design and report quality studies to contribute to evidence-based venous ulcer healing.

  12. Rhamnogalacturonan from Acmella oleracea (L.) R.K. Jansen: Gastroprotective and Ulcer Healing Properties in Rats

    PubMed Central

    Maria-Ferreira, Daniele; da Silva, Luisa Mota; Mendes, Daniel Augusto Gasparin Bueno; Cabrini, Daniela de Almeida; Nascimento, Adamara Machado; Iacomini, Marcello; Cipriani, Thales Ricardo; Santos, Adair Roberto Soares; de Paula Werner, Maria Fernanda; Baggio, Cristiane Hatsuko

    2014-01-01

    A rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen administered by oral route showed gastroprotective activity against acute lesions induced by ethanol. In this study, we investigated the gastric ulcer healing effect of RGal and its mechanisms of action. Intraperitoneal treatment of animals with RGal protected the gastric mucosa against acute lesions induced by ethanol, with participation of gastric mucus. Furthermore, in the chronic ulcer model, oral administration of RGal accelerates the gastric ulcer healing, accompanied by increasing of cellular proliferation and gastric mucus content, reducing inflammatory parameters and oxidative stress. In addition, the repeated 7 days-treatment of animals with RGal did not show alterations of clinical and behavioral symptoms, body and organs weights or plasmatic biochemical parameters. Collectively, these results showed that RGal has an interesting antiulcerogenic activity and could constitute an attractive molecule of interest for the development of new antiulcer agents. PMID:24416280

  13. Rhamnogalacturonan from Acmella oleracea (L.) R.K. Jansen: gastroprotective and ulcer healing properties in rats.

    PubMed

    Maria-Ferreira, Daniele; da Silva, Luisa Mota; Mendes, Daniel Augusto Gasparin Bueno; Cabrini, Daniela de Almeida; Nascimento, Adamara Machado; Iacomini, Marcello; Cipriani, Thales Ricardo; Santos, Adair Roberto Soares; Werner, Maria Fernanda de Paula; Baggio, Cristiane Hatsuko

    2014-01-01

    A rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen administered by oral route showed gastroprotective activity against acute lesions induced by ethanol. In this study, we investigated the gastric ulcer healing effect of RGal and its mechanisms of action. Intraperitoneal treatment of animals with RGal protected the gastric mucosa against acute lesions induced by ethanol, with participation of gastric mucus. Furthermore, in the chronic ulcer model, oral administration of RGal accelerates the gastric ulcer healing, accompanied by increasing of cellular proliferation and gastric mucus content, reducing inflammatory parameters and oxidative stress. In addition, the repeated 7 days-treatment of animals with RGal did not show alterations of clinical and behavioral symptoms, body and organs weights or plasmatic biochemical parameters. Collectively, these results showed that RGal has an interesting antiulcerogenic activity and could constitute an attractive molecule of interest for the development of new antiulcer agents.

  14. Autoradiographic study on healing process of cysteamine-induced duodenal ulcer in rat. Possible importance of Brunner's glands in ulcer healing

    SciTech Connect

    Fuse, Y.; Tsuchihashi, Y.; Sugihara, H.; Kodama, T.; Takino, T.; Fujita, S.

    1988-09-01

    The healing process of cysteamine-induced duodenal ulcer was studied by (/sup 3/H)thymidine autoradiography. After the development of ulcer in the duodenum, cell proliferation was markedly activated not only in the crypts but also in the Brunner's glands near the ulcer. In the initial stages of ulcer healing, they both contributed to form the surface covering regenerating epithelium. Granulation tissue also proliferated at the base of the ulcer. In later stages of ulcer healing, new crypts were formed in the floor of the ulcer. New villi regenerated from these crypts and Brunner's glands regenerated by proliferation in situ. The ulcer base then was completely covered with new villi and granulation tissue was replaced by dense fibrous connective tissue. The present study suggested that the Brunner's glands, together with the crypts of Lieberkuehn, play an important role in the healing process of cysteamine-induced duodenal ulcer.

  15. Effect and mechanism of SHED on ulcer wound healing in Sprague-Dawley rat models with diabetic ulcer

    PubMed Central

    Lv, Yue; Ge, Lihong; Zhao, Yuming

    2017-01-01

    To evaluate the effect of stem cells from human exfoliated deciduous teeth (SHED) upon the ulcer wound healing and evaluate the mechanism underlying the role of SHED in Sprague-Dawley rat models with diabetic foot ulcer. The rats with diabetic ulcer were established and treated with SHED, mesenchymal stem cell (MSC) and PBS, respectively. The expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-2 (MMP-2) and MMP9 at both protein and RNA levels was quantitatively measured. The serum levels of VEGF, IL-1β, TNF-1α and IL-10 were detected by ELISA. The remaining tissues were fixed in 4% chloral hydrate for hematoxylin and eosin (H.E) staining and immunohistochemical staining. MSC and SHED administration could reduce ulceration area and accelerate wound healing at 7 and 14 d after treatment as compared with the control group (all P<0.05), which were validated by H.E and immunohistochemical staining. Western blot results revealed that the expression levels of VEGF, eNOS, MMP2 and MMP9 proteins in the MSC and SHED groups were considerably up-regulated compared with those in the control group at different time points (all P<0.05). The same trend was also observed in the mRNA expression of these cytokines detected by RT-PCR. At 3-d after treatment, no statistical significance was noted in the IL-10 level among three groups, but the IL-10 concentration in the SHED and MSC groups was significantly down-regulated at 7- and 14-d post-treatment (all P<0.05). SHED administration, similar to MSCs, could accelerate wound healing, promote angiogenesis and suppress inflammatory responses in rat models with diabetic ulceration. PMID:28337277

  16. Impedance sensing device for monitoring ulcer healing in human patients.

    PubMed

    Liao, Amy; Lin, Monica C; Ritz, Lauren C; Swisher, Sarah L; Ni, David; Mann, Kaylee; Khan, Yasser; Roy, Shuvo; Harrison, Michael R; Arias, Ana C; Subramanian, Vivek; Young, David; Maharbiz, Michel M

    2015-01-01

    Chronic skin wounds affect millions of people each year and take billions of dollars to treat. Ulcers are a type of chronic skin wound that can be especially painful for patients and are tricky to treat because current monitoring solutions are subjective. We have developed an impedance sensing tool to objectively monitor the progression of healing in ulcers, and have begun a clinical trial to evaluate the safety and feasibility of our device to map damaged regions of skin. Impedance data has been collected on five patients with ulcers, and impedance was found to correlate with tissue health. A damage threshold was applied to effectively identify certain regions of skin as "damaged tissue".

  17. Healing, Antioxidant and Cytoprotective Properties of Indigofera truxillensis in Different Models of Gastric Ulcer in Rats

    PubMed Central

    Luiz-Ferreira, Anderson; Cola, Maira; Barbastefano, Victor; de-Faria, Felipe Meira; de Almeida, Ana Beatriz A.; Farias-Silva, Elisângela; Calvo, Tamara Regina; Hiruma-Lima, Clélia A.; Vilegas, Wagner; Souza-Brito, Alba Regina M.

    2012-01-01

    The present study evaluated the antiulcerogenic activity and mechanisms of the aqueous (AqF 100 mg/kg) and ethyl acetate (AcF 50 mg/kg) fractions from Indigofera truxillensis leaves. This dose was selected to assess its activity on ulcer healing and its action on gastric acid and mucus secretion, prostaglandin production and antioxidant enzyme activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd)). Gastric ulcer was induced by absolute ethanol. Antisecretory action, mucus and prostaglandin production, healing and antioxidant enzyme activities were evaluated for both fractions. AqF and AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant at 100 and 50 mg/kg compared with the vehicle. Neither fraction interfered with gastric secretion. AcF increased the PGE2 production, and both fractions increased mucus production. l-NAME did not alter the gastroprotection exerted by the fractions, but N-ethylmaleimide attenuated only AcF. In the ischemia/reperfusion model both fractions inhibited the mucosal damage. AcF increased SOD, GSH-Px and GSH-Rd activity, but AqF increased only SOD and GSH-Px. In the acetic acid-induced ulcer model AcF only accelerated ulcer healing. These results showed that Indigofera truxillensis acted as a gastroprotective agent, stimulating protective factors and antioxidants enzymes. PMID:23203107

  18. Gastric cytoprotection beyond prostaglandins: cellular and molecular mechanisms of gastroprotective and ulcer healing actions of antacids.

    PubMed

    Tarnawski, Andrzej; Ahluwalia, Amrita; Jones, Michael K

    2013-01-01

    This article updates current views on gastric mucosal defense, injury, protection and ulcer healing with a focus on mucosal protective and ulcer healing actions of antacids. The gastric mucosa is continuously exposed to a variety of noxious factors, both endogenous such as: 0.1N hydrochloric acid, pepsin, bile acids, lysolecithin, H. pylori toxins and exogenous such as NSAIDs, ethanol and others. Gastric mucosal integrity is maintained by pre-epithelial, epithelial and post-epithelial defense mechanisms permitting the mucosa to withstand exposure to the above damaging factors. When mucosal defense is weakened or overwhelmed by injurious factors, injury develops in the form of erosions or ulcers. In the late 1970s Andre Robert and coworkers discovered that microgram amounts of a prostaglandin E2 analog protects the gastric mucosa against a variety of ulcerogenic and necrotizing agents - even such strong inducers of injury as 100% ethanol and boiling water. They proposed a new concept of cytoprotection. Subsequently, other compounds, such as sulfhydryls, sucralfate and epidermal growth factor were shown to exert protective action on gastric mucosa. Additionally, some antacids have been shown to exert a potent mucosal protective action against a variety of injurious factors and accelerate healing of erosions and gastric ulcers. These actions of antacids, especially hydrotalcite - the newest and the most extensively studied antacid - are due to activation of prostaglandin synthesis; binding to and inactivation of pepsin, bile acids and H. pylori toxins; induction of heat shock proteins; and, activation of genes encoding growth factors and their receptors.

  19. Healing determinants in older people with leg ulcers.

    PubMed

    Johnson, M

    1995-10-01

    A descriptive correlational design was used to identify the physiologic, therapeutic, and psychosocial determinants of leg ulcer healing in community-residing older people with venous and venous-arterial disease (N = 156). A regression model with healing rate as the dependent variable explained 49% of the variance. Increased pain when mobilizing, increased hours with limbs horizontal to the torso, and moderate and severe liposclerosis (hardening and induration of the skin) were associated with poorer healing rates. Higher wound status scores were associated with more rapid healing rates. Self-efficacy beliefs and social support were not significant factors. The findings suggest the need for early detection and management of limb pain that interferes with normal mobility. Limb position and edema assessment prior to the application of compression bandages is recommended, with bandages that provide clients with high compression when ambulant and low compression when resting being potentially beneficial.

  20. Electrical stimulation to accelerate wound healing

    PubMed Central

    Thakral, Gaurav; LaFontaine, Javier; Najafi, Bijan; Talal, Talal K.; Kim, Paul; Lavery, Lawrence A.

    2013-01-01

    Background There are several applications of electrical stimulation described in medical literature to accelerate wound healing and improve cutaneous perfusion. This is a simple technique that could be incorporated as an adjunctive therapy in plastic surgery. The objective of this review was to evaluate the results of randomized clinical trials that use electrical stimulation for wound healing. Method We identified 21 randomized clinical trials that used electrical stimulation for wound healing. We did not include five studies with treatment groups with less than eight subjects. Results Electrical stimulation was associated with faster wound area reduction or a higher proportion of wounds that healed in 14 out of 16 wound randomized clinical trials. The type of electrical stimulation, waveform, and duration of therapy vary in the literature. Conclusion Electrical stimulation has been shown to accelerate wound healing and increase cutaneous perfusion in human studies. Electrical stimulation is an adjunctive therapy that is underutilized in plastic surgery and could improve flap and graft survival, accelerate postoperative recovery, and decrease necrosis following foot reconstruction. PMID:24049559

  1. Accelerated wound healing with combined NPWT and IPC: a case series.

    PubMed

    Arvesen, Kristian; Nielsen, Camilla Bak; Fogh, Karsten

    2017-03-01

    Negative pressure wound therapy (NPWT) and intermittent pneumatic compression (IPC) have traditionally been used in patients with chronic complicated non-healing wounds. The aim of this study (retrospective case series) was to describe the use of NPWT in combination with IPC in patients with a relatively short history (2-6 months) of ulcers. All wounds showed improved healing during the treatment period with marked or moderate reduction in ulcer size, and granulation tissue formation was markedly stimulated. Oedema was markedly reduced due to IPC. Treatment was generally well tolerated. The results of this study indicate that combined NPWT and IPC can accelerate wound healing and reduce oedema, thus shortening the treatment period. Therefore, patients may have a shorter healing period and may avoid entering a chronic wound phase. However, controlled studies of longer duration are needed in order to show the long-term effect of a more accelerated treatment course.

  2. Use of a topical haemoglobin spray for oxygenating pressure ulcers: healing outcomes.

    PubMed

    Tickle, Joy; Bateman, Sharon Dawn

    2015-12-01

    A published evaluation ( Tickle, 2015 ) of the use of a topical haemoglobin spray plus standard care in 18 patients with pressure ulcers showed that, following 4 weeks of treatment, the wound size reduced in 17 wounds and there was a progression toward healing in all 18. All but one of the wounds were over 2 months in duration at baseline. This article reports the results of the healing rates at 3 months of the 11 patients who continued to be treated with the haemoglobin spray. Nine of the 11 wounds healed, and 2 reduced in size by week 12 (i.e. 1 wound reduced from 30 cm(2) at baseline to 7 cm(2), while the other reduced from 6 cm(2) to 4 cm(2)). Of the 10 patients who were experiencing wound pain at baseline, 9 were pain free by week 8. Rapid elimination of slough was observed in all patients. The 82% healing rate achieved at 3 months and the fact that most patients continued to receive the same standard care as they had in the 4 weeks before recruitment into the evaluation increases the likelihood that the clinical outcomes observed here can be attributed to the haemoglobin spray. Topical haemoglobin shows promise in terms of its ability to accelerate healing in chronic pressure ulcers.

  3. Effect of antisecretory agents and vagotomy on healing of chronic cysteamine-induced duodenal ulcers in rats

    SciTech Connect

    Poulsen, S.S.; Raaberg, L.; Therkelsen, K.; Skov Olsen, P.; Kirkegaard, P.

    1986-07-01

    Penetrated cysteamine-induced duodenal ulcers in rats have a very prolonged course of healing. In this study, it was investigated how much the healing of these ulcers is accelerated by some treatments. The treatments included omeprazole, cimetidine, and truncal vagotomy. In addition, the effect of omeprazole and cimetidine on gastric acid secretion was investigated in chronic gastric fistula rats. After 25 days of treatment, significantly more rats in the treated groups had healed ulcers than in the control group. There was little further improvement up to 100 days of treatment, and the difference between treated and untreated groups decreased. The morphology of healing ulcers in treated and untreated rats was also compared. In controls, there was a simultaneous regeneration of mucosa and the submucosal Brunner's glands from the edges of the ulcer, the slow proliferation rate of the latter probably being decisive for the prolonged healing. In the treated rats, the mucosa first regenerated with formation of crypts and low villi and subsequently, the Brunner's glands were formed by proliferation from the bottom of the crypts.

  4. Gallic Acid Enriched Fraction of Phyllanthus emblica Potentiates Indomethacin-Induced Gastric Ulcer Healing via e-NOS-Dependent Pathway.

    PubMed

    Chatterjee, Ananya; Chatterjee, Sirshendu; Biswas, Angshuman; Bhattacharya, Sayanti; Chattopadhyay, Subrata; Bandyopadhyay, Sandip K

    2012-01-01

    The healing activity of gallic acid enriched ethanolic extract (GAE) of Phyllanthus emblica fruits (amla) against the indomethacin-induced gastric ulceration in mice was investigated. The activity was correlated with the ability of GAE to alter the cyclooxygenase- (COX-) dependent healing pathways. Histology of the stomach tissues revealed maximum ulceration on the 3rd day after indomethacin (18 mg/kg, single dose) administration that was associated with significant increase in inflammatory factors, namely, mucosal myeloperoxidase (MPO) activity and inducible nitric oxide synthase (i-NOS) expression. Proangiogenic parameters such as the levels of prostaglandin (PG) E(2), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), von Willebrand Factor VIII, and endothelial NOS (e-NOS) were downregulated by indomethacin. Treatment with GAE (5 mg/kg/day) and omeprazole (3 mg/kg/day) for 3 days led to effective healing of the acute ulceration, while GAE could reverse the indomethacin-induced proinflammatory changes of the designated biochemical parameters. The ulcer healing activity of GAE was, however, compromised by coadministration of the nonspecific NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME), but not the i-NOS-specific inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL). Taken together, these results suggested that the GAE treatment accelerates ulcer healing by inducing PGE(2) synthesis and augmenting e-NOS/i-NOS ratio.

  5. Ulcer healing after peripheral intervention-can we predict it before revascularization?

    PubMed

    Azuma, Nobuyoshi; Koya, Atsuhiro; Uchida, Daiki; Saito, Yukihiro; Uchida, Hisashi

    2014-01-01

    Complete ulcer healing is one of the most important goals of treatment for critical limb ischemia; however, it is still difficult to inform patients of the time to ulcer healing before performing revascularization. The time to ulcer healing has a great impact on the cost of treatment and patient's quality of life. To predict it, the factors that influence delayed ulcer healing should be explored. According to a review of the literature investigating ulcer healing after revascularization, the influential factors can be classified into 5 categories: (1) systemic factors; (2) clinical state of tissue defect; (3) infection; (4) wound management strategy; and (5) revascularization strategy (endovascular or open repair, the angiosome concept). It is also important to ensure sufficient blood supply to predict ulcer healing probability in the individual patient. Several new methodologies, such as measuring tissue circulation around the tissue defect and intraoperative imaging techniques, have been reported. Because the status of ischemic tissue loss and wound healing ability can affect the decision-making process in selecting the revascularization strategy, understanding the many factors that influence ulcer healing after revascularization is indispensable for physicians performing revascularization. Accumulating ulcer healing data via well-designed clinical research can help to establish a new paradigm for the revascularization strategy from the viewpoint of ulcer healing.

  6. Healing process of venous ulcers: the role of microcirculation.

    PubMed

    Ambrózy, Ewald; Waczulíková, Iveta; Willfort, Andrea; Böhler, Kornelia; Cauza, Karla; Ehringer, Herbert; Heinz, Gottfried; Koppensteiner, Renate; Marić, Snezana; Gschwandtner, Michael E

    2013-02-01

    In order to describe adequately the process of healing in the intermediate degrees, we investigated microcirculatory changes in the venous ulcers at well-defined stages of wound repair. We investigated dynamic changes in microcirculation during the healing process of venous ulcers. Ten venous ulcers were investigated in three consecutive clinical stages of wound healing: non granulation tissue (NGTA), GTA and scar. Subpapillary microcirculation was measured by laser Doppler perfusion (LDP) imaging and expressed using LDP values in arbitrary units. Nutritive perfusion by capillary microscopy and expressed as capillary density (CD) - the number of capillaries per square millimetre. Before the development of GTA the LDP was low (median 1·35; lower-upper quartiles 0·71-1·83) accompanied with zero CD in all but one patient who had a density of 1. With the first appearance of GTA in the same area, the LDP was improved (2·22; 1·12-2·33; P = 0·0024) when compared with NGTA, in combination with a significant increase in CD (1·75; 0-3; P = 0·0054). In scar, the LDP was similar to that in the NGTA (1·03; 0·77-1·83; P = 0·278), combined with the highest CD (5·75; 4·5-8) in comparison with the previous stages of the area (for both pairs, P < 0·0001). Venous ulcers are caused by poor nutritive and subpapillary perfusion. Subpapillary perfusion plays a major role in the formation of GTA. In a scar, the increased nutritive perfusion is sufficient to cover the blood supply and keep skin viable while subpapillary perfusion is low.

  7. Acceleration Of Wound Healing Ny Photodynamic Therapy

    SciTech Connect

    Hasan, Tayyaba; Hamblin, Michael R.; Trauner, Kenneth

    2000-08-22

    Disclosed is a method for accelerating wound healing in a mammal. The method includes identifying an unhealed wound site or partially-healed wound site in a mammal; administering a photosensitizer to the mammal; waiting for a time period wherein the photosensitizer reaches an effective tissue concentration at the wound site; and photoactivating the photosensitizer at the wound site. The dose of photodynamic therapy is selected to stimulate the production of one or more growth factor by cells at the wound site, without causing tissue destruction.

  8. Factors That Influence Perforator Thrombosis and Predict Healing Perforator Sclerotherapy for Venous Ulceration Without Axial Reflux

    PubMed Central

    Kiguchi, Misaki M.; Hager, Eric S.; Winger, Daniel G.; Hirsch, Stanley A.; Chaer, Rabih A.; Dillavou, Ellen D.

    2014-01-01

    OBJECTIVES Refluxing perforators contribute to venous ulceration. We sought to describe patient characteristics and procedural factors that (1) impact rates of incompetent perforator vein (IPV) thrombosis with ultrasound-guided sclerotherapy (UGS) and (2) impact the healing of venous ulcers (CEAP 6) without axial reflux. METHODS Retrospective review of UGS of IPV injections from 1/2010–11/2012 identified 73 treated venous ulcers in 62 patients. Patients had no other superficial/axial reflux and were treated with standard wound care and compression. Ultrasound was used to screen for refluxing perforators near ulcer(s), and these were injected with sodium tetradecyl sulfate or polidocanol foam and assessed for thrombosis at 2 weeks. Demographic data, comorbidities, treatment details and outcomes were analyzed. Univariate and multivariable modeling was performed to determine covariates predicting IPV thrombosis and ulcer healing. RESULTS 62 patients with active ulcers for an average of 28 months with compression therapy prior to perforator treatment had an average age of 57.1 years, were 55% male, 36% had a history of DVT and 30% had deep venous reflux. 32 patients (52%) healed ulcers, while 30 patients (48%) had non-healed ulcer(s) in mean follow-up of 30.2 months. Ulcers were treated with 189 injections, with average thrombosis rate of 54%. Of 73 ulcers, 43 ulcers healed (59%), and 30 ulcers did not heal (41%). Patients that healed ulcers had an IPV thrombosis rate of 69 % vs. 38% in patients who did not heal (P<.001). Multivariate models demonstrated male gender and warfarin use negatively predicted thrombosis of IPVs (P=.03, P=.01). Multivariate model for ulcer healing found complete IPV thrombosis was a positive predictor (P=.02), while large initial ulcer area was a negative predictor (P=.08). Increased age was associated with fewer ulcer recurrences (P=.05). Hypertension and increased follow-up time predicted increased ulcer recurrences (P=.04, P=.02). Calf

  9. [Melatonin as a therapeutic factor in gastric ulcer healing under experimental diabetes].

    PubMed

    Magierowski, Marcin; Jasnos, Katarzyna; Brzozowska, Iwona; Drozdowicz, Danuta; Sliwowski, Zbigniew; Nawrot, Elizbieta; Szczyrk, Urszula; Kwiecień, Sławomir

    2013-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is a hormon secreted mostly by the pineal gland in the brain which maintains the body's circadian rhythm. Interestingly, this indol derivative is produced by enterochromaffin-like cells (ECL) in the gastrointestinal tract (GIT) in amount about 400 fold greater than detected in the pinealocytes. Previous studies revealed that melatonin exerts beneficial action against acute gastric damage induced by stress ethanol, aspirin and ischemia-reperfusion. Hyperglycemia, which is the main symptom of diabetes mellitus, is known to induce mitochondrial dysfunction and endoplasmic reticulum stress, both promoting the generation of reactive oxygen species (ROS). ROS were shown to exhibit higher activity than molecular oxygen under basal conditions due to unpaired electron in its outermost shell of electrons. ROS lead to damage of cellular proteins, nucleic acids and membrane polyunsaturated fatty lipids. In this study, we induced diabetes mellitus by the application of strep. tozocin in presence of gastric ulcers. Male Wistar rats were used in this model. 9 days after gastric ulcers and diabetes mellitus induction, groups of rats were treated with saline or melatonin (20 mg/kg i.g.). At the termination of the experiment, rats were anesthetized, abdomen was opened and gastric blood flow (GBF) was measured. Stomachs were removed for determination of gastric ulcers area by planimetry. Tissue samples were collected for biochemical assays. We demonstrated that melatonin significantly accelerates gastric ulcers healing with and without coexistence of diabetes mellitus. This effect was accompanied by increase of GBF level. Moreover, we observed an increase in superoxide dismutase (SOD) activity and an decrease in lipid peroxidation products concentration within gastric tissue homogenates of animals treated with melatonin, as compared with control group. Melatonin application accelerates gastric ulcers healing with and without presence of

  10. New insight into non-healing corneal ulcers: iatrogenic crystals

    PubMed Central

    Livingstone, I; Stefanowicz, F; Moggach, S; Connolly, J; Ramamurthi, S; Mantry, S; Ramaesh, K

    2013-01-01

    Aims To characterise and correlate crystalline precipitations implicated in non-healing corneal ulceration in two patients with a previous history of acanthamoeba keratitis. Materials and methods Persistence of acanthamoeba and secondary bacterial infection was excluded with negative corneal scrapes. Confocal microscopy identified crystal-like deposits within the corneal stroma. To investigate possible precipitating combinations, all concurrent treatments at the time of presentation were mixed in wells, with observation of precipitate formation. Precipitates were observed with phase-contrast microscopy, and subsequently characterised via crystallography techniques and electrospray ionisation mass spectrometry. Results Combinations of dexamethasone 0.1% minims and chlorhexidine gluconate 0.2% formed an amorphous material characterised by electrospray ionisation mass spectrometry as an insoluble chlorhexidine salt. Combinations of chloramphenicol drops and timolol 0.5% formed a crystal identified via X-ray crystallography as santite (K(B5O6(OH)4).(H2O)2). This is a borate mineral identified in nature, arising from thermal springs, but never reported in biological tissues. Clinical improvement was observed following the cessation of the implicated precipitating combinations. Conclusion Our observations suggest iatrogenic precipitate formation, with a potential deleterious effect upon healing. The substrates for these precipitates include several frequently prescribed topical ophthalmic treatments. These findings shed new light on the aetiopathogenesis of non-healing corneal ulceration, and have broad implications on topical prescribing for this challenging condition. PMID:23558213

  11. Acceleration of cutaneous wound healing by brassinosteroids.

    PubMed

    Esposito, Debora; Rathinasabapathy, Thirumurugan; Schmidt, Barbara; Shakarjian, Michael P; Komarnytsky, Slavko; Raskin, Ilya

    2013-01-01

    Brassinosteroids are plant growth hormones involved in cell growth, division, and differentiation. Their effects in animals are largely unknown, although recent studies showed that the anabolic properties of brassinosteroids are possibly mediated through the phosphoinositide 3-kinase/protein kinase B signaling pathway. Here, we examined biological activity of homobrassinolide (HB) and its synthetic analogues in in vitro proliferation and migration assays in murine fibroblast and primary keratinocyte cell culture. HB stimulated fibroblast proliferation and migration and weakly induced keratinocyte proliferation in vitro. The effects of topical HB administration on progression of wound closure were further tested in the mouse model of cutaneous wound healing. C57BL/6J mice were given a full-thickness dermal wound, and the rate of wound closure was assessed daily for 10 days, with adenosine receptor agonist CGS-21680 as a positive control. Topical application of brassinosteroid significantly reduced wound size and accelerated wound healing in treated animals. mRNA levels of transforming growth factor beta and intercellular adhesion molecule 1 were significantly lower, while tumor necrosis factor alpha was nearly suppressed in the wounds from treated mice. Our data suggest that topical application of brassinosteroids accelerates wound healing by positively modulating inflammatory and reepithelialization phases of the wound repair process, in part by enhancing Akt signaling in the skin at the edges of the wound and enhancing migration of fibroblasts in the wounded area. Targeting this signaling pathway with brassinosteroids may represent a promising approach to the therapy of delayed wound healing.

  12. Calf muscle pump impairment and delayed healing of venous leg ulcers: air plethysmographic findings.

    PubMed

    Simka, Marian

    2007-08-01

    There is a need for a diagnostic tool to predict clinical outcome of venous leg ulcer patients, as the prognosis of healing based on clinical data alone has not appeared to be satisfactory. Air plethysmographic assessment of calf muscle pump was performed in the supine and upright position in 129 patients with active ulcers on their legs. All patients were managed in a specialized leg ulcer clinic. Results of air plethysmography were compared to clinical data and time of healing of ulcers. Muscle pump failure was found in 42.6% of extremities (supine position, 33.3%; upright, 22.5%; both, 12.4%). Patients with insufficient pump were older, and their ulcers were larger. Failure of pump was found more often in patients who began the treatment after long, unsuccessful, non-specialized care. Healing time of ulcers was prolonged in cases with insufficient pump. Regarding the subgroups with good clinical prognosis (patients with small ulcers or with a short history of ulceration), it was found that insufficiency of muscle pump correlated with delayed healing. It could be summarized that venous leg ulcers associated with calf muscle failure were larger, long-standing, and that their healing even after specialized treatment was delayed. Impaired muscle pump function revealed in plethysmographic examination can be a prognostic factor of delayed healing of leg ulcer. Ulcers with poor prognosis according to plethysmographic findings, and no quick recovery after standard management, should be considered for advanced therapies.

  13. Epidermal growth factor (EGF) in the gastroprotective and ulcer healing actions of colloidal bismuth subcitrate (De-Nol) in rats.

    PubMed Central

    Konturek, S J; Dembinski, A; Warzecha, Z; Bielanski, W; Brzozowski, T; Drozdowicz, D

    1988-01-01

    Colloidal bismuth subcitrate (CBS; De-Nol) exhibits gastroprotective properties in experimental animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether epidermal growth factor (EGF), which also has gastroprotective and ulcer healing properties, contributes to the action of De-Nol on the stomach in rats. It was found that De-Nol protects the gastric mucosa against ethanol damage and that this is accompanied by increased mucosal generation of prostaglandins (PG). Removal of the endogenous source of EGF (sialoadenectomy) did not significantly decrease the protective and PG stimulating effects of De-Nol. Pretreatment with exogenous EGF partially protected the stomach against ethanol injury, but did not influence the protective action of De-Nol in sialoadenectomised animals. De-Nol, like EGF given orally, enhanced the healing of chronic gastric and duodenal ulcers induced by serosal acetic acid. De-Nol was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer area. Thus the peptide is available locally in high concentrations to accelerate the re-epithelialisation and tissue repair of the ulcerated mucosa. These ulcer healing effects of De-Nol were reduced by sialoadenectomy and restored in part by oral administration of EGF. We conclude that salivary glands in rats are not essential for the gastroprotection induced by De-Nol, but seem to play an important role in the ulcer healing action of this drug possibly via an EGF mediated mechanism. PMID:3260885

  14. Dipeptidyl peptidase IV inhibition prevents the formation and promotes the healing of indomethacin-induced intestinal ulcers in rats

    PubMed Central

    Inoue, Takuya; Higashiyama, Masaaki; Kaji, Izumi; Rudenkyy, Sergiy; Higuchi, Kazuhide; Guth, Paul H.; Engel, Eli; Kaunitz, Jonathan D; Akiba, Yasutada

    2014-01-01

    Backgrounds & Aims We studied the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) as a possible therapy for non-steroidal anti-inflammatory drug (NSAID)-induced intestinal ulcers. Luminal nutrients release endogenous GLP-2 from enteroendocrine L cells. Since GLP-2 is degraded by dipeptidyl peptidase IV (DPPIV), we hypothesized that DPPIV inhibition combined with luminal administration of nutrients potentiates the effects of endogenous GLP-2 on intestinal injury. Methods Intestinal injury was induced by indomethacin (10 mg/kg, sc) in fed rats. The long-acting DPPIV inhibitor K579 was intragastrically (ig) or intraperitoneally (ip) given before or after indomethacin treatment. L-alanine (L-Ala) and 5′-inosine monophosphate (IMP) were co-administered ig after the treatment. Results Indomethacin treatment induced intestinal ulcers which gradually healed after treatment. Pretreatment with ig or ip K579 given either at 1 mg/kg reduced total ulcer length, whereas K579 at 3 mg/kg had no effect. Exogenous GLP-2 also reduced intestinal ulcers. The preventive effect of K579 was dose-dependently inhibited by a GLP-2 receptor antagonist. Daily treatment with K579 (1 mg/kg), GLP-2, or L-Ala + IMP after indomethacin treatment reduced total ulcer length. Co-administration (ig) of K579 and L-Ala + IMP further accelerated intestinal ulcer healing. Conclusion DPPIV inhibition and exogenous GLP-2 prevented the formation and promoted the healing of indomethacin-induced intestinal ulcers, although high-dose DPPIV inhibition reversed the preventive effect. Umami receptor agonists also enhanced the healing effects of the DPPIV inhibitor. The combination of DPPIV inhibition and luminal nutrient-induced GLP-2 release may be a useful therapeutic tool for the treatment of NSAIDs-induced intestinal ulcers. PMID:24379150

  15. Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing

    PubMed Central

    Henshaw, F. R.; Boughton, P.; Lo, L.; McLennan, S. V.; Twigg, S. M.

    2015-01-01

    Aims/Hypothesis. Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Methods. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid. Results. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Wound α-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r = 0.406; P < 0.001). Conclusions/Interpretation. These data collectively increasingly substantiate a functional role for CTGF in human diabetic foot ulcers. PMID:25789327

  16. Do Capacity Coupled Electric Fields Accelerate Tibial Stress Fracture Healing

    DTIC Science & Technology

    2006-12-01

    DAMD17-98-1-8519 TITLE: Do Capacity Coupled Electric Fields Accelerate Tibial Stress Fracture Healing PRINCIPAL INVESTIGATOR...2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Do Capacity Coupled Electric Fields Accelerate Tibial Stress Fracture Healing 5b. GRANT NUMBER...To determine the effect of capacitively coupled electric field stimulation on tibial stress fracture healing in men and women. Methods: A

  17. Comparison of cimetidine and tripotassium dicitrato bismuthate in healing and relapse of duodenal ulcers.

    PubMed

    Shreeve, D R; Klass, H J; Jones, P E

    1983-01-01

    A comparison between cimetidine and tripotassium dicitrato bismuthate liquid (TDB) in the treatment of endoscopically diagnosed duodenal ulcer by single-blind randomized trial in 48 patients has shown 18 (75%) out of 24 patients receiving TDB and 13 (54%) out of 24 patients receiving cimetidine healed after 4 weeks' therapy. Symptomatic improvement within 1 month was seen in 19 patients on TDB and 18 patients on cimetidine, but did not only occur in patients whose ulcers healed. On follow-up, endoscopically proven relapse occurred within 1 year in 47% of patients whose ulcers had healed during treatment with TDB in comparison with 60% of those healing on cimetidine.

  18. The efficacy of topical Royal Jelly on diabetic foot ulcers healing: A case series*

    PubMed Central

    Siavash, Mansour; Shokri, Saeideh; Haghighi, Sepehr; Mohammadi, Mahbubeh; Shahtalebi, Mohammad Ali; Farajzadehgan, Ziba

    2011-01-01

    BACKGROUND: Foot ulcers and infections are the major sources of morbidity in individuals with diabetes mellitus. This study aimed to evaluate the efficacy of topical Royal Jelly (a worker honey bee product) on healing diabetic foot ulcers. METHODS: Diabetic patients with foot ulcers that were referred to our clinic at Khorshid Hospital, Isfahan, Iran; were evaluated three times a week and treated according to standard treatments consisted of offloading, infection control, vascular improvement and debridement if required. In addition, all ulcers were measured and then topical sterile 5% Royal Jelly was applied on the total surface area of the wounds. Eventually, they were covered with sterile dressings. Each patient was followed for a period of three months or until the complete healing. RESULTS: A total of eight patients were enrolled in this study. Of these, two had two ulcers and, therefore, ten ulcers were evaluated. Two ulcers were excluded. Seven of the remained eight ulcers healed. Mean duration of complete healing was 41 days. One ulcer did not completely heal but improved to 40% smaller in length, 32% in width and 28% in depth. The mean length, width and depth reduction rates were 0.35 mm/day, 0.28 mm/day and 0.11 mm/day, respectively. CONCLUSIONS: Royal Jelly dressing may be an effective method for treating diabetic foot ulcers besides standard treatments. PMID:22279458

  19. Enhancement of Gastric Ulcer Healing and Angiogenesis by Hepatocyte Growth Factor Gene Mediated by Attenuated Salmonella in Rats

    PubMed Central

    2017-01-01

    The present study developed an oral hepatocyte growth factor (HGF) gene therapy strategy for gastric ulcers treatment. An attenuated Salmonella typhimurium that stably expressed high HGF (named as TPH) was constructed, and the antiulcerogenic effect of TPH was evaluated in a rat model of gastric ulcers that created by acetic acid subserosal injection. From day 5 after injection, TPH (1 × 109 cfu), vehicle (TP, 1 × 109 cfu), or sodium bicarbonate (model control) was administered orally every alternate day for three times. Then ulcer size was measured at day 21 after ulcer induction. The ulcer area in TPH-treated group was 10.56 ± 3.30 mm2, which was smaller when compared with those in the TP-treated and model control groups (43.47 ± 4.18 and 56.25 ± 6.38 mm2, respectively). A higher level of reepithelialization was found in TPH-treated group and the crawling length of gastric epithelial cells was significantly longer than in the other two groups (P < 0.05). The microvessel density in the ulcer granulation tissues of the TPH-treated rats was 39.9 vessels/mm2, which was greater than in the TP-treated and model control rats, with a significant statistical difference. These results suggest that TPH treatment significantly accelerates the healing of gastric ulcers via stimulating proliferation of gastric epithelial cells and enhancing angiogenesis on gastric ulcer site. PMID:28049228

  20. Chitosan-alginate membranes accelerate wound healing.

    PubMed

    Caetano, Guilherme Ferreira; Frade, Marco Andrey Cipriani; Andrade, Thiago Antônio Moretti; Leite, Marcel Nani; Bueno, Cecilia Zorzi; Moraes, Ângela Maria; Ribeiro-Paes, João Tadeu

    2015-07-01

    The purpose of this study was to evaluate the efficacy of chitosan-alginate membrane to accelerate wound healing in experimental cutaneous wounds. Two wounds were performed in Wistar rats by punching (1.5 cm diameter), treated with membranes moistened with saline solution (CAM group) or with saline only (SL group). After 2, 7, 14, and 21 days of surgery, five rats of each group were euthanized and reepithelialization was evaluated. The wounds/scars were harvested for histological, flow cytometry, neutrophil infiltrate, and hydroxyproline analysis. CAM group presented higher inflammatory cells recruitment as compared to SL group on 2(nd) day. On the 7(th) day, CAM group showed higher CD11b(+) level and lower of neutrophils than SL group. The CAM group presented higher CD4(+) cells influx than SL group on 2(nd) day, but it decreased during the follow up and became lower on 14(th) and 21(st) days. Higher fibroplasia was noticed on days 7 and 14 as well as higher collagenesis on 21(st) in the CAM group in comparison to SL group. CAM group showed faster reepithelialization on 7(th) day than SL group, although similar in other days. In conclusion, chitosan-alginate membrane modulated the inflammatory phase, stimulated fibroplasia and collagenesis, accelerating wound healing process in rats.

  1. Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

    PubMed Central

    Sun, Chenglin

    2017-01-01

    Mesenchymal stem cells (MSCs), an ideal cell source for regenerative therapy with no ethical issues, play an important role in diabetic foot ulcer (DFU). Growing evidence has demonstrated that MSCs transplantation can accelerate wound closure, ameliorate clinical parameters, and avoid amputation. In this review, we clarify the mechanism of preclinical studies, as well as safety and efficacy of clinical trials in the treatment of DFU. Bone marrow-derived mesenchymal stem cells (BM-MSCs), compared with MSCs derived from other tissues, may be a suitable cell type that can provide easy, effective, and cost-efficient transplantation to treat DFU and protect patients from amputation. PMID:28386568

  2. Treatment of a Non-Healing Diabetic Foot Ulcer With Platelet-Rich Plasma

    PubMed Central

    Suresh, Deepak H; Suryanarayan, Shwetha; Sarvajnamurthy, Sacchidanand; Puvvadi, Srikanth

    2014-01-01

    Lower extremity ulcers and amputations are an increasing problem among individuals with diabetes. Among diabetes mellitus-related complications, foot ulceration is the most common, affecting approximately 15% of diabetic patients during their lifetime. The pathogenesis of diabetic ulcer is peripheral sensory neuropathy, calluses, oedema and peripheral vascular disease. Diabetic ulcer is managed by adequate control of infections and blood sugar levels, surgical debridement with various dressings and off loading of the foot from pressure. In spite of these standard measures, some recalcitrant non-healing ulcers need additional growth factors for healing. Autologous platelet-rich plasma is easy and cost-effective method in treating diabetic ulcers as it provides necessary growth factors which enhance healing. PMID:25722604

  3. [Is the successful eradication of Helicobacter pylori sufficient for the healing of peptic ulcer?].

    PubMed

    Pregun, István; Herszényi, László; Juhász, Márk; Miheller, Pál; Tulassay, Zsolt

    2006-03-12

    Helicobacter pylori has a major role in the pathogenesis of peptic ulcer disease. Cure of the infection is essential in ulcer healing, but an additional PPI therapy after completing eradication treatment is widespread in clinical practice. In the present work clinical studies evaluating peptic ulcer healing followed or not by PPI treatment after eradication therapy were analyzed. The results of these trials are concordant that only a minority of patients with duodenal ulcer would benefit from prolonged acid suppressive treatment, a successful eradication therapy (that counts for a large proportion) is sufficient. There are less data available concerning gastric ulcer: successful eradication is also essential to ulcer healing and to avoid relapse, however it seems that post-eradication PPI therapy might be beneficial.

  4. Platelets modulate gastric ulcer healing: role of endostatin and vascular endothelial growth factor release.

    PubMed

    Ma, L; Elliott, S N; Cirino, G; Buret, A; Ignarro, L J; Wallace, J L

    2001-05-22

    Bleeding and delayed healing of ulcers are well recognized clinical problems associated with the use of aspirin and other nonsteroidal antiinflammatory drugs, which have been attributed to their antiaggregatory effects on platelets. We hypothesized that antiplatelet drugs might interfere with gastric ulcer healing by suppressing the release of growth factors, such as vascular endothelial growth factor (VEGF), from platelets. Gastric ulcers were induced in rats by serosal application of acetic acid. Daily oral treatment with vehicle, aspirin, or ticlopidine (an ADP receptor antagonist) was started 3 days later and continued for 1 week. Ulcer induction resulted in a significant increase in serum levels of VEGF and a significant decrease in serum levels of endostatin (an antiangiogenic factor). Although both aspirin and ticlopidine markedly suppressed platelet aggregation, only ticlopidine impaired gastric ulcer healing and angiogenesis as well as reversing the ulcer-associated changes in serum levels of VEGF and endostatin. The effects of ticlopidine on ulcer healing and angiogenesis were mimicked by immunodepletion of circulating platelets, and ticlopidine did not influence ulcer healing when given to thrombocytopenic rats. Incubation of human umbilical vein endothelial cells with serum from ticlopidine-treated rats significantly reduced proliferation and increased apoptosis, effects reversed by an antibody directed against endostatin. Ticlopidine treatment resulted in increased platelet endostatin content and release. These results demonstrate a previously unrecognized contribution of platelets to the regulation of gastric ulcer healing. Such effects likely are mediated through the release from platelets of endostatin and possibly VEGF. As shown with ticlopidine, drugs that influence gastric ulcer healing may do so in part through altering the ability of platelets to release growth factors.

  5. Reduction of diabetic foot ulcer healing times through use of advanced treatment modalities.

    PubMed

    Mulder, Gerit; Tenenhaus, Mayer; D'Souza, Gehaan F

    2014-12-01

    Diabetic wounds are a major health care problem associated with delayed healing and high amputation rates. This review systematically evaluated newer wound care therapies for the treatment of diabetic wounds. More recent means of approaching diabetic foot ulcers include various dressings, off-loading shoes, and bioengineered skin constructs and growth factors. Electrical stimulation, phototherapy, electromagnetic fields, and shockwave therapy have been further proposed as potential treatments. A brief overview of these treatments is presented using peer-reviewed evidenced-based literature. A review of the literature demonstrated that treatment of diabetic wounds has focused on either prevention of the wounds in the form of off-loading shoes or adequate protective dressings or on direct treatment of wounds with bioengineered skin constructs, growth factors, or medical devices that accelerate wound healing. The authors' conclusion, following extensive literature review, is that although excellent national and international guidelines exist regarding suggested approaches to the treatment of the diabetic foot ulcer, there is no definitive or universal consensus on the choice of specific treatment modalities. The importance of optimizing comorbidities and the disease state, hemodynamics, local and peripheral skin and wound care, and metabolic challenges while reducing biological and bacterial burden and minimizing trauma remain the primary approach, followed by choice of the most appropriate treatment material or product.

  6. Topical Administration of Pirfenidone Increases Healing of Chronic Diabetic Foot Ulcers: A Randomized Crossover Study.

    PubMed

    Janka-Zires, Marcela; Almeda-Valdes, Paloma; Uribe-Wiechers, Ana Cecilia; Juárez-Comboni, Sonia Citlali; López-Gutiérrez, Joel; Escobar-Jiménez, Jarod Jazek; Gómez-Pérez, Francisco J

    2016-01-01

    Only 30 percent of chronic diabetic foot ulcers heal after 20 weeks of standard treatment. Pirfenidone is a drug with biological, anti-inflammatory, and antifibrotic effects. The aim of this study was to evaluate the effect of topical pirfenidone added to conventional treatment in noninfected chronic diabetic foot ulcers. This was a randomized crossover study. Group 1 received topical pirfenidone plus conventional treatment for 8 weeks; after this period, they were switched to receive conventional treatment only for 8 more weeks. In group 2, the order of the treatments was the opposite. The end points were complete ulcer healing and size reduction. Final data were obtained from 35 ulcers in 24 patients. Fifty-two percent of ulcers treated with pirfenidone healed before 8 weeks versus 14.3% treated with conventional treatment only (P = 0.025). Between 8 and 16 weeks, 30.8% ulcers that received pirfenidone healed versus 0% with conventional treatment (P = 0.081). By week 8, the reduction in ulcer size was 100% [73-100] with pirfenidone versus 57.5% with conventional treatment [28.9-74] (P = 0.011). By week 16, the reduction was 93% [42.7-100] with pirfenidone and 21.8% [8-77.5] with conventional treatment (P = 0.050). The addition of topical pirfenidone to conventional treatment significantly improves the healing of chronic diabetic noninfected foot ulcers.

  7. Topical Administration of Pirfenidone Increases Healing of Chronic Diabetic Foot Ulcers: A Randomized Crossover Study

    PubMed Central

    Janka-Zires, Marcela; Uribe-Wiechers, Ana Cecilia; Juárez-Comboni, Sonia Citlali; López-Gutiérrez, Joel; Escobar-Jiménez, Jarod Jazek; Gómez-Pérez, Francisco J.

    2016-01-01

    Only 30 percent of chronic diabetic foot ulcers heal after 20 weeks of standard treatment. Pirfenidone is a drug with biological, anti-inflammatory, and antifibrotic effects. The aim of this study was to evaluate the effect of topical pirfenidone added to conventional treatment in noninfected chronic diabetic foot ulcers. This was a randomized crossover study. Group 1 received topical pirfenidone plus conventional treatment for 8 weeks; after this period, they were switched to receive conventional treatment only for 8 more weeks. In group 2, the order of the treatments was the opposite. The end points were complete ulcer healing and size reduction. Final data were obtained from 35 ulcers in 24 patients. Fifty-two percent of ulcers treated with pirfenidone healed before 8 weeks versus 14.3% treated with conventional treatment only (P = 0.025). Between 8 and 16 weeks, 30.8% ulcers that received pirfenidone healed versus 0% with conventional treatment (P = 0.081). By week 8, the reduction in ulcer size was 100% [73–100] with pirfenidone versus 57.5% with conventional treatment [28.9–74] (P = 0.011). By week 16, the reduction was 93% [42.7–100] with pirfenidone and 21.8% [8–77.5] with conventional treatment (P = 0.050). The addition of topical pirfenidone to conventional treatment significantly improves the healing of chronic diabetic noninfected foot ulcers. PMID:27478849

  8. Healing of aspirin-associated peptic ulcer disease despite continued salicylate ingestion.

    PubMed

    O'Laughlin, J C; Silvoso, G R; Ivey, K J

    1981-05-01

    Patients who have rheumatic disease and who are undergoing long-term aspirin therapy have a high incidence of peptic ulcer disease. Whether it is possible to heal long-term aspirin-related peptic ulcer disease if aspirin intake is continued is unknown. Nine patients with rheumatic disease who were receiving long-term aspirin therapy and who had 15 endoscopically verified gastric and/or duodenal ulcers were studied. Patients were treated daily with 1,200 mg of cimetidine plus at least 120 mL of antacid (Mylanta II), while continuing aspirin therapy at the same dose and type. By eight weeks, 14 ulcers had healed. This study shows that some aspirin-associated peptic ulcers can be healed, despite continued aspirin intake, by intensive medical therapy aimed at lowering intragastric acidity.

  9. Accelerated healing of excisional skin wounds by PL 14736 in alloxan-hyperglycemic rats.

    PubMed

    Seveljević-Jaran, D; Cuzić, S; Dominis-Kramarić, M; Glojnarić, I; Ivetić, V; Radosević, S; Parnham, M J

    2006-01-01

    PL 14736 is a synthetic peptide, originally isolated from human gastric juice, that has anti-inflammatory and tissue-protective actions in experimental models of gastrointestinal inflammation. To investigate its possible benefit in poorly healing skin wounds, the effects of the topical application of PL 14736 in a gel formulation have been studied on full-thickness excisional wounds in rats, either healthy or made hyperglycemic by alloxan (175 mg/kg s.c.) 5 days previously. The effects of becaplermin gel (platelet-derived growth factor, PDGF-BB, Regranex, a standard therapy for diabetic foot ulcers, were investigated for comparison. Healing was evaluated for up to 7 days after wounding, using digital planimetry analysis, macroscopic scoring and histology. While healing was too rapid in healthy rats to observe enhancement by either treatment, in the hyperglycemic rats which exhibited delayed healing, PL 14736 (10-1,000 microg/wound) produced a dose-dependent acceleration of wound healing (determined by macroscopic scoring) equivalent at the highest doses to that observed with becaplermin. The beneficial effect on healing was associated with increased deposition of organized granulation tissue by day 7 for both PL 14736 and becaplermin, as determined histologically. PL 14736 tended to have a greater effect than becaplermin on the formation of granulation tissue containing mature collagen. Wound contraction, as measured by planimetry, was not significantly affected. In conclusion, topical PL 14736 produces a dose-dependent acceleration of deficient skin wound healing in hyperglycemic rats by facilitating granulation tissue formation, similar to the response seen with topical becaplermin, the standard therapy for diabetic skin wounds. PL 14736 may represent an alternative therapy for delayed wound healing, such as that seen with diabetic foot ulcers, without the proliferative concerns or immunogenicity associated with growth factors.

  10. Effect of Infrared Radiation on the Healing of Diabetic Foot Ulcer

    PubMed Central

    Hakim, Ashrafalsadat; Sadeghi Moghadam, Ali; Shariati, Abdalali; karimi, Hamid; Haghighizadeh, Mohamad Hossien

    2016-01-01

    Background Diabetic foot ulcer is a worldwide health care concern affecting tens of thousands of patients. If these ulcers left untreated, they can create severe complications. Objectives This study was designed to examine the effect of infrared radiation on the healing of diabetic foot ulcer. Patients and Methods This clinical trial was performed on 50 patients referred to Dr. Ganjavian hospital in Dezful city, Iran, with diabetic foot ulcer degree 1 and 2 (based on Wegener Scale). Sample size was determined based on relevant studies of the recent decade. Patients were classified into the intervention and control groups (n = 25 in each group) in terms of age, gender, degree of ulcer, ulcer site and body mass index. In this study, work progress was evaluated according to the checklist of diabetic foot ulcer healing evaluation. Results The results of the current study showed that there was a statistically significant difference in healing ulcers (P < 0.05) and mean healing time (P < 0.05) between the two groups. Conclusions Using the infrared plus routine dressing is more effective than using merely routine dressing. PMID:27942260

  11. Omeprazole versus famotidine in the healing and relapse of duodenal ulcer.

    PubMed

    Misra, S C; Dasarathy, S; Sharma, M P

    1993-08-01

    Sixty patients with symptomatic duodenal ulcer were randomized to receive either omeprazole (20 mg each morning) or famotidine (40 mg at night time) for 2-4 weeks in a double-blind parallel group clinical trial. Healing rates were higher with omeprazole in comparison with famotidine after 2 weeks (77% vs. 40%, P < 0.001) and 4 weeks (93% vs. 80%, P = 0.2) of treatment. Assessment of daily diary cards completed by all patients revealed that omeprazole rapidly relieved ulcer-related day pain and nocturnal pain in comparison to famotidine. Treatment with omeprazole for 2 weeks was also associated with lower cumulative antacid intake (P < 0.05) and reduced absenteeism from work. Helicobacter pylori infection was present in all patients and remained unaffected by treatment with either of the drugs. None of the drugs produced any significant adverse effects. During 6 months follow-up of all the patients after ulcer healing (without maintenance therapy), ulcer relapse was seen in 40% of omeprazole- and 37% of famotidine-treated patients (P > 0.1). The duration of ulcer-free period following initial healing of ulcer was also similar in both the groups (median time: 22 weeks for omeprazole, 21 weeks for famotidine). We conclude that omeprazole is superior to famotidine in rapidly healing duodenal ulcers and achieving more rapid pain relief, but does not influence subsequent ulcer relapse.

  12. High probability of healing without amputation of plantar forefoot ulcers in patients with diabetes.

    PubMed

    Örneholm, Hedvig; Apelqvist, Jan; Larsson, Jan; Eneroth, Magnus

    2015-01-01

    Diabetic foot ulcer is an important entity which in many cases is the first serious complication in diabetes. Although a plantar forefoot location is common, there are few studies on larger cohorts and in such studies there is often a combination of various types of ulcer and ulcer locations. The purpose of this study is to discern the outcome of plantar forefoot ulcers and their specific characteristics in a large cohort. All patients (n = 770), presenting with a plantar forefoot ulcer at a multidisciplinary diabetes foot clinic from January 1, 1983 to December 31, 2012 were considered for the study. Seven hundred one patients (median age 67 [22-95]) fulfilled the inclusion criteria and were followed according to a preset protocol until final outcome (healing or death). Severe peripheral vascular disease was present in 26% of the patients and 14% had evidence of deep infection upon arrival at the foot clinic. Fifty-five percent (385/701) of the patients healed without foot surgery, 25% (173/701) healed after major debridement, 9% (60/701) healed after minor or major amputation and 12% (83/701) died unhealed. Median healing time was 17 weeks. An ulcer classified as Wagner grade 1 or 2 at inclusion and independent living were factors associated with a higher healing rate. Seventy-nine percent of 701 patients with diabetes and a plantar forefoot ulcer treated at a multidisciplinary diabetes foot clinic healed without amputation. For one third some form of foot surgery was needed to achieve healing.

  13. Ulcer healing potential of ethanolic extract of Caralluma attenuata on experimental diabetic rats

    PubMed Central

    Garg, Sunil; Srivastava, Sajal; Singh, Kisanpal; Sharma, Alok; Garg, Kavita

    2016-01-01

    Introduction: Available data indicated that diabetes mellitus (DM) increases the vulnerability of the gastric ulcers and the need of the hour is to develop effective agents to treat ulcer with diabetes for better patient compliance and cost effectiveness. The ulcer-healing properties of ethanolic extract of Caralluma attenuata (CAEt) against both chemically- and physically induced gastric ulcers in experimental rats are recently studied. Aim: To assess the ulcer healing potential of Ethanolic Extract of Caralluma attenuata on Experimental Diabetic Rats. Material and Methods: The current study aimed to evaluate ulcer healing properties of CAEt on the aspirin induced gastric ulcer in rats with streptozotocin induced DM. The hypothesis is based on the fact that DM results in compromising the mucosal defensive factors associated with delay in gastric ulcer healing, and if these changes can be corrected by using agents known for their antidiabetic and antiulcer properties. Experimental albino rats were divided into six groups. Except for Group I, other groups contained streptozotocin-induced diabetic rats. Group I (normal control) and Group II (diabetic control) were administered vehicle, Groups III and IV (diabetic experimental) were administered CAEt in dose of 100 mg/kg and 250 mg/kg, respectively, and Groups V and VI (positive controls) were respectively administered oral standard drugs omeprazole, 20 mg/kg, and tolbutamide 10 mg/kg. Result: The results confirmed that the CAEt significantly decreases the ulcer index (P < 0.05) in the aspirin-induced gastric ulcers and also significantly exhibit antioxidant and glucose lowering activity in the diabetic ulcer rats. The study showed that C. attenuata has the potential to be used as an antiulcer agent in experimental diabetic rats. PMID:27621520

  14. Evaluation of Diabetic Foot Ulcer Healing With Hyperspectral Imaging of Oxyhemoglobin and Deoxyhemoglobin

    PubMed Central

    Nouvong, Aksone; Hoogwerf, Byron; Mohler, Emile; Davis, Brian; Tajaddini, Azita; Medenilla, Elizabeth

    2009-01-01

    OBJECTIVE Foot ulceration remains a major health problem for diabetic patients and has a major impact on the cost of diabetes treatment. We tested a hyperspectral imaging technology that quantifies cutaneous tissue hemoglobin oxygenation and generated anatomically relevant tissue oxygenation maps to assess the healing potential of diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS A prospective single-arm blinded study was completed in which 66 patients with type 1 and type 2 diabetes were enrolled and followed over a 24-week period. Clinical, medical, and diabetes histories were collected. Transcutaneous oxygen tension was measured at the ankles. Superficial tissue oxyhemoglobin (oxy) and deoxyhemoglobin (deoxy) were measured with hyperspectral imaging from intact tissue bordering the ulcer. A healing index derived from oxy and deoxy values was used to assess the potential for healing. RESULTS Fifty-four patients with 73 ulcers completed the study; at 24 weeks, 54 ulcers healed while 19 ulcers did not heal. When using the healing index to predict healing, the sensitivity was 80% (43 of 54), the specificity was 74% (14 of 19), and the positive predictive value was 90% (43 of 48). The sensitivity, specificity, and positive predictive values increased to 86, 88, and 96%, respectively, when removing three false-positive osteomyelitis cases and four false-negative cases due to measurements on a callus. The results indicate that cutaneous tissue oxygenation correlates with wound healing in diabetic patients. CONCLUSIONS Hyperspectral imaging of tissue oxy and deoxy may predict the healing of DFUs with high sensitivity and specificity based on information obtained from a single visit. PMID:19641161

  15. The role of methylglyoxal-modified proteins in gastric ulcer healing.

    PubMed

    Takagi, T; Naito, Y; Oya-Ito, T; Yoshikawa, T

    2012-01-01

    Methylglyoxal is a reactive dicarbonyl compound produced from cellular glycolytic intermediates that reacts nonenzymatically with proteins to form products such as argpyrimidine at arginine residues. Abnormal accumulation of methylglyoxal and methylglyoxal-derived advanced glycation end products (AGEs) occurs under hyperglycemic conditions and has been implicated in endothelium dysfunction, arterial stiffening, and microvascular complications in diabetes. However, the role of methylglyoxal in the healing process of diabetic gastric ulcers has not been fully investigated. Recently, methylglyoxal modification of peroxiredoxin-VI was found to be associated with delayed healing of diabetic gastric ulcers. Thus, inhibition of methylglyoxal modification might have therapeutic potential for the treatment of such ulcers. In this review, we present what is currently known regarding the role of methylglyoxal in the healing of diabetic gastric ulcers.

  16. Difference in relapse rates of duodenal ulcer after healing with cimetidine or tripotassium dicitrato bismuthate.

    PubMed

    Martin, D F; Hollanders, D; May, S J; Ravenscroft, M M; Tweedle, D E; Miller, J P

    1981-01-03

    In a double-blind randomised trial in 75 patients with duodenal ulceration diagnosed endoscopically, 38 patients were given tripotassium dicitrato bismuthate and 37 cimetidine. There was no significant difference in the healing rates between the two drugs after 1 and 2 months, although relief of symptoms was marginally quicker with cimetidine. During follow-up for at least a year, relapse was significantly more common in patients whose ulcers had healed during treatment with cimetidine than in those whose ulcers had healed during treatment with tripotassium dicitrato bismuthate. This difference appears to be related to the medication rather than to any other difference between the two groups of patients. These results suggest that drug treatment given for a short period in duodenal-ulcer disease influences the progress of the disease.

  17. Increased healing of gastric and duodenal ulcers in a controlled trial using tripotassium dicitrato-bismuthate.

    PubMed

    Lee, S P; Nicholson, G I

    1977-05-28

    Thirty-seven outpatients with benign gastric ulcers proved by endoscopy were randomized and treated with tripotassium dicitrato-bismuthate (TDB) and a placebo for four weeks. They were assessed on the basis of symptoms and endoscopy examination. Ulcer healing observed by endoscopy was significantly better in the TDB treated group (18 of 20) than in the placebo treated group (six of 17). There was no statistical difference in symptomatic improvement. Nineteen patients with duodenal ulcers proved by endoscopy were randomized in a double-blind trial and given TDB and a placebo for four weeks. Ulcer healing in the TDB treated group (eight of nine) was significantly better than in the placebo treated group (two of 10). No significant difference was found in the symptomatic improvement of both groups. It is concluded that TDB is an effective agent for the treatment of chronic gastric and duodenal ulcers.

  18. A Predictive Model for Diabetic Foot Ulcer Outcome: The Wound Healing Index

    PubMed Central

    Fife, Caroline E.; Horn, Susan D.; Smout, Randall J.; Barrett, Ryan S.; Thomson, Brett

    2016-01-01

    Objective: To develop a healing index for patients with diabetic foot ulcers (DFUs) for use in clinical practice, research analysis, and clinical trials. Approach: U.S. Wound Registry data were examined retrospectively and assigned a clear outcome (healed, amputated, etc.). Significant variables were identified with bivariate analyses. A multivariable logistic regression model was created based on significant factors (p < 0.05) and tested on a hold-out sample of data. Out of 13,266 DFUs from the original dataset, 6,440 were eligible for analysis. The logistic regression model included 5,239 ulcers, of which 3,462 healed (66.1%). The 10% validation sample utilized 555 ulcers, of which 377 healed (67.9%). Results: Variables that significantly predicted healing were as follows: wound age (duration in days), wound size, number of concurrent wounds of any etiology, evidence of bioburden/infection, patient age, Wagner grade, being nonambulatory, renal dialysis, renal transplant, peripheral vascular disease, and patient hospitalization for any reason. Innovation: We present a validated stratification system, previously described as the Wound Healing Index (WHI), which predicts healing likelihood of patients with DFUs, incorporating patient- and wound-specific variables. Conclusion: The DFU WHI is a comprehensive and user-friendly validated predictive model for DFU healing. It can risk stratify patients enrolled in clinical research trials, stratify patient data for quality reporting and benchmarking activities, and identify patients most likely to require costly therapy to heal. PMID:27366589

  19. L-Theanine healed NSAID-induced gastric ulcer by modulating pro/antioxidant balance in gastric ulcer margin.

    PubMed

    Chatterjee, Sirshendu; Chatterjee, Ananya; Roy, Surmi; Bera, Biswajit; Bandyopadhyay, Sandip K

    2014-10-01

    L-Theanine is a unique non-protein-forming amino acid present in tea [Camellia sinensis (L.) O. Kuntze]. In the present work, we evaluated the healing effect of L-theanine on NSAID (indomethacin)-induced gastric ulcer. Histology of the stomach tissues revealed maximum ulceration on the third day after indomethacin administration (18 mg/kg, single dose p.o.) which was accompanied by increased lipid peroxidation; protein carbonylation; Th1 cytokine synthesis, and depletion of thiol, mucin, prostaglandin (PG) E, Th2 cytokine synthesis; and total antioxidant status in mice. L-Theanine healed gastric ulcer at a dose of 10 mg/kg b.w. but aggravated the ulcerated condition at a higher dose of 40 mg/kg b.w. At 10 mg/kg b.w., L-theanine significantly alleviated the adverse oxidative effect of indomethacin through enhanced synthesis of PGE2 by modulation of cyclo-oxygenase-1 and 2 [COX-1 and COX-2] expression, Th1/Th2 cytokine balance, and restoration of cellular antioxidant status at the gastric ulcer margin. The present study revealed for the first time the dose-dependent biphasic effect of a natural neuroprotective agent, L-theanine, on gastric ulcer disease.

  20. Healing and recurrence of duodenal ulcer after treatment with tripotassium dicitrato bismuthate (TDB) tablets or cimetidine.

    PubMed

    Hamilton, I; O'Connor, H J; Wood, N C; Bradbury, I; Axon, A T

    1986-01-01

    Eighty patients with duodenal ulcer were randomly allocated to treatment with tripotassium dicitrato bismuthate (TDB) tablets or cimetidine. Ulcers healed in 78% of patients treated with TDB and in 74% treated with cimetidine, supporting previous observations that the efficacy of these two agents is similar. Duodenal ulcer recurred in 43% of patients in the 12 months after treatment with TDB and in 78% of patients treated with cimetidine, with a significantly greater incidence of recurrence 6-12 months after cimetidine treatment. Tripotassium dicitrato bismuthate tablets may be preferable to cimetidine in the initial management of duodenal ulcer, because they offer a smaller likelihood of recurrence in the 12 months after successful treatment.

  1. Factors that influence healing of chronic venous leg ulcers: a retrospective cohort*

    PubMed Central

    Scotton, Marilia Formentini; Miot, Hélio Amante; Abbade, Luciana Patricia Fernandes

    2014-01-01

    BACKGROUND Venous ulcers have a significant impact on patient quality of life, and constitute a worldwide public health problem. Treatment is complex, with high failure rates. OBJECTIVES To identify clinical and therapeutic factors that influence healing of venous ulcers. METHODS Retrospective cohort study of patients with venous ulcers. Ulcer area was measured at the first visit (T0) and after 6 months (T6) and 1 year (T12). A reduction in ulcer area of 50% or more at T6 and T12 was the outcome of interest, weighted by clinical, demographic and treatment aspects. RESULTS Ninety-four patients were included (137 ulcers). A reduction in ulcer area of 50% or more was seen in 40.1% of patients (95%CI 31.9 to 48.4%) at T6 and 49.6% (95%CI 41.2 to 58.1%) at T12. Complete healing occurred in 16.8% (95%CI 10.5 to 23.1%) at T6 and 27% (95%CI 19.5 to 39.5%) at T12. The lowest ulcer area reductions at T6 were associated with longstanding ulcer (RR=0.95; 95%CI 0.91 to 0.98), poor adherence to compression therapy (RR=4.04; 95%CI 1.31 to 12.41), and infection episodes (RR= 0.42; 95%CI 0.23 to 0.76). At T12, lower reductions were associated with longstanding ulcer (RR=0.95; 95%CI 0.92 to 0.98), longer topical antibiotic use (RR=0.93; 95%CI 0.87 to 0.99), and systemic antibiotic use (RR=0.63; 95%CI 0.40 to 0.99). CONCLUSIONS Longstanding ulcer, infection, poor adherence to compression therapy, and longer topical and systemic antibiotic use were independently correlated with worse healing rates. PMID:24937814

  2. Topical Aloe Vera (Aloe barbadensis Miller) Extract Does Not Accelerate the Oral Wound Healing in Rats.

    PubMed

    Coelho, Fernanda Hack; Salvadori, Gabriela; Rados, Pantelis Varvaki; Magnusson, Alessandra; Danilevicz, Chris Krebs; Meurer, Luise; Martins, Manoela Domingues

    2015-07-01

    The effect of topical application of Aloe Vera (Aloe barbadensis Miller) extract was assessed on the healing of rat oral wounds in an in vivo model using 72 male Wistar rats divided into three groups (n = 24): control, placebo and Aloe Vera (0.5% extract hydroalcoholic). Traumatic ulcers were caused in the dorsum of the tongue using a 3-mm punch tool. The Aloe Vera and placebo group received two daily applications. The animals were sacrificed after 1, 5, 10 and 14 days. Clinical analysis (ulcer area and percentage of repair) and histopathological analysis (degree of re-epithelialization and inflammation) were performed. The comparison of the differences between scores based on group and experimental period, both in quantitative and semi-quantitative analyses, was performed using the Kruskal-Wallis test. The significance level was 5%. On day 1, all groups showed predominantly acute inflammatory infiltrate. On day 5, there was partial epithelialization and chronic inflammatory infiltrate. On the days 10 and 14 total repair of ulcers was observed. There was no significant difference between groups in the repair of mouth ulcers. It is concluded that treatment using Aloe Vera as an herbal formulation did not accelerate oral wound healing in rats.

  3. α-Gal Nanoparticles in Wound and Burn Healing Acceleration

    PubMed Central

    Galili, Uri

    2017-01-01

    Significance: Rapid recruitment and activation of macrophages may accelerate wound healing. Such accelerated healing was observed in wounds and burns of experimental animals treated with α-gal nanoparticles. Recent Advances: α-Gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). α-Gal nanoparticles applied to wounds bind anti-Gal (the most abundant antibody in humans) and generate chemotactic complement peptides, which rapidly recruit macrophages. Fc/Fc receptor interaction between anti-Gal coating the α-gal nanoparticles and recruited macrophages activates macrophages to produce cytokines that accelerate healing. α-Gal nanoparticles applied to burns and wounds in mice and pigs producing anti-Gal, decreased healing time by 40–60%. In mice, this accelerated healing avoided scar formation. α-Gal nanoparticle-treated wounds, in diabetic mice producing anti-Gal, healed within 12 days, whereas saline-treated wounds became chronic wounds. α-Gal nanoparticles are stable for years and may be applied dried, in suspension, aerosol, ointments, or within biodegradable materials. Critical Issues: α-Gal nanoparticle therapy can be evaluated only in mammalian models producing anti-Gal, including α1,3-galactosyltransferase knockout mice and pigs or Old World primates. Traditional experimental animal models synthesize α-gal epitopes and lack anti-Gal. Future Directions: Since anti-Gal is naturally produced in all humans, it is of interest to determine safety and efficacy of α-gal nanoparticles in accelerating wound and burn healing in healthy individuals and in patients with impaired wound healing such as diabetic patients and elderly individuals. In addition, efficacy of α-gal nanoparticle therapy should be studied in healing and regeneration of internal injuries such as surgical incisions, ischemic myocardium following myocardial infarction, and injured nerves. PMID:28289553

  4. Low level diode laser accelerates wound healing.

    PubMed

    Dawood, Munqith S; Salman, Saif Dawood

    2013-05-01

    The effect of wound illumination time by pulsed diode laser on the wound healing process was studied in this paper. For this purpose, the original electronic drive circuit of a 650-nm wavelength CW diode laser was reconstructed to give pulsed output laser of 50 % duty cycle and 1 MHz pulse repetition frequency. Twenty male mice, 3 months old were used to follow up the laser photobiostimulation effect on the wound healing progress. They were subdivided into two groups and then the wounds were made on the bilateral back sides of each mouse. Two sessions of pulsed laser therapy were carried along 15 days. Each mice group wounds were illuminated by this pulsed laser for 12 or 18 min per session during these 12 days. The results of this study were compared with the results of our previous wound healing therapy study by using the same type of laser. The mice wounds in that study received only 5 min of illumination time therapy in the first and second days of healing process. In this study, we found that the wounds, which were illuminated for 12 min/session healed in about 3 days earlier than those which were illuminated for 18 min/session. Both of them were healed earlier in about 10-11 days than the control group did.

  5. Continuous delivery of stromal cell-derived factor-1 from alginate scaffolds accelerates wound healing.

    PubMed

    Rabbany, Sina Y; Pastore, Joseph; Yamamoto, Masaya; Miller, Tim; Rafii, Shahin; Aras, Rahul; Penn, Marc

    2010-01-01

    Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics. Our study utilized an alginate hydrogel patch to deliver stromal cell-derived factor-1 (SDF-1), a naturally occurring chemokine that is rapidly overexpressed in response to tissue injury, to assess the potential effects SDF-1 therapy on wound closure rates and scar formation. Alginate patches were loaded with either purified recombinant human SDF-1 protein or plasmid expressing SDF-1 and the kinetics of SDF-1 release were measured both in vitro and in vivo in mice. Our studies demonstrate that although SDF-1 plasmid- and protein-loaded patches were able to release therapeutic product over hours to days, SDF-1 protein was released faster (in vivo K(d) 0.55 days) than SDF-1 plasmid (in vivo K(d) 3.67 days). We hypothesized that chronic SDF-1 delivery would be more effective in accelerating the rate of dermal wound closure in Yorkshire pigs with acute surgical wounds, a model that closely mimics human wound healing. Wounds treated with SDF-1 protein (n = 10) and plasmid (n = 6) loaded patches healed faster than sham (n = 4) or control (n = 4). At day 9, SDF-1-treated wounds significantly accelerated wound closure (55.0 +/- 14.3% healed) compared to nontreated controls (8.2 +/- 6.0%, p < 0.05). Furthermore, 38% of SDF-1-treated wounds were fully healed at day 9 (vs. none in controls) with very little evidence of scarring. These data suggest that patch-mediated SDF-1 delivery may ultimately provide a novel therapy for accelerating healing and reducing scarring in clinical wounds.

  6. Effect of hyperbaric oxygen therapy on healing of diabetic foot ulcers.

    PubMed

    Duzgun, Arife Polat; Satir, Hakan Ziya; Ozozan, Omer; Saylam, Baris; Kulah, Bahadir; Coskun, Faruk

    2008-01-01

    Hyperbaric oxygen therapy can be used as an adjunct to standard wound care in the treatment of diabetic patients with foot ulcers. We undertook a prospective, randomized investigation of the use of hyperbaric oxygen therapy versus standard therapy for the treatment of foot ulcers in diabetic patients. A number of demographic variables were analyzed in regard to wound healing. We noted that foot ulcers in patients in the hyperbaric oxygen therapy group were more likely to heal, and were more likely to undergo amputation distal to the metatarsophalangeal joint compared with those patients receiving standard therapy without hyperbaric oxygen. We feel that hyperbaric oxygen therapy should be considered a useful adjunct in the management of foot ulcers in diabetic patients.

  7. New objective criterion for determining, noninvasively, the healing potential of an ischemic ulcer

    SciTech Connect

    Siegel, M.E.; Stewart, C.A.; Wagner, W.; Sakimura, I.

    1981-02-01

    Peripheral vascular perfusion studies using intravenously administered thallium-201 were performed on 13 patients suffering from ischemic ulcer of the lower extermities. Scintillation camera views and point counting over the lesion and adjacent region were utilized to define qualitatively and quantitatively the relative hyperemia of the lesion. The preliminary findings demonstrate that when the relative hyperemia was equal to or greater than 1.5, 100% (seven of seven) went on to heal their ulcer with conservative management. Of those without this degree of hyperemia, 83% (five of six) will require amputation. Based on this limited series, noninvasive assessment of the relative hyperemia of an ischemic ulcer using thallium-201 is a new, useful, and objective indicator of the healing potential of a so-called ischemic ulcer.

  8. Effectiveness of an acellular synthetic matrix in the treatment of hard-to-heal leg ulcers.

    PubMed

    Harding, Keith; Aldons, Pat; Edwards, Helen; Stacey, Michael; Finlayson, Kathleen; Gibb, Michelle; Jenkins, Liz; Shooter, Gary; Lonkhuyzen, Derek Van; Lynam, Emily; Heinrichs, Eva-Lisa; Upton, Zee

    2014-04-01

    Hard-to-heal leg ulcers are a major cause of morbidity in the elderly population. Despite improvements in wound care, some wounds will not heal and they present a significant challenge for patients and health care providers. A multi-centre cohort study was conducted to evaluate the effectiveness and safety of a synthetic, extracellular matrix protein as an adjunct to standard care in the treatment of hard-to-heal venous or mixed leg ulcers. Primary effectiveness criteria were (i) reduction in wound size evaluated by percentage change in wound area and (ii) healing assessed by number of patients healed by end of the 12 week study. Pain reduction was assessed as a secondary effectiveness criteria using VAS. A total of 45 patients completed the study and no difference was observed between cohorts for treatment frequency. Healing was achieved in 35·6% and wound size decreased in 93·3% of patients. Median wound area percentage reduction was 70·8%. Over 50% of patients reported pain on first visit and 87·0% of these reported no pain at the end of the study. Median time to first reporting of no pain was 14 days after treatment initiation. The authors consider the extracellular synthetic matrix protein an effective and safe adjunct to standard care in the treatment of hard-to-heal leg ulcers.

  9. Inhibition of nocturnal acidity is important but not essential for duodenal ulcer healing.

    PubMed Central

    Bianchi Porro, G; Parente, F; Sangaletti, O

    1990-01-01

    We have determined the relative importance of day and night time gastric acid inhibition for duodenal ulcer healing by comparing the anti-ulcer efficacy of a single morning with that of a single bedtime dose of ranitidine. One hundred and thirty patients with active duodenal ulcer were randomly assigned to a double-blind therapy with ranitidine 300 mg at 8 am or the same dose at 10 pm for up to eight weeks. The antisecretory effects of these regimens were also assessed by 24 h intragastric pH monitoring in 18 of these patients. At four weeks ulcers had healed in 41/61 (67%) of patients taking the morning dose and in 47/63 (75%) of those receiving the nocturnal dose (95% CI for the difference -0.09 +0.25; p ns). At eight weeks, the corresponding healing rates were 82% and 85.5%, respectively (95% CI for the difference -0.11 +0.17; p ns). Both treatments were significantly superior to placebo in raising 24 h intragastric pH, although the effects of the morning dose were of shorter duration than those of the nocturnal dose. These findings suggest that suppression of nocturnal acidity is important but not essential to promote healing of duodenal ulcers; a prolonged period of acid inhibition during the day (as obtained with a single large morning dose of H2-blockers) may be equally effective. PMID:2186980

  10. Solcoseryl in prevention of stress-induced gastric lesions and healing of chronic ulcers.

    PubMed

    Konturek, S J; Drozdowicz, D; Pytko-Polonczyk, J; Brzozowski, T; Bielański, W

    1991-03-01

    Solcoseryl, a deproteinized extract of calf blood, protects the gastric mucosa against various topical irritants and enhances the healing of chronic gastric ulcerations but the mechanisms of these effects have been little studied. This study was designed to elucidate the active principle in Solcoseryl and to determine the role of prostaglandins (PG) and polyamines in the antiulcer properties of this agent. Using both, the radioimmunoassay and radioreceptor assay, EGF-like material was detected in Solcoseryl preparation. Solcoseryl given s.c. prevented the formation of stress-induced gastric lesions and this was accompanied by an increase in the generation of PGE2 in the gastric mucosa. Similar effects were obtained with EGF. Pretreatment with indomethacin, to suppress mucosal generation of prostaglandins (PG), greatly augmented stress-induced gastric ulcerations and antagonized the protection exerted by both Solcoseryl and EGF. Solcoseryl, like EGF, enhanced the healing of chronic gastro-duodenal ulcerations. This effect was abolished by the pretreatment with difluoromethylornithine, an inhibitor of ornithine decarboxylase, the key enzyme in the biosynthesis of polyamines. The healing effects of Solcoseryl and EGF was also reduced by prednisolone which decreased the angiogenesis in the granulation tissue in the ulcer area. These results indicate that Solcoseryl 1. contains EGF-like material, 2. displays the protective and ulcer healing effects similar to those of EGF and involving both PG and polyamines and 3. acts via similar mechanism as does EGF.

  11. Roles of platelets and proteinase-activated receptors in gastric ulcer healing.

    PubMed

    Perini, Rafael; Wallace, John L; Ma, Li

    2005-10-01

    Proteinase-activated receptors (PARs) are expressed on the surface of many cells, but those on the platelet have been among the most thoroughly characterized. PARs act as key receptors mediating the proaggregatory and pro-secretory effects of thrombin. In addition to contributing to hemostasis, platelets are increasingly being viewed as important contributors to healing and to tumor growth. This is attributable to the many pro- and anti-angiogenic factors that are stored within platelets, which can be released at the sites of injury and new vessel growth. In this paper, we review the importance of the platelet in gastric ulcer healing, the contribution of platelet-contained angiogenic factors to the healing of gastric ulcers, and the role of PARs in regulating the release of angiogenic factors from platelets. Taken together, our results suggest that PARs, including those expressed on platelets, are a rational therapeutic target for modulating healing processes and tumor growth.

  12. Generation of self-healing and transverse accelerating optical vortices

    NASA Astrophysics Data System (ADS)

    Wei, Bing-Yan; Chen, Peng; Ge, Shi-Jun; Duan, Wei; Hu, Wei; Lu, Yan-Qing

    2016-09-01

    Self-healing and transverse accelerating optical vortices are generated via modulating Gaussian beams through subsequent liquid crystal q-plate and polarization Airy mask. We analyze the propagation dynamics of these vortex Airy beams, and find that they possess the features of both optical vortices and Airy beams. Topological charges and characteristics of nondiffraction, self-healing, and transverse acceleration are experimentally verified. In addition, vortex Airy beams with both topological charge and radial index are demonstrated and mode switch among Gaussian, vortex, vector, Airy beams and their combinations can be acquired easily. Our design provides a flexible and highly efficient way to generate unique optical vortices with self-healing and transverse acceleration properties, and facilitates prospective applications in optics and photonics.

  13. Effect of capsaicin and cimetidine on the healing of acetic acid induced gastric ulceration in the rat.

    PubMed Central

    Kang, J Y; Teng, C H; Chen, F C

    1996-01-01

    BACKGROUND: Capsaicin protects the gastric mucosa against experimental injury while capsaicin desensitisation reduces the rate of gastric ulcer healing. The effect of exogenous capsaicin on gastric ulcer healing has not to date been reported. AIM/METHOD: To investigate the effect of capsaicin, cimetidine, and in combination, given intragastrically in the healing of acetic acid induced chronic gastric ulcer in the rat. Treatment started immediately after ulcer induction. RESULTS: At the end of one week, capsaicin, cimetidine, and in combination increased ulcer healing but the effect of combined treatment was less than that of capsaicin alone. In an in vivo gastric chamber preparation, capsaicin increased, while cimetidine decreased, gastric mucosal blood flow measured by laser Doppler flowmetry. A dose response effect in reduction of gastric mucosal blood flow could be demonstrated for cimetidine. The gastric hyperaemic effect of capsaicin was blunted by prior administration of cimetidine. In contrast, capsaicin had no effect on gastric acid secretion and its addition to cimetidine did not affect the acid suppressant effect of the latter. CONCLUSIONS: Capsaicin promotes the healing of acetic acid induced gastric ulcer, probably by its gastric hyperaemic effect. Although cimetidine also promotes ulcer healing due to its inhibitory effect on acid secretion it may have an antagonistic effect on the gastric ulcer healing effect of capsaicin by virtue of inhibition of gastric hyperaemia. PMID:8984019

  14. Novel mechanisms and signaling pathways of esophageal ulcer healing: the role of prostaglandin EP2 receptors, cAMP, and pCREB.

    PubMed

    Ahluwalia, Amrita; Baatar, Dolgor; Jones, Michael K; Tarnawski, Andrzej S

    2014-09-15

    Clinical studies indicate that prostaglandins of E class (PGEs) may promote healing of tissue injury e.g., gastroduodenal and dermal ulcers. However, the precise roles of PGEs, their E-prostanoid (EP) receptors, signaling pathways including cAMP and cAMP response element-binding protein (CREB), and their relation to VEGF and angiogenesis in the tissue injury healing process remain unknown, forming the rationale for this study. Using an esophageal ulcer model in rats, we demonstrated that esophageal mucosa expresses predominantly EP2 receptors and that esophageal ulceration triggers an increase in expression of the EP2 receptor, activation of CREB (the downstream target of the cAMP signaling), and enhanced VEGF gene expression. Treatment of rats with misoprostol, a PGE1 analog capable of activating EP receptors, enhanced phosphorylation of CREB, stimulated VEGF expression and angiogenesis, and accelerated esophageal ulcer healing. In cultured human esophageal epithelial (HET-1A) cells, misoprostol increased intracellular cAMP levels (by 163-fold), induced phosphorylation of CREB, and stimulated VEGF expression. A cAMP analog (Sp-cAMP) mimicked, whereas an inhibitor of cAMP-dependent protein kinase A (Rp-cAMP) blocked, these effects of misoprostol. These results indicate that the EP2/cAMP/protein kinase A pathway mediates the stimulatory effect of PGEs on angiogenesis essential for tissue injury healing via the induction of CREB activity and VEGF expression.

  15. Effects of a comprehensive nutritional program on pressure ulcer healing, length of hospital stay, and charges to patients.

    PubMed

    Allen, Beverlin

    2013-05-01

    The burden of pressure ulcers will intensify because of a rapidly increasing elderly population. The aim of this study was to examine the effects of a comprehensive, interdisciplinary nutritional protocol on pressure ulcer wound healing, length of hospital stays, and charges for pressure ulcer management. The pre/post quasi-experimental design study comprised of 100 patients (50 patients in each group) 60 years or older with pressure ulcer. Research questions were analyzed using descriptive statistics, frequencies, chi-square tests, and t tests. Study findings indicate that the intervention was effective in improving pressure ulcer wound healing, decreasing both hospital length of stay (LOS) for treatment of pressure ulcer and total hospital LOS, while showing no significant additional charges for treatment of pressure ulcers. The older adults are at the highest risk of developing pressure ulcers that result in prolonged hospitalization, high health care costs, increased mortality, and decreased quality of life.

  16. Successes and pitfalls in the healing of neuropathic forefoot ulcerations with the IPOS postoperative shoe.

    PubMed

    Needleman, R L

    1997-07-01

    Unnecessary amputations can be avoided with the healing of foot ulcerations in neuropathic feet. Traditional approaches have relied on relieving plantar and other extrinsic foot pressures. A retrospective review was performed of the office records of patients with Wagner grade 1 and 2 neuropathic forefoot ulcerations who were prescribed an IPOS (Niagara Falls, NY) postoperative shoe. A total of .33 patients were in the chart review. Twenty-three of these patients were located and agreed to participate in a telephone survey. Patients showed a compliance of 78%. Seventy-seven percent of the patients healed their ulcers and wore prescription inserts and extra-depth shoes at a mean of 8 weeks. Seventy-eight percent of our telephone survey patients were either satisfied or satisfied with reservations. Problems or complications from wearing the IPOS postoperative shoe occurred with 38% of all patients.

  17. Comparing the Effects of Two Teaching Methods on Healing of Diabetic Foot Ulcer

    PubMed Central

    Adib-Hajbaghery, Mohsen; Alinaqipoor, Tahereh

    2012-01-01

    Introduction: Some studies have reported that diabetic patients do not adhere well to the foot care recommendations. Reasons for non-adherence are less evident and the methods used in education programs may have an effect. Therefore, the aim of the present study was to compare the effects of lecture method and combined method of education on foot care of patients and healing rates of diabetic foot ulcers. Methods: A matched controlled trial study was conducted on a sample of 45 diabetic patients with foot ulcers. The two intervention groups were taught with similar content but different methods. Patients’ foot care and healing rates of diabetic foot ulcers were assessed at the beginning of study and after 3 months in the two training groups as well as the control group. Results: Ulcer surface was decreased by 46%, 61% and 81.6% in the control, lecture group and com-bined group, respectively. The ulcer depth was also decreased by 66.7%, 97.5% and 69.1% in the three groups respectively. A significant relationship was observed between the group adherence of the self-care program and the amount of decrease in the ulcer surface area (r = 0.36, p = 0.04). Conclusion: The foot care education could significantly affect the healing of diabetic foot ulcer, especially in terms of the ulcers’ surface area. Therefore, a self-care education program should be integrated in the health system to empower those living with diabetes to manage their own foot appropriately. PMID:25276671

  18. [Present status of research in bone marrow-derived mesenchymal stem cells for promoting the healing of diabetic ulcer].

    PubMed

    Zheng, Shu-Juan; Jia, Chi-Yu

    2012-08-01

    The delayed healing of diabetic ulcer has been haunting the surgeons and researchers for a long time. Although we have been researching and exploring the effective therapies for many years, the progress has been limited. Bone marrow-derived mesenchymal stem cells (BMSCs) have gradually won worldwide attention for their characteristics of differentiating into tissue repair cells and secreting multiple cytokines as well as growth factors. In recent years, the role of BMSCs in the treatment of diabetic ulcer has been drawing more and more attention. This article reviewed the advancement in the research of BMSCs in promoting the healing of diabetic ulcer. Through a discussion of the treatment of diabetic ulcer, the related research in BMSCs, as well as its role in diabetic ulcer treatment, the mechanism of BMSCs in promoting healing of diabetic ulcers is discussed. We expect through further research, unified criteria for the quality of BMSCs, application approach and dosage of BMSCs could be established.

  19. Radionuclide angiography and blood pool imaging to assess skin ulcer healing prognosis in patients with peripheral vascular disease

    SciTech Connect

    Alazraki, N.; Lawrence, P.F.; Syverud, J.B.

    1984-01-01

    Several non-invasive diagnostic techniques including segmental limb blood pressures, skin fluoresence, and photo plethysmography, have been evaluated as predictors of skin ulcer healing in patients with peripheral vascular disease, but none are widely used. Using 20mCi of Tc-99m phosphate compounds, four phase bone scans were obtained, including (1) radionuclide angiogram (2) blood pool image (3) 2 hour and 4-6 hour static images and (4) 24 hour static delayed images. The first two phases were used to assess vacularity to the region of distal extremity ulceration; the last two phases evaluated presence or absence of osteomyelitis. Studies were performed in 30 patients with non-healing ulcers of the lower extremities. Perfusion to the regions of ulceration on images was graded as normal, increased, or reduced with respect to the opposite (presumed normal) limb or some other normal reference area. Hypervascular response was interpreted as good prognosis for healing unless osteomyelitis was present. Clinicians followed patients for 14 days to assess limb healing with optimum care. If there was no improvement, angiography and/or surgery (reconstructive surgery, sympathectomy, or amputation) was done. Results showed: sensitivity for predicting ulcer healing was 94%, specificity 89%. Patients who failed to heal their ulcers showed reduced perfusion, no hypervascular response, or osteomyelitis. Microcirculatory adequacy for ulcer healing appear predictable by this technique.

  20. Honey for wound healing, ulcers, and burns; data supporting its use in clinical practice.

    PubMed

    Al-Waili, Noori; Salom, Khelod; Al-Ghamdi, Ahmad A

    2011-04-05

    The widespread existence of unhealed wounds, ulcers, and burns has a great impact on public health and economy. Many interventions, including new medications and technologies, are being used to help achieve significant wound healing and to eliminate infections. Therefore, to find an intervention that has both therapeutic effect on the healing process and the ability to kill microbes is of great value. Honey is a natural product that has been recently introduced in modern medical practice. Honey's antibacterial properties and its effects on wound healing have been thoroughly investigated. Laboratory studies and clinical trials have shown that honey is an effective broad-spectrum antibacterial agent. This paper reviews data that support the effectiveness of natural honey in wound healing and its ability to sterilize infected wounds. Studies on the therapeutic effects of honey collected in different geographical areas on skin wounds, skin and gastric ulcers, and burns are reviewed and mechanisms of action are discussed. (Ulcers and burns are included as an example of challenging wounds.) The data show that the wound healing properties of honey include stimulation of tissue growth, enhanced epithelialization, and minimized scar formation. These effects are ascribed to honey's acidity, hydrogen peroxide content, osmotic effect, nutritional and antioxidant contents, stimulation of immunity, and to unidentified compounds. Prostaglandins and nitric oxide play a major role in inflammation, microbial killing, and the healing process. Honey was found to lower prostaglandin levels and elevate nitric oxide end products. These properties might help to explain some biological and therapeutic properties of honey, particularly as an antibacterial agent or wound healer. The data presented here demonstrate that honeys from different geographical areas have considerable therapeutic effects on chronic wounds, ulcers, and burns. The results encourage the use of honey in clinical

  1. A short peptide from frog skin accelerates diabetic wound healing.

    PubMed

    Liu, Han; Duan, Zilei; Tang, Jing; Lv, Qiumin; Rong, Mingqiang; Lai, Ren

    2014-10-01

    Delayed wound healing will result in the development of chronic wounds in some diseases, such as diabetes. Amphibian skins possess excellent wound-healing ability and represent a resource for prospective wound-healing promoting compounds. A potential wound-healing promoting peptide (CW49; amino acid sequence APFRMGICTTN) was identified from the frog skin of Odorrana grahami. It promotes wound healing in a murine model with a full-thickness dermal wound in both normal and diabetic animals. In addition to its strong angiogenic ability with respect to the upregulation of some angiogenic proteins, CW49 also showed a significant anti-inflammatory effect in diabetic wounds, which was very important for healing chronic wounds. CW49 had little effect on re-epithelialization, resulting in no significant effect on wound closure rate compared to a vehicle control. Altogether, this indicated that CW49 might accelerate diabetic wound healing by promoting angiogenesis and preventing any excessive inflammatory response. Considering its favorable traits as a small peptide that significantly promotes angiogenesis, CW49 might be an excellent candidate or template for the development of a drug for use in the treatment of diabetic wounds.

  2. Effects of omeprazole on healing of naturally-occurring gastric ulcers in thoroughbred racehorses.

    PubMed

    Murray, M J; Haven, M L; Eichorn, E S; Zhang, D; Eagleson, J; Hickey, G J

    1997-11-01

    Seventeen Thoroughbred horses with moderate to severe gastric ulceration were purchased from a race track within 10 days of racing and were treated once daily with either omeprazole (9 horses) or vehicle (8 horses) and evaluated gastroscopically for ulcer healing. Horses were administered omeprazole (1.5 mg/kg bwt/day) or vehicle by nasogastric tube once daily. Gastroscopic examination was performed on Days 0, 4, 7, 11, 14, 17, 21, 24 and 28, until lesions healed completely. Selected images of gastric lesions were captured by computer at each endoscopic examination, with a measuring caliper included in captured images. The area and perimeter of lesions were measured by computer and healing rates of specific lesions were determined by calculating the rate of linear advance of the margins toward the centre of the lesion. Additionally, the number of days to complete healing of the entire gastric squamous mucosa was compared between treatment groups. Gastric lesions healed at a significantly faster rate in horses receiving omeprazole than in vehicle-treated horses (P < 0.001). Complete healing of the entire stomach occurred in 10-21 days in omeprazole-treated horses, and 14-28 days in 3 of 8 vehicle-treated horses, with the remaining vehicle-treated horses having unhealed lesions on Day 28. In addition, 5 vehicle-treated horses developed new lesions in the squamous epithelial mucosa during the trial; no new lesions were observed in the omeprazole-treated group.

  3. Novel Wound Healing Powder Formulation for the Treatment of Venous Leg Ulcers

    PubMed Central

    Ghatnekar, Angela V.; Elstrom, Tuan; Ghatnekar, Gautam S.; Kelechi, Teresa

    2011-01-01

    Chronic venous disorders are common in the Western world. The current treatment of venous leg ulcers is unsatisfactory despite the availability of well-documented standards of care. Patients today are interested in alternative approaches to modern medicine. We have developed a wound-healing powder containing natural ingredients with absorptive, aromatic, antiseptic, and anti-inflammatory synergistic properties. This report describes 3 cases that were successfully treated with the powder, demonstrating the potential of herbal remedies in the clinical treatment of venous leg ulcers. PMID:24527167

  4. The effect of cimetidine on the maintenance of healing of gastric ulceration.

    PubMed Central

    Kinloch, J. D.; Pearson, A. J.; Woolf, I. L.; Young, P. H.

    1984-01-01

    The rate of endoscopically confirmed gastric ulcer relapse was compared in two groups of patients with newly healed benign gastric ulcers, receiving either cimetidine 400 mg nocte or matching placebo, over a period of 1 year. Six of 24 (25%) patients on cimetidine and 16 of 27 (59%) patients on placebo had endoscopically confirmed relapse. These included two patients in each group with asymptomatic relapses. The difference in the rate of relapse between the two groups was statistically significant (P = 0.01). PMID:6387689

  5. Somatic pain sensitivity during formation and healing of acetic acid-induced gastric ulcers in conscious rats.

    PubMed

    Yarushkina, Natalya; Bogdanov, Anatoly; Filaretova, Ludmila

    2006-06-30

    A classical feature of visceral pain is its referring to somatic locations. Gastric ulcer is a source of visceral pain. In the present study we investigated whether gastric ulcers may trigger the changes in somatic nociception. For this aim somatic pain sensitivity was estimated under conditions of gastric ulcer development and healing. Gastric ulcers were induced by luminal application of 60% acetic acid under surgical conditions. Control rats were subjected to the same surgical procedure, but with the application of saline instead of the acid. Somatic pain sensitivity (tail flick latency), plasma corticosterone level, adrenal and thymus weight were investigated under conditions of the formation and the healing of gastric ulcers. The application of the acid resulted in the formation of kissing gastric ulcers, the increase of somatic pain sensitivity (the decrease of tail flick latency) as well as the appearance of typical signs of chronic stress: long-lasting increase of plasma corticosterone level, adrenal gland hypertrophy and thymus gland involution. Natural healing of gastric ulcers was accompanied by restoration of pain sensitivity as well as attenuation of the signs of chronic stress. Delay of ulcer healing by the daily indomethacin administration (2 mg/kg, s.c.) prevented the restoration of somatic pain sensitivity. The results suggest that chronic gastric ulcers may trigger somatic hypersensitivity.

  6. Non-healing foot ulcers in diabetic patients: general and local interfering conditions and management options with advanced wound dressings.

    PubMed

    Uccioli, Luigi; Izzo, Valentina; Meloni, Marco; Vainieri, Erika; Ruotolo, Valeria; Giurato, Laura

    2015-04-01

    Medical knowledge about wound management has improved as recent studies have investigated the healing process and its biochemical background. Despite this, foot ulcers remain an important clinical problem, often resulting in costly, prolonged treatment. A non-healing ulcer is also a strong risk factor for major amputation. Many factors can interfere with wound healing, including the patient's general health status (i.e., nutritional condition indicated by albumin levels) or drugs such as steroids that can interfere with normal healing. Diabetic complications (i.e., renal insufficiency) may delay healing and account for higher amputation rates observed in diabetic patients under dialysis treatment. Wound environment (e.g., presence of neuropathy, ischaemia, and infection) may significantly influence healing by interfering with the physiological healing cascade and adding local release of factors that may worsen the wound. The timely and well-orchestrated release of factors regulating the healing process, observed in acute wounds, is impaired in non-healing wounds that are blocked in a chronic inflammatory phase without progressing to healing. This chronic phase is characterised by elevated protease activity (EPA) of metalloproteinases (MMPs) and serine proteases (e.g., human neutrophil elastase) that interfere with collagen synthesis, as well as growth factor release and action. EPA (mainly MMP 9, MMP-8 and elastase) and inflammatory factors present in the wound bed (such as IL-1, IL-6, and TNFa) account for the catabolic state of non-healing ulcers. The availability of wound dressings that modulate EPA has added new therapeutic options for treating non-healing ulcers. The literature confirms advantages obtained by reducing protease activity in the wound bed, with better outcomes achieved by using these dressings compared with traditional ones. New technologies also allow a physician to know the status of the wound bed environment, particularly EPA, in a clinical

  7. Accelerated endothelial wound healing on microstructured substrates under flow.

    PubMed

    Franco, Davide; Milde, Florian; Klingauf, Mirko; Orsenigo, Fabrizio; Dejana, Elisabetta; Poulikakos, Dimos; Cecchini, Marco; Koumoutsakos, Petros; Ferrari, Aldo; Kurtcuoglu, Vartan

    2013-02-01

    Understanding and accelerating the mechanisms of endothelial wound healing is of fundamental interest for biotechnology and of significant medical utility in repairing pathologic changes to the vasculature induced by invasive medical interventions. We report the fundamental mechanisms that determine the influence of substrate topography and flow on the efficiency of endothelial regeneration. We exposed endothelial monolayers, grown on topographically engineered substrates (gratings), to controlled levels of flow-induced shear stress. The wound healing dynamics were recorded and analyzed in various configurations, defined by the relative orientation of an inflicted wound, the topography and the flow direction. Under flow perpendicular to the wound, the speed of endothelial regeneration was significantly increased on substrates with gratings oriented in the direction of the flow when compared to flat substrates. This behavior is linked to the dynamic state of cell-to-cell adhesions in the monolayer. In particular, interactions with the substrate topography counteract Vascular Endothelial Cadherin phosphorylation induced by the flow and the wounding. This effect contributes to modulating the mechanical connection between migrating cells to an optimal level, increasing their coordination and resulting in coherent cell motility and preservation of the monolayer integrity, thus accelerating wound healing. We further demonstrate that the reduction of vascular endothelial cadherin phosphorylation, through specific inhibition of Src activity, enhances endothelial wound healing in flows over flat substrates.

  8. Substance P enhances EPC mobilization for accelerated wound healing.

    PubMed

    Um, Jihyun; Jung, Nunggum; Chin, Sukbum; Cho, Younggil; Choi, Sanghyuk; Park, Ki-Sook

    2016-03-01

    Wound healing is essential for the survival and tissue homeostasis of unicellular and multicellular organisms. The current study demonstrated that the neuropeptide substance P (SP) accelerated the wound healing process, particularly in the skin. Subcutaneous treatment of SP accelerated wound closing, increased the population of α-smooth muscle actin positive myofibroblasts, and increased extracellular matrix deposition at the wound site. Moreover, SP treatment enhances angiogenesis without a local increase in the expression levels of vascular endothelial growth factor and stromal cell-derived factor-1. Importantly, SP treatment increased both the population of circulating endothelial progenitor cells in the peripheral blood and in CD31 positive cells in Matrigel plugs. The tube forming potential of endothelial cells was also enhanced by SP treatment. The results suggested that the subcutaneous injection of SP accelerated the wound healing in the skin via better reconstitution of blood vessels, which possibly followed an increase in the systemic mobilization of endothelial progenitor cells and a more effective assembly of endothelial cells into tubes.

  9. Mixture of sugar and povidone-iodine stimulates healing of MRSA-infected skin ulcers on db/db mice.

    PubMed

    Shi, Chong-Ming; Nakao, Hiroshi; Yamazaki, Masashi; Tsuboi, Ryoji; Ogawa, Hideoki

    2007-11-01

    The topical application of a mixture of sugar and povidone-iodine (PI) has been reported to accelerate the healing of cutaneous wounds and ulcers by promoting reepithelialization and granulation tissue formation, as well as by having an anti-microbial effect. In order to clarify the efficacy of a 70% sugar and 3% PI paste (U-PASTA(SP) on infectious skin ulcers, we made a bacterial infection model using methicillin-resistant Staphylococcus aureus (MRSA) on the skin of diabetic db/db mice, and investigated the effect of the paste on the healing process of wounds. Full-thickness wounds were made on the backs of female diabetic mice, (C57BL/ksJ db/db) and inoculated with S. aureus. SP was applied to the closed wounds for 8 days. The degree of repair was evaluated using three histological parameters: The degree of reepithelialization was given a percentage value of 0-100%; the amount of granulation tissue was quantified by measuring the area of granulation (mm(2)); and the number of capillary lumens in the granulation tissue was counted in the complete wound cross-section at 100x magnification. In addition, the colony-forming units (CFU) of MRSA on the wounds were counted. Continuous MRSA infection in the wounds of db/db mice was demonstrated with macroscopic and histopathological images. Wounding and infection caused by MRSA on the back of the diabetic mice significantly induced delayed reepithelialization, granulation tissue formation with inflammatory cell infiltrate and increased CFU on wounds (P < 0.01, respectively) compared to those of the MRSA-infected normal mice. Application of SP significantly accelerated reepithelialization (P < 0.01) and decreased CFU (P < 0.05) of the ulcers in the MRSA-infected wounds, compared to the non-treated group. Histopathological evaluation and CFU on this animal model revealed no significant difference between Methicilin-sensitive Staphylococcus aureus and MRSA infection. These results indicate that wounding on db/db mice

  10. HoxD3 accelerates wound healing in diabetic mice

    SciTech Connect

    Hansen, Scott L.; Myers, Connie A.; Charboneau, Aubri; Young, David M.; and Boudreau, Nancy

    2003-12-01

    Poorly healing diabetic wounds are characterized by diminished collagen production and impaired angiogenesis. HoxD3, a homeobox transcription factor that promotes angiogenesis and collagen synthesis, is up-regulated during normal wound repair whereas its expression is diminished in poorly healing wounds of the genetically diabetic (db/db) mouse. To determine whether restoring expression of HoxD3 would accelerate diabetic wound healing, we devised a novel method of gene transfer, which incorporates HoxD3 plasmid DNA into a methylcellulose film that is placed on wounds created on db/db mice. The HoxD3 transgene was expressed in endothelial cells, fibroblasts, and keratinocytes of the wounds for up to 10 days. More importantly, a single application of HoxD3 to db/db mice resulted in a statistically significant acceleration of wound closure compared to control-treated wounds. Furthermore, we also observed that the HoxD3-mediated improvement in diabetic wound repair was accompanied by increases in mRNA expression of the HoxD3 target genes, Col1A1 and beta 3-integrin leading to enhanced angiogenesis and collagen deposition in the wounds. Although HoxD3-treated wounds also show improved re-epithelialization as compared to control db/db wounds, this effect was not due to direct stimulation of keratinocyte migration by HoxD3. Finally, we show that despite the dramatic increase in collagen synthesis and deposition in HoxD3-treated wounds, these wounds showed normal remodeling and we found no evidence of abnormal wound healing. These results indicate that HoxD3 may provide a means to directly improve collagen deposition, angiogenesis and closure in poorly healing diabetic wounds.

  11. Role of Endothelial Progenitor Cells and Inflammatory Cytokines in Healing of Diabetic Foot Ulcers

    PubMed Central

    Tecilazich, Francesco; Dinh, Thanh; Pradhan-Nabzdyk, Leena; Leal, Ermelindo; Tellechea, Ana; Kafanas, Antonios; Gnardellis, Charalambos; Magargee, Mary L.; Dejam, Andre; Toxavidis, Vasilis; Tigges, John C.; Carvalho, Eugenia; Lyons, Thomas E.; Veves, Aristidis

    2013-01-01

    Background To evaluate changes in endothelial progenitor cells (EPCs) and cytokines in patients with diabetic foot ulceration (DFU) in association with wound healing. Methods We studied healthy subjects, diabetic patients not at risk of DFU, at risk of DFU and with active DFU. We prospectively followed the DFU patients over a 12-week period. We also investigated similar changes in diabetic rabbit and mouse models of wound healing. Results All EPC phenotypes except the kinase insert domain receptor (KDR)+CD133+ were reduced in the at risk and the DFU groups compared to the controls. There were no major EPC differences between the control and not at risk group, and between the at risk and DFU groups. Serum stromal-cell derived factor-1 (SDF-1) and stem cell factor (SCF) were increased in DFU patients. DFU patients who healed their ulcers had lower CD34+KDR+ count at visits 3 and 4, serum c-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at visit 1, interleukin-1 (IL-1) at visits 1 and 4. EPCs tended to be higher in both diabetic animal models when compared to their non-diabetic counterparts both before and ten days after wounding. Conclusions Uncomplicated diabetes does not affect EPCs. EPCs are reduced in patients at risk or with DFU while complete wound healing is associated with CD34+KDR+ reduction, suggesting possible increased homing. Low baseline CRP, IL-1α and GM-CSF serum levels were associated with complete wound healing and may potentially serve as prognostic markers of DFU healing. No animal model alone is representative of the human condition, indicating the need for multiple experimental models. PMID:24358275

  12. Healing of ulcers due to cryofibrinogenemia with colchicine and high-dose pentoxifylline.

    PubMed

    Chartier, Molly; Falanga, Vincent

    2009-01-01

    Cryofibrinogenemia is due to the presence of reversibly cold-precipitating plasma proteins and material, consisting mostly of fibrinogen, fibronectin, and fibrin. This condition can be idiopathic or secondary to infection, thromboembolic states, neoplasm, or connective tissue disease. The characteristic lesions of cryofibrinogenemia include purpura and ulcerations. Histologically, the lesions of cryofibrinogenemia demonstrate fibrin thrombi within vessels, with no evidence of vasculitis. Treatment of cryofibrinogenemia should be directed at the underlying disease process, if one can be found. Other treatments have included the anabolic steroid stanozolol, which is presently unavailable, anticoagulants, immunosuppressive agents, plasmapheresis, and the combination of streptokinase and streptodornase. We report a case of a 61-year-old male smoker with a 10-year history of intermittent ulcerations of both legs and feet. Two separate biopsies showed epidermal ulceration and thrombi within superficial dermal vessels without evidence of vasculitis. These findings, together with the presence of elevated plasma cryofibrinogen, led to the diagnosis of cryofibrinogenemia. The patient continued to have ulcerations despite efforts to control his high blood pressure, cold avoidance, local wound care, and treatment with pentoxifylline 800 mg three times daily. However, when colchicine 0.6 mg twice daily was added to the patient's care, this led to rapid healing of his ulcerations. He has remained ulcer free for 2 years taking the combination of colchicine and high-dose pentoxifylline. Efforts to reduce the dose of these agents have repeatedly led to recurrences, and remission has promptly followed re-establishment of the combination. To our knowledge, this is the first report documenting use of the combination of colchicine and high-dose pentoxifylline to successfully treat ulcers due to cryofibrinogenemia.

  13. Coacervate delivery of HB-EGF accelerates healing of type 2 diabetic wounds.

    PubMed

    Johnson, Noah R; Wang, Yadong

    2015-01-01

    Chronic wounds such as diabetic ulcers pose a significant challenge as a number of underlying deficiencies prevent natural healing. In pursuit of a regenerative wound therapy, we developed a heparin-based coacervate delivery system that provides controlled release of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) within the wound bed. In this study, we used a polygenic type 2 diabetic mouse model to evaluate the capacity of HB-EGF coacervate to overcome the deficiencies of diabetic wound healing. In full-thickness excisional wounds on NONcNZO10 diabetic mice, HB-EGF coacervate enhanced the proliferation and migration of epidermal keratinocytes, leading to accelerated epithelialization. Furthermore, increased collagen deposition within the wound bed led to faster wound contraction and greater wound vascularization. Additionally, in vitro assays demonstrated that HB-EGF released from the coacervate successfully increased migration of diabetic human keratinocytes. The multifunctional role of HB-EGF in the healing process and its enhanced efficacy when delivered by the coacervate make it a promising therapy for diabetic wounds.

  14. Effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality: A clinical observation study

    PubMed Central

    Yang, Rui-Qi; Mao, Hua; Huang, Li-Yun; Su, Pei-Zhu; Lu, Min

    2017-01-01

    AIM To evaluate the effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality. METHODS Forty-eight patients diagnosed with gastric ulcer between June 2014 and February 2016 were randomly allocated to the combination therapy group or monotherapy group. The former received hydrotalcite combined with esomeprazole, and the latter received esomeprazole alone, for 8 wk. Twenty-four healthy volunteers were recruited and acted as the healthy control group. Endoscopic ulcer healing was observed using white light endoscopy and narrow band imaging magnifying endoscopy. The composition of collagen fibers, amount of collagen deposition, expression of factor VIII and TGF-β1, and hydroxyproline content were analyzed by Masson staining, immunohistochemistry, immunofluorescent imaging and ELISA. RESULTS Following treatment, changes in the gastric microvascular network were statistically different between the combination therapy group and the monotherapy group (P < 0.05). There were significant differences (P < 0.05) in collagen deposition, expression level of Factor VIII and TGF-β1, and hydroxyproline content in the two treatment groups compared with the healthy control group. These parameters in the combination therapy group were significantly higher than in the monotherapy group (P < 0.05). The ratio of collagen I to collagen III was statistically different among the three groups, and was significantly higher in the combination therapy group than in the monotherapy group (P < 0.05). CONCLUSION Hydrotalcite combined with esomeprazole is superior to esomeprazole alone in improving gastric ulcer healing quality in terms of improving microvascular morphology, degree of structure maturity and function of regenerated mucosa. PMID:28275307

  15. A Pilot Randomized, Controlled Study of Nanocrystalline Silver, Manuka Honey, and Conventional Dressing in Healing Diabetic Foot Ulcer

    PubMed Central

    Kwong, Enid Wai-Yung; To, Tony Shing-Shun; Wong, Thomas Kwok-Shing

    2017-01-01

    Nanocrystalline silver (nAg) and Manuka honey (MH) dressing have increasing popularity for treating diabetic foot ulcer (DFU). This study was an open-label randomized controlled trial with three parallel groups' design in examining the preliminary effectiveness of nAg against MH and conventional dressing in healing DFU in terms of ulcer healing, ulcer infection, and inflammation. 31 participants (11 in the nAg group, 10 in the MH group, and 10 in the convention group) diagnosed with type 2 diabetes were enrolled. Wound cleaning, debridement, and topical dressing application were performed according to the group allocation in each visit at weeks 1, 2, 3, 4, 6, 8, 10, and 12. The results found that the proportions of complete ulcer healing were 81.8%, 50%, and 40% in the nAg, MH, and conventional groups, respectively. The ulcer size reduction rate was potentially higher in the nAg group (97.45%) than the MH group (86.21%) and the conventional group (75.17%). In bacteriology, nAg showed a greater rate of microorganism reduction although it was not significant. To conclude, nAg alginate was potentially superior to MH and conventional dressing in healing diabetic foot ulcer in terms of ulcer size reduction rate. PMID:28239398

  16. Acceleration of palatal wound healing in Smad3-deficient mice.

    PubMed

    Jinno, K; Takahashi, T; Tsuchida, K; Tanaka, E; Moriyama, K

    2009-08-01

    Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. It is suggested that transforming growth factor (TGF)-beta/Smad3 signaling is involved in wound healing. The purpose of this study was to investigate the role of TGF-beta/Smad3 signaling in palatal wound healing in Smad3-deficient (Smad3(-/-)) mice. Histological examination showed that wound closure was accelerated by the proliferation of epithelium and dermal cells in Smad3(-/-) mice compared with wild-type (WT) mice. Macrophage/monocyte infiltration at wounded regions in Smad3(-/-) mice was decreased in parallel with the diminished production of TGF-beta1, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha compared with WT mice. Fibrocytes, expressing hematopoietic surface marker and fibroblast products, were recruited and produced alpha-smooth-muscle actin in WT mice, but were not observed in Smad3(-/-) mice. These results suggest that TGF-beta/Smad3 signaling may play an important role in the regulation of palatal wound healing.

  17. Aseptically Processed Placental Membrane Improves Healing of Diabetic Foot Ulcerations: Prospective, Randomized Clinical Trial

    PubMed Central

    DiDomenico, Lawrence A.; Orgill, Dennis P.; Galiano, Robert D.; Serena, Thomas E.; Carter, Marissa J.; Kaufman, Jarrod P.; Young, Nathan J.

    2016-01-01

    Background: Allogeneic grafts derived from amnion/chorion are known to be efficacious in healing chronic diabetic foot ulcerations (DFUs). The goal of this study was to compare aseptically processed dehydrated human amnion and chorion allograft (dHACA) versus standard of care (SOC) in facilitating wound closure in nonhealing DFUs. Methods: Patients with DFUs treated with SOC (off-loading, appropriate debridement, and moist wound care) after a 2-week screening period were randomized to either SOC or wound-size-specific dHACA (AmnioBand, Musculoskeletal Transplant Foundation, Edison, N.J.) applied weekly for up to 12 weeks plus SOC. Primary endpoint was the percentage of wounds healed at 6 weeks between groups. Results: At 6 weeks, 70% (14/20) of the dHACA-treated DFUs healed compared with 15% (3/20) treated with SOC alone. Furthermore, at 12 weeks, 85% (17/20) of the DFUs in the dHACA group healed compared with 25% (5/20) in the SOC group, with a corresponding mean time to heal of 36 and 70 days, respectively. At 12 weeks, the mean number of grafts used per healed wound for the dHACA group was 3.8 (median 3.0), and mean cost of the tissue to heal a DFU was $1400. The mean wastage at 12 weeks was 40%. One adverse event and 1 serious adverse event occurred in the dHACA group; neither was graft related. Three adverse events and 1 serious adverse event occurred in the SOC group. Conclusion: Aseptically processed dHACA heals diabetic foot wounds significantly faster than SOC at 6 and 12 weeks with minimal graft wastage. PMID:27826487

  18. An economic assessment of Apligraf (Graftskin) for the treatment of hard-to-heal venous leg ulcers.

    PubMed

    Schonfeld, W H; Villa, K F; Fastenau, J M; Mazonson, P D; Falanga, V

    2000-01-01

    Several recent advances in wound care may offer promise for the treatment of hard-to-heal venous leg ulcers. One such treatment is Apligraf (Graftskin), a bilayered, living human skin construct. To assess the economic impact of Graftskin, a model was constructed to compare the annual medical costs and cost-effectiveness of treating hard-to-heal venous leg ulcers with Graftskin vs. compression therapy using Unna's boot. A semi-Markov model was used to describe the pattern of ulcer treatment, healing, and recurrence among patients with venous leg ulcers. Patients received 1 of 2 treatment regimens, Graftskin or Unna's boot, and were followed in the model for a 12-month period. The analysis was done from the perspective of a commercial health plan; therefore, only direct medical costs were included. Health care resource use included the primary therapeutic intervention, additional compression dressings, physician office visits, home health visits, laboratory tests and procedures, management of adverse events, and hospitalizations. The model estimated the annual medical cost of managing patients with hard-to-heal venous leg ulcers to be $20,041 for those treated with Graftskin and $27,493 for those treated with Unna's boot. In addition, treatment with Graftskin led to approximately 3 more months in the healed state per person per year than did treatment with Unna's boot. Because patients treated with Graftskin experienced improved healing compared with those treated with compression therapy using Unna's boot, they required fewer months of treatment for unhealed ulcers. As a result, the use of Graftskin for treating hard-to-heal venous leg ulcers resulted in lower overall treatment costs.

  19. Role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in gastric ulcer healing in mice.

    PubMed

    Kawahara, Y; Nakase, Y; Isomoto, Y; Matsuda, N; Amagase, K; Kato, S; Takeuchi, K

    2011-08-01

    We examined the role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in the healing of gastric ulcers in mice. Male M-CSF-deficient (op/op) and M-CSF-expressing heterozygote (+/?) mice were used. Gastric ulcers were induced by thermal cauterization under ether anesthesia, and healing was observed for 14 days after ulceration. The numbers of macrophages and microvessels in the gastric mucosa were determined immunohistochemically with anti-CD68 and anti-CD31 antibodies, respectively. Expression of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF) mRNA was determined via real-time reverse transcription-polymerase chain reaction (RT-PCR), and the mucosal content of prostaglandin (PG) E(2) was determined via enzyme immunoassay on day 10 after ulceration. The healing of gastric ulcers was significantly delayed in op/op mice compared with +/? mice. Further, significantly fewer macrophages were observed in the normal gastric mucosa of op/op mice than in +/? mice. Ulcer induction caused a marked accumulation of macrophages around the ulcer base in +/? mice, but this response was attenuated in op/op mice. The mucosal PGE(2) content as well as the expression of COX-2, VEGF, and TNF-α mRNA were all upregulated in the ulcerated area of +/? mice but significantly suppressed in op/op mice. The degree of vascularization in the ulcerated area was significantly lower in op/op mice than in +/? mice. Taken together, these results suggest that M-CSF-dependent macrophages play an important role in the healing of gastric ulcers, and that this action may be associated with angiogenesis promoted by upregulation of COX-2/PGE(2) production.

  20. Potential of oncostatin M to accelerate diabetic wound healing.

    PubMed

    Shin, Soo Hye; Han, Seung-Kyu; Jeong, Seong-Ho; Kim, Woo-Kyung

    2014-08-01

    Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti-inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full-thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left-side wounds (n = 10) and phosphate-buffered saline was applied on the two right-side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM-treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P < 0·05). The results of this study indicate that topical application of OSM may have the potential to accelerate healing of diabetic wounds.

  1. Quality Randomized Clinical Trials of Topical Diabetic Foot Ulcer Healing Agents

    PubMed Central

    Bolton, Laura L.

    2016-01-01

    Significance: Diabetic foot ulcers (DFU) significantly add to global economic, social, and clinical burdens. Healing a DFU fast and well limits complications that can lead to lower extremity amputation, morbidity, and mortality. Recent Advances: Many promising topical DFU healing agents have been studied in randomized clinical trials (RCT), but only one, becaplermin, has been cleared for this use by the United States Food and Drug Administration (FDA). Critical Issues: This critical review of DFU topical healing RCTs summarizes issues identified in their design and conduct, highlighting ways to improve study quality so researchers can increase the likelihood of RCT success in propelling effective topical DFU healing agents toward clinical use. Key issues include (1) inadequate sample size, (2) risk of bias, (3) irrelevant or unreported inclusion criteria, (4) substandard outcome measures, (5) unmatched group characteristics that predict nonhealing at baseline, (6) unequal or uncontrolled concurrent interventions or standard of care, (7) heterogeneous subject or DFU samples (8) unblinded allocation, treatment, or outcome measures, or (9) inadequate follow-up for clinical relevance. These can add bias or unexplained variability to RCT outcomes, limiting clinical or statistical significance and accuracy of results. Future Directions: This critical review summarizes ways to overcome these deficiencies to optimize DFU clinical trial design and conduct. It provides a blueprint for future excellence in RCTs testing safety and efficacy of topical DFU healing agents and smoothing the path to their clinical use. PMID:26989579

  2. Epidermal Graft Accelerates the Healing of Acute Wound: A Self-controlled Case Report

    PubMed Central

    Bystrzonowski, Nicola; Hachach-Haram, Nadine; Richards, Toby; Mosahebi, Afshin

    2016-01-01

    Summary: Wound care represents a significant socioeconomic burden, with over half of chronic wounds taking up to a year to heal. Measures to accelerate wound healing are beneficial to patients and also reduce the cost and burden of wound management. Epidermal grafting (EG) is an emerging option for autologous skin grafting in the outpatient setting to improve wound healing. Although several case series have previously reported good clinical outcome with EG, the healing rate in comparison to conservative wound management is not known. In this report, we compare the weekly healing rate of 2 separate wounds in the same patient, one treated with EG and the other with dressings. The treated wound showed accelerated healing, with the healing rate being the highest at the first 2 weeks after EG. The average healing time of the treated wound was 40% faster compared with the control wound. EG accelerates healing of acute wounds, potentially reducing the healthcare cost and surgical burden. PMID:27975024

  3. Investigation into the microbial flora of healing and non-healing decubitus ulcers.

    PubMed Central

    Daltrey, D C; Rhodes, B; Chattwood, J G

    1981-01-01

    Seventy-four pressure lesions in fifty-three geriatric patients were observed at weekly intervals to determine the bacterial flora and the healing index of each lesion, expressed as initial area of lesion (cm2) - final area of lesion (cm2) divided by time in days. The micro-organisms which caused infection included Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis and Bacteroides asaccharolyticus. Many lesions contained a mixed flora. P mirabilis and Ps aeruginosa were associated with necrotic (p less than 0.005) and enlarging (p less than 5 x 10(-7)) lesions. Bacteroides spp were associated with necrotic lesions (p less than 0.05). The presence of S aureus in a lesion was not associated with any particular trend in healing index. The implications of the microbiological findings are discussed. PMID:6790579

  4. Comparison of solcoseryl and epidermal growth factors (EGF) in healing of chronic gastroduodenal ulcerations and mucosal growth in rats.

    PubMed

    Konturek, S J; Brzozowski, T; Dembinski, A; Warzecha, A; Drozdowicz, D

    1988-02-01

    Solcoseryl, a deproteinized extract of calf blood, and EGF, produced by salivary glands, have been shown to enhance the healing of peptic ulcerations, but the mechanism of this effect is unknown. Since both solcoseryl and EGF have been reported to stimulate cell proliferation, we designed the study to compare the ulcer healing and growth promoting actions of these two agents in the same animals. Gastric and duodenal ulcerations were produced by serosal application of 100% acetic acid on an area of 13.8 mm2 of gastric and duodenal wall, respectively. In the control animals, 7 days after ulcer induction, the mean ulcer area was reduced to 7.1 +/- 1.2 mm2 in the stomach, and to 6.1 +/- 0.8 mm2 in the duodenum. After 14 days all ulcers were healed, both in the stomach and duodenum. Oral administration of solcoseryl (10 ml/kg-day) or EGF (30 micrograms/kg-day) for 7 days after ulcer induction resulted in a significant reduction in the ulcer area in the stomach, and to a greater extent in the duodenum. This enhancement of ulcer healing by solcoseryl was accompanied by a significant increase in the weight of the duodenal mucosa and the total contents of DNA and RNA after 7 days of treatment, and in the weight and nucleic acid contents in both the gastric and duodenal mucosa after 14 days of treatment. EGF also increased the weights and the nucleic acid contents in gastric and duodenal mucosa, but this was significant only after 14 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Comparison of tri-potassium di-citrato bismuthate tablets with ranitidine in healing and relapse of duodenal ulcers.

    PubMed

    Lee, F I; Samloff, I M; Hardman, M

    1985-06-08

    120 patients were randomly allocated to receive ranitidine 150 mg twice daily or a tri-potassium di-citrato bismuthate (TDB) tablet four times a day in a trial comparing the effects of these drugs in the short-term healing and post-healing relapse rates of duodenal ulceration. At 4 weeks 81% of those on ranitidine and 90% of those on TDB had healed ulcer craters. At 8 weeks 97% of those on ranitidine and 97% of those on TDB had healed. These differences are not significant. After ulcer healing, the cumulative rates of relapse, as determined endoscopically, for symptomatic and symptomless ulcers were 74% for ranitidine and 41% for TDB at 4 months (p less than 0.001), 87% for ranitidine and 55% for TDB at 8 months (p less than 0.001), and 89% for ranitidine and 62% for TDB at 12 months (p less than 0.001). Females had significantly lower relapse rates than males. In the ranitidine group smokers had a higher rate of early relapse and failure to remain healed at 12 months than did non-smokers; no such difference occurred in the TDB-treated group.

  6. Use of Sugar on the Healing of Diabetic Ulcers: A Review

    PubMed Central

    Biswas, Atanu; Bharara, Manish; Hurst, Craig; Gruessner, Rainer; Armstrong, David; Rilo, Horacio

    2010-01-01

    With the advent of several innovative wound care management tools, the choice of products and treatment modalities available to clinicians continues to expand. High costs associated with wound care, especially diabetic foot wounds, make it important for clinician scientists to research alternative therapies and optimally incorporate them into wound care protocols appropriately. This article reviews using sugar as a treatment option in diabetic foot care and provides a guide to its appropriate use in healing foot ulcers. In addition to a clinical case study, the physiological significance and advantages of sugar are discussed. PMID:20920433

  7. Ulcers

    MedlinePlus

    An ulcer is a crater-like sore on the skin or mucous membrane . Ulcers form when the top layers of skin or ... Ulcers can be caused by inflammation or infection. Some ulcers may be caused by a cancer.

  8. Mobilised bone marrow-derived cells accelerate wound healing.

    PubMed

    Wang, Yu; Sun, Yu; Yang, Xiao-Yan; Ji, Shi-Zhao; Han, Shu; Xia, Zhao-Fan

    2013-08-01

    Massive skin defects caused by severe burn and trauma are a clinical challenge to surgeons. Timely and effective wound closure is often hindered by the lack of skin donor site. Bone marrow-derived cells (BMDCs) have been shown to 'differentiate' into multiple tissue cells. In this study we focused on the direct manipulation of endogenous BMDCs, avoiding the immunocompatibility issues and complicated cell isolation, purification, identification and amplification procedures in vitro on wound repair. We found that mobilisation of the BMDCs into the circulation significantly increased the amount of BMDCs at the injury site which in turn accelerated healing of large open wound. We used a chimeric green fluorescent protein (GFP) mouse model to track BMDCs and to investigate their role in full-thickness skin excisional wounds. We have shown that bone marrow mobilisation by granulocyte colony stimulating factor (G-CSF) exerted multiple beneficial effects on skin repair, both by increasing the engraftment of BMDCs into the skin to differentiate into multiple skin cell types and by upregulating essential cytokine mRNAs critical to wound repair. The potential trophic effects of G-CSF on bone marrow stem cells to accelerate wound healing could have a significant clinical impact.

  9. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice.

    PubMed

    Geiger, Adolf; Walker, Audrey; Nissen, Erwin

    2015-11-13

    Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers.

  10. Atypical Diabetic Foot Ulcer Keratinocyte Protein Signaling Correlates with Impaired Wound Healing

    PubMed Central

    Hoke, Glenn D.; Ramos, Corrine; Hoke, Nicholas N.; Crossland, Mary C.; Shawler, Lisa G.

    2016-01-01

    Diabetes mellitus is associated with chronic diabetic foot ulcers (DFUs) and wound infections often resulting in lower extremity amputations. The protein signaling architecture of the mechanisms responsible for impaired DFU healing has not been characterized. In this preliminary clinical study, the intracellular levels of proteins involved in signal transduction networks relevant to wound healing were non-biasedly measured using reverse-phase protein arrays (RPPA) in keratinocytes isolated from DFU wound biopsies. RPPA allows for the simultaneous documentation and assessment of the signaling pathways active in each DFU. Thus, RPPA provides for the accurate mapping of wound healing pathways associated with apoptosis, proliferation, senescence, survival, and angiogenesis. From the study data, we have identified potential diagnostic, or predictive, biomarkers for DFU wound healing derived from the ratios of quantified signaling protein expressions within interconnected pathways. These biomarkers may allow physicians to personalize therapeutic strategies for DFU management on an individual basis based upon the signaling architecture present in each wound. Additionally, we have identified altered, interconnected signaling pathways within DFU keratinocytes that may help guide the development of therapeutics to modulate these dysregulated pathways, many of which parallel the therapeutic targets which are the hallmarks of molecular therapies for treating cancer. PMID:27840833

  11. Effects of insulin on the skin: possible healing benefits for diabetic foot ulcers.

    PubMed

    Emanuelli, T; Burgeiro, A; Carvalho, E

    2016-12-01

    Diabetic foot ulcers affect 15-20 % of all diabetic patients and remain an important challenge since the available therapies have limited efficacy and some of the novel therapeutic approaches, which include growth factors and stem cells, are highly expensive and their safety remains to be evaluated. Despite its low cost and safety, the interest for topical insulin as a healing agent has increased only in the last 20 years. The molecular mechanisms of insulin signaling and its metabolic effects have been well studied in its classical target tissues. However, little is known about the specific effects of insulin in healthy or even diabetic skin. In addition, the mechanisms involved in the effects of insulin on wound healing have been virtually unknown until about 10 years ago. This paper will review the most recent advances in the cellular and molecular mechanisms that underlie the beneficial effects of insulin on skin wound healing in diabetes. Emerging evidence that links dysfunction of key cellular organelles, namely the endoplasmic reticulum and the mitochondria, to changes in the autophagy response, as well as the impaired wound healing in diabetic patients will also be discussed along with the putative mechanisms whereby insulin could regulate/modulate these alterations.

  12. Micronized, particulate dermal matrix to manage a non-healing pressure ulcer with undermined wound edges: a case report.

    PubMed

    Allam, Reynald C

    2007-04-01

    Pressure ulcers with undermined edges are generally hard to treat and may require surgical debridement and flap coverage. A woman with a 5-month history of a non-healing, undermined, sacro-coccygeal pressure ulcer presented for care at the author's wound care center. Because traditional wound care had failed and surgical debridement and repair was contraindicated due to her overall poor general health and malnutrition, an injectable dermal filler was applied inside the wound. The matrix filler was covered with secondary and tertiary dressings and the wound healed after 8 weeks with no adverse effects or infection. The results of this and previously published case studies suggest that injectable dermal matrix may be a viable option for non-surgical treatment of difficult-to-heal pressure ulcers with undermining. Additional safety, efficacy, and cost-effectiveness studies seem warranted.

  13. The Healing Effect of Low-Temperature Atmospheric-Pressure Plasma in Pressure Ulcer: A Randomized Controlled Trial.

    PubMed

    Chuangsuwanich, Apirag; Assadamongkol, Tananchai; Boonyawan, Dheerawan

    2016-08-31

    Pressure ulcers are difficult to treat. Recent reports of low-temperature atmospheric-pressure plasma (LTAPP) indicated its safe and effectiveness in chronic wound care management. It has been shown both in vitro and vivo studies that LTAPP not only helps facilitate wound healing but also has antimicrobial efficacy due to its composition of ion and electron, free radicals, and ultraviolet ray. We studied the beneficial effect of LTAPP specifically on pressure ulcers. In a prospective randomized study, 50 patients with pressure ulcers were divided into 2 groups: Control group received standard wound care and the study group was treated with LTAPP once every week for 8 consecutive weeks in addition to standard wound care. We found that the group treated with LTAPP had significantly better PUSH (Pressure Ulcer Scale for Healing) scores and exudate amount after 1 week of treatment. There was also a reduction in bacterial load after 1 treatment regardless of the species of bacteria identified.

  14. The n-Hexane, ethylacetate, and butanol fractions from Hydnocarpi Semen enhanced wound healing in a mice ulcer model.

    PubMed

    Lee, Geum Seon; Yim, Dongsool; Cheong, Jae Hoon; Kang, Tae Jin

    2012-12-01

    Our previous report showed that Hydnocarpi Semen (HS) extract has wound repair activity at ulcer lesion in diabetic mice. In this study, fractions of n-Hexane, ethylacetate (EtOAc), and butanol (BuOH) from HS crude extract were evaluated for their wound healing activity by using in vivo diabetic ulcer models and in vitro acute inflammation model. Although n-Hexane and EtOAc fractions promote wound healing in mice with ulcer, the BuOH fraction exhibited the most potent wound healing activity and the wound area score significantly decreased after treatment of BuOH fraction even at dose of 2 mg/kg. BuOH fraction stimulated macrophages to increase the production of nitric oxide (NO) and TNF-α. The BuOH fraction also enhanced the production of TGF-β and VEGF, which were involved in fibroblast activation and angiogenesis. The mRNA expression and activation of MMP-9 were increased by three fractions and the activity was higher in BuOH fraction-treated group compared to the other groups. The mechanism that the HS helps to promote healing of diabetic ulcer is possibly associated with the production of TNF-α, a proinflammatory cytokine, as well as the secretion of VEGF, TGF-β, and MMP-9, which were involved in proliferation of capillaries and fibroblasts. These results suggest that HS can be a new candidate material for the treatment of wound in skin ulcer.

  15. Imaging Mass Spectrometry for Assessing Cutaneous Wound Healing: Analysis of Pressure Ulcers

    PubMed Central

    2015-01-01

    Imaging mass spectrometry (IMS) was employed for the analysis of frozen skin biopsies to investigate the differences between stage IV pressure ulcers that remain stalled, stagnant, and unhealed versus those exhibiting clinical and histological signs of improvement. Our data reveal a rich diversity of proteins that are dynamically modulated, and we selectively highlight a family of calcium binding proteins (S-100 molecules) including calcyclin (S100-A6), calgranulins A (S100-A8) and B (S100-A9), and calgizzarin (S100-A11). IMS allowed us to target three discrete regions of interest: the wound bed, adjacent dermis, and hypertrophic epidermis. Plots derived using unsupervised principal component analysis of the global protein signatures within these three spatial niches indicate that these data from wound signatures have potential as a prognostic tool since they appear to delineate wounds that are favorably responding to therapeutic interventions versus those that remain stagnant or intractable in their healing status. Our discovery-based approach with IMS augments current knowledge of the molecular signatures within pressure ulcers while providing a rationale for a focused examination of the role of calcium modulators within the context of impaired wound healing. PMID:25488653

  16. Healing with basic fibroblast growth factor is associated with reduced indomethacin induced relapse in a human model of gastric ulceration.

    PubMed Central

    Hull, M A; Knifton, A; Filipowicz, B; Brough, J L; Vautier, G; Hawkey, C J

    1997-01-01

    BACKGROUND: Acid stable basic fibroblast growth factor (bFGF) promotes angiogenesis and healing of gastric ulcers in rats and reduces subsequent non-steroidal anti-inflammatory drug (NSAID) induced relapse. AIMS: To test in a double blind, placebo controlled, three way crossover study whether bFGF promotes healing and reduces subsequent relapse in a human model of gastric ulceration. SUBJECTS: Twelve healthy volunteers. METHODS: Subjects took aspirin 900 mg twice daily (days 1-3) with bFGF 0.1 mg twice daily or cimetidine 400 mg twice daily or placebo (days 1-14) and then indomethacin 50 mg thrice daily (days 15-21). Endoscopy was performed on days 1, 4, 8, 15, and 22 during each treatment period. Eight antral biopsy specimens were taken on day 1 and the number of unhealed biopsy induced mini-ulcers and NSAID induced erosions counted during subsequent endoscopies. RESULTS: Basic FGF and cimetidine were protective against aspirin and indomethacin induced duodenal (but not gastric) injury compared with placebo. There was significant relapse of biopsy induced mini-ulcers after indomethacin only in the placebo group (0 (0-0) before v 1 (0-4.5) after; p > 0.05). TGP-580 was detected in serum of one volunteer. CONCLUSIONS: Healing with bFGF (and cimetidine) was associated with reduced NSAID induced ulcer relapse in this model of gastric ulceration. PMID:9071932

  17. Gastroprotective and Ulcer Healing Effects of Essential Oil of Hyptis martiusii Benth. (Lamiaceae)

    PubMed Central

    Caldas, Germana Freire Rocha; Oliveira, Alisson Rodrigo da Silva; Araújo, Alice Valença; Quixabeira, Dafne Carolina Alves; Silva-Neto, Jacinto da Costa; Costa-Silva, João Henrique; de Menezes, Irwin Rose Alencar; Ferreira, Fabiano; Leite, Ana Cristina Lima; da Costa, José Galberto Martins; Wanderley, Almir Gonçalves

    2014-01-01

    Hyptis martiusii Benth. is an aromatic plant found in abundance in northeastern Brazil that is used in ethnomedicine to treat gastric disorders. The aim of this study was to elucidate the mechanisms of action involved in the gastroprotection of the essential oil of Hyptis martiusii (EOHM) and to evaluate its healing capacity. Wistar rats were exposed to different protocols and subsequently were treated with 1% Tween-80 aqueous solution (negative control), pantoprazole, carbenoxolone, N-acetylcysteine (depending on the specificity of each model) or EOHM. The antisecretory activity (basal or stimulated) was determined using the pyloric ligature method. The gastroprotective action of nitric oxide and sulphydryl groups (–SH groups), as well as the quantification of adherent mucus and the levels of malondialdehyde and –SH groups in gastric mucosa, were evaluated using ethanol-induced gastric ulcer model. The healing ability was evaluated using the acetic acid-induced gastric ulcer model and histological and immunohistochemical analysis (HE, PAS and PCNA). EOHM (400 mg/kg) reduced the volume and acidity of gastric secretion stimulated by histamine and pentagastrin. The gastroprotective effect of EOHM involves the participation of endogenous sulfhydryl groups. EOHM increased mucus production (54.8%), reduced levels of MDA (72.5%) and prevented the depletion of –SH groups (73.8%) in the gastric mucosa. The treatment with EOHM reduced in 70.3% the gastric lesion area, promoting significant regeneration of the gastric mucosa, as confirmed by histological analysis and analysis of proliferating cell nuclear antigen. The results show that gastroprotective effect of EOHM is mediated by cytoprotective and antioxidant mechanisms and by their antisecretory activity, and suggest that the essential oil of Hyptis martiusii is a promising candidate for the treatment of gastric ulcers. PMID:24454726

  18. Hydrogen sulfide accelerates wound healing in diabetic rats

    PubMed Central

    Wang, Guoguang; Li, Wei; Chen, Qingying; Jiang, Yuxin; Lu, Xiaohua; Zhao, Xue

    2015-01-01

    Aim: The aim of this study was to explore the role of hydrogen sulfide on wound healing in diabetic rats. Methods: Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (STZ) (in 0.1 mol/L citrate buffer, Ph 4.5) at dose of 70 mg/kg. Diabetic and age-matched non-diabetic rats were randomly assigned to three groups: untreated diabetic controls (UDC), treated diabetic administrations (TDA), and non-diabetic controls (NDC). Wound Healing Model was prepared by making a round incision (2.0 cm in diameter) in full thickness. Rats from TDA receive 2% sodium bisulfide ointment on wound, and animals from UDC and NDC receive control cream. After treatment of 21 days with sodium bisulfide, blood samples were collected for determination of vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), antioxidant effects. Granulation tissues from the wound were processed for histological examination and analysis of western blot. Results: The study indicated a significant increase in levels of VEGF and ICAM-1 and a decline in activity of coagulation in diabetic rats treated with sodium bisulfide. Sodium bisulfide treatment raised the activity of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein expression, and decreased tumor necrosis factor α (TNF-α) protein expression in diabetic rats. Conclusions: The findings in present study suggested that hydrogen sulfide accelerates the wound healing in rats with diabetes. The beneficial effect of H2S may be associated with formation of granulation, anti-inflammation, antioxidant, and the increased level of vascular endothelial growth factor (VEGF). PMID:26191204

  19. Effects of esomeprazole on the healing process of post-endoscopic submucosal dissection gastric ulcers: a single arm, prospective trial

    PubMed Central

    Ichida, Takashi; Kusano, Fumihiko; Sakai, Yoshinori

    2016-01-01

    Objectives: Gastric endoscopic submucosal dissection (ESD) is currently a standard procedure. ESD enables en-bloc resection of large lesions, while inducing larger artificial ulcers to a greater extent than conventional procedures. Several studies have reported that proton pump inhibitors (PPIs) prevent delayed bleeding and expedite the artificial ulcer healing process. Esomeprazole, an S-isomer of omeprazole, is reportedly one of strongest inhibitors of gastric acid secretion. Previous studies have examined the effectiveness of esomeprazole. Our goal was to verify the effects of esomeprazole on artificial ulcers in a prospective study. Methods: A total of 185 patients underwent ESD for gastric neoplasms at our hospital between January 2013 and June 2015. Among these 185 patients, 49 post-ESD scar lesions were included in this prospective trial. First, 20 mg esomeprazole was orally administered to all subjects before and after the procedure. We then evaluated the delayed bleeding rate and ulcer scarring rates at 4 weeks and 8 weeks after the procedure by using a gastric ulcer stage system. Results: There was one case of delayed bleeding (2.0%). Regardless of Helicobacter pylori infection status, ulcer scarring rates at weeks 4 and 8 were respectively 28.6% (14/49) and 98% (48/49). Conclusions: Our results suggest that oral administration of esomeprazole alone may be sufficient for prompt healing of artificial gastric ulcers induced by ESD (UMIN000009367). PMID:27928455

  20. Preliminary investigation of topical nitroglycerin formulations containing natural wound healing agent in diabetes-induced foot ulcer.

    PubMed

    Hotkar, Mukesh S; Avachat, Amelia M; Bhosale, Sagar S; Oswal, Yogesh M

    2015-04-01

    Nitroglycerin (NTG) is an organic nitrate rapidly denitrated by enzymes to release free radical nitric oxide and shows improved wound healing and tissue protection from oxidative damage. The purpose of this study was to evaluate whether topical application of NTG in the form of gel/ointment along with a natural wound healing agent, aloe vera, would bring about wound healing by using diabetes-induced foot ulcer model and rat excision wound model. All these formulations were evaluated for pH, viscosity, drug content and ex vivo diffusion studies using rat skin. Based on ex vivo permeation studies, the formulation consisting of carbopol 974p as a gelling agent and aloe vera was found to be suitable. The in vivo study used streptozotocin-induced diabetic foot ulcer and rat excision wound models to analyse wound healing activity. The wound size in animals of all treated groups was significantly reduced compared with that of the diabetic control and marketed treated animals. This study showed that the gel formed with carbopol 974p (1%) and aloe vera promotes significant wound healing and closure in diabetic rats compared with the commercial product and provides a promising product to be used in diabetes-induced foot ulcer.

  1. Effectiveness of Removable Walker Cast Versus Nonremovable Fiberglass Off-Bearing Cast in the Healing of Diabetic Plantar Foot Ulcer

    PubMed Central

    Faglia, Ezio; Caravaggi, Carlo; Clerici, Giacomo; Sganzaroli, Adriana; Curci, Vincenzo; Vailati, Wanda; Simonetti, Daniele; Sommalvico, Francesco

    2010-01-01

    OBJECTIVE To evaluate the efficacy of a removable cast walker compared with that of a nonremovable fiberglass off-bearing cast in the treatment of diabetic plantar foot ulcer. RESEARCH DESIGN AND METHODS Forty-five adult diabetic patients with nonischemic, noninfected neuropathic plantar ulcer were randomly assigned for treatment with a nonremovable fiberglass off-bearing cast (total contact cast [TCC] group) or walker cast (Stabil-D group). Treatment duration was 90 days. Percent reduction in ulcer surface area and total healing rates were evaluated after treatment. RESULTS A total of 48 patients were screened; however, 2 patients in the TCC group and 1 patient in the Stabil-D group did not complete the study and were considered dropouts. There were no significant differences in demographic and clinic characteristics of the 45 patients completing the study. Ulcer surface decreased from 1.41 to 0.21 cm2 (P < 0.001) in the TCC group and from 2.18 to 0.45 cm2 (P < 0.001) in the Stabil-D group, with no significant differences between groups (P = 0.722). Seventeen patients (73.9%) in the TCC group and 16 patients (72.7%) in the Stabil-D group achieved healing (P = 0.794). Average healing time was 35.3 ± 3.1 and 39.7 ± 4.2 days in the TCC and Stabil-D group, respectively (P = 0.708). CONCLUSIONS The Stabil-D cast walker, although removable, was equivalent in efficacy to the TCC in terms of ulcer size reduction and total healing rate. The easier use of Stabil-D may help increase the use of off-loading devices in the management of plantar neuropathic diabetic foot ulcers. PMID:20357377

  2. Ulcers

    MedlinePlus

    ... give me an ulcer!" "There's been so much stress at work lately, I'm sure I'll get an ulcer." "Don't worry so much. Do you want an ulcer?" When people talk like this, it sounds like ulcers are easy to give and easy to get. It also sounds like stress is to blame. But is that the real ...

  3. The effect of flexor tenotomy on healing and prevention of neuropathic diabetic foot ulcers on the distal end of the toe

    PubMed Central

    2013-01-01

    Background Flexor tenotomy is a minimally invasive surgical alternative for the treatment of neuropathic diabetic foot ulcers on the distal end of the toe. The influence of infection on healing and time to heal after flexor tenotomy is unknown. Flexor tenotomy can also be used as a prophylactic treatment. The effectiveness as a prophylactic treatment has not been described before. Methods A retrospective study was performed with the inclusion of all consecutive flexor tenotomies from one hospital between January 2005 and December 2011. Results From 38 ulcers, 35 healed (92%), with a mean time to heal of 22 ± 26 days. The longest duration for healing was found for infected ulcers that were penetrating to bone (35 days; p = .042). Cases of prophylactic flexor tenotomies (n=9) did not result in any ulcer or other complications during follow-up. Conclusions The results of this study suggest that flexor tenotomy may be beneficial for neuropathic diabetic foot ulcers on the distal end of the toe, with a high healing percentage and a short mean time to heal. Infected ulcers that penetrated to bone took a significantly longer time to heal. Prospective research, to confirm the results of this retrospective study, should be performed. PMID:23347589

  4. Histological healing favors lower risk of colon carcinoma in extensive ulcerative colitis

    PubMed Central

    Korelitz, Burton I; Sultan, Keith; Kothari, Megha; Arapos, Leo; Schneider, Judy; Panagopoulos, Georgia

    2014-01-01

    AIM: To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer (CC) or high grade dysplasia (HGD). METHODS: This is a single center (Lenox Hill Hospital) retrospective cohort and descriptive study of extensive ulcerative colitis (UC) for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis. Data analyzed included: duration of UC, date of diagnosis of (CC) or (HGD), number of surveillance colonoscopies, and biopsies showing histological inflammation and its severity in each of 6 segments when endoscopic appearance is normal. Two subgroups of patients were compared: group 1 patients who developed CC/HGD and group 2 patients who did not develop CC/HGD. RESULTS: Of 115 patients with longstanding UC reviewed, 68 patients met the inclusion criteria. Twenty patients were in group 1 and 48 in group 2. We identified the number of times for each patient when the endoscopic appearance was normal but biopsies nevertheless showed inflammation. Overall, histological disease activity in the absence of gross/endoscopic disease was found in 31.2% (95%CI: 28%-35%) of colonoscopies performed on the entire cohort of 68 patients. Histological disease activity when the colonoscopy showed an absence of gross disease activity was more common in group 1 than group 2 patients, 88% (95%CI: 72%-97%) vs 59% (95%CI: 53%-64%). Only 3/20 (15%) of patients in group 1 ever had a colonoscopy completely without demonstrated disease activity (i.e., no endoscopic or histological activity) as compared to 37/48 (77%) of patients in group 2, and only 3.3% (95%CI: 0.09%-8.3%) of colonoscopies in group 1 had no histological inflammation compared to 23% (95%CI: 20%-27%) in group 2. CONCLUSION: Progression to HGD or CC in extensive ulcerative colitis of long standing was more frequently encountered among

  5. Clinical efficacy of a silver-releasing foam dressing in venous leg ulcer healing: a randomised controlled trial.

    PubMed

    Senet, Patricia; Bause, Renzo; Jørgensen, Bo; Fogh, Karsten

    2014-12-01

    Biatain and Biatain-Ag are two identical wound dressings except the fact that Biatain-Ag releases silver. In the present multinational double-blinded randomised controlled trial the effect of the two dressings were compared for treatment of venous leg ulcers. A total of 181 patients were treated for 6 weeks with either Biatain or Biatain-Ag followed by 4 weeks treatment with Biatain. Biatain-Ag showed superior performance in relative wound area reduction after 6 weeks treatment and the estimated treatment difference increased after 10 weeks indicating that the effect of silver continues at least for 4 weeks after treatment. A subgroup of the patients differed significantly from the others with respect to parameters associated with a poor healing prognosis; patients were older, had significant history of venous thrombosis, larger ulcers with longer duration and more often recurrent. For this subgroup of patients Biatain-Ag showed significant (P < 0·05) better performance in terms of relative ulcer area reduction and healing rate. In conclusion, this study suggests the superior performance of Biatain-Ag compared with the non silver-releasing dressing Biatain in particular for patients having ulcers associated with a poor healing prognosis.

  6. Transdermal Wound Oxygen Therapy on Pressure Ulcer Healing: A Single-Blind Multi-Center Randomized Controlled Trial

    PubMed Central

    Azimian, Jalil; Dehghan Nayeri, Nahid; Pourkhaleghi, Enis; Ansari, Monireh

    2015-01-01

    Background: Although healthcare quality has considerably improved in many countries, pressure ulcer is still a major health challenge worldwide. Objectives: The current study aimed to evaluate the effects of TWOT on the healing of pressure ulcers. Patients and Methods: This study was a randomized controlled trial, and the convenient sample including 100 patients hospitalized in two university-affiliated medical-surgical intensive care units and one neurology unit located in Qazvin, Iran were studied. Patients with stage II-IV pressure ulcer on the sacral or ischial areas were randomly assigned to either the control or the experimental groups. The experimental group received a 12-day transdermal wound oxygen therapy. Wound status was assessed seven times before the intervention, as well as two, four, six, eight, ten, and twelve days after the intervention. Results: After 12 days of wound oxygen therapy, the number of patients with complete wound healing in the experimental group was significantly greater than that of the control group. Moreover, the total mean of wound area in the experimental group was significantly lower than that of the control group. Conclusions: Transdermal wound oxygen therapy can effectively promote wound healing in patients with pressure ulcers. PMID:26734476

  7. Gastric Ulcers in Middle-Aged Rats: The Healing Effect of Essential Oil from Citrus aurantium L. (Rutaceae)

    PubMed Central

    Polo, C. M.; Moraes, T. M.; Pellizzon, C. H.; Marques, M. O.; Rocha, L. R. M.; Hiruma-Lima, C. A.

    2012-01-01

    The elderly population has experienced increased life expectancy as well as the increased incidence of gastric ulcers. The peels of fruits from Citrus aurantium L., popularly known in Brazil as orange bitter, are commonly used asatea form for the treatment of gastrointestinal tract disorders, such as ulcer and gastritis. We evaluated the healing effects of essential oil from the peels of Citrus aurantium fruits (OEC) on gastric ulcers in middle-aged rats. We examined the effects of a 14-day chronic OEC treatment on gastric mucosa in middle-aged male Wistar rats that were given acetic-acid-induced gastric lesions by morphometric and immunohistological analyses. Oral OEC treatment significantly reduced the lesion area (76%) within the gastric mucosa and significantly increased (P < .05) the height of regenerated mucosa (59%) when compared to the negative control group. Immunohistochemical analysis of the molecular markers such as COX-2, HSP-70, VEGF, and PCNA in the gastric mucosa confirmed that OEC treatment induced healing effects by increasing the number of new blood vessels and by augmenting gastric mucus in the mucosa glands. These results suggest that the oil from Citrus aurantium effectively heals gastric ulcers in middle-aged animals; however, safe use of OEC demands special care and precautions. PMID:23243451

  8. Delayed Healing of Sickle Cell Ulcers Is due to Impaired Angiogenesis and CXCL12 Secretion in Skin Wounds.

    PubMed

    Nguyen, Van Tuan; Nassar, Dany; Batteux, Fréderic; Raymond, Karine; Tharaux, Pierre-Louis; Aractingi, Sélim

    2016-02-01

    Leg ulcers are a major complication of sickle cell disease that occur in 2.5-40% of patients. Leg ulcers are responsible for frequent complications because they are often long-lasting and are highly resistant to therapy. Although their occurrence is associated with hyperhemolysis, the mechanisms underlying sickle cell ulcers remain poorly understood. In this study, we show that skin wound healing is severely altered in old SAD sickle cell mice but is normal in young animals, consistent with reports in humans. Alterations of wound healing were associated with impaired blood and lymphatic angiogenesis in the wound beds and poor endothelial progenitor cell mobilization from the bone marrow. CXCL12 secretion by keratinocytes and inflammatory cells was low in the wounds of SAD mice. Local therapy with endothelial progenitor cells or recombinant CXCL12 injections restored wound angiogenesis and rescued the healing defect together with mobilization of circulating endothelial progenitor cells. To our knowledge, this is a previously unreported study of the cellular and molecular mechanisms of sickle cell ulcers in a murine model that provides promising therapeutic perspectives for clinical trials.

  9. Osthole Promotes Endochondral Ossification and Accelerates Fracture Healing in Mice.

    PubMed

    Zhang, Zhongrong; Leung, Wing Nang; Li, Gang; Lai, Yau Ming; Chan, Chun Wai

    2016-12-01

    Osthole has been found to restore bone mass in preclinical osteoporotic models. In the present study, we investigated the effects of osthole on bone fracture repair in mice. Adult C57BL/6 mice were subjected to transverse femoral fractures and administrated orally with 20 mg/kg osthole and vehicle solvent daily from week 1 post-operation. Fracture callus were analyzed by plain radiography, micro-computed tomography, histology, molecular imaging and immunohistochemistry and tartrate-resistant acid phosphatase staining. Results demonstrated that osthole treatment enhanced removal of cartilage and bony union during reparative stage without significant interfering on remodeling process. In vivo molecular imaging showed bone formation rate of the treatment group was almost twofold of control group at week 2 post-operation. Osthole augmented the expression of alkaline phosphatase and collagen type X in hypertrophic chondrocytes as well as expression of bone morphogenetic protein-2, osteocalcin and alkaline phosphatase in osteoblastic cells, indicating it promoted mineralization of hypertrophic cartilage and woven bone growth simultaneously during endochondral healing. In summary, osthole promotes endochondral ossification via upregulation of maturation osteogenic marker genes in chondrocytes and subsequently accelerates fracture repair and bony fusion.

  10. Venous ulcer review

    PubMed Central

    Bevis, Paul; Earnshaw, Jonothan

    2011-01-01

    Clinical question: What is the best treatment for venous ulcers? Results: Compression aids ulcer healing. Pentoxifylline can aid ulcer healing. Artificial skin grafts are more effective than other skin grafts in helping ulcer healing. Correction of underlying venous incompetence reduces ulcer recurrence. Implementation: Potential pitfalls to avoid are: Failure to exclude underlying arterial disease before application of compression.Unusual-looking ulcers or those slow to heal should be biopsied to exclude malignant transformation. PMID:21673869

  11. Culture-Based Screening of Aerobic Microbiome in Diabetic Foot Subjects and Developing Non-healing Ulcers

    PubMed Central

    Noor, Saba; Ahmad, Jamal; Parwez, Iqbal; Ozair, Maaz

    2016-01-01

    The study was carried on diabetic foot patients to deduce clinical attributes, the occurrence of the range of aerobic microbial flora and to assess their comparative in vitro susceptibility to the customarily used antimicrobials. We also studied the potential risk factors involved in the development of non-healing ulcers. A total of 87 organisms were isolated from 70 specimens, including Escherichia coli (19.5%) among the Gram-negative and Staphylococcus aureus (18.4%) among the Gram-positive as the predominant aerobes explored. Pseudomonas aeruginosa and E. coli were predominant isolates of non-healing ulcers. The antimicrobial sensitivity pattern revealed that vancomycin (100%) and amikacin (90.4%) exhibited highest sensitivity to Gram-positive cocci, while all strains of P. aeruginosa were sensitive toward imipenem (100%). The prevalent uncontrolled glycemic status, altered lipid spectra, the existence of neuropathy, and peripheral vascular disease, suggested predisposition toward the development of non-healing lesions. The study has underlined the need for continuous surveillance of bacteria and their antimicrobial sensitivity blueprints to provide the basis for empirical therapy and to minimize the risk of complications. Further, stringent clinical evaluation, and medical history will help in revealing the risk of developing non-healing status in diabetic foot ulcers. PMID:27920754

  12. The efficacy of topical royal jelly on healing of diabetic foot ulcers: a double-blind placebo-controlled clinical trial.

    PubMed

    Siavash, Mansour; Shokri, Saeideh; Haghighi, Sepehr; Shahtalebi, Mohammad Ali; Farajzadehgan, Ziba

    2015-04-01

    Foot ulcers are major sources of morbidity in individuals with diabetes mellitus. As royal jelly (RJ, a worker honey bee product) contains enzymatic, antibacterial and vasodilative properties, it can potentially help in healing of diabetic foot ulcers (DFUs). This study aimed to evaluate the efficacy of topical RJ on healing of DFUs. Diabetic patients with foot ulcers who were referred to us at Khorshid Hospital, Isfahan, Iran, were managed by offloading, infection control, vascular improvement and debridement (if required). Then, all ulcers were randomly selected to receive either 5% sterile topical RJ or placebo on their total surface area. Patients were followed for 3 months or until complete healing. Twenty-five patients (6 females and 19 males) and a total of 64 ulcers were included and randomly allocated to case or control group (32 per group). Four ulcers were excluded and 60 ulcers included in the final analysis. Healing parameters including depth, length and width reduction rate, duration of complete healing and incidence of complete healing did not show any significant difference (P = 0·69, 0·95, 0·7, 0·74 and 0·6, respectively) between groups. We did not observe any side effect of topical RJ application. This study could not confirm any significant superiority of 5% topical RJ over placebo for the treatment of DFUs.

  13. Evaluation of wound healing in diabetic foot ulcer using platelet-rich plasma gel: A single-arm clinical trial.

    PubMed

    Mohammadi, Mohammad Hossein; Molavi, Behnam; Mohammadi, Saeed; Nikbakht, Mohsen; Mohammadi, Ashraf Malek; Mostafaei, Shayan; Norooznezhad, Amir Hossein; Ghorbani Abdegah, Ali; Ghavamzadeh, Ardeshir

    2016-11-02

    The aim of the present study was to evaluate the effectiveness of using autologous platelet-rich plasma (PRP) gel for treatment of diabetic foot ulcer (DFU) during the first 4 weeks of the treatment. In this longitudinal and single-arm trial, 100 patients were randomly selected after meeting certain inclusion and exclusion criteria; of these 100 patients, 70 (70%) were enrolled in the trial. After the primary care actions such as wound debridement, the area of each wound was calculated and recorded. The PRP therapy (2mL/cm(2) of ulcers) was performed weekly until the healing time for each patient. We used one sample T-test for healing wounds and Bootstrap resampling approach for reporting confidence interval with 1000 Bootstrap samples. The p-value<0.05 were considered statistically significant. The mean (SD) of DFU duration was 19.71 weeks (4.94) for units sampling. The ratio of subjects who withdrew from the study was calculated to be 2 (2.8%). Average area of 71 ulcers in the mentioned number of cases was calculated to be 6.11cm(2) (SD: 4.37). Also, the mean, median (SD) of healing time was 8.7, 8 weeks (SD: 3.93) except for 2 mentioned cases. According to one sample T-test, wound area (cm(2)), on average, significantly decreased to 51.9% (CI: 46.7-57.1) through the first four weeks of therapy. Furthermore, significant correlation (0.22) was not found between area of ulcers and healing duration (p-value>0.5). According to the results, PRP could be considered as a candidate treatment for non-healing DFUs as it may prevent future complications such as amputation or death in this pathological phenomenon.

  14. Circadian rhythms accelerate wound healing in female Siberian hamsters.

    PubMed

    Cable, Erin J; Onishi, Kenneth G; Prendergast, Brian J

    2017-03-15

    Circadian rhythms (CRs) provide temporal regulation and coordination of numerous physiological traits, including immune function. CRs in multiple aspects of immune function are impaired in rodents that have been rendered circadian-arrhythmic through various methods. In Siberian hamsters, circadian arrhythmia can be induced by disruptive light treatments (DPS). Here we examined CRs in wound healing, and the effects of circadian disruption on wound healing in DPS-arrhythmic hamsters. Circadian entrained/rhythmic (RHYTH) and behaviorally-arrhythmic (ARR) female hamsters were administered a cutaneous wound either 3h after light onset (ZT03) or 2h after dark onset (ZT18); wound size was quantified daily using image analyses. Among RHYTH hamsters, ZT03 wounds healed faster than ZT18 wounds, whereas in ARR hamsters, circadian phase did not affect wound healing. In addition, wounds healed slower in ARR hamsters. The results document a clear CR in wound healing, and indicate that the mere presence of organismal circadian organization enhances this aspect of immune function. Faster wound healing in CR-competent hamsters may be mediated by CR-driven coordination of the temporal order of mechanisms (inflammation, leukocyte trafficking, tissue remodeling) underlying cutaneous wound healing.

  15. The debridement of hard to heal leg ulcers by means of a new device based on Fluidjet technology.

    PubMed

    Mosti, Giovanni; Iabichella, Maria Letizia; Picerni, Pietro; Magliaro, Antonio; Mattaliano, Vincenzo

    2005-12-01

    Debridement plays an essential role in the wound-bed preparation of necrotic and sloughy ulcers, being a mandatory step to achieve a well-debrided bed, proceeding towards healing. This study reports our experience with Versajet [Versajet Hydrosurgery System (Smith & Nephew, Hull, UK)], a new device for the debridement of exudating ulcers, based on Fluidjet technology, which excises and aspirates the unwanted tissue by using the Venturi effect. In a 10-month time period, a total of 68 patients, out of a setting of 167 patients, hospitalised as affected by chronic, hard-to-heal leg ulcers, stuck in the inflammatory phase, were treated with Versajet. Based on ulcer characteristics and clinical conditions, the remaining 99 patients underwent traditional debridement with moist dressings (controls). In the majority of Versajet-treated cases (46), an adequately debrided wound bed was achieved with one operative procedure; two and three procedures were required in 17 and 5 patients, respectively. Almost all the procedures were performed in the ward at the patient's bedside. This procedure is quick (mean time per treatment is about 5 minutes); when compared with a traditional treatment with moist dressings, Versajet considerably shortens the in-hospital stay and promotes a quicker healing process. When used by an experienced surgeon, Versajet allows a selective debridement, as it makes it possible to remove only the tissue centred in the working end and spare the healthy tissue. Debriding with Versajet is highly effective in reducing the bacterial load of the ulcer bed. The pain caused by Versajet is well tolerated, especially when set for gentle debridement. If multiple treatments are required, the combined use with moist dressings is synergistic, as the dressings soften the necrotic tissue, thus facilitating the following Versajet debridement. The results indicate that Versajet offers more precision than standard mechanical debridement and, at high settings, offers an

  16. Successful Endoscopic Management of Non-Healing Perforated Duodenal Ulcer with Polyglycolic Acid Sheet and Fibrin Glue

    PubMed Central

    Shibagaki, Kotaro; Matsuda, Kayo; Fukuyama, Chika; Okada, Mayumi; Mikami, Hironobu; Izumi, Daisuke; Yamashita, Noritsugu; Okimoto, Eiko; Fukuda, Naoki; Aimi, Masahito; Fukuba, Nobuhiko; Oshima, Naoki; Takanashi, Toshihiro; Matsubara, Takeshi; Ishimura, Norihisa; Ishihara, Shunji; Kinoshita, Yoshikazu

    2016-01-01

    In recent years, treatment techniques in which polyglycolic acid sheets are applied to various situations with fibrin glue have exhibited great clinical potential, and previous studies have reported safety and efficacy. We describe closure of a non-healing perforated duodenal ulcer with the use of a polyglycolic acid sheet and fibrin glue in an elderly patient who was not a candidate for surgery. PMID:28119948

  17. Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis

    PubMed Central

    Shinzaki, Shinichiro; Matsuoka, Katsuyoshi; Iijima, Hideki; Mizuno, Shinta; Serada, Satoshi; Fujimoto, Minoru; Arai, Norimitsu; Koyama, Noriyuki; Morii, Eiichi; Watanabe, Mamoru; Hibi, Toshifumi; Kanai, Takanori; Takehara, Tetsuo

    2017-01-01

    Background and Aims: Although several noninvasive and easily accessible biomarkers for inflammatory bowel disease [IBD] are available, their sensitivity and specificity are not adequate to be used as single markers and do not overrule the need for endoscopic evaluation. We previously reported that serum leucine-rich alpha-2 glycoprotein [LRG] was a novel biomarker for rheumatoid arthritis and IBD. We herein investigated whether LRG could indicate endoscopic activity in patients with ulcerative colitis [UC]. Methods: Serum LRG concentrations were determined by enzyme-linked immunosorbent assay [ELISA] in consecutive 129 patients with UC in two tertiary care hospitals, and associations of LRG with clinical and endoscopic activities were evaluated. Clinical activity index [CAI] < 6 was defined as clinical remission, and mucosal healing [MH] and complete mucosal healing were defined as Matts’ endoscopic grades of 1 or 2 and grade of 1, respectively. Results: Serum LRG levels were significantly increased and correlated with clinical and endoscopic activities in patients with UC. LRG levels were associated with both clinical and endoscopic activities even in patients with normal serum C-reactive protein [CRP] levels. Furthermore, LRG levels were significantly lower in patients with complete MH and deep remission. Serial measurements of LRG levels in a subset of patients demonstrated that LRG was significantly elevated during the endoscopically active stage compared with that during the MH stage. Conclusions: Serum LRG is a novel biomarker for detecting MH during disease course in patients with UC and a surrogate marker of endoscopic inflammation in patients with normal CRP levels. PMID:27466171

  18. Microgrooved Polymer Substrates Promote Collective Cell Migration To Accelerate Fracture Healing in an in Vitro Model.

    PubMed

    Zhang, Qing; Dong, Hua; Li, Yuli; Zhu, Ye; Zeng, Lei; Gao, Huichang; Yuan, Bo; Chen, Xiaofeng; Mao, Chuanbin

    2015-10-21

    Surface topography can affect cell adhesion, morphology, polarity, cytoskeleton organization, and osteogenesis. However, little is known about the effect of topography on the fracture healing in repairing nonunion and large bone defects. Microgrooved topography on the surface of bone implants may promote cell migration into the fracture gap to accelerate fracture healing. To prove this hypothesis, we used an in vitro fracture (wound) healing assay on the microgrooved polycaprolactone substrates to study the effect of microgroove widths and depths on the osteoblast-like cell (MG-63) migration and the subsequent healing. We found that the microgrooved substrates promoted MG-63 cells to migrate collectively into the wound gap, which serves as a fracture model, along the grooves and ridges as compared with the flat substrates. Moreover, the groove widths did not show obvious influence on the wound healing whereas the smaller groove depths tended to favor the collective cell migration and thus subsequent healing. The microgrooved substrates accelerated the wound healing by facilitating the collective cell migration into the wound gaps but not by promoting the cell proliferation. Furthermore, microgrooves were also found to promote the migration of human mesenchymal stem cells (hMSCs) to heal the fracture model. Though osteogenic differentiation of hMSCs was not improved on the microgrooved substrate, collagen I and minerals deposited by hMSCs were organized in a way similar to those in the extracellular matrix of natural bone. These findings suggest the necessity in using microgrooved implants in enhancing fracture healing in bone repair.

  19. Accelerated fracture healing in mice lacking the 5-lipoxygenase gene

    PubMed Central

    2010-01-01

    Background and purpose Cyclooxygenase-2 (COX-2) promotes inflammation by synthesizing pro-inflammatory prostaglandins from arachidonic acid. Inflammation is an early response to bone fracture, and ablation of COX-2 activity impairs fracture healing. Arachidonic acid is also converted into leukotrienes by 5-lipoxygenase (5-LO). We hypothesized that 5-LO is a negative regulator of fracture healing and that in the absence of COX-2, excess leukotrienes synthesized by 5-LO will impair fracture healing. Methods Fracture healing was assessed in mice with a targeted 5-LO mutation (5-LOKO mice) and control mice by radiographic and histological observations, and measured by histomorphometry and torsional mechanical testing. To assess effects on arachidonic acid metabolism, prostaglandin E2, F2α, and leukotriene B4 levels were measured in the fracture calluses of control, 5-LOKO COX-1KO, and COX-2KO mice by enzyme linked immunoassays. Results Femur fractures in 5-LOKO mice rapidly developed a cartilaginous callus that was replaced with bone to heal fractures faster than in control mice. Femurs from 5-LOKO mice had substantially better mechanical properties after 1 month of healing than did control mice. Callus leukotriene levels were 4-fold higher in mice homozygous for a targeted mutation in the COX-2 gene (COX-2KO), which indicated that arachidonic acid was shunted into the 5-LO pathway in the absence of COX-2. Interpretation These experiments show that 5-LO negatively regulates fracture healing and that shunting of arachidonic acid into the 5-LO pathway may account, at least in part, for the impaired fracture healing response observed in COX-2KO mice. PMID:21067431

  20. Targeting Epithelial Cell Migration to Accelerate Wound Healing

    DTIC Science & Technology

    2012-02-01

    consisting of the proteins Rsu1, Integrin Linked Kinase (ILK), PINCH, and Parvin. The correct association of these proteins in a functional complex...impacting integrin function and actin polymerization. 15. SUBJECT TERMS Wound healing, cell migration, protein kinase C, protein kinase A 16. SECURITY...epithelial cell migration in wound healing. In addition, the correct association of these proteins in a functional complex depends on their phosphorylation

  1. Matrix Metalloproteinase-3 Accelerates Wound Healing following Dental Pulp Injury

    PubMed Central

    Zheng, Li; Amano, Kazuharu; Iohara, Koichiro; Ito, Masataka; Imabayashi, Kiyomi; Into, Takeshi; Matsushita, Kenji; Nakamura, Hiroshi; Nakashima, Misako

    2009-01-01

    Matrix metalloproteinases (MMPs) are implicated in a wide range of physiological and pathological processes, including morphogenesis, wound healing, angiogenesis, inflammation, and cancer. Angiogenesis is essential for reparative dentin formation during pulp wound healing. The mechanism of angiogenesis, however, still remains unclear. We hypothesized that certain MMPs expressed during pulp wound healing may support recovery processes. To address this issue, a rat pulp injury model was established to investigate expression of MMPs during wound healing. Real-time RT-PCR analysis showed that expression MMP-3 and MMP-9 (albeit lower extent) was up-regulated at 24 and 12 hours after pulp injury, respectively, whereas expression of MMP-2 and MMP-14 was not changed. MMP-3 mRNA and protein were localized in endothelial cells and/or endothelial progenitor cells in injured pulp in vivo. In addition, MMP-3 enhanced proliferation, migration, and survival of human umbilical vein endothelial cells in vitro. Furthermore, the topical application of MMP-3 protein on the rat-injured pulp tissue in vivo induced angiogenesis and reparative dentin formation at significantly higher levels compared with controls at 24 and 72 hours after treatment, respectively. Inhibition of endogenous MMP-3 by N-Isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid resulted in untoward wound healing. These results provide suggestive evidence that MMP-3 released from endothelial cells and/or endothelial progenitor cells in injured pulp plays critical roles in angiogenesis and pulp wound healing. PMID:19834065

  2. Disruption of thrombospondin-2 accelerates ischemic fracture healing.

    PubMed

    Miedel, Emily; Dishowitz, Michael I; Myers, Marc H; Dopkin, Derek; Yu, Yan-Yiu; Miclau, Ted S; Marcucio, Ralph; Ahn, Jaimo; Hankenson, Kurt D

    2013-06-01

    Thrombospondin-2 (TSP2) is a matricellular protein that is highly up-regulated during fracture healing. TSP2 negatively regulates vascularity, vascular reperfusion following ischemia, and cutaneous wound healing. As well, TSP2-null mice show increased endocortical bone formation due to an enhanced number of mesenchymal progenitor cells and show increased cortical thickness. Mice deficient in TSP2 (TSP2-null) show an alteration in fracture healing, that is unrelated to their cortical bone phenotype, which is characterized by enhanced vascularization with a shift towards an intramembranous healing phenotype; thus, we hypothesized that there would be enhanced ischemic fracture healing in the absence of TSP2. We investigated whether an absence of TSP2 would enhance ischemic fracture healing utilizing Laser doppler, µCT and histological analysis. Ischemic tibial fractures were created in wildtype (WT) and TSP2-null mice and harvested 10, 20, or 40 days post-fracture. TSP2-null mice show enhanced vascular perfusion following ischemic fracture. At day 10 post-fracture, TSP2-null mice have 115% greater bone volume than WT mice. This is associated with a 122% increase in vessel density, 20% increase in cell proliferation, and 15% decrease in apoptosis compared to WT. At day 20, TSP2-null mice have 34% more bone volume, 51% greater bone volume fraction, and 37% more bone tissue mineral density than WT. By 40 days after fracture the TSP2-null mice have a 24% increase in bone volume fraction, but other parameters show no significant differences. These findings indicate TSP2 is a negative regulator of ischemic fracture healing and that in the absence of TSP2 bone regeneration is enhanced.

  3. A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing.

    PubMed

    Idrovo, Juan Pablo; Jacob, Asha; Yang, Weng Lang; Wang, Zhimin; Yen, Hao Ting; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2016-02-01

    Chronic or non-healing wounds are a major concern in clinical practice and these wounds are mostly associated with diabetes, and venous and pressure ulcers. Wound healing is a complex process involving overlapping phases and the primary phase in this complex cascade is the inflammatory state. While inflammation is necessary for wound healing, a prolonged inflammatory phase leads to impaired healing. Cold-inducible RNA-binding protein (CIRP) belongs to a family of cold-shock proteins that are expressed in high levels under stress conditions. Recently, we demonstrated that a deficiency in CIRP led to decreased inflammation and mortality in an experimental model of hemorrhagic shock. Thus, we hypothesized that a deficiency in CIRP would accelerate the inflammatory phase and lead to an improvement in cutaneous wound healing. In this study, to examine this hypothesis, a full-thickness wound was created on the dorsum of wild-type (WT) and CIRP-/- mice. The wound size was measured every other day for 14 days. The wound area was significantly decreased in the CIRP-/- mice by day 9 and continued to decrease until day 14 compared to the WT mice. In a separate cohort, mice were sacrificed on days 3 and 7 after wounding and the skin tissues were harvested for histological analysis and RNA measurements. On day 3, the mRNA expression of tumor necrossis factor (TNF)-α in the skin tissues was increased by 16-fold in the WT mice, whereas these levels were increased by 65-fold in the CIRP-/- mice. Of note on day 7, while the levels of TNF-α remained high in the WT mice, these levels were significantly decreased in the CIRP-/- mice. The histological analysis of the wounded skin tissue indicated an improvement as early as day 3 in the CIRP-/- mice, whereas in the WT mice, infiltrated immune cells were still present on day 7. On day 7 in the CIRP-/- mice, Gr-1 expression was low and CD31 expression was high, whereas in the WT mice, Gr-1 expression was high and CD31 expression was low

  4. Cyclooxygenase 2—implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives

    PubMed Central

    HALTER, F; TARNAWSKI, A; SCHMASSMANN, A; PESKAR, B

    2001-01-01

    A SCHMASSMANN Gastrointestinal Unit, University of Berne
Inselspital, Berne, Switzerland
 B M PESKAR Department of Experimental Clinical Medicine
Ruhr-University, Bochum, Germany
 Cyclooxygenase (COX), the key enzyme for synthesis of prostaglandins, exists in two isoforms (COX-1 and COX-2). COX-1 is constitutively expressed in the gastrointestinal tract in large quantities and has been suggested to maintain mucosal integrity through continuous generation of prostaglandins. COX-2 is induced predominantly during inflammation. On this premise selective COX-2 inhibitors not affecting COX-1 in the gastrointestinal tract mucosa have been developed as gastrointestinal sparing anti-inflammatory drugs. They appear to be well tolerated by experimental animals and humans following acute and chronic (three or more months) administration. However, there is increasing evidence that COX-2 has a greater physiological role than merely mediating pain and inflammation. Thus gastric and intestinal lesions do not develop when COX-1 is inhibited but only when the activity of both COX-1 and COX-2 is suppressed. Selective COX-2 inhibitors delay the healing of experimental gastric ulcers to the same extent as non-COX-2 specific non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, when given chronically to experimental animals, they can activate experimental colitis and cause intestinal perforation. The direct involvement of COX-2 in ulcer healing has been supported by observations that expression of COX-2 mRNA and protein is upregulated at the ulcer margin in a temporal and spatial relation to enhanced epithelial cell proliferation and increased expression of growth factors. Moreover, there is increasing evidence that upregulation of COX-2 mRNA and protein occurs during exposure of the gastric mucosa to noxious agents or to ischaemia-reperfusion. These observations support the concept that COX-2 represents (in addition to COX-1) a further line of defence for the

  5. Acceleration of diabetic wound healing using a novel protease-anti-protease combination therapy.

    PubMed

    Gao, Ming; Nguyen, Trung T; Suckow, Mark A; Wolter, William R; Gooyit, Major; Mobashery, Shahriar; Chang, Mayland

    2015-12-08

    Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body's response to wound healing and that the latter is the pathological consequence of the disease with detrimental effects. Here we demonstrate that the use of compound ND-336, a novel highly selective inhibitor of gelatinases (MMP-2 and MMP-9) and MMP-14, accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of MMP-9 in the pathology of diabetic wounds was confirmed further by the study of diabetic MMP-9-knockout mice, which exhibited wounds more prone to healing. Furthermore, topical administration of active recombinant MMP-8 also accelerated diabetic wound healing as a consequence of complete re-epithelialization, diminished inflammation, and enhanced angiogenesis. The combined topical application of ND-336 (a small molecule) and the active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds.

  6. Acceleration of diabetic wound healing using a novel protease–anti-protease combination therapy

    PubMed Central

    Gao, Ming; Nguyen, Trung T.; Suckow, Mark A.; Wolter, William R.; Gooyit, Major; Mobashery, Shahriar; Chang, Mayland

    2015-01-01

    Nonhealing chronic wounds are major complications of diabetes resulting in >70,000 annual lower-limb amputations in the United States alone. The reasons the diabetic wound is recalcitrant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate its repair. We previously identified two active forms of matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of db/db mice. We argued that the former might play a role in the body’s response to wound healing and that the latter is the pathological consequence of the disease with detrimental effects. Here we demonstrate that the use of compound ND-336, a novel highly selective inhibitor of gelatinases (MMP-2 and MMP-9) and MMP-14, accelerates diabetic wound healing by lowering inflammation and by enhancing angiogenesis and re-epithelialization of the wound, thereby reversing the pathological condition. The detrimental role of MMP-9 in the pathology of diabetic wounds was confirmed further by the study of diabetic MMP-9–knockout mice, which exhibited wounds more prone to healing. Furthermore, topical administration of active recombinant MMP-8 also accelerated diabetic wound healing as a consequence of complete re-epithelialization, diminished inflammation, and enhanced angiogenesis. The combined topical application of ND-336 (a small molecule) and the active recombinant MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds. PMID:26598687

  7. Comparative healing property of kombucha tea and black tea against indomethacin-induced gastric ulceration in mice: possible mechanism of action.

    PubMed

    Banerjee, Debashish; Hassarajani, Sham A; Maity, Biswanath; Narayan, Geetha; Bandyopadhyay, Sandip K; Chattopadhyay, Subrata

    2010-12-01

    The healing activity of black tea (BT) and BT fermented with Candida parapsilosis and kombucha culture, designated as CT and KT respectively against the indomethacin-induced stomach ulceration has been studied in a mouse model. The KT sample (KT4) produced by fermenting BT for four days, showed the best DPPH radical scavenging capacity and phenolics contents. Hence the ulcer-healing activity of KT4 was compared with those of CT4 and BT. All the tea extracts (15 mg kg(-1)) could effectively heal the gastric ulceration as revealed from the histopathological and biochemical studies, with relative efficacy as KT4 > CT4 ∼ BT. The healing capacities of the tea extracts could be attributed to their antioxidant activity as well as the ability to protect the mucin content of the gastric tissues. In addition, the ability of KT4 to reduce gastric acid secretion might also contribute to its ulcer-healing activity. The tea preparation KT4 (15 mg kg(-1)) was as effective as the positive control, omeprazole (3 mg kg(-1)) in ulcer healing.

  8. N-Acetylcysteine accelerates amputation stump healing in the setting of diabetes.

    PubMed

    Zayed, Mohamed A; Wei, Xiachao; Park, Kyoung-Mi; Belaygorod, Larisa; Naim, Uzma; Harvey, Joseph; Yin, Li; Blumer, Kendall; Semenkovich, Clay F

    2017-03-09

    Over 60% of lower extremity amputations are performed in patients with diabetes and peripheral arterial disease, and at least 25% require subsequent reamputation due to poor surgical site healing. The mechanisms underlying poor amputation stump healing in the setting of diabetes are not understood. N-acetylcysteine (NAC) is known to promote endothelial cell function and angiogenesis and may have therapeutic benefits in the setting of diabetes. We tested the hypothesis that NAC alters the vascular milieu to improve healing of amputation stumps in diabetes using a novel in vivo murine hindlimb ischemia-amputation model. Amputation stump tissue perfusion and healing were evaluated in C57BL/6J adult mice with streptozotocin-induced diabetes. Compared with controls, mice treated with daily NAC demonstrated improved postamputation stump healing, perfusion, adductor muscle neovascularization, and decreased muscle fiber damage. Additionally, NAC stimulated HUVEC migration and proliferation in a phospholipase C β-dependent fashion and decreased Gαq palmitoylation. Similarly, NAC treatment also decreased Gαq palmitoylation in ischemic and nonischemic hindlimbs in vivo In summary, we demonstrate that NAC accelerates healing of amputation stumps in the setting of diabetes and ischemia. The underlying mechanism appears to involve a previously unrecognized effect of NAC on Gαq palmitoylation and phospholipase C β-mediated signaling in endothelial cells.-Zayed, M. A., Wei, X., Park, K., Belaygorod, L., Naim, U., Harvey, J., Yin, L., Blumer, K., Semenkovich, C. F. N-acetylcysteine accelerates amputation stump healing in the setting of diabetes.

  9. Targeting Epithelial Cell Migration to Accelerate Wound Healing

    DTIC Science & Technology

    2010-12-01

    the protein kinase C (PKC) family and the process can be enhanced or inhibited by modulating the levels of the RIPP complex proteins as well by...HACAT cells indicates that PKC may modulate migration on two-dimensional surface. 15. SUBJECT TERMS Wound healing, cell migration, protein kinase C ...ABSTRACT U c . THIS PAGE U UU 11 19b. TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18

  10. Effectiveness of an Innovative Pulsed Electromagnetic Fields Stimulation in Healing of Untreatable Skin Ulcers in the Frail Elderly: Two Case Reports

    PubMed Central

    Guerriero, Fabio; Botarelli, Emanuele; Mele, Gianni; Polo, Lorenzo; Zoncu, Daniele; Renati, Paolo; Sgarlata, Carmelo; Rollone, Marco; Ricevuti, Giovannoi; Maurizi, Niccolò; Francis, Matthew; Rondanelli, Mariangela; Perna, Simone; Guido, Davide; Mannu, Piero

    2015-01-01

    Introduction. Recalcitrant skin ulcers are a major burden in elderly patients. Specifically, chronic wounds result in significant morbidity and mortality and have a profound economic impact. Pulsed electromagnetic fields (PEMFs) have proved to be a promising therapy for wound healing. Here we describe the first reported case of an innovative PEMF therapy, Emysimmetric Bilateral Stimulation (EBS), used to successfully treat refractory skin ulcers in two elderly and fragile patients. Case Presentation. Two elderly patients developed multiple chronic skin ulcerations. Despite appropriate treatment, the ulcers showed little improvement and the risk of amputation was high. Both patients underwent daily EBS therapy and standard dressing. After few weeks of treatment, major improvements were observed and all ulcers had healed. Conclusion. In patients with refractory ulceration, EBS therapy may be of real benefit in terms of faster healing. This case supports the supportive role for PEMFs in the treatment of skin ulceration in diabetes and is suggestive of a potential benefit of EBS in this clinical condition. PMID:26634159

  11. A Randomized, Controlled Trial to Assess the Effect of Topical Insulin Versus Normal Saline in Pressure Ulcer Healing.

    PubMed

    Stephen, Shine; Agnihotri, Meenakshi; Kaur, Sukhpal

    2016-06-01

    Insulin has been used in wound healing to increase wound collagen, granulation tissue, wound tensile strength, and local production of insulin-like growth factors by fibroblasts. Saline is a widely used irrigating and wound dressing solution. Patients admitted to an acute care facility who had a Grade 2 or Grade 3 pressure ulcer were recruited to participate in a randomized, controlled trial to compare the effect of normal saline-impregnated gauze and insulin dressing in pressure ulcer healing. Persons with immunodeficiency, diabetes mellitus, pregnancy, osteomyelitis, and peripheral vascular illness were not eligible for the study. Study participants were randomized to receive either normal saline dressing gauze or insulin dressing twice daily for 7 days. At baseline, patient demographic data and ulcer history were recorded. Baseline and follow-up ulcer assessments (days 4 and day 7) included ulcer measurement (length and width) and completion of the Pressure Ulcer Scale for Healing (PUSH version 3.0) tool. Patients in the control group received dressings of sterile gauze soaked with normal saline; patients in the intervention group received topical insulin (1 U/cm2 wound area). The insulin was sprayed over the wound surface with an insulin syringe, allowed to dry for 15 minutes, and then covered with sterile gauze. To ascertain the safety of study participants, blood glucose levels were measured with a glucometer 10 minutes before and 1 hour after the topical insulin application in the intervention group. Treatment efficacy was deter- mined by assessing the reduction in wound area and PUSH scores at follow-up. Statistical analysis was performed; data are expressed as mean ± SD and percentage for continuous and categorical variables respectively. The differences in PUSH score and ulcer sizes between the 2 groups were analyzed using independent t-test, and within-group differences were analyzed using ANOVA with repeated measures; Greenhouse-Geisser correction was

  12. Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid.

    PubMed

    Dos Reis Lívero, Francislaine Aparecida; da Silva, Luisa Mota; Ferreira, Daniele Maria; Galuppo, Larissa Favaretto; Borato, Debora Gasparin; Prando, Thiago Bruno Lima; Lourenço, Emerson Luiz Botelho; Strapasson, Regiane Lauriano Batista; Stefanello, Maria Élida Alves; Werner, Maria Fernanda de Paula; Acco, Alexandra

    2016-09-01

    Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity.

  13. The effect of tri-potassium di-citrato bismuthate (De-Nol) on the healing of chronic duodenal ulcers.

    PubMed

    Coughlin, G P; Kupa, A; Alp, M H

    1977-02-26

    Forty-six patients suffering from chronic duodenal ulcer, proven endoscopically, were treated in a randomized double-blind cross-over trial with either tri-potassium di-citrato bismuthate (De-Nol) or placebo for four weeks and assessed symptomatically and endoscopically. Those patients who failed to heal after treatment with either agent were crossed over to the alternative preparation and reassessed after a further 28 days. Forty-two patients completed the study involving 57 patient treatments. A highly significant improvement in both symptomatic response (P less than 0.01) and endoscopic healing (P less than 0.01) was seen in those patients receiving tri-potassium di-citrato bismuthate (De-Nol) as against placebo therapy.

  14. Treatment of venous leg ulcers with sulodexide.

    PubMed

    Scondotto, G; Aloisi, D; Ferrari, P; Martini, L

    1999-11-01

    Venous ulcers are still today one of the main socioeconomic problems of medical interest in terms of prevalence, morbidity, and costs to the health service. In the past, various studies have been carried out to identify a systemic pharmacologic treatment able to accelerate venous ulcer healing times, but frequently the results have not been satisfactory. The aim of this study was to evaluate the efficacy of sulodexide, a drug with profibrinolytic and antithrombotic activity, in accelerating venous ulcer's healing time. Ninety-four patients (32 men and 62 women), aged 72 years old on average, were randomly distributed between two groups. In the first group ("control group") a standard treatment was applied, which consisted of cleansing by washing with physiological solution and the application of elastic compression with short-extensibility, removable bandages. The second group ("sulodexide group") received the standard treatment plus sulodexide (600 lipoprotein lipase releasing units [LRU] by im route per day for 30 consecutive days, followed by 500 LRU by oral route per day for a further 30 days). After 2 months the venous ulcers were found healed in 15 patients (36%) in the control group and in 30 patients (58%) in the sulodexide group (p = 0.03). The life table showed that the healing times were shorter in the sulodexide group in the first 2 months of treatment. Total healing times amounted to 110 days in the control group and 72 days in the sulodexide group (p = 0.08) and the results were in proportion to the initial severity of the lesion. A significant correlation was noted between ulcer healing times and severity of the initial ulcerous lesion, the duration of the ulcer, and the group the patient belonged to. No correlation was found between age, gender of the patient and the etiology of the ulcer. In conclusion sulodexide was shown effective in the treatment of venous leg ulcers, yielding healing more quickly than the standard treatment.

  15. Arginine Silicate Inositol Complex Accelerates Cutaneous Wound Healing.

    PubMed

    Durmus, Ali Said; Tuzcu, Mehmet; Ozdemir, Oguzhan; Orhan, Cemal; Sahin, Nurhan; Ozercan, Ibrahim Hanifi; Komorowski, James Richard; Ali, Shakir; Sahin, Kazim

    2016-10-14

    Arginine silicate inositol (ASI) complex is a composition of arginine, silicon, and inositol that has been shown to have beneficial effects on vascular health. This study reports the effects of an ASI ointment on wound healing in rats. A full-thickness excision wound was created by using a disposable 5 mm diameter skin punch biopsy tool. In this placebo-controlled study, the treatment group's wound areas were covered by 4 or 10 % ASI ointments twice a day for 5, 10, or 15 days. The rats were sacrificed either 5, 10, or 15 days after the wounds were created, and biopsy samples were taken for biochemical and histopathological analysis. Granulation tissue appeared significantly faster in the ASI-treated groups than in the control groups (P < 0.05). The mean unhealed wound area was significantly smaller, and the mean percentage of total wound healing was significantly higher in ASI-treated wounds than in the control wounds. Hydroxyproline, collagen, and matrix metalloproteinases were measured in the granulated tissue and found to be affected. Inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), collagen, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and various cytokines (TNF-α and IL-1β) measured in this study showed a significant fall in expression level in ASI-treated wounds. The results suggest that topical application of ASI ointment (especially 4 % concentration) has beneficial effects on the healing response of an excisional wound.

  16. Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice

    PubMed Central

    Marrotte, Eric J.; Chen, Dan-Dan; Hakim, Jeffrey S.; Chen, Alex F.

    2010-01-01

    Amputation as a result of impaired wound healing is a serious complication of diabetes. Inadequate angiogenesis contributes to poor wound healing in diabetic patients. Endothelial progenitor cells (EPCs) normally augment angiogenesis and wound repair but are functionally impaired in diabetics. Here we report that decreased expression of manganese superoxide dismutase (MnSOD) in EPCs contributes to impaired would healing in a mouse model of type 2 diabetes. A decreased frequency of circulating EPCs was detected in type 2 diabetic (db/db) mice, and when isolated, these cells exhibited decreased expression and activity of MnSOD. Wound healing and angiogenesis were markedly delayed in diabetic mice compared with normal controls. For cell therapy, topical transplantation of EPCs onto excisional wounds in diabetic mice demonstrated that diabetic EPCs were less effective than normal EPCs at accelerating wound closure. Transplantation of diabetic EPCs after MnSOD gene therapy restored their ability to mediate angiogenesis and wound repair. Conversely, siRNA-mediated knockdown of MnSOD in normal EPCs reduced their activity in diabetic wound healing assays. Increasing the number of transplanted diabetic EPCs also improved the rate of wound closure. Our findings demonstrate that cell therapy using diabetic EPCs after ex vivo MnSOD gene transfer accelerates their ability to heal wounds in a mouse model of type 2 diabetes. PMID:21060152

  17. Topical treatment with the opioid antagonist naltrexone accelerates the remodeling phase of full-thickness wound healing in type 1 diabetic rats.

    PubMed

    Immonen, Jessica A; Zagon, Ian S; Lewis, Gregory S; McLaughlin, Patricia J

    2013-10-01

    Wound repair involves a series of overlapping phases that include inflammation, proliferation, and tissue remodeling, with the latter phase requiring months for proper healing. Delays in any of these processes can result in infection, chronic ulceration, and possible amputation. Diabetes is a major risk factor for improper wound repair, and impaired wound healing is a major complication for more than 26 million people in the US diagnosed with diabetes. Previous studies have demonstrated that the opioid antagonist naltrexone (NTX) dissolved in moisturizing cream reverses delays in wound closure in streptozotocin-induced type 1 diabetic (T1D) rats. NTX accelerated DNA synthesis and increased the number of epithelial and mast cells, as well as new blood vessel formation. In this study, remodeling was evaluated in T1D rats up to eight weeks after initial wounding. Twenty days following wounding, diabetic rats treated with vehicle had elevated numbers of MMP-2+ fibroblasts, suggesting delayed healing processes; birefringence of granulation tissue stained with Sirius red revealed diminished collagen formation and maturation. Wound tissue from NTX-treated T1D rats had comparable numbers of MMP-2+ fibroblasts to control specimens, as well as accelerated maturation of granulation tissue. The integrity of wounded skin was evaluated by tensile strength measurements. T1D resulted in delayed wound healing, and wounded skin that displayed reduced tensile strength relative to normal rats. Topical NTX applied to wounds in T1D rats resulted in enhanced collagen formation and maturation over a 60-day period of time. Moreover, the force required to tear skin of NTX-treated T1D rats was elevated relative to the force necessary to tear the skin of vehicle-treated T1D rats, and comparable to that for normal rats. These data reveal that complications in wound healing associated with T1D involve the novel OGF-OGFr pathway, and that topical NTX is an effective treatment to enhance wound

  18. Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats

    PubMed Central

    Ji, Yuanyuan; Zhang, Aijun; Chen, Xiaobin; Che, Xiaoxia; Zhou, Kai; Wang, Zhidong

    2016-01-01

    Sodium humate (HA-Na) has been topically used as a wound healing and anti-inflammatory agent in folk medicine. In the present study, HA-Na was investigated for cutaneous wound healing in Sprague–Dawley rats. HA-Na solution (1.0%, w/v) was topically administered to rats undergoing excision wound models. Healing was assessed with a recombinant bovine basic fibroblast growth factor for external use as positive control. Wound healing rates were calculated on Day 3, 6, 9, 14 and 21 after injury, and tissues were also harvested after the same intervals for histological analysis. In addition, tissue hydroxyproline levels were measured. Furthermore, mRNA levels and protein expressions of transforming growth factor-β1, 2, 3 (TGF-β1, 2, 3) were determined by RT-PCR and western blot. Protein expression levels of Smad-2, -3, -4 and -7 were also detected by western blot. Our study demonstrates that HA-Na has the capacity to promote wound healing in rats via accelerated wound contraction and increased hydroxyproline content. More importantly, these wound healing effects of HA-Na might be mediated through the TGF-β/Smad signaling pathway. HA-Na may be an effective agent for enhanced wound healing. PMID:27006897

  19. Biafine topical emulsion accelerates excisional and burn wound healing in mice.

    PubMed

    Krausz, Aimee E; Adler, Brandon L; Landriscina, Angelo; Rosen, Jamie M; Musaev, Tagai; Nosanchuk, Joshua D; Friedman, Adam J

    2015-09-01

    Macrophages play a fundamental role in wound healing; therefore, employing a strategy that enhances macrophage recruitment would be ideal. It was previously suggested that the mechanism by which Biafine topical emulsion improves wound healing is via enhanced macrophage infiltration into the wound bed. The purpose of this study was to confirm this observation through gross and histologic assessments of wound healing using murine full-thickness excisional and burn wound models, and compare to common standards, Vaseline and silver sulfadiazine (SSD). Full-thickness excisional and burn wounds were created on two groups of 60 mice. In the excisional arm, mice were divided into untreated control, Biafine, and Vaseline groups. In the burn arm, mice were divided into untreated control, Biafine, and SSD groups. Daily treatments were administered and healing was measured over time. Wound tissue was excised and stained to appropriately visualize morphology, collagen, macrophages, and neutrophils. Collagen deposition was measured and cell counts were performed. Biafine enhanced wound healing in murine full-thickness excisional and burn wounds compared to control, and surpassed Vaseline and SSD in respective wound types. Biafine treatment accelerated wound closure clinically, with greater epidermal/dermal maturity, granulation tissue formation, and collagen quality and arrangement compared to other groups histologically. Biafine application was associated with greater macrophage and lower neutrophil infiltration at earlier stages of healing when compared to other study groups. In conclusion, Biafine can be considered an alternative topical therapy for full-thickness excisional and burn wounds, owing to its advantageous biologically based wound healing properties.

  20. Increasing gastric juice pH level prior to anti-Helicobacter pylori therapy may be beneficial to the healing of duodenal ulcers.

    PubMed

    Fan, Hong-Yun; Wang, Juan; Yan, Guo-Chao; Huo, Xiao-Hui; Mu, Li-Juan; Chu, Jian-Kun; Niu, Wei-Wei; Duan, Zhi-Ying; Ma, Jin-Cheng; Wang, Jing; Wang, Zhi-Yu

    2013-03-01

    The aim of this study was to observe the efficacy of clarithromycin-based triple therapy for Helicobacter pylori (Hp)-infected duodenal ulcer when combined with different pH levels of gastric juices. A total of 160 patients with Hp-infected duodenal ulcers were randomly allocated into two groups. Patients in the treatment group (n=80) were administered a 20-mg dose of omeprazole twice daily for 1 week and then the treatment and control groups (n=80) received therapy for Hp infection and duodenal ulcers. We observed the ulcer healing stage, the content of anti-Hp IgA in gastric juice and the Hp eradication rate before and after proton pump inhibitor therapy in the two groups. Results revealed that the Hp eradication rate in the treatment group was 93% compared with 81% in the control group, and the difference was statistically significant (P<0.05). The ulcer healing rate in the treatment group was 93%, compared with 70% in the control group (P<0.05). A positive linear correlation was observed between gastric pH and the content of anti-Hp IgA in gastric juice (P<0.05). Increasing gastric pH prior to anti-Hp therapy may be beneficial to the eradication of Hp and for promoting the healing of duodenal ulcers.

  1. Alginate-hyaluronan composite hydrogels accelerate wound healing process.

    PubMed

    Catanzano, O; D'Esposito, V; Acierno, S; Ambrosio, M R; De Caro, C; Avagliano, C; Russo, P; Russo, R; Miro, A; Ungaro, F; Calignano, A; Formisano, P; Quaglia, F

    2015-10-20

    In this paper we propose polysaccharide hydrogels combining alginate (ALG) and hyaluronan (HA) as biofunctional platform for dermal wound repair. Hydrogels produced by internal gelation were homogeneous and easy to handle. Rheological evaluation of gelation kinetics of ALG/HA mixtures at different ratios allowed understanding the HA effect on ALG cross-linking process. Disk-shaped hydrogels, at different ALG/HA ratio, were characterized for morphology, homogeneity and mechanical properties. Results suggest that, although the presence of HA does significantly slow down gelation kinetics, the concentration of cross-links reached at the end of gelation is scarcely affected. The in vitro activity of ALG/HA dressings was tested on adipose derived multipotent adult stem cells (Ad-MSC) and an immortalized keratinocyte cell line (HaCaT). Hydrogels did not interfere with cell viability in both cells lines, but significantly promoted gap closure in a scratch assay at early (1 day) and late (5 days) stages as compared to hydrogels made of ALG alone (p<0.01 and 0.001 for Ad-MSC and HaCaT, respectively). In vivo wound healing studies, conducted on a rat model of excised wound indicated that after 5 days ALG/HA hydrogels significantly promoted wound closure as compared to ALG ones (p<0.001). Overall results demonstrate that the integration of HA in a physically cross-linked ALG hydrogel can be a versatile strategy to promote wound healing that can be easily translated in a clinical setting.

  2. The Healing Effect of Teucrium polium in Acetic Acid-Induced Ulcerative Colitis in the Dog as an Animal Model

    PubMed Central

    Mehrabani, Davood; Bahrami, Faranak; Hosseini, Seyed Vahid; Ashraf, Mohammad Javad; Tanideh, Nader; Rezaianzadeh, Abbas; Amini, Masoud; Amini, Afshin

    2012-01-01

    BACKGROUND Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn’s disease (CD), are debilitating and chronic disorders with unpredictable courses and complicated treatment measures. Therefore, an efficient treatment protocol seems necessary as therapeutic prophylaxis for these disorders. This study aims to determine the healing effect of Teucrium polium (T. polium) in acetic acid-induced UC in an experimental dog model. METHODS From September to December 2010, eight male (20-25 kg) crossbred dogs were used for induction of UC by 6% acetic acid, transrectally. After one week, three biopsies (10, 20 and 30 cm proximal to the anal verge) were taken from the colon of each animal for histological studies. In the presence of UC, 400 mg/kg/day of T. polium extract was administered orally and transrectally (via enema) for 30 days in six of the dogs. The remaining two dogs were used as controls and did not receive T. polium. Multiple biopsies were taken 7, 14, and 30 days after discontinuation of T. polium in the same manner as before treatment. RESULTS After administration of acetic acid, we noted the presence of multiple ulcers, diffuse inflammation, PMN infiltration in the lamina propria, glandular destruction and goblet cell depletion. Treatment with T. polium restored the colonic architecture with an increased number of healthy cells and a reduction in inflammatory cells. Damage of the surface epithelial cells and mucosal layer of the lumen were reversed, which lead to faster ulcer healing. CONCLUSION T. polium may be a treatment choice for UC and can broaden the current therapy options for UC. PMID:24829634

  3. Ulcers

    MedlinePlus

    ... if they cause heartburn.Does what I eat affect my ulcer?It may. But this isn't true for everyone. Certain foods and drinks may be more likely to make your pain worse. These include both regular and decaffeinated coffee, tea, chocolate, meat extracts, alcohol, black pepper, chili powder, mustard ...

  4. Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia

    PubMed Central

    Smout, Michael J.; Sotillo, Javier; Laha, Thewarach; Papatpremsiri, Atiroch; Rinaldi, Gabriel; Pimenta, Rafael N.; Chan, Lai Yue; Johnson, Michael S.; Turnbull, Lynne; Whitchurch, Cynthia B.; Giacomin, Paul R.; Moran, Corey S.; Golledge, Jonathan; Daly, Norelle; Sripa, Banchob; Mulvenna, Jason P.

    2015-01-01

    Abstract Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated with wound healing and cancer pathways. Given the notable but seemingly paradoxical properties of liver fluke granulin in promoting not only wound healing but also a carcinogenic microenvironment, Ov-GRN-1 likely holds marked potential as a therapeutic wound-healing agent and as a vaccine against an infection-induced cancer of major public health significance in the developing world. PMID:26485648

  5. Tripotassium dicitrate bismuthate and ranitidine in duodenal ulcer. Healing and influence on recurrence.

    PubMed

    Bianchi Porro, G; Lazzaroni, M; Barbara, L; Corinaldesi, R; Dal Monte, P R; D'Imperio, N; Mazzacca, G; D'Arienzo, A; Cheli, R; Bovero, E

    1988-12-01

    One hundred patients were entered into a double-blind, double-dummy comparison of tripotassium dicitrate bismuthate (TDB) versus ranitidine, to evaluate short-term healing rates, and successfully healed patients were then entered into a follow-up phase to observe relapse rates. At 4 weeks 84% of patients treated with TDB and 68% of those treated with ranitidine had healed. At 8 weeks these figures had risen to 96% and 90%, respectively (p = NS). After a year's follow-up study 84% of patients healed initially with ranitidine had relapsed, whereas in the case of patients healed initially with TDB the relapse rate was 67% (p less than 0.05). The results confirm that in the short term, TDB is as effective as ranitidine, whereas the significantly better protection against relapse offered by TDB compared with ranitidine underlines the importance of restoring mucosal defence, an approach that to date has been somewhat overlooked.

  6. Duodenocutaneous fistula in rats as a model for "wound healing-therapy" in ulcer healing: the effect of pentadecapeptide BPC 157, L-nitro-arginine methyl ester and L-arginine.

    PubMed

    Skorjanec, S; Kokot, A; Drmic, D; Radic, B; Sever, M; Klicek, R; Kolenc, D; Zenko, A; Lovric Bencic, M; Belosic Halle, Z; Situm, A; Zivanovic Posilovic, G; Masnec, S; Suran, J; Aralica, G; Seiwerth, S; Sikiric, P

    2015-08-01

    While very rarely reported, duodenocutanenous fistula research might alter the duodenal ulcer disease background and therapy. Our research focused on rat duodenocutaneous fistulas, therapy, stable gastric pentadecapeptide BPC 157, an anti-ulcer peptide that healed other fistulas, nitric oxide synthase-substrate L-arginine, and nitric oxide synthase-inhibitor L-nitro-arginine methyl ester (L-NAME). The hypothesis was, duodenal ulcer-healing, like the skin ulcer, using the successful BPC 157, with nitric oxide-system involvement, the "wound healing-therapy", to heal the duodenal ulcer, the fistula-model that recently highlighted gastric and skin ulcer healing. Pressure in the lower esophageal and pyloric sphincters was simultaneously assessed. Duodenocutaneous fistula-rats received BPC 157 (10 μg/kg or 10 ng/kg, intraperitoneally or perorally (in drinking water)), L-NAME (5 mg/kg intraperitoneally), L-arginine (100 mg/kg intraperitoneally) alone and/or together, throughout 21 days. Duodenocutaneous fistula-rats maintained persistent defects, continuous fistula leakage, sphincter failure, mortality rate at 40% until the 4(th) day, all fully counteracted in all BPC 157-rats. The BPC 157-rats experienced rapidly improved complete presentation (maximal volume instilled already at 7(th) day). L-NAME further aggravated the duodenocutaneous fistula-course (mortality at 70% until the 4(th) day); L-arginine was beneficial (no mortality; however, maximal volume instilled not before 21(st) day). L-NAME-worsening was counteracted to the control level with the L-arginine effect, and vice versa, while BPC 157 annulled the L-NAME effects (L-NAME + L-arginine; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157 brought below the level of the control). It is likely that duodenocutaneous fistulas, duodenal/skin defect simultaneous healing, reinstated sphincter function, are a new nitric oxide-system related phenomenon. In conclusion, resolving the duodenocutanenous fistulashealing

  7. A large Italian observational multicentre study on vascular ulcers of the lower limbs (Studio Ulcere Vascolari).

    PubMed

    Apollonio, Alessandro; Antignani, Pier L; Di Salvo, Michelangelo; Failla, Giacomo; Guarnera, Giorgio; Mosti, Giovanni; Ricci, Elia

    2016-02-01

    An observational study of 2 years was promoted by the Italian Association for Cutaneous Ulcers (AIUC) in order to monitor the epidemiology of leg ulcers, the trend of healing and the more frequent therapeutic approaches in lower limb ulcers. Fifty-nine sites in 14 different Italian regions involved in the study, with 1333 enrolled patients (1163 patients fully evaluated and followed up for 9 months). A prevalence of females (62%) was observed with a mean age of 70 years and a high rate of hypertension (62%), diabetes (38%) and obesity (29%). Venous ulcer was most frequent (55%), followed by mixed (25%) and diabetic (8·3%) ulcers. Basically, all patients received a local therapy (LT) (compression and advanced local therapies), while 63% of patients have an associated systemic pharmaceutical treatment. Ulcer healing rates progressively increased throughout the study and despite the type of observational study does not allow conclusions on the treatment, it was observed that the patients receiving additional systemic drugs were associated with a more rapid acceleration of healing rates of ulcers compared to LT alone (3 months: 39·7% versus 29·2%; 6 months: 62·0% versus 47·0%; 9 months: 74·7% versus 63·8%). In particular, the Studio Ulcere Vascolari (SUV) study showed that a combination treatment with sulodexide and compression therapy allows for a greater increase in the healing rates in venous ulcers.

  8. Combination of low level light therapy and nitrosyl-cobinamide accelerates wound healing

    NASA Astrophysics Data System (ADS)

    Spitler, Ryan; Ho, Hsiang; Norpetlian, Frederique; Kong, Xiangduo; Jiang, Jingjing; Yokomori, Kyoko; Andersen, Bogi; Boss, Gerry R.; Berns, Michael W.

    2015-05-01

    Low level light therapy (LLLT) has numerous therapeutic benefits, including improving wound healing, but the precise mechanisms involved are not well established; in particular, the underlying role of cytochrome C oxidase (C-ox) as the primary photoacceptor and the associated biochemical mechanisms still require further investigation. We previously showed the nitric oxide (NO) donating drug nitrosyl-cobinamide (NO-Cbi) enhances wound healing through a cGMP/cGMP-dependent protein kinase/ERK1/2 mechanism. Here, we show that the combination of LLLT and NO-Cbi markedly improves wound healing compared to either treatment alone. LLLT-enhanced wound healing proceeded through an electron transport chain-C-ox-dependent mechanism with a reduction of reactive oxygen species and increased adenosine triphosphate production. C-ox was validated as the primary photoacceptor by three observations: increased oxygen consumption, reduced wound healing in the presence of sodium azide, and disassociation of cyanide, a known C-ox ligand, following LLLT. We conclude that LLLT and NO-Cbi accelerate wound healing through two independent mechanisms, the electron transport chain-C-ox pathway and cGMP signaling, respectively, with both resulting in ERK1/2 activation.

  9. A synthetic uric acid analog accelerates cutaneous wound healing in mice.

    PubMed

    Chigurupati, Srinivasulu; Mughal, Mohamed R; Chan, Sic L; Arumugam, Thiruma V; Baharani, Akanksha; Tang, Sung-Chun; Yu, Qian-Sheng; Holloway, Harold W; Wheeler, Ross; Poosala, Suresh; Greig, Nigel H; Mattson, Mark P

    2010-04-06

    Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions.

  10. Biodegradable nanocomposite coatings accelerate bone healing: In vivo evaluation

    PubMed Central

    Mehdikhani-Nahrkhalaji, Mehdi; Fathi, Mohammad Hossein; Mortazavi, Vajihesadat; Mousavi, Sayed Behrouz; Akhavan, Ali; Haghighat, Abbas; Hashemi-Beni, Batool; Razavi, Sayed Mohammad; Mashhadiabbas, Fatemeh

    2015-01-01

    Background: The aim of this study was to evaluate the interaction of bioactive and biodegradable poly (lactide-co-glycolide)/bioactive glass/hydroxyapatite (PBGHA) and poly (lactide-co-glycolide)/bioactive glass (PBG) nanocomposite coatings with bone. Materials and Methods: Sol-gel derived 58S bioactive glass nanoparticles, 50/50 wt% poly (lactic acid)/poly (glycolic acid) and hydroxyapatite nanoparticles were used to prepare the coatings. The nanocomposite coatings were characterized by scanning electron microscopy, X-ray diffraction and atomic force microscopy. Mechanical stability of the prepared nanocomposite coatings was studied during intramedullary implantation of coated Kirschner wires (K-wires) into rabbit tibia. Titanium mini-screws coated with nanocomposite coatings and without coating were implanted intramedullary in rabbit tibia. Bone tissue interaction with the prepared nanocomposite coatings was evaluated 30 and 60 days after surgery. The non-parametric paired Friedman and Kruskal-Wallis tests were used to compare the samples. For all tests, the level of significance was P < 0.05. Results: The results showed that nanocomposite coatings remained stable on the K-wires with a minimum of 96% of the original coating mass. Tissue around the coated implants showed no adverse reactions to the coatings. Woven and trabecular bone formation were observed around the coated samples with a minimum inflammatory reaction. PBG nanocomposite coating induced more rapid bone healing than PBGHA nanocomposite coating and titanium without coating (P < 0.05). Conclusion: It was concluded that PBG nanocomposite coating provides an ideal surface for bone formation and it could be used as a candidate for coating dental and orthopedic implants. PMID:25709681

  11. Histological Evaluation of Wound Healing Process after Photodynamic Therapy of Rat Oral Mucosal Ulcer

    PubMed Central

    Deyhimi, Parviz; Khademi, Heidar; Birang, Reza; Akhoondzadeh, Mohammad

    2016-01-01

    Statement of the Problem When the body defense is compromised, wounds can act as a route for entrance and colonization of microorganisms in the body. Photodynamic therapy with methylene blue is known as a promising antimicrobial modality. Purpose The present study aimed to investigate the effects of this procedure on wound healing processes. Materials and Method In this experimental study, 48 male Wistar rats were recruited. Experimental wounds were surgically made on their buccal mucosa. Based on the treatment modality, they were divided into 3 groups (n=16) of control (CG), laser (LG), photosensitizer+ laser (PLG) by methylene blue (MB). The treatment procedure in the two latter groups was done in days 1-4 and 6-9. After sacrificing on 2, 4, 7 and 14-day follow-ups, the microscopic grade of healing of the wounds was assigned on each interval according to histological grading criteria. Results A qualitative result was obtained that showed a healing progression in PLG at day 2 of follow-up. At day 4 of follow-up, no difference was seen in healing stage among the groups. However on day 7 of follow-up, samples of the LG showed a lower degree of healing compared with the other two groups. Likewise, on day 14 of follow- up, both PLG and LG showed lower degree of healing than CG. Conclusion This study qualitatively showed that MB- mediated photodynamic therapy would have an inhibitory effect on healing process after 14 days of the wound creation. PMID:26966708

  12. The use of a portable, wearable form of pulsed radio frequency electromagnetic energy device for the healing of recalcitrant ulcers: a case report.

    PubMed

    Rawe, Ian M; Vlahovic, Tracey C

    2012-06-01

    Pulsed radio frequency energy (PRFE) has successfully been used to treat diabetic and venous stasis ulcers. In this case report, a lightweight wearable form of a PFRE device was evaluated and used to treat three diabetic foot ulcers and one venous stasis ulcer. The ulcers were present on the four patients for more than 3 months and had failed to heal after conventional treatment. A lightweight battery-powered, wearable form of PRFE device was introduced as a treatment and used 6-8 hours per day for a period of 6 weeks. All patients after 1 week of therapy showed improvement and wound size was seen to decrease. Patient 1 had a venous stasis ulcer, and reported significant pain relief after 2 weeks treatment. Patients 2 and 3 achieved complete healing after 3 weeks treatment, and patients 1 and 4 had a 95% and 88% reduction in wound size, respectively, after the 6-week study period. Both these patients continued to complete healing using the PRFE device after the 6-week study period. PRFE treatment delivered in the form of a wearable lightweight patch appears to offer promise in the treatment of recalcitrant chronic wounds.

  13. Improvement of wound healing by water-filtered infrared-A (wIRA) in patients with chronic venous stasis ulcers of the lower legs including evaluation using infrared thermography

    PubMed Central

    Mercer, James B.; Nielsen, Stig Pors; Hoffmann, Gerd

    2008-01-01

    clear reduction of pain and pain medication consumption (e.g. from 15 to 0 pain tablets per day), and a normalization of the thermographic image (before the beginning of the therapy typically hyperthermic rim of the ulcer with relative hypothermic ulcer base, up to 4.5°C temperature difference). In one patient the therapy of an ulcer of one leg was performed with the fully active radiator (wIRA(+VIS)), while the therapy of an ulcer of the other leg was made with a control group radiator (only VIS without wIRA), showing a clear difference in favour of the wIRA treatment. All mentioned VAS ratings improved remarkably during the period of irradiation treatment, representing an increased quality of life. Failures of complete or nearly complete wound healing were seen only in patients with arterial insufficiency, in smokers or in patients who did not have venous compression garment therapy. Discussion and conclusions: wIRA can alleviate pain considerably (with an impressive decrease of the consumption of analgesics) and accelerate wound healing or improve a stagnating wound healing process and diminish an elevated wound exudation and inflammation both in acute and in chronic wounds (in this study shown in chronic venous stasis ulcers of the lower legs) and in problem wounds including infected wounds. In chronic recalcitrant wounds complete healing is achieved, which was not reached before. Other studies have shown that even without a disturbance of wound healing an acute wound healing process can be improved (e.g. reduced pain) by wIRA. wIRA is a contact-free, easily used and pleasantly felt procedure without consumption of material with a good penetration effect, which is similar to solar heat radiation on the surface of the earth in moderate climatic zones. Wound healing and infection defence (e.g. granulocyte function including antibacterial oxygen radical formation of the granulocytes) are critically dependent on a sufficient energy supply (and on sufficient oxygen

  14. Acceleration of wound healing by growth hormone-releasing hormone and its agonists.

    PubMed

    Dioufa, Nikolina; Schally, Andrew V; Chatzistamou, Ioulia; Moustou, Evi; Block, Norman L; Owens, Gary K; Papavassiliou, Athanasios G; Kiaris, Hippokratis

    2010-10-26

    Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). Exposure of MEFs to 100 nM and 500 nM GHRH or the GHRH agonist JI-38 stimulated the expression of α-smooth muscle actin (αSMA) based on immunoblot analyses as well as the expression of an αSMA-β-galactosidase reporter transgene in primary cultures of fibroblasts isolated from transgenic mice. Consistent with this induction of αSMA expression, results of transwell-based migration assays and in vitro wound healing (scratch) assays showed that both GHRH and GHRH agonist JI-38 stimulated the migration of MEFs in vitro. In vivo, local application of GHRH or JI-38 accelerated healing in skin wounds of mice. Histological evaluation of skin biopsies showed that wounds treated with GHRH and JI-38 were both characterized by increased abundance of fibroblasts during the early stages of wound healing and accelerated reformation of the covering epithelium at later stages. These results identify another function of GHRH in promoting skin tissue wound healing and repair. Our findings suggest that GHRH may have clinical utility for augmenting healing of skin wounds resulting from trauma, surgery, or disease.

  15. Accelerated healing of full-thickness wounds by genipin-crosslinked silk sericin/PVA scaffolds.

    PubMed

    Aramwit, Pornanong; Siritienthong, Tippawan; Srichana, Teerapol; Ratanavaraporn, Juthamas

    2013-01-01

    Silk sericin has recently been studied for its advantageous biological properties, including its ability to promote wound healing. This study developed a delivery system to accelerate the healing of full-thickness wounds. Three-dimensional scaffolds were fabricated from poly(vinyl alcohol) (PVA), glycerin (as a plasticizer) and genipin (as a crosslinking agent), with or without sericin. The physical and biological properties of the genipin-crosslinked sericin/PVA scaffolds were investigated and compared with those of scaffolds without sericin. The genipin-crosslinked sericin/PVA scaffolds exhibited a higher compressive modulus and greater swelling in water than the scaffolds without sericin. Sericin also exhibited controlled release from the scaffolds. The genipin-crosslinked sericin/PVA scaffolds promoted the attachment and proliferation of L929 mouse fibroblasts. After application to full-thickness rat wounds, the wounds treated with genipin-crosslinked sericin/PVA scaffolds showed a significantly greater reduction in wound size, collagen formation and epithelialization compared with the control scaffolds without sericin but lower numbers of macrophages and multinucleated giant cells. These results indicate that the delivery of sericin from the novel genipin-crosslinked scaffolds efficiently healed the wound. Therefore, these genipin-crosslinked sericin/PVA scaffolds represent a promising candidate for the accelerated healing of full-thickness wounds.

  16. A bioengineered drug-Eluting scaffold accelerated cutaneous wound healing In diabetic mice.

    PubMed

    Yin, Hao; Ding, Guoshan; Shi, Xiaoming; Guo, Wenyuan; Ni, Zhijia; Fu, Hong; Fu, Zhiren

    2016-09-01

    Hyperglycemia in diabetic patients can greatly hinder the wound healing process. In this study we investigated if the engagement of F4/80(+) murine macrophages could accelerate the cutaneous wound healing in streptozotocin induced diabetic mice. To facilitate the engagement of macrophages, we engineered a drug-eluting electrospun scaffold with a payload of monocyte chemoattractant protein-1 (MCP-1). MCP-1 could be readily released from the scaffold within 3 days. The electrospun scaffold showed no cytotoxic effects on human keratinocytes in vitro. Full-thickness excisional cutaneous wound was created in diabetic mice. The wound fully recovered within 10 days in mice treated with the drug-eluting scaffold. In contrast, the wound took 14 days to fully recover in control groups. The use of drug-eluting scaffold also improved the re-epithelialization. Furthermore, we observed a larger population of F4/80(+) macrophages in the wound bed of mice treated with drug-eluting scaffolds on day 3. This marked increase of macrophages in the wound bed could have contributed to the accelerated wound healing. Our study shed new light on an immuno-engineering solution for wound healing management in diabetic patients.

  17. IL-33 accelerates cutaneous wound healing involved in upregulation of alternatively activated macrophages.

    PubMed

    Yin, Hui; Li, Xiangyong; Hu, Shilian; Liu, Tao; Yuan, Baohong; Gu, Hongbiao; Ni, Qian; Zhang, Xiaofan; Zheng, Fang

    2013-12-01

    IL-33 is a recently recognized member of the IL-1 family and has been best identified as a potent inducer of Th2-type immune responses. Increasing evidence, however, indicates that IL-33 also represents an important mediator of mucosal healing and epithelial restoration and repair. In this study, we further explore the potential effect of IL-33 in cutaneous wound healing. A full-thickness skin wound was generated on the back of mice and treated with IL-33 or vehicle intraperitoneally. Our results revealed that the levels of IL-33 mRNA and protein were significantly enhanced in incisional wound skin. Meantime, administration of IL-33 obviously accelerated wound healing with wounds gaping narrower and exhibiting enhanced reepithelialization. IL-33 upregulation also promoted the collagen deposition and the expression of extracellular matrix (ECM)-associated genes such as fibronectin and collagen IIIa, which implies a direct effect of IL-33 on matrix synthesis. Furthermore, IL-33 facilitated the development of alternatively activated macrophages (AAM) in incisional wound tissue, which closely related to resolution of inflammation and promotion of wound repair. Taken together, these findings suggest that IL-33 may play a pivotal role in maintenance of cutaneous homeostasis and acceleration of normal wound healing.

  18. Reduced FOXO1 expression accelerates skin wound healing and attenuates scarring.

    PubMed

    Mori, Ryoichi; Tanaka, Katsuya; de Kerckhove, Maiko; Okamoto, Momoko; Kashiyama, Kazuya; Tanaka, Katsumi; Kim, Sangeun; Kawata, Takuya; Komatsu, Toshimitsu; Park, Seongjoon; Ikematsu, Kazuya; Hirano, Akiyoshi; Martin, Paul; Shimokawa, Isao

    2014-09-01

    The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1(+/-) mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a(-/-) mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1(+/-) mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring.

  19. Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis.

    PubMed

    Asai, Jun; Takenaka, Hideya; Hirakawa, Satoshi; Sakabe, Jun-ichi; Hagura, Asami; Kishimoto, Saburo; Maruyama, Kazuichi; Kajiya, Kentaro; Kinoshita, Shigeru; Tokura, Yoshiki; Katoh, Norito

    2012-12-01

    Impaired wound healing is a major complication of diabetes. Recent studies have reported reduced lymphangiogenesis and angiogenesis during diabetic wound healing, which are thought to be new therapeutic targets. Statins have effects beyond cholesterol reduction and can stimulate angiogenesis when used systemically. However, the effects of topically applied statins on wound healing have not been well investigated. The present study tested the hypothesis that topical application of simvastatin would promote lymphangiogenesis and angiogenesis during wound healing in genetically diabetic mice. A full-thickness skin wound was generated on the back of the diabetic mice and treated with simvastatin or vehicle topically. Simvastatin administration resulted in significant acceleration of wound recovery, which was notable for increases in both angiogenesis and lymphangiogenesis. Furthermore, simvastatin promoted infiltration of macrophages, which produced vascular endothelial growth factor C in granulation tissues. In vitro, simvastatin directly promoted capillary morphogenesis and exerted an antiapoptotic effect on lymphatic endothelial cells. These results suggest that the favorable effects of simvastatin on lymphangiogenesis are due to both a direct influence on lymphatics and indirect effects via macrophages homing to the wound. In conclusion, a simple strategy of topically applied simvastatin may have significant therapeutic potential for enhanced wound healing in patients with impaired microcirculation such as that in diabetes.

  20. Comparison of healing rate in diabetes-related foot ulcers with low frequency ultrasonic debridement versus non-surgical sharps debridement: a randomised trial protocol

    PubMed Central

    2014-01-01

    Background Foot ulceration has been reported as the leading cause of hospital admission and amputation in individuals with diabetes. Diabetes-related foot ulcers require multidisciplinary management and best practice care, including debridement, offloading, dressings, management of infection, modified footwear and management of extrinsic factors. Ulcer debridement is a commonly applied management approach involving removal of non-viable tissue from the ulcer bed. Different methods of debridement have been reported in the literature including autolytic debridement via moist wound healing, mechanical debridement utilising wet to dry dressings, theatre based sharps debridement, biological debridement, non-surgical sharps debridement and newer technology such as low frequency ultrasonic debridement. Methods People with diabetes and a foot ulcer, referred to and treated by the Podiatry Department at Monash Health and who meet the inclusion criteria will be invited to participate in this randomised controlled trial. Participants will be randomly and equally allocated to either the non-surgical sharps debridement (control) or low frequency ultrasonic debridement (intervention) group (n = 322 ulcers/n = 108 participants). Where participants have more than one ulcer, only the participant will be randomised, not the ulcer. An investigator not involved in participant recruitment or assessment will be responsible for preparing the random allocation sequence and envelopes. Each participant will receive weekly treatment for six months including best practice podiatric management. Each ulcer will be measured on a weekly basis by calculating total area in centimetres squared. Measurement will be undertaken by a trained research assistant to ensure outcomes are blinded from the treating podiatrist. Another member of the research team will assess the final primary outcome. Discussion The primary aim of this study is to compare healing rates for diabetes-related foot ulcers

  1. Extensive, Non-Healing Scalp Ulcer Associated with Trauma-Induced Chronic Osteomyelitis

    PubMed Central

    Gómez-Duaso, Anselmo Javier; Rivero, Pino; Vilar, Jaime; Dehesa, Luis; Santana, Néstor; Carretero, Gregorio

    2011-01-01

    A 77-year-old woman presented with a trauma to the scalp caused from the blade of a windmill. The condition was persistent from the past 50 years. At the initial examination, a deep, foul-smelling and well-circumscribed ulcer was apparent on the head region, involving the majority of the cranium. Skin biopsy specimens of the lesion were nonspecific. The bone biopsy showed extensive necrotic areas of bone and soft tissues, with lymphocytic exudate foci. A computed tomography scan of the head revealed bone destruction principally involving both the parietal bones, and parts of the frontal and occipital bones. Streptococcus parasanguis was isolated from the skin culture, and Proteus mirabilis and Peptostreptococcus sp. were identified in the cultures from the bone. A long-term treatment with amoxicillin-clavulanic acid (1 g/12 h) and levofloxacin (500 mg/day) was prescribed, but even after 6 months, the lesion remained unchanged. The frequency of occurrence of scalp ulcers in dermatological patients is less, principally because of the rich blood supply to this area. We have not found any similar case report of a scalp ulcer secondary to chronic osteomyelitis discovered more than 50 years after the causal trauma. We want to highlight the importance of complete cutaneous evaluation including skin and bone biopsies, when scalp osteomyelitis is suspected. PMID:22346279

  2. Healing

    PubMed Central

    Ventres, William B.

    2016-01-01

    My personal ethos of healing is an expression of the belief that I can and do act to heal patients while I attend to the traditional goals of medicine. The 7 supporting principles that inform my ethos are dignity, authenticity, integrity, transparency, solidarity, generosity, and resiliency. I invite others, including medical students, residents, and practicing physicians, to reflect and discover their own ethos of healing and the principles that guide their professional growth. A short digital documentary accompanies this essay for use as a reflective prompt to encourage personal and professional development. PMID:26755787

  3. Skin wound healing is accelerated and scarless in the absence of commensal microbiota.

    PubMed

    Canesso, Maria C C; Vieira, Angélica T; Castro, Tiago B R; Schirmer, Brígida G A; Cisalpino, Daniel; Martins, Flaviano S; Rachid, Milene A; Nicoli, Jacques R; Teixeira, Mauro M; Barcelos, Lucíola S

    2014-11-15

    The commensal microbiota has a high impact on health and disease by modulating the development and homeostasis of host immune system. Immune cells are involved in virtually every aspect of the wound repair process; however, the impact of commensal microbiota on skin wound healing is largely unknown. In this study, we evaluated the influence of commensal microbiota on tissue repair of excisional skin wounds by using germ-free (GF) Swiss mice. We observed that macroscopic wound closure rate is accelerated in the absence of commensal microbiota. Accordantly, histologically assessed wound epithelization was accelerated in GF in comparison with conventional (CV) Swiss mice. The wounds of GF mice presented a significant decrease in neutrophil accumulation and an increase in mast cell and macrophage infiltration into wounds. Interestingly, alternatively activated healing macrophage-related genes were highly expressed in the wound tissue of GF mice. Moreover, levels of the anti-inflammatory cytokine IL-10, the angiogenic growth factor VEGF and angiogenesis were higher in the wound tissue of those mice. Conversely, scarring and levels of the profibrogenic factor TGF-β1 were greatly reduced in GF mice wounded skin when compared with CV mice. Of note, conventionalization of GF mice with CV microbiota restored wound closure rate, neutrophil and macrophage accumulation, cytokine production, and scarring to the same extent as CV mice. Overall, our findings suggest that, in the absence of any contact with microbiota, skin wound healing is accelerated and scarless, partially because of reduced accumulation of neutrophils, increased accumulation of alternatively activated healing macrophages, and better angiogenesis at wound sites.

  4. Low level laser therapy (GaAlInP 660 nm) in healing of a chronic venous ulcer: a case study

    NASA Astrophysics Data System (ADS)

    Botaro, C. A.; Faria, L. A.; Oliveira, R. G.; Bruno, R. X.; Rocha, C. A. Q. C.; Paiva-Oliveira, E. L.

    2015-07-01

    The venous ulcer represents approximately 70% to 90% of inferior member ulcers, and the most common etiological factor is venous insufficiency, triggered by venous hypertension. Currently in Brazil there are several types of lasers used in physiotherapy, which benefit biological potential, emitting low power radiation, with anti-inflammatory, analgesic, healing and circulatory effects. This study aimed at the analysis of low level laser therapy effects (LLLT) on the process of tissue repair in chronic venous ulcers. We conducted a case study of a patient with a venous ulcer in the lateral region of the right inferior member. The patient underwent LLLT, which used a GaAlInP diode laser, with a wavelength of 660 nm and energy density of 4 J cm-2 applied punctually at the edges of the wound, with an average distance of 1 cm between the points with a pen-laser perpendicular wrapped in paper and a plastic wrap, keeping contact with the tissue. After four months of therapy and a total of 21 sessions, an improvement was noticeable in the gross appearance of the wound, but after a month and a half without therapy, the dimensions of the wound increased in length and width. Analyzing the results of this case study allows us to conclude that the LLLT GaAlInP (660 nm) with an energy density of 4 J cm-2, was not successful in the healing of venous ulcers.

  5. Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review.

    PubMed

    Brownrigg, J R W; Hinchliffe, R J; Apelqvist, J; Boyko, E J; Fitridge, R; Mills, J L; Reekers, J; Shearman, C P; Zierler, R E; Schaper, N C

    2016-01-01

    Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates varied from 3% to 19%. Among 10 studies, skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg (and ≥ 45 mmHg) and transcutaneous pressure of oxygen (TcPO2 ) ≥ 25 mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle pressure < 70 mmHg and fluorescein toe slope < 18 units each increased the likelihood of major amputation by around 25%. The combined test of ankle pressure < 50 mmHg or an ankle brachial index (ABI) < 0.5 increased the likelihood of major amputation by approximately 40%. Among patients with diabetic foot ulceration, the measurement of skin perfusion pressures, toe pressures and TcPO2 appear to be more useful in predicting ulcer healing than ankle pressures or the ABI. Conversely, an ankle pressure of < 50 mmHg or an ABI < 0.5 is associated with a significant increase in the incidence of major amputation.

  6. [Cellular therapy and leg ulcers: Future approaches].

    PubMed

    Senet, P

    2015-01-01

    The prevalence of leg ulcers, which are most commonly caused by venous insufficiency, is high in Europe. Current treatments are fairly unsatisfactory, with long healing times in many cases, as well as a high risk of relapse. Over the last 15 years, improved understanding of the cellular and molecular mechanisms at work in delayed wound healing has contributed to the development of cellular therapy in this field. The use of keratinocytes or cultured fibroblasts, whether autogenic or allogenic, has been of little value in terms of either healing times or rates of complete healing. For the moment, there are very few allogenic skin substitutes available; they are expensive and have been insufficiently studied in the indication of leg ulcers. Pluripotent mesenchymal adult stem cells have proved capable of accelerating wound healing in animal models and their study in chronic wounds in humans is currently awaited.

  7. Application of coenzyme Q10 for accelerating soft tissue wound healing after tooth extraction in rats.

    PubMed

    Yoneda, Toshiki; Tomofuji, Takaaki; Kawabata, Yuya; Ekuni, Daisuke; Azuma, Tetsuji; Kataoka, Kota; Kunitomo, Muneyoshi; Morita, Manabu

    2014-12-10

    Accelerating wound healing after tooth extraction is beneficial in dental treatment. Application of antioxidants, such as reduced coenzyme Q10 (rCoQ10), may promote wound healing after tooth extraction. In this study, we examined the effects of topical application of rCoQ10 on wound healing after tooth extraction in rats. After maxillary first molars were extracted, male Fischer 344 rats (8 weeks old) (n = 27) received topical application of ointment containing 5% rCoQ10 (experimental group) or control ointment (control group) to the sockets for 3 or 8 days (n = 6-7/group). At 3 days after extraction, the experimental group showed higher collagen density and lower numbers of polymorphonuclear leukocytes in the upper part of socket, as compared to the control group (p < 0.05). Gene expression of interleukin-1β, tumor necrosis factor-α and nuclear factor-κB were also lower in the experimental group than in the control group (p < 0.05). At 8 days after tooth extraction, there were no significant differences in collagen density, number of polymorphonuclear leukocytes and bone fill between the groups. Our results suggest that topical application of rCoQ10 promotes wound healing in the soft tissue of the alveolar socket, but that rCoQ10 has a limited effect on bone remodeling in rats.

  8. Accelerated wound healing in tumor necrosis factor receptor p55-deficient mice with reduced leukocyte infiltration.

    PubMed

    Mori, Ryoichi; Kondo, Toshikazu; Ohshima, Tohru; Ishida, Yuko; Mukaida, Naofumi

    2002-07-01

    To clarify biological roles of tumor necrosis factor receptor p55 (TNF-Rp55) -mediated signals in wound healing, skin excisions were prepared in BALB/c (WT) and TNF-Rp55-deficient (KO) mice. In WT mice, the wound area was reduced to 50% of the original area 6 days after injury, with angiogenesis and collagen accumulation. Histopathologically, reepithelialization rate was approximately 80% 6 days. Myeloperoxidase activity and macrophage recruitment were the most evident 1 and 6 days after injury, respectively. Gene expression of adhesion molecules, interleukin 1alpha (IL-1alpha), IL-1beta, monocyte chemoattractant protein 1, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-2, transforming growth factor beta1 (TGF-beta1) connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF), Flt-1, and Flk-1 was enhanced at the wound site. In KO mice, an enhancement in angiogenesis, collagen content, and reepithelialization was accelerated with the increased gene expression of TGF-beta1, CTGF, VEGF, Flt-1, and Flk-1 at the wound sites, resulting in accelerated wound healing compared with WT mice. In contrast, leukocyte infiltration, mRNA expression of adhesion molecules, and cytokines were significantly reduced in KO mice. These observations suggest that TNF-Rp55-mediated signals have some role in promoting leukocyte infiltration at the wound site and negatively affect wound healing, probably by reducing angiogenesis and collagen accumulation.

  9. Salidroside accelerates fracture healing through cell-autonomous and non-autonomous effects on osteoblasts.

    PubMed

    Guo, Xiao Qin; Qi, Lin; Yang, Jing; Wang, Yue; Wang, Chuan; Li, Zong Min; Li, Ling; Qu, Ye; Wang, Dan; Han, Ze Min

    2017-02-01

    Salidroside (SAL), a major active component of Rhodiola rosea L., exhibits diverse pharmacological effects. However, the direct roles of SAL in fracture healing remain largely unknown. Here, we demonstrate that SAL significantly promotes proliferation by altering the cell-cycle distribution of osteoblastic cells. SAL also greatly stimulates osteoblast differentiation and mineralization by inducing the expression of Runx2 and Osterix. In addition to its osteoblast-autonomous effects, SAL can activate the HIF-1α pathway coupling of angiogenesis and osteogenesis through cell-non-autonomous effects. Our in vitro results suggest that SAL significantly up-regulates HIF-1α expression at the mRNA and protein levels. Furthermore, the nuclear translocation and transcriptional activity of HIF-1α and the HIF-responsive gene VEGF increase following SAL treatment. Our mechanistic study revealed that the regulation of osteoblastic proliferation and HIF-1α expression partly involves MAPK/ERK and PI3K/Akt signaling. Our in vivo analysis also demonstrated that SAL can promote angiogenesis within the callus and accelerate fracture healing. Thus, SAL promotes skeletal regeneration in cell-autonomous and cell-non-autonomous ways and might be a potential therapy for accelerating fracture healing.

  10. Effectiveness of platelet-rich plasma in healing necrobiosis lipoidica diabeticorum ulcers.

    PubMed

    Motolese, A; Vignati, F; Antelmi, A; Saturni, V

    2015-01-01

    Necrobiosis lipoidica diabeticorum (NLD) is a chronic condition, which is characterized by single or multiple lesions on the legs, and occurs in 0.3% of patients with diabetes. Recently, platelet-rich plasma (PRP) has been used in several clinical settings to promote sustained healing and better outcome. We propose the use of PRP for the treatment of NLD-associated recalcitrant wounds. In this study, 15 patients were treated with homologous PRP; all showed marked enhancement in wound healing without any adverse effects. After PRP application, advanced dressings were used until closure of the lesion was obtained, which was complete for all our patients. We therefore propose the use of PRP for recalcitrant wounds in patients with NLD.

  11. Young coconut juice can accelerate the healing process of cutaneous wounds

    PubMed Central

    2012-01-01

    Background Estrogen has been reported to accelerate cutaneous wound healing. This research studies the effect of young coconut juice (YCJ), presumably containing estrogen-like substances, on cutaneous wound healing in ovairectomized rats. Methods Four groups of female rats (6 in each group) were included in this study. These included sham-operated, ovariectomized (ovx), ovx receiving estradiol benzoate (EB) injections intraperitoneally, and ovx receiving YCJ orally. Two equidistant 1-cm full-thickness skin incisional wounds were made two weeks after ovariectomy. The rats were sacrificed at the end of the third and the fourth week of the study, and their serum estradiol (E2) level was measured by chemiluminescent immunoassay. The skin was excised and examined in histological sections stained with H&E, and immunostained using anti-estrogen receptor (ER-α an ER-β) antibodies. Results Wound healing was accelerated in ovx rats receiving YCJ, as compared to controls. This was associated with significantly higher density of immunostaining for ER-α an ER-β in keratinocytes, fibroblasts, white blood cells, fat cells, sebaceous gland, skeletal muscles, and hair shafts and follicles. This was also associated with thicker epidermis and dermis, but with thinner hypodermis. In addition, the number and size of immunoreactive hair follicles for both ER-α and ER-β were the highest in the ovx+YCJ group, as compared to the ovx+EB group. Conclusions This study demonstrates that YCJ has estrogen-like characteristics, which in turn seem to have beneficial effects on cutaneous wound healing. PMID:23234369

  12. Knockout of Endothelial Cell-Derived Endothelin-1 Attenuates Skin Fibrosis but Accelerates Cutaneous Wound Healing

    PubMed Central

    Makino, Katsunari; Jinnin, Masatoshi; Aoi, Jun; Kajihara, Ikko; Makino, Takamitsu; Fukushima, Satoshi; Sakai, Keisuke; Nakayama, Kazuhiko; Emoto, Noriaki; Yanagisawa, Masashi; Ihn, Hironobu

    2014-01-01

    Endothelin (ET)-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF)-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF)-α and connective tissue growth factor (CTGF) were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach. PMID:24853267

  13. Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing

    PubMed Central

    Hsu, I; Parkinson, L G; Shen, Y; Toro, A; Brown, T; Zhao, H; Bleackley, R C; Granville, D J

    2014-01-01

    Chronic, non-healing wounds are a major complication of diabetes and are characterized by chronic inflammation and excessive protease activity. Although once thought to function primarily as a pro-apoptotic serine protease, granzyme B (GzmB) can also accumulate in the extracellular matrix (ECM) during chronic inflammation and cleave ECM proteins that are essential for proper wound healing, including fibronectin. We hypothesized that GzmB contributes to the pathogenesis of impaired diabetic wound healing through excessive ECM degradation. In the present study, the murine serine protease inhibitor, serpina3n (SA3N), was administered to excisional wounds created on the dorsum of genetically induced type-II diabetic mice. Wound closure was monitored and skin wound samples were collected for analyses. Wound closure, including both re-epithelialization and contraction, were significantly increased in SA3N-treated wounds. Histological and immunohistochemical analyses of SA3N-treated wounds revealed a more mature, proliferative granulation tissue phenotype as indicated by increased cell proliferation, vascularization, fibroblast maturation and differentiation, and collagen deposition. Skin homogenates from SA3N-treated wounds also exhibited greater levels of full-length intact fibronectin compared with that of vehicle wounds. In addition, GzmB-induced detachment of mouse embryonic fibroblasts correlated with a rounded and clustered phenotype that was prevented by SA3N. In summary, topical administration of SA3N accelerated wound healing. Our findings suggest that GzmB contributes to the pathogenesis of diabetic wound healing through the proteolytic cleavage of fibronectin that is essential for normal wound closure, and that SA3N promotes granulation tissue maturation and collagen deposition. PMID:25299783

  14. Boric Acid Reduces the Formation of DNA Double Strand Breaks and Accelerates Wound Healing Process.

    PubMed

    Tepedelen, Burcu Erbaykent; Soya, Elif; Korkmaz, Mehmet

    2016-12-01

    Boron is absorbed by the digestive and respiratory system, and it was considered that it is converted to boric acid (BA), which was distributed to all tissues above 90 %. The biochemical essentiality of boron element is caused by boric acid because it affects the activity of several enzymes involved in the metabolism. DNA damage repair mechanisms and oxidative stress regulation is quite important in the transition stage from normal to cancerous cells; thus, this study was conducted to investigate the protective effect of boric acid on DNA damage and wound healing in human epithelial cell line. For this purpose, the amount of DNA damage occurred with irinotecan (CPT-11), etoposide (ETP), doxorubicin (Doxo), and H2O2 was determined by immunofluorescence through phosphorylation of H2AX((Ser139)) and pATM((Ser1981)) in the absence and presence of BA. Moreover, the effect of BA on wound healing has been investigated in epithelial cells treated with these agents. Our results demonstrated that H2AX((Ser139)) foci numbers were significantly decreased in the presence of BA while wound healing was accelerated by BA compared to that in the control and only drug-treated cells. Eventually, the results indicate that BA reduced the formation of DNA double strand breaks caused by agents as well as improving the wound healing process. Therefore, we suggest that boric acid has important therapeutical effectiveness and may be used in the treatment of inflammatory diseases where oxidative stress and wound healing process plays an important role.

  15. Prophylaxis and treatment of acute radiation ulcers in rats with low-power infrared laser radiation

    NASA Astrophysics Data System (ADS)

    Kursova, Larisa V.; Kaplan, Michael A.; Nikitina, Rosa G.; Maligina, Antonina I.

    1999-12-01

    Exposure of radiation ulcers in rats to low-power infrared laser radiation (LPLR) (wavelength--890 nm, pulse power--6 W, frequency--150 and 300 Hz, irradiation time--10 min) noticeably accelerates their healing, reduces exudative processes, increases number of specialized cells in wound. Application of LPLR prior to radiation damage decreases ulcer dimensions.

  16. Novel locally active estrogens accelerate cutaneous wound healing. A preliminary study.

    PubMed

    Brufani, Mario; Ceccacci, Francesca; Filocamo, Luigi; Garofalo, Barbara; Joudioux, Roberta; La Bella, Angela; Leonelli, Francesca; Migneco, Luisa M; Bettolo, Rinaldo Marini; Farina, Paolo M; Ashcroft, Gillian S; Routley, Claire; Hardman, Matthew; Meda, Clara; Rando, Gianpaolo; Maggi, Adriana

    2009-01-01

    New 17beta-estradiol (E2) derivatives 1-11 were synthesized from an estrone derivative by addition of organometallic reagents prepared from protected alpha,omega-alkynols and further elaboration of the addition products. The estrogenic activity of these novel compounds was determined using in vitro binding competition assay and transactivation analysis. Among the E2 derivatives synthesized, compound 2 showed the highest transactivation potency and was therefore tested for its ability to modulate cutaneous wound healing in vivo. Compound 2's ability to accelerate wound healing in ovariectomized mice and decrease the production of inflammatory molecules was comparable to that of E2. However, the activity of compound 2 was not superimposable to E2 with regard to the cells involved in the wound repairing process. When locally administered, compound 2 did not show any systemic activity on ER. This class of compounds with clear beneficial effects on wound healing and suitable for topical administration may lead to the generation of innovative drugs for an area of unmet clinical need.

  17. Supplementary vitamin C does not accelerate bone healing in a rat tibia fracture model

    PubMed Central

    Giordano, Vincenzo; Albuquerque, Rodrigo Pires e; do Amaral, Ney Pecegueiro; Chame, Cristiano Curcio; de Souza, Fabio; Apfel, Mara Íbis Rodrigues

    2012-01-01

    Objective To investigate the role of ascorbic acid supplementation on bone healing after rat tibia fracture. Methods Thirty male Wistar rats were randomly divided into Vitamin C (Group A) and sham (Group B) groups (15 rats each). Group A received 200 mg intraperitoneally per kg per day of ascorbic acid and Group B was given saline 5 ml per kg per day intraperitoneally once a day. The animals were caged in pairs and allowed free access to tap water and a standard rodent chow ad libitum. Fractures were produced manually, they were not stabilized, and unprotected weight-bearing was allowed. At two, four, and six weeks post-fracture, the rats in both groups were anesthetized and sacrificed by cervical dislocation. Callus tissue was dissected, prepared, and analyzed histologically. Histomorphological analysis was performed at six weeks post-fracture and the extent of fracture healing was determined using a five-point scale. Results There were no histological and histomorphological differences between drug-treated animals and the sham in the three different stages studied. By six weeks post-fracture, the five animals of each group had a complete bone union. Conclusion Under the studied conditions, intraperitoneal Vitamin C supplementation does not accelerate the fracture healing process after experimental tibia fracture in rats. Level of evidence: Level 2, individual study with experimental design. PMID:24453572

  18. Umbilical Cord Mesenchymal Stem Cells Combined With a Collagenfibrin Double-layered Membrane Accelerates Wound Healing.

    PubMed

    Nan, Wenbin; Liu, Rui; Chen, Hongli; Xu, Zhihao; Chen, Jiannan; Wang, Manman; Yuan, Zhiqing

    2015-05-01

    The aim of this study was to examine the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) in combination with a collagen-fibrin double-layered membrane on wound healing in mice. A collagen-fibrin double-layered membrane was prepared, and the surface properties of the support material were investigated using a scanning electron microscope. Twenty-four mice were prepared for use as full-thickness skin wound models and randomly divided into 3 groups: group A, a control group in which the wounds were bound using a conventional method; group B, a group treated with hUCMSCs combined with a collagen membrane; and group C, a group treated with hUCMSCs combined with a collagen-fibrin double-layered membrane. The postoperative concrescence of the wounds was observed daily to evaluate the effects of the different treatments. Scanning electron microscope observation showed the collagen-fibrin scaffolds exhibited a highly porous and interconnected structure, and wound healing in the double-layered membrane group was better than in groups A or B. Treatment with hUCMSCs combined with a collagen-fibrin double-layered membrane accelerated wound healing.

  19. Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse

    PubMed Central

    Nakarai, Asuka; Kato, Jun; Hiraoka, Sakiko; Takashima, Shiho; Takei, Daisuke; Inokuchi, Toshihiro; Sugihara, Yuusaku; Takahara, Masahiro; Harada, Keita; Okada, Hiroyuki

    2016-01-01

    AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results. METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results. RESULTS: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤ 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23). CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk. PMID:27275100

  20. Predictive value of intracutaneous xenon clearance for healing of amputation and cutaneous ulcer sites

    SciTech Connect

    Silberstein, E.B.; Thomas, S.; Cline, J.; Kempczinski, R.; Gottesman, L.

    1983-04-01

    A previously reported technique for the assessment of skin blood flow in the lower extremities of patients with ischemic lesions was evaluated using intracutaneous xenon clearance. The radioisotope was injected above and below both the ankle and the knee and flow was measured using a gamma camera with a low-energy collimator, 88-keV photopeak, and a 20% window. Healing was more frequent when skin blood flow was equal to or greater than 2.4 ml/min/100 g (38/39 patients) than when flow was less than 2.4 ml/min/100 g (4/7 patients). The authors conclude that this technique can be used to help determine the appropriate site for amputation in lower limb ischemic lesions.

  1. Predictive value of intracutaneous xenon clearance for healing of amputation and cutaneous ulcer sites

    SciTech Connect

    Silberstein, E.B.; Thomas, S.; Cline, J.; Kempczinski, R.; Gottesman, L.

    1983-04-01

    A previously reported technique for the assessment of skin blood flow in the lower extremities of patients with ischemic lesions was evaluated using intracutaeous xenon clearance. The radioisotope was injected above and below both the ankle and the knee and flow was measured using a gamma camera with a low-energy collimator, 88-keV photopeak, and a 20% window. Healing was more frequent when skin blood flow was equal to or greater than 2.4 ml/min/100 g (38/39 patients) than when flow was less than 2.4 ml/min/100 g (4/7 patients). The authors conclude that this technique can be used to help determine the appropriate site for amputation in lower limb ischemic lesions.

  2. Accelerated healing of cutaneous leishmaniasis in non-healing BALB/c mice using water soluble amphotericin B-polymethacrylic acid

    PubMed Central

    Corware, Karina; Harris, Debra; Teo, Ian; Rogers, Matthew; Naresh, Kikkeri; Müller, Ingrid; Shaunak, Sunil

    2011-01-01

    Cutaneous leishmaniasis (CL) is a neglected tropical disease that causes prominent skin scaring. No water soluble, non-toxic, short course and low cost treatment exists. We developed a new water soluble amphotericin B-polymethacrylic acid (AmB-PMA) using established and scalable chemistries. AmB-PMA was stable for 9 months during storage. In vitro, it was effective against Leishmania spp. promastigotes and amastigote infected macrophages. It was also less toxic and more effective than deoxycholate-AmB, and similar to liposomal AmB. Its in vivo activity was determined in both early and established CL lesion models of Leishmania major infection in genetically susceptible non-healing BALB/c mice. Intradermal AmB-PMA at a total dose of 18 mg of AmB/kg body weight led to rapid parasite killing and lesion healing. No toxicity was seen. No parasite relapse occurred after 80 days follow-up. Histological studies confirmed rapid parasite clearance from macrophages followed by accelerated fibroblast mediated tissue repair, regeneration and cure of the infection. Quantitative mRNA studies of the CL lesions showed that accelerated healing was associated with increased Tumor Necrosis Factor-α and Interferon-γ, and reduced Interleukin-10. These results suggest that a cost-effective AmB-PMA could be used to pharmacologically treat and immunotherapeutically accelerate the healing of CL lesions. PMID:21807409

  3. A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization.

    PubMed

    Kawakami, Yohei; Ii, Masaaki; Matsumoto, Tomoyuki; Kawamoto, Atsuhiko; Kuroda, Ryosuke; Akimaru, Hiroshi; Mifune, Yutaka; Shoji, Taro; Fukui, Tomoaki; Asahi, Michio; Kurosaka, Masahiro; Asahara, Takayuki

    2013-09-01

    Lnk, an intracellular adapter protein, is expressed in hematopoietic cell lineages, which has recently been proved as an essential inhibitory signaling molecule for stem cell self-renewal in the stem cell factor-c-Kit signaling pathway with enhanced hematopoietic and osteogenic reconstitution in Lnk-deficient mice. Moreover, the therapeutic potential of hematopoietic stem/endothelial progenitor cells (EPCs) for fracture healing has been demonstrated with mechanistic insight into vasculogenesis/angiogenesis and osteogenesis enhancement in the fracture sites. We report here, Lnk siRNA-transfected endothelial commitment of c-kit+/Sca-1+/lineage- subpopulations of bone marrow cells have high EPC colony-forming capacity exhibiting endothelial markers, VE-Cad, VEGF and Ang-1. Lnk siRNA-transfected osteoblasts also show highly osteoblastic capacity. In vivo, locally transfected Lnk siRNA could successfully downregulate the expression of Lnk at the fracture site up to 1 week, and radiological and histological examination showed extremely accelerated fracture healing in Lnk siRNA-transfected mice. Moreover, Lnk siRNA-transfected mice exhibited sufficient therapeutic outcomes with intrinstic enhancement of angiogenesis and osteogenesis, specifically, the mice demonstrated better blood flow recovery in the sites of fracture. In our series of experiments, we clarified that a negatively regulated Lnk system contributed to a favorable circumstance for fracture healing by enhancing vasculogenesis/angiogenesis and osteogenesis. These findings suggest that downregulation of Lnk system may have the clinical potential for faster fracture healing, which contributes to the reduction of delayed unions or non-unions.

  4. Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice

    PubMed Central

    Fujita, Kosuke; Kuge, Katsunori; Ozawa, Noriyasu; Sahara, Shunya; Zaiki, Kaori; Nakaoji, Koichi; Hamada, Kazuhiko; Takenaka, Yukiko; Tanahashi, Takao; Tamai, Katsuto; Kaneda, Yasufumi; Maeda, Akito

    2015-01-01

    Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on

  5. Cinnamtannin B-1 Promotes Migration of Mesenchymal Stem Cells and Accelerates Wound Healing in Mice.

    PubMed

    Fujita, Kosuke; Kuge, Katsunori; Ozawa, Noriyasu; Sahara, Shunya; Zaiki, Kaori; Nakaoji, Koichi; Hamada, Kazuhiko; Takenaka, Yukiko; Tanahashi, Takao; Tamai, Katsuto; Kaneda, Yasufumi; Maeda, Akito

    2015-01-01

    Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on

  6. Effect of ethanol extract of Piper betle Linn leaf on healing of NSAID-induced experimental ulcer--a novel role of free radical scavenging action.

    PubMed

    Majumdar, Biswajit; Ray Chaudhuri, Susri Guha; Ray, Arun; Bandyopadhyay, Sandip K

    2003-04-01

    Treatment with ethanol extract of leaf of P. betle at a dose of 150 mg/kg body weight daily for 10 days, after induction of peptic ulcer by NSAID in albino rats, produced significant healing effect. During healing process, on treatment with the extractive, antioxidative factor, e.g. superoxide dismutase and catalase activity, mucus and total gastric tissue sulfhydryl group were increased. In contrast, oxidised lipid and oxidatively modified proteins were reduced to near normalcy, within 7 to 10 days, however, change in the untreated group was not significant. The extract also showed significant in vitro free radical scavenging action. The results suggest that the antioxidant or free radical scavenging activity of the plant extract, may be responsible for its healing action.

  7. N-Acetylated Proline-Glycine-Proline Accelerates Cutaneous Wound Healing and Neovascularization by Human Endothelial Progenitor Cells

    PubMed Central

    Kwon, Yang Woo; Heo, Soon Chul; Lee, Tae Wook; Park, Gyu Tae; Yoon, Jung Won; Jang, Il Ho; Kim, Seung-Chul; Ko, Hyun-Chang; Ryu, Youngjae; Kang, Hyeona; Ha, Chang Man; Lee, Sang Chul; Kim, Jae Ho

    2017-01-01

    Human endothelial progenitor cells (hEPCs) are promising therapeutic resources for wound repair through stimulating neovascularization. However, the hEPCs-based cell therapy has been hampered by poor engraftment of transplanted cells. In this study, we explored the effects of N-acetylated Proline-Glycine-Proline (Ac-PGP), a degradation product of collagen, on hEPC-mediated cutaneous wound healing and neovascularization. Treatment of hEPCs with Ac-PGP increased migration, proliferation, and tube-forming activity of hEPCs in vitro. Knockdown of CXCR2 expression in hEPCs abrogated the stimulatory effects of Ac-PGP on migration and tube formation. In a cutaneous wound healing model of rats and mice, topical application of Ac-PGP accelerated cutaneous wound healing with promotion of neovascularization. The positive effects of Ac-PGP on wound healing and neovascularization were blocked in CXCR2 knockout mice. In nude mice, the individual application of Ac-PGP treatment or hEPC injection accelerated wound healing by increasing neovascularization. Moreover, the combination of Ac-PGP treatment and hEPC injection further stimulated wound healing and neovascularization. Topical administration of Ac-PGP onto wound bed stimulated migration and engraftment of transplanted hEPCs into cutaneous dermal wounds. Therefore, these results suggest novel applications of Ac-PGP in promoting wound healing and augmenting the therapeutic efficacy of hEPCs. PMID:28230162

  8. Treatment of venous leg ulcers with ultrasound-guided foam sclerotherapy: Healing, long-term recurrence and quality of life evaluation.

    PubMed

    Lloret, Pedro; Redondo, Pedro; Cabrera, Juan; Sierra, Alejandro

    2015-01-01

    Venous leg ulcers (VLU) generally have slow healing rates (HR) and frequent recurrence rates (RR). The underlying etiology is venous hypertension. The present observational cohort study was to determine healing and RR in VLU treated with ultrasound-guided foam sclerotherapy (UGFS). One hundred and eighty VLU were treated with polidocanol microfoam monthly under ultrasound control. Median follow-up was 30 months (range: 17-40). One hundred seventy-two (95.6%) ulcers healed during the study. The overall twenty-four week HR was 79.4% and was significantly higher (95.1%) in patients with isolated great saphenous vein incompetence than in those with great saphenous vein plus perforator (91.7%) or exclusive perforator incompetence (78.9%) (p < 0.01). Patients without deep vein incompetence had a significantly higher 6-month HR (89.8%) than those with (67.4%) (p < 0.01). Multivariate analysis identified the following independent risk factors: chronicity > 12 months (OR 7.69), area > 6 cm(2) (OR 4.24), lipodermatoesclerosis (OR 12.22), history of > 3 previous ulcers (OR 5.57) and history of deep vein thrombosis (OR 6.18). One, two and three year ulcer RR were 8.1%, 14.9%, and 20.8%, respectively. Isolated perforator incompetence and previous history of venous surgery were significantly (p = 0.03) associated with a higher RR. VLU treated with microfoam sclerotherapy are associated with high HR and low mid-term RR.

  9. A single-arm trial indirect comparison investigation: a proof-of-concept method to predict venous leg ulcer healing time for a new acellular synthetic matrix matched to standard care control.

    PubMed

    Shannon, Ronald; Nelson, Andrea

    2016-11-20

    To compare data on time to healing from two separate cohorts: one treated with a new acellular synthetic matrix plus standard care (SC) and one matched from four large UK pragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence network]. We introduce a new proof-of-concept strategy to a VLU clinical evidence network, propensity score matching and sensitivity analysis to predict the feasibility of the new acellular synthetic matrix plus SC for success in future randomised, controlled clinical trials. Prospective data on chronic VLUs from a safety and effectiveness study on an acellular synthetic matrix conducted in one wound centre in the UK (17 patients) and three wound centres in Australia (36 patients) were compared retrospectively to propensity score-matched data from patients with comparable leg ulcer disease aetiology, age, baseline ulcer area, ulcer duration, multi-layer compression bandaging and majority of care completed in specialist wound centres (average of 1 visit per week), with the outcome measures at comparable follow-up periods from patients enrolled in four prospective, multicentre, pragmatic, randomised studies of venous ulcers in the UK (the comparison group; VLU evidence network). Analysis using Kaplan-Meier survival curves showed a mean healing time of 73·1 days for ASM plus SC (ASM) treated ulcers in comparison with 83·5 days for comparison group ulcers treated with SC alone (Log rank test, χ(2) 5·779, P = 0·016) within 12 weeks. Sensitivity analysis indicates that an unobserved covariate would have to change the odds of healing for SC by a factor of 1·1 to impact the baseline results. Results from this study predict a significant effect on healing time when using a new ASM as an adjunct to SC in the treatment of non-healing venous ulcers in the UK, but results are sensitive to unobserved covariates that may be important in healing time comparison.

  10. Acceleration of wound healing by α-gal nanoparticles interacting with the natural anti-Gal antibody.

    PubMed

    Galili, Uri

    2015-01-01

    Application of α-gal nanoparticles to wounds and burns induces accelerated healing by harnessing the natural anti-Gal antibody which constitutes ~1% of human immunoglobulins. α-gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R), the carbohydrate ligand of anti-Gal. Studied α-gal nanoparticles were comprised of glycolipids with α-gal epitopes, phospholipids, and cholesterol. Binding of anti-Gal to α-gal nanoparticles in wounds activates the complement cascade, resulting in formation of chemotactic complement cleavage peptides that induce rapid recruitment of many macrophages. The Fc/Fcγ receptors interaction between anti-Gal coating α-gal nanoparticles and the recruited macrophages activates macrophages to produce cytokines/growth factors that promote wound healing and recruit stem cells. Studies of wound healing by α-gal nanoparticles were feasible in α1,3galactosyltransferase knockout mice and pigs. In contrast to other nonprimate mammals, these mice and pigs lack the α-gal epitope, and thus they are not immunotolerant to it and produce anti-Gal. Treatment of skin wounds and burns with α-gal nanoparticles resulted in 40-60% decrease in healing time in comparison with control wounds treated with saline. This accelerated healing is associated with increased recruitment of macrophages and extensive angiogenesis in wounds, faster regrowth of epidermis, and regeneration of the dermis. The accelerated healing further decreases and may completely eliminate fibrosis and scar formation in wounds. Since healing of internal injuries is mediated by mechanisms similar to those in external wound healing, it is suggested that α-gal nanoparticles treatment may also improve regeneration and restoration of biological function following internal injuries such as surgical incisions, myocardial ischemia following infarction, and nerve injuries.

  11. The effectiveness of hydrocolloid dressings versus other dressings in the healing of pressure ulcers in adults and older adults: a systematic review and meta-analysis1

    PubMed Central

    Pott, Franciele Soares; Meier, Marineli Joaquim; Stocco, Janislei Giseli Dorociak; Crozeta, Karla; Ribas, Janyne Dayane

    2014-01-01

    Objective to evaluate the effectiveness of hydrocolloids in the healing of pressure ulcers in adult and older adult patients. Method systematic review with meta-analysis, based on the recommendations of the Cochrane Handbook. The search was undertaken in the databases: Medical Literature Analysis and Retrieval System Online, Latin American and Caribbean Health Sciences Literature (LILACS), Cochrane Database, Cumulative Index to Nursing and Allied Health Literature, Web of Science and the Scientific Electronic Library Online. Results 646 primary studies were identified, 69 were evaluated and nine were selected, referring to the use of the hydrocolloid dressing in healing; of these, four studies allowed meta-analysis. There was no statistically significant difference between the hydrocolloid group and the foams group (p value=0.84; Odds Ratio 1.06, CI 95% 0.61-1.86). A slight superiority of the polyurethane dressings was observed in relation to the hydrocolloid dressings. Conclusion the evidence is not sufficient to affirm whether the efficacy of hydrocolloid dressings is superior to that of other dressings. It is suggested that clinical randomized trials be undertaken so as to ascertain the efficacy of this intervention in the healing of pressure ulcers, in relation to other treatments. PMID:25029065

  12. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    PubMed Central

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa. PMID:26798415

  13. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    PubMed

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  14. Electrospun tilapia collagen nanofibers accelerating wound healing via inducing keratinocytes proliferation and differentiation.

    PubMed

    Zhou, Tian; Wang, Nanping; Xue, Yang; Ding, Tingting; Liu, Xin; Mo, Xiumei; Sun, Jiao

    2016-07-01

    The development of biomaterials with the ability to induce skin wound healing is a great challenge in biomedicine. In this study, tilapia skin collagen sponge and electrospun nanofibers were developed for wound dressing. The collagen sponge was composed of at least two α-peptides. It did not change the number of spleen-derived lymphocytes in BALB/c mice, the ratio of CD4(+)/CD8(+) lymphocytes, and the level of IgG or IgM in Sprague-Dawley rats. The tensile strength and contact angle of collagen nanofibers were 6.72±0.44MPa and 26.71±4.88°, respectively. They also had good thermal stability and swelling property. Furthermore, the nanofibers could significantly promote the proliferation of human keratinocytes (HaCaTs) and stimulate epidermal differentiation through the up-regulated gene expression of involucrin, filaggrin, and type I transglutaminase in HaCaTs. The collagen nanofibers could also facilitate rat skin regeneration. In the present study, electrospun biomimetic tilapia skin collagen nanofibers were succesfully prepared, were proved to have good bioactivity and could accelerate rat wound healing rapidly and effectively. These biological effects might be attributed to the biomimic extracellular matrix structure and the multiple amino acids of the collagen nanofibers. Therefore, the cost-efficient tilapia collagen nanofibers could be used as novel wound dressing, meanwhile effectively avoiding the risk of transmitting animal disease in the future clinical apllication.

  15. Combined use of omeprazole and a novel antioxidative cytoprotectant for the treatment of peptic ulcer. Facilitation of ulcer healing in experimental animals.

    PubMed

    Kim, Ju Mi; Choi, Seul Min; Kim, Dong Hwan; Oh, Tae Young; Ahn, Byoung Ok; Kwon, Jong Won; Kim, Won Bae

    2005-01-01

    Peptic ulcer and gastroesophageal reflux are common acid-peptic related diseases. The pathophysiology of peptic ulcer disease has been centered on an imbalance between aggressive and defensive factors. This study was conducted to examine whether the combined use of omeprazole (CAS 73590-58-6), a proton pump inhibitor, and DA-9601, a novel anti-ulcer formulation of the extract of Artemisia asiatica Nakai, has synergistic effects on various peptic ulcers and gastroesophageal reflux diseases in animal models. An optimal combination ratio of omeprazole and DA-9601 was investigated in an acetic acid-induced ulcer model. In the results, oral pretreatment with omeprazole and DA-9601 (combination ratio, 1:3) significantly reduced alcohol-, indometacin-, acetic acid-, and cysteamine-induced gastrointestinal lesions in a synergistical manner in rats. The combination treatment also significantly attenuated the gross and histopathological lesions in an experimental reflux esophagitis model as compared to the single treatment of omeprazole or DA-9601. In an alcohol-induced gastritis model, the combined treatment resulted in a significant decrease in lipid peroxidation with concomitant increases in glutathione content and prostaglandin E2 level, which was proportional to the inhibitory effect of the combination therapy. These results suggest that the combined therapy with omeprazole and DA-9601, a cytoprotectant, can be beneficial for the treatment of peptic ulcer and reflux esophagitis.

  16. Healing effects of Musa sapientum var. paradisiaca in diabetic rats with co-occurring gastric ulcer: cytokines and growth factor by PCR amplification

    PubMed Central

    2013-01-01

    Background The present study evaluates the effects of extract of Musa sapientum fruit (MSE) on ulcer index, blood glucose level and gastric mucosal cytokines, TNF-α and IL-1β and growth factor, TGF-α (affected in diabetes and chronic ulcer) in acetic acid (AA)-induced gastric ulcer (GU) in diabetic (DR) rat. Methods MSE (100 mg/kg, oral), omeprazole (OMZ, 2.0 mg/kg, oral), insulin (INS, 4 U/kg, sc) or pentoxyphylline (PTX, 10 mg/kg, oral) were given once daily for 10 days in 14 days post-streptozotocin (60 mg/kg, intraperitoneal)-induced diabetic rats while, the normal/diabetic rats received CMC for the same period after induction of GU with AA. Ulcer index was calculated based upon the product of length and width (mm2/rat) of ulcers while, TNF-α, IL-1β and TGF-α were estimated in the gastric mucosal homogenate from the intact/ulcer region. Phytochemical screening and HPTLC analysis of MSE was done following standard procedures. Results An increase in ulcer index, TNF-α and IL-1β were observed in normal (NR)-AA rat compared to NR-normal saline rat, which were further increased in DR-AA rat while, treatments of DR-AA rat with MSE, OMZ, INS and PTX reversed them, more so with MSE and PTX. Significant increase in TGF-α was found in NR-AA rat which did not increase further in DR-AA rat. MSE and PTX tended to increase while, OMZ and INS showed little or no effect on TGF-α in AA-DR rat. Phytochemical screening of MSE showed the presence of saponins, flavonoids, glycosides, steroids and alkaloids and HPTLC analysis indicated the presence of eight active compounds. Conclusion MSE showed antidiabetic and better ulcer healing effects compared with OMZ (antiulcer) or INS (antidiabetic) in diabetic rat and could be more effective in diabetes with concurrent gastric ulcer. PMID:24192345

  17. Non-healing tongue ulcer in a rheumatoid arthritis patient medicated with leflunomide. An adverse drug event?

    PubMed

    Kalogirou, Eleni-Marina; Katsoulas, Nikolaos; Tosios, Konstantinos I; Lazaris, Andreas C; Sklavounou, Alexandra

    2017-02-01

    Leflunomide is a member of the disease modifying anti-rheumatic drugs group used as a treatment modality in active rheumatoid and psoriatic arthritis. "Oral ulcers" are reported in 3-5% of leflunomide medicated rheumatoid arthritis patients with adverse events, but they are not described in detail in the literature. We present a case of an ulcer in the tongue of a rheumatoid arthritis patient managed with leflunomide and contemplate on its pathogenesis. Key words:Leflunomide, oral ulcer, DHODH.

  18. Healing Acceleration of Acetic Acid-induced Colitis by Marigold (Calendula officinalis) in Male Rats

    PubMed Central

    Tanideh, Nader; Jamshidzadeh, Akram; Sepehrimanesh, Masood; Hosseinzadeh, Masood; Koohi-Hosseinabadi, Omid; Najibi, Asma; Raam, Mozhdeh; Daneshi, Sajad; Asadi-Yousefabad, Seyedeh-Leili

    2016-01-01

    Background/Aim: Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. Materials and Methods: Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and oral doses of C. officinalis extract, 1500 and 3000 mg/kg, and enema (gel 10% and 20%) were given. Two groups as positive controls were given asacol (enema) and oral mesalamine. Negative control groups were given normal saline and base gel. On days 3 and 7, intestinal histopathology and weight changes, plus oxidative stress indices including malondialdehyde (MDA) level and myeloperoxidase (MPO) activity were assayed. Results: A significant increase in the body weight of rats was seen in the group given C. officinalis extract 3000 mg/kg orally, oral mesalamine, and 20% intracolonic gel form of marigold extract compared with negative control and base gel groups during the experimental period. Acute inflammation and granular atrophy after UC induction were resolved completely completely by both 20% intracolonic gel and 3000 mg/kg orally. An increase in MPO activity and a decrease in MDA level in response to oral and intracolonic gel form of C. officinalis were observed 3 and and 7 days after treatment (P < 0.05). Conclusion: Our results indicate that oral and enema forms of hydroalcoholic extract of C. officinalis can be offered as are potential therapeutic agents for UC induced in rats. PMID:26831607

  19. Antioxidant potential of bilirubin-accelerated wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Ram, Mahendra; Singh, Vishakha; Kumar, Dhirendra; Kumawat, Sanjay; Gopalakrishnan, Anu; Lingaraju, Madhu C; Gupta, Priyanka; Tandan, Surendra Kumar; Kumar, Dinesh

    2014-10-01

    Oxidative injury is markedly responsible for wound complications in diabetes mellitus. The biological actions of bilirubin may be relevant to prevent oxidant-mediated cell death, as bilirubin application at a low concentration scavenges reactive oxygen species. Hence, we hypothesized that topical bilirubin application might improve wound healing in diabetic rats. Diabetes was induced in adult male Wistar rats, which were divided into two groups, i.e., diabetic control and diabetic treated. Non-diabetic healthy rats were also taken as healthy control group. Wound area was measured on days 3, 7, 14, and 19 post-wounding. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in the granulation tissue. There was a significant increase in percent wound closure in healthy control and diabetic treated rats on days 7, 14, and 19, as compared to diabetic control rats on days 7, 14, and 19. There was significant decrease in MDA levels on days 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. Levels of GSH were significantly increased on days 3, 7, 14, and 19 in diabetic treated rats, as compared to diabetic control rats. GPx, SOD, and CAT activities were significantly higher on days 3, 7, and 14 in diabetic treated rats, as compared to diabetic control rats. The findings indicate that bilirubin is effective in reducing the oxidant status in wounds of diabetic rats which might have accelerated wound healing in these rats.

  20. Accelerating skin wound healing by M-CSF through generating SSEA-1 and -3 stem cells in the injured sites

    PubMed Central

    Li, Yunyuan; Jalili, Reza Baradar; Ghahary, Aziz

    2016-01-01

    Wound healing is a complicated process requiring the collaborative efforts of different cell lineages. Our recent studies have found that one subset of hematopoietic cells can be induced to dedifferentiate into multipotent stem cells by means of a proliferating fibroblast releasable factor, M-CSF. Understanding the importance of stem cells on skin wound healing, here we evaluate the biological significance of M-CSF on skin wound healing. In an in vivo mouse skin excisional wound model, we found that SSEA-positive stem cells were present in wounded but not normal skin. After isolating skin cells from either normal or wounded skin by collagenase digestion, and analyzing the SSEA-1 positive cells by flow cytometry, we found a significant increase in the number of SSEA-1 positive cells in wounded skin. Topical application of M-CSF in skin wounds accelerated healing remarkably, while application of M-CSF-neutralizing antibody slowed wound healing. Furthermore, injection of EGFP-labeled hematopoietic cell-derived stem cells generated from M-CSF treated splenocytes resulted in EGFP-labeled cells being enriched in the skin wound site and further differentiated into functional organ-specific cells. Together, these data demonstrated that M-CSF makes a significant contribution to the healing process by inducing hematopoietic cell dedifferentiation into stem cells. PMID:27363517

  1. Combined nitric oxide-releasing poly(vinyl alcohol) film/F127 hydrogel for accelerating wound healing.

    PubMed

    Schanuel, Fernanda Seabra; Raggio Santos, Karen Slis; Monte-Alto-Costa, Andréa; de Oliveira, Marcelo G

    2015-06-01

    Nitric oxide (NO) releasing biomaterials represent a potential strategy for use as active wound dressings capable of accelerating wound healing. Topical NO-releasing poly(vinyl alcohol) (PVA) films and Pluronic F127 hydrogels (F127) have already exhibited effective skin vasodilation and wound healing actions. In this study, we functionalized PVA films with SNO groups via esterification with a mixture of mercaptosucinic acid (MSA) and thiolactic acid (TLA) followed by S-nitrosation of the SH moieties. These films were combined with an underlying layer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), i.e., PEO-PPO-PEO (Pluronic F127) hydrogel and used for the topical treatment of skin lesions in an animal model. The mixed esterification of PVA with MSA and TLA led to chemically crosslinked PVA-SNO films with a high swelling capacity capable of spontaneously releasing NO. Real time NO-release measurements revealed that the hydrogel layer reduces the initial NO burst from the PVA-SNO films. We demonstrate that the combination of PVA-SNO films with F127 hydrogel accelerates wound contraction, decreases wound gap and cellular density and accelerates the inflammatory phase of the lesion. These results were reflected in an increase in myofibroblastic differentiation and collagen type III expression in the cicatricial tissue. Therefore, PVA-SNO films combined with F127 hydrogel may represent a new approach for active wound dressings capable of accelerating wound healing.

  2. Novel lipoproteoplex delivers Keap1 siRNA based gene therapy to accelerate diabetic wound healing.

    PubMed

    Rabbani, Piul S; Zhou, Anna; Borab, Zachary M; Frezzo, Joseph A; Srivastava, Nikita; More, Haresh T; Rifkin, William J; David, Joshua A; Berens, Samuel J; Chen, Raymond; Hameedi, Sophia; Junejo, Muhammad H; Kim, Camille; Sartor, Rita A; Liu, Che F; Saadeh, Pierre B; Montclare, Jin K; Ceradini, Daniel J

    2017-04-03

    Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC). Addition of a cationic engineered supercharged coiled-coil protein (CSP) in a 10:1:1 ratio of DNC:CSP:siRNA produced a stable lipoproteoplex (LPP) nanoparticle, with optimal siRNA complexation, minimal cytotoxicity, and increased transfection efficacy. In a humanized murine diabetic wound healing model, our optimized LPP formulation successfully delivered siRNA targeted against Keap1, key repressor of Nrf2 which is a central regulator of redox mechanisms. Application of LPP complexing siKeap1 restored Nrf2 antioxidant function, accelerated diabetic tissue regeneration, and augmented reduction-oxidation homeostasis in the wound environment. Our topical LPP delivery system can readily be translated into clinical use for the treatment of diabetic wounds and can be extended to other cutaneous diseases with genetic components.

  3. Acceleration of diabetic-wound healing with PEGylated rhaFGF in healing-impaired streptozocin diabetic rats.

    PubMed

    Huang, Zhifeng; Lu, Meifei; Zhu, Guanghui; Gao, Hongchang; Xie, Liyun; Zhang, Xiaoqin; Ye, Chaohui; Wang, Yan; Sun, Chuanchuan; Li, Xiaokun

    2011-01-01

    Molecular modification with polyethylene glycol (PEGylation) is an effective approach to improve protein biostability, in vivo lifetime and therapeutic potency. In the present study, the recombinant human acid fibroblast growth factor (rhaFGF) was site-selectively PEGylated with 20 kDa mPEG-butyraldehyde. Mono-PEGylated rhaFGF was purified to near homogeneity by Sephadex G 25-gel filtration followed by a Heparin Sepharose TM CL-6B affinity chromatography. PEGylated rhaFGF has less effect than the native rhaFGF on the stimulation of 3T3 cell proliferation in vitro; however, its relative thermal stability at normal physiological temperature and structural stability were significantly enhanced, and its half-life time in vivo was significantly extended. Then, the physiological function of PEGylated rhaFGF on diabetic-wound healing was evaluated in type 1 diabetic Sprague Dawley rats. The results showed that, compared with the group of animal treated with native rhaFGF, the group treated with PEGylated rhaFGF exhibited better therapeutic efficacy with shorter healing time, quicker tissue collagen generation, earlier and higher transforming growth factor (TGF)-β expression, and dermal cell proliferation. In addition, in vivo analysis showed that both native and PEGylated rhaFGF were more effective in the wound healing in the diabetic group compared with the nondiabetic one. Taken together, these results suggest that PEGylation of rhaFGF could be a more effective approach to the pharmacological and therapeutic application of native rhaFGF.

  4. Use of 16S rRNA sequencing and quantitative PCR to correlate venous leg ulcer bacterial bioburden dynamics with wound expansion, antibiotic therapy, and healing

    PubMed Central

    Sprockett, Daniel D.; Ammons, Christine G.; Tuttle, Marie S.

    2016-01-01

    Clinical diagnosis of infection in chronic wounds is currently limited to subjective clinical signs and culture-based methods that underestimate the complexity of wound microbial bioburden as revealed by DNA-based microbial identification methods. Here, we use 16S rRNA next generation sequencing and quantitative polymerase chain reaction to characterize weekly changes in bacterial load, community structure, and diversity associated with a chronic venous leg ulcer over the 15-week course of treatment and healing. Our DNA-based methods and detailed sampling scheme reveal that the bacterial bioburden of the wound is unexpectedly dynamic, including changes in the bacterial load and community structure that correlate with wound expansion, antibiotic therapy, and healing. We demonstrate that these multidimensional changes in bacterial bioburden can be summarized using swabs taken prior to debridement, and therefore, can be more easily collected serially than debridement or biopsy samples. Overall, this case illustrates the importance of detailed clinical indicators and longitudinal sampling to determine the pathogenic significance of chronic wound microbial dynamics and guide best use of antimicrobials for improvement of healing outcomes. PMID:25902876

  5. Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

    PubMed

    Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

    2015-12-01

    Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers.

  6. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts

    PubMed Central

    Hu, Li; Wang, Juan; Zhou, Xin; Xiong, Zehuan; Zhao, Jiajia; Yu, Ran; Huang, Fang; Zhang, Handong; Chen, Lili

    2016-01-01

    Prolonged healing and scar formation are two major challenges in the treatment of soft tissue trauma. Adipose mesenchymal stem cells (ASCs) play an important role in tissue regeneration, and recent studies have suggested that exosomes secreted by stem cells may contribute to paracrine signaling. In this study, we investigated the roles of ASCs-derived exosomes (ASCs-Exos) in cutaneous wound healing. We found that ASCs-Exos could be taken up and internalized by fibroblasts to stimulate cell migration, proliferation and collagen synthesis in a dose-dependent manner, with increased genes expression of N-cadherin, cyclin-1, PCNA and collagen I, III. In vivo tracing experiments demonstrated that ASCs-Exos can be recruited to soft tissue wound area in a mouse skin incision model and significantly accelerated cutaneous wound healing. Histological analysis showed increased collagen I and III production by systemic administration of exosomes in the early stage of wound healing, while in the late stage, exosomes might inhibit collagen expression to reduce scar formation. Collectively, our findings indicate that ASCs-Exos can facilitate cutaneous wound healing via optimizing the characteristics of fibroblasts. Our results provide a new perspective and therapeutic strategy for the use of ASCs-Exos in soft tissue repair. PMID:27615560

  7. Accelerated healing of skin burns by anti-Gal/alpha-gal liposomes interaction.

    PubMed

    Galili, Uri; Wigglesworth, Kim; Abdel-Motal, Ussama M

    2010-03-01

    Topical application of alpha-gal liposomes on burns results in rapid local recruitment of neutrophils and macrophages. Recruited macrophages are pivotal for healing of burns because they secrete cytokines/growth factors that induce epidermis regeneration and tissue repair. alpha-Gal liposomes have glycolipids with alpha-gal epitopes (Galalpha1-3Galbeta1-4GlcNAc-R) which bind anti-Gal, the most abundant natural antibody in humans constituting approximately 1% of immunoglobulins. Interaction of alpha-gal liposomes with anti-Gal within the fluid film formed on burns, activates complement and generates chemotactic complement cleavage peptides which effectively recruit neutrophils and macrophages. Anti-Gal IgG coating alpha-gal liposomes further binds to Fcgamma receptors on macrophages and activates them to secrete cytokines/growth factors. Efficacy of alpha-gal liposomes treatment in accelerating burn healing is demonstrated in the experimental model of alpha1,3galactosyltransferase knockout mice. These mice are the only available nonprimate mammals that can produce anti-Gal in titers similar to those in humans. Pairs of burns in mice were covered either with a spot bandage coated with 10mg alpha-gal liposomes, or with a control spot bandage coated with saline. On Day 3 post-treatment, the alpha-gal liposomes treated burns contained approximately 5-fold as many neutrophils as control burns, whereas macrophages were found only in alpha-gal liposomes treated burns. On Day 6, 50-100% of the surface area of alpha-gal liposomes treated burns were covered with regenerating epidermis (re-epithelialization), whereas almost no epidermis was found in control burns. The extensive recruitment of macrophages by anti-Gal/alpha-gal liposomes interaction was further demonstrated in vivo with polyvinyl alcohol (PVA) sponge discs containing alpha-gal liposomes, implanted subcutaneously. Since anti-Gal is abundant in all humans, it is suggested that treatment with alpha-gal liposomes

  8. Rebamipide: A Novel Agent in the Treatment of Recurrent Aphthous Ulcer and Behcet's Syndrome

    PubMed Central

    Kudur, Mohan H; Hulmani, Manjunath

    2013-01-01

    Rebamipide is an amino acid analog of 2 (1H)-quinolinone. It is being introduced and used since 1980 for the treatment of peptic ulcer. Its therapeutic use in recurrent aphthous ulcer was not known. It acts by the decrease in oxygen radicals, increase in blood flow and production of protective prostaglandins in ulcer mucosa, which accelerates the process of healing. In this article, we focus on the pharmacodynamics, pharmacokinetics, side-effects and other therapeutic uses of Rebamipide. It will be a new and effective drug in the dermatologists’ drug armamentarium for the treatment of aphthous ulcers and related diseases. PMID:24082178

  9. Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients

    PubMed Central

    Ochoa-Gonzalez, Fatima; Cervantes-Villagrana, Alberto R.; Fernandez-Ruiz, Julio C.; Nava-Ramirez, Hilda S.; Hernandez-Correa, Adriana C.; Enciso-Moreno, Jose A.; Castañeda-Delgado, Julio E.

    2016-01-01

    Background Several epidemiological studies in diabetic patients have demonstrated a protective effect of metformin to the development of several types of cancer. The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. However, little is known about the role that metformin treatment have on other cell types such as keratinocytes and whether exposure to metformin of these cells might have serious repercussions in wound healing delay and in the development of complications in diabetic patients with foot ulcers or in their exacerbation. Material and Methods HaCaT Cells were exposed to various concentrations of metformin and cell viability was evaluated by a Resazurin assay; Proliferation was also evaluated with a colony formation assay and with CFSE dilution assay by flow cytometry. Cell cycle was also evaluated by flow cytometry by PI staining. An animal model of wound healing was used to evaluate the effect of metformin in wound closure. Also, an analysis of patients receiving metformin treatment was performed to determine the effect of metformin treatment on the outcome and wound area. Statistical analysis was performed on SPSS v. 18 and GraphPad software v.5. Results Metformin treatment significantly reduces cell proliferation; colony formation and alterations of the cell cycle are observed also in the metformin treated cells, particularly in the S phase. There is a significant increase in the area of the wound of the metformin treated animals at different time points (P<0.05). There is also a significant increase in the size and wound area of the patients with diabetic foot ulcers at the time of hospitalization. A protective effect of metformin was observed for amputation, probably associated with the anti inflammatory effects reported of metformin. Conclusions Metformin treatment reduces cell proliferation and reduces wound healing in an animal model

  10. 1,25-Dihydroxyvitamin D3 Induces LL-37 and HBD-2 Production in Keratinocytes from Diabetic Foot Ulcers Promoting Wound Healing: An In Vitro Model

    PubMed Central

    Gonzalez-Curiel, Irma; Trujillo, Valentin; Montoya-Rosales, Alejandra; Rincon, Kublai; Rivas-Calderon, Bruno; deHaro-Acosta, Jeny; Marin-Luevano, Paulina; Lozano-Lopez, Daniel; Enciso-Moreno, Jose A.; Rivas-Santiago, Bruno

    2014-01-01

    Diabetic foot ulcers (DFU) are one of the most common diabetes-related cause of hospitalization and often lead to severe infections and poor healing. It has been recently reported that patients with DFU have lower levels of antimicrobial peptides (AMPs) at the lesion area, which contributes with the impairment of wound healing. The aim of this study was to determine whether 1,25-dihydroxyvitamin D3 (1,25 (OH)2 D3) and L-isoleucine induced HBD-2 and LL-37 in primary cultures from DFU. We developed primary cell cultures from skin biopsies from 15 patients with DFU and 15 from healthy donors. Cultures were treated with 1,25 (OH)2D3 or L-isoleucine for 18 h. Keratinocytes phenotype was identified by western blot and flow cytometry. Real time qPCR for DEFB4, CAMP and VDR gene expression was performed as well as an ELISA to measure HBD-2 and LL-37 in supernatant. Antimicrobial activity, in vitro, wound healing and proliferation assays were performed with conditioned supernatant. The results show that primary culture from DFU treated with 1,25(OH)2D3, increased DEFB4 and CAMP gene expression and increased the production of HBD-2 and LL-37 in the culture supernatant. These supernatants had antimicrobial activity over E. coli and induced remarkable keratinocyte migration. In conclusion the 1,25(OH)2D3 restored the production of AMPs in primary cell from DFU which were capable to improve the in vitro wound healing assays, suggesting their potential therapeutic use on the treatment of DFU. PMID:25337708

  11. 1,25-dihydroxyvitamin D3 induces LL-37 and HBD-2 production in keratinocytes from diabetic foot ulcers promoting wound healing: an in vitro model.

    PubMed

    Gonzalez-Curiel, Irma; Trujillo, Valentin; Montoya-Rosales, Alejandra; Rincon, Kublai; Rivas-Calderon, Bruno; deHaro-Acosta, Jeny; Marin-Luevano, Paulina; Lozano-Lopez, Daniel; Enciso-Moreno, Jose A; Rivas-Santiago, Bruno

    2014-01-01

    Diabetic foot ulcers (DFU) are one of the most common diabetes-related cause of hospitalization and often lead to severe infections and poor healing. It has been recently reported that patients with DFU have lower levels of antimicrobial peptides (AMPs) at the lesion area, which contributes with the impairment of wound healing. The aim of this study was to determine whether 1,25-dihydroxyvitamin D3 (1,25 (OH)2 D3) and L-isoleucine induced HBD-2 and LL-37 in primary cultures from DFU. We developed primary cell cultures from skin biopsies from 15 patients with DFU and 15 from healthy donors. Cultures were treated with 1,25 (OH)2D3 or L-isoleucine for 18 h. Keratinocytes phenotype was identified by western blot and flow cytometry. Real time qPCR for DEFB4, CAMP and VDR gene expression was performed as well as an ELISA to measure HBD-2 and LL-37 in supernatant. Antimicrobial activity, in vitro, wound healing and proliferation assays were performed with conditioned supernatant. The results show that primary culture from DFU treated with 1,25(OH)2D3, increased DEFB4 and CAMP gene expression and increased the production of HBD-2 and LL-37 in the culture supernatant. These supernatants had antimicrobial activity over E. coli and induced remarkable keratinocyte migration. In conclusion the 1,25(OH)2D3 restored the production of AMPs in primary cell from DFU which were capable to improve the in vitro wound healing assays, suggesting their potential therapeutic use on the treatment of DFU.

  12. Non-healing tongue ulcer in a rheumatoid arthritis patient medicated with leflunomide. An adverse drug event?

    PubMed Central

    Kalogirou, Eleni-Marina; Tosios, Konstantinos I.; Lazaris, Andreas C.; Sklavounou, Alexandra

    2017-01-01

    Leflunomide is a member of the disease modifying anti-rheumatic drugs group used as a treatment modality in active rheumatoid and psoriatic arthritis. “Oral ulcers” are reported in 3-5% of leflunomide medicated rheumatoid arthritis patients with adverse events, but they are not described in detail in the literature. We present a case of an ulcer in the tongue of a rheumatoid arthritis patient managed with leflunomide and contemplate on its pathogenesis. Key words:Leflunomide, oral ulcer, DHODH. PMID:28210457

  13. The accelerating effect of chitosan-silica hybrid dressing materials on the early phase of wound healing.

    PubMed

    Park, Ji-Ung; Jung, Hyun-Do; Song, Eun-Ho; Choi, Tae-Hyun; Kim, Hyoun-Ee; Song, Juha; Kim, Sukwha

    2016-05-24

    Commercialized dressing materials with or without silver have played a passive role in early-phase wound healing, protecting the skin defects from infections, absorbing exudate, and preventing dehydration. Chitosan (CTS)-based sponges have been developed in pure or hybrid forms for accelerating wound healing, but their wound-healing capabilities have not been extensively compared with widely used commercial dressing materials, providing limited information in a practical aspect. In this study, we have developed CTS-silica (CTS-Si) hybrid sponges with water absorption, flexibility, and mechanical behavior similar to those of CTS sponges. In vitro and in vivo tests were performed to compare the CTS-Si sponges with three commercial dressing materials [gauze, polyurethane (PU), and silver-containing hydrofiber (HF-Ag)] in addition to CTS sponges. Both in vitro and in vivo tests showed that CTS-Si sponges promoted fibroblast proliferation, leading to accelerated collagen synthesis, whereas the CTS sponges did not exhibit significant differences in fibroblast proliferation and collagen synthesis from gauze, PU, and HF-Ag sponges. In case of CTS-Si, the inflammatory cells were actively recruited to the wound by the influence of the released silicon ions from CTS-Si sponges, which, in return, led to an enhanced secretion of growth factors, particularly TGF-β during the early stage. The higher level of TGF-β likely improved the proliferation of fibroblasts, and as a result, collagen synthesis by fibroblasts became remarkably productive, thereby increasing collagen density at the wound site. Therefore, the CTS-Si hybrid sponges have considerable potential as a wound-dressing material for accelerating wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

  14. Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells.

    PubMed

    Milan, P Brouki; Lotfibakhshaiesh, N; Joghataie, M T; Ai, J; Pazouki, A; Kaplan, D L; Kargozar, S; Amini, N; Hamblin, M R; Mozafari, M; Samadikuchaksaraei, A

    2016-11-01

    There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation.

  15. Rapid recruitment and activation of macrophages by anti-Gal/α-Gal liposome interaction accelerates wound healing.

    PubMed

    Wigglesworth, Kim M; Racki, Waldemar J; Mishra, Rabinarayan; Szomolanyi-Tsuda, Eva; Greiner, Dale L; Galili, Uri

    2011-04-01

    Macrophages are pivotal in promoting wound healing. We hypothesized that topical application of liposomes with glycolipids that carry Galα1-3Galβ1-4GlcNAc-R epitopes (α-gal liposomes) on wounds may accelerate the healing process by rapid recruitment and activation of macrophages in wounds. Immune complexes of the natural anti-Gal Ab (constituting ∼1% of Ig in humans) bound to its ligand, the α-gal epitope on α-gal liposomes would induce local activation of complement and generation of complement chemotactic factors that rapidly recruit macrophages. Subsequent binding of the Fc portion of anti-Gal coating α-gal liposomes to FcγRs on recruited macrophages may activate macrophage genes encoding cytokines that mediate wound healing. We documented the efficacy of this treatment in α1,3galactosyltrasferase knockout mice. In contrast to wild-type mice, these knockout mice lack α-gal epitopes and can produce the anti-Gal Ab. The healing time of excisional skin wounds treated with α-gal liposomes in these mice is twice as fast as that of control wounds. Moreover, scar formation in α-gal liposome-treated wounds is much lower than in physiologic healing. Additional sonication of α-gal liposomes resulted in their conversion into submicroscopic α-gal nanoparticles. These α-gal nanoparticles diffused more efficiently in wounds and further increased the efficacy of the treatment, resulting in 95-100% regeneration of the epidermis in wounds within 6 d. The study suggests that α-gal liposome and α-gal nanoparticle treatment may enhance wound healing in the clinic because of the presence of high complement activity and high anti-Gal Ab titers in humans.

  16. Chitosan-based copper nanocomposite accelerates healing in excision wound model in rats.

    PubMed

    Gopal, Anu; Kant, Vinay; Gopalakrishnan, Anu; Tandan, Surendra K; Kumar, Dinesh

    2014-05-15

    Copper possesses efficacy in wound healing which is a complex phenomenon involving various cells, cytokines and growth factors. Copper nanoparticles modulate cells, cytokines and growth factors involved in wound healing in a better way than copper ions. Chitosan has been shown to be beneficial in healing because of its antibacterial, antifungal, biocompatible and biodegradable polymeric nature. In the present study, chitosan-based copper nanocomposite (CCNC) was prepared by mixing chitosan and copper nanoparticles. CCNC was applied topically to evaluate its wound healing potential and to study its effects on some important components of healing process in open excision wound model in adult Wistar rats. Significant increase in wound contraction was observed in the CCNC-treated rats. The up-regulation of vascular endothelial growth factor (VEGF) and transforming growth factor-beta1(TGF-β1) by CCNC-treatment revealed its role in facilitating angiogenesis, fibroblast proliferation and collagen deposition. The tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were significantly decreased and increased, respectively, in CCNC-treated rats. Histological evaluation showed more fibroblast proliferation, collagen deposition and intact re-epithelialization in CCNC-treated rats. Immunohistochemistry of CD31 revealed marked increase in angiogenesis. Thus, we concluded that chitosan-based copper nanocomposite efficiently enhanced cutaneous wound healing by modulation of various cells, cytokines and growth factors during different phases of healing process.

  17. Bacterial cellulose/acrylic acid hydrogel synthesized via electron beam irradiation: accelerated burn wound healing in an animal model.

    PubMed

    Mohamad, Najwa; Mohd Amin, Mohd Cairul Iqbal; Pandey, Manisha; Ahmad, Naveed; Rajab, Nor Fadilah

    2014-12-19

    Natural polymer-based hydrogels are of interest to health care professionals as wound dressings owing to their ability to absorb exudates and provide hydration for healing. The aims of this study were to develop and characterize bacterial cellulose/acrylic acid (BC/AA) hydrogels synthesized by electron beam irradiation and investigate its wound healing potential in an animal model. The BC/AA hydrogels were characterized by SEM, tensile strength, water absorptivity, and water vapor transmission rate (WVTR). The cytotoxicity of the hydrogels was investigated in L929 cells. Skin irritation and wound healing properties were evaluated in Sprague-Dawley rats. BC/AA hydrogels had a macroporous network structure, high swelling ratio (4000-6000% at 24h), and high WVTR (2175-2280 g/m(2)/day). The hydrogels were non-toxic in the cell viability assay. In vivo experiments indicated that hydrogels promoted faster wound-healing, enhanced epithelialization, and accelerated fibroblast proliferation compared to that in the control group. These results suggest that BC/AA hydrogels are promising materials for burn dressings.

  18. A cold plasma jet accelerates wound healing in a murine model of full-thickness skin wounds.

    PubMed

    Schmidt, Anke; Bekeschus, Sander; Wende, Kristian; Vollmar, Brigitte; von Woedtke, Thomas

    2017-02-01

    Cold plasma has been successfully applied in several fields of medicine that require, for example, pathogen inactivation, implant functionalization or alteration of cellular activity. Previous studies have provided evidence that plasma supports the healing of wounds owing to its beneficial mixtures of reactive species and modulation of inflammation in cells and tissues. To investigate the wound healing activity of an atmospheric pressure plasma jet in vivo, we examined the cold plasma's efficacy on dermal regeneration in a murine model of dermal full-thickness ear wound. Over 14 days, female mice received daily plasma treatment. Quantitative analysis by transmitted light microscopy demonstrated a significantly accelerated wound re-epithelialization at days 3-9 in comparison with untreated controls. In vitro, cold plasma altered keratinocyte and fibroblast migration, while both cell types showed significant stimulation resulting in accelerated closure of gaps in scratch assays. This plasma effect correlated with the downregulation of the gap junctional protein connexin 43 which is thought to be important in the regulation of wound healing. In addition, plasma induced profound changes in adherence junctions and cytoskeletal dynamics as shown by downregulation of E-cadherin and several integrins as well as actin reorganization. Our results theorize cold plasma to be a beneficial treatment option supplementing existing wound therapies.

  19. Increased growth factors play a role in wound healing promoted by noninvasive oxygen-ozone therapy in diabetic patients with foot ulcers.

    PubMed

    Zhang, Jing; Guan, Meiping; Xie, Cuihua; Luo, Xiangrong; Zhang, Qian; Xue, Yaoming

    2014-01-01

    Management of diabetic foot ulcers (DFUs) is a great challenge for clinicians. Although the oxygen-ozone treatment improves the diabetic outcome, there are few clinical trials to verify the efficacy and illuminate the underlying mechanisms of oxygen-ozone treatment on DFUs. In the present study, a total of 50 type 2 diabetic patients complicated with DFUs, Wagner stage 2~4, were randomized into control group treated by standard therapy only and ozone group treated by standard therapy plus oxygen-ozone treatment. The therapeutic effects were graded into 4 levels from grade 0 (no change) to grade 3 (wound healing). The wound sizes were measured at baseline and day 20, respectively. Tissue biopsies were performed at baseline and day 11. The expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and platelet-derived growth factor (PDGF) proteins in the pathologic specimens were determined by immunohistochemical examinations. The effective rate of ozone group was significantly higher than that of control group (92% versus 64%, P < 0.05). The wound size reduction was significantly more in ozone group than in control group (P < 0.001). After treatment, the expressions of VEGF, TGF-β, and PDGF proteins at day 11 were significantly higher in ozone group than in control group. Ozone therapy promotes the wound healing of DFUs via potential induction of VEGF, TGF-β, and PDGF at early stage of the treatment. (Clinical trial registry number is ChiCTR-TRC-14004415).

  20. Increased Growth Factors Play a Role in Wound Healing Promoted by Noninvasive Oxygen-Ozone Therapy in Diabetic Patients with Foot Ulcers

    PubMed Central

    Zhang, Jing; Guan, Meiping; Xie, Cuihua; Luo, Xiangrong; Zhang, Qian; Xue, Yaoming

    2014-01-01

    Management of diabetic foot ulcers (DFUs) is a great challenge for clinicians. Although the oxygen-ozone treatment improves the diabetic outcome, there are few clinical trials to verify the efficacy and illuminate the underlying mechanisms of oxygen-ozone treatment on DFUs. In the present study, a total of 50 type 2 diabetic patients complicated with DFUs, Wagner stage 2~4, were randomized into control group treated by standard therapy only and ozone group treated by standard therapy plus oxygen-ozone treatment. The therapeutic effects were graded into 4 levels from grade 0 (no change) to grade 3 (wound healing). The wound sizes were measured at baseline and day 20, respectively. Tissue biopsies were performed at baseline and day 11. The expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and platelet-derived growth factor (PDGF) proteins in the pathologic specimens were determined by immunohistochemical examinations. The effective rate of ozone group was significantly higher than that of control group (92% versus 64%, P < 0.05). The wound size reduction was significantly more in ozone group than in control group (P < 0.001). After treatment, the expressions of VEGF, TGF-β, and PDGF proteins at day 11 were significantly higher in ozone group than in control group. Ozone therapy promotes the wound healing of DFUs via potential induction of VEGF, TGF-β, and PDGF at early stage of the treatment. (Clinical trial registry number is ChiCTR-TRC-14004415). PMID:25089169

  1. Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats.

    PubMed

    Kwon, David S; Gao, Xiaohua; Liu, Yong Bo; Dulchavsky, Deborah S; Danyluk, Andrew L; Bansal, Mona; Chopp, Michael; McIntosh, Kevin; Arbab, Ali S; Dulchavsky, Scott A; Gautam, Subhash C

    2008-06-01

    Bone marrow stem cells participate in tissue repair processes and may have a role in wound healing. Diabetes is characterised by delayed and poor wound healing. We investigated the potential of bone marrow-derived mesenchymal stromal cells (BMSCs) to promote healing of fascial wounds in diabetic rats. After manifestation of streptozotocin (STZ)-induced diabetic state for 5 weeks in male adult Sprague-Dawley rats, healing of fascial wounds was severely compromised. Compromised wound healing in diabetic rats was characterised by excessive polymorphonuclear cell infiltration, lack of granulation tissue formation, deficit of collagen and growth factor [transforming growth factor (TGF-beta), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor PDGF-BB and keratinocyte growth factor (KGF)] expression in the wound tissue and significant decrease in biomechanical strength of wounds. Treatment with BMSC systemically or locally at the wound site improved the wound-breaking strength (WBS) of fascial wounds. The improvement in WBS was associated with an immediate and significant increase in collagen levels (types I-V) in the wound bed. In addition, treatment with BMSCs increased the expression of growth factors critical to proper repair and regeneration of the damaged tissue moderately (TGF-beta, KGF) to markedly (EGF, VEGF, PDGF-BB). These data suggest that cell therapy with BMSCs has the potential to augment healing of the diabetic wounds.

  2. Fibrin biomatrix-conjugated platelet-derived growth factor AB accelerates wound healing in severe thermal injury.

    PubMed

    Mittermayr, Rainer; Branski, Ludwik; Moritz, Martina; Jeschke, Marc G; Herndon, David N; Traber, Daniel; Schense, Jason; Gampfer, Jörg; Goppelt, Andreas; Redl, Heinz

    2016-05-01

    Controlled delivery of growth factors from biodegradable biomatrices could accelerate and improve impaired wound healing. The study aim was to determine whether platelet-derived growth factor AB (PDGF.AB) with a transglutaminase (TG) crosslinking substrate site released from a fibrin biomatrix improves wound healing in severe thermal injury. The binding and release kinetics of TG-PDGF.AB were determined in vitro. Third-degree contact burns (dorsum of Yorkshire pigs) underwent epifascial necrosectomy 24 h post-burn. Wound sites were covered with autologous meshed (3:1) split-thickness skin autografts and either secured with staples or attached with sprayed fibrin sealant (FS; n = 8/group). TG-PDGF.AB binds to the fibrin biomatrix using the TG activity of factor XIIIa, and is subsequently released through enzymatic cleavage. Three doses of TG-PDGF.AB in FS (100 ng, 1 µg and 11 µg/ml FS) were tested. TG-PDGF.AB was bound to the fibrin biomatrix as evidenced by western blot analysis and subsequently released by enzymatic cleavage. A significantly accelerated and improved wound healing was achieved using sprayed FS containing TG-PDGF.AB compared to staples alone. Low concentrations (100 ng-1 µg TG-PDGF.AB/ml final FS clot) demonstrated to be sufficient to attain a nearly complete closure of mesh interstices 14 days after grafting. TG-PDGF.AB incorporated in FS via a specific binding technology was shown to be effective in grafted third-degree burn wounds. The adhesive properties of the fibrin matrix in conjunction with the prolonged growth factor stimulus enabled by this binding technology could be favourable in many pathological situations associated with wound-healing disturbances. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Development of ethyl alcohol-precipitated silk sericin/polyvinyl alcohol scaffolds for accelerated healing of full-thickness wounds.

    PubMed

    Siritienthong, Tippawan; Ratanavaraporn, Juthamas; Aramwit, Pornanong

    2012-12-15

    Silk sericin has been recently reported for its advantageous biological properties to promote wound healing. In this study, we established that the ethyl alcohol (EtOH) could be used to precipitate sericin and form the stable sericin/polyvinyl alcohol (PVA) scaffolds without the crosslinking. The sericin/PVA scaffolds were fabricated via freeze-drying and subsequently precipitating in various concentrations of EtOH. The EtOH-precipitated sericin/PVA scaffolds showed denser structure, higher compressive modulus, but lower water swelling ability than the non-precipitated scaffolds. Sericin could be released from the EtOH-precipitated sericin/PVA scaffolds in a sustained manner. After cultured with L929 mouse fibroblasts, the 70 vol% EtOH-precipitated sericin/PVA scaffolds showed the highest potential to promote cell proliferation. After applied to the full-thickness wounds of rats, the 70 vol% EtOH-precipitated sericin/PVA scaffolds showed significantly higher percentage of wound size reduction and higher extent of type III collagen formation and epithelialization, compared with the control scaffolds without sericin. The accelerated wound healing by the 70 vol% EtOH-precipitated sericin/PVA scaffolds was possibly due to (1) the bioactivity of sericin itself to promote wound healing, (2) the sustained release of precipitated sericin from the scaffolds, and (3) the activation and recruitment of wound healing-macrophages by sericin to the wounds. This finding suggested that the EtOH-precipitated sericin/PVA scaffolds were more effective for the wound healing, comparing with the EtOH-precipitated PVA scaffolds without sericin.

  4. Exosomes derived from human amniotic epithelial cells accelerate wound healing and inhibit scar formation.

    PubMed

    Zhao, Bin; Zhang, Yijie; Han, Shichao; Zhang, Wei; Zhou, Qin; Guan, Hao; Liu, Jiaqi; Shi, Jihong; Su, Linlin; Hu, Dahai

    2017-04-01

    Wound healing is a highly orchestrated physiological process consisting of a complex events, and scarless wound healing is highly desired for the development and application in clinical medicine. Recently, we have demonstrated that human amniotic epithelial cells (hAECs) promoted wound healing and inhibited scar formation through a paracrine mechanism. However, exosomes (Exo) are one of the most important paracrine factors. Whether exosomes derived from human amniotic epithelial cells (hAECs-Exo) have positive effects on scarless wound healing have not been reported yet. In this study, we examined the role of hAECs-Exo on wound healing in a rat model. We found that hAECs, which exhibit characteristics of both embryonic and mesenchymal stem cells, have the potential to differentiate into all three germ layers. hAECs-Exo ranged from 50 to 150 nm in diameter, and positive for exosomal markers CD9, CD63, CD81, Alix, TSG101 and HLA-G. Internalization of hAECs-Exo promoted the migration and proliferation of fibroblasts. Moreover, the deposition of extracellular matrix (ECM) were partly abolished by the treatment of high concentration of hAECs-Exo (100 μg/mL), which may be through stimulating the expression of matrix metalloproteinase-1 (MMP-1). In vivo animal experiments showed that hAECs-Exo improved the skin wound healing with well-organized collagen fibers. Taken together, These findings represent that hAECs-Exo can be used as a novel hope in cell-free therapy for scarless wound healing.

  5. Deletion of the α2A/α2C-adrenoceptors accelerates cutaneous wound healing in mice

    PubMed Central

    Romana-Souza, Bruna; Nascimento, Adriana P; Brum, Patricia C; Monte-Alto-Costa, Andréa

    2014-01-01

    The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A/α2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A/α2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A/α2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A/α2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A/α2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A/α2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A/α2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A/α2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A/α2C-adrenoceptor deletion accelerates cutaneous wound healing in mice. PMID:25186490

  6. Inhibition of Prostaglandin Transporter (PGT) Promotes Perfusion and Vascularization and Accelerates Wound Healing in Non-Diabetic and Diabetic Rats

    PubMed Central

    Liu, Zhongbo; Benard, Outhiriaradjou; Syeda, Mahrukh M.; Schuster, Victor L.; Chi, Yuling

    2015-01-01

    Peripheral ischemia, resulting from diminished arterial flow and defective local vascularization, is one of the main causes of impaired wound healing in diabetes. Vasodilatory prostaglandins (PGs), including PGE2 and PGI2, regulate blood flow in peripheral tissues. PGs also stimulate angiogenesis by inducing vascular endothelial growth factor. However, PG levels are reduced in diabetes mainly due to enhanced degradation. We hypothesized that inhibition of the prostaglandin transporter (PGT) (SLCO2A1), which mediates the degradation of PGs, would increase blood flow and stimulate vascularization, thereby mitigating peripheral ischemia and accelerating wound healing in diabetes. Here we report that inhibiting PGT with intravenously injected PGT inhibitor, T26A, increased blood flow in ischemic hind limbs created in non-diabetic rats and streptozotocin induced diabetic rats. Systemic, or combined with topical, T26A accelerated closure of cutaneous wounds. Immunohistochemical examination revealed that inhibition of PGT enhanced vascularization (marked by larger numbers of vessels formed by CD34+ cells), and accelerated re-epithelialization of cutaneous wounds. In cultured primary human bone marrow CD34+ cells and human epidermal keratinocytes (HEKs) either inhibiting or silencing PGT increased migration in both cell lines. Thus PGT directly regulates mobilization of endothelial progenitor cells (EPCs) and HEKs, which could contribute to PGT-mediated vascularization and re-epithelialization. At the molecular level, systemic inhibition of PGT raised circulating PGE2. Taken together, our data demonstrate that PGT modulates arterial blood flow, mobilization of EPCs and HEKs, and vascularization and epithelialization in wound healing by regulating vasodilatory and pro-angiogenic PGs. PMID:26230411

  7. Deletion of the α2A/α2C-adrenoceptors accelerates cutaneous wound healing in mice.

    PubMed

    Romana-Souza, Bruna; Nascimento, Adriana P; Brum, Patricia C; Monte-Alto-Costa, Andréa

    2014-10-01

    The α2-adrenoceptors regulate the sympathetic nervous system, controlling presynaptic catecholamine release. However, the role of the α2-adrenoceptors in cutaneous wound healing is poorly understood. Mice lacking both the α2A/α2C-adrenoceptors were used to evaluate the participation of the α2-adrenoceptor during cutaneous wound healing. A full-thickness excisional lesion was performed on the dorsal skin of the α2A/α2C-adrenoceptor knockout and wild-type mice. Seven or fourteen days later, the animals were euthanized and the lesions were formalin-fixed and paraffin-embedded or frozen. Murine skin fibroblasts were also isolated from α2A/α2C-adrenoceptor knockout and wild-type mice, and fibroblast activity was evaluated. The in vivo study demonstrated that α2A/α2C-adrenoceptor depletion accelerated wound contraction and re-epithelialization. A reduction in the number of neutrophils and macrophages was observed in the α2A/α2C-adrenoceptor knockout mice compared with wild-type mice. In addition, α2A/α2C-adrenoceptor depletion enhanced the levels of nitrite and hydroxyproline, and the protein expression of transforming growth factor-β and vascular endothelial growth factor. Furthermore, α2A/α2C-adrenoceptor depletion accelerated blood vessel formation and myofibroblast differentiation. The in vitro study demonstrated that skin fibroblasts isolated from α2A/α2C-adrenoceptor knockout mice exhibited enhanced cell migration, α-smooth muscle actin _protein expression and collagen deposition compared with wild-type skin fibroblasts. In conclusion, α2A/α2C-adrenoceptor deletion accelerates cutaneous wound healing in mice.

  8. Autologous adipose-derived stem cells: Basic science, technique, and rationale for application in ulcer and wound healing.

    PubMed

    Zollino, Ilaria; Zuolo, Michele; Gianesini, Sergio; Pedriali, Massimo; Sibilla, Maria Grazia; Tessari, Mirko; Carinci, Francesco; Occhionorelli, Savino; Zamboni, Paolo

    2017-04-01

    Objectives The present review represents a translational boundary between basic research and surgery, particularly focusing on the promising application of adipose-derived stem cells harvested intra-operatively during debridement of venous leg ulcers. Methods We reviewed 830 out of 5578 articles on MEDLINE starting from 1997 and sorted by the relevance option. Results The technique currently used for adipose-derived stem cells intra-operative harvesting is presented, including a safety evaluation on a cohort of 5089 revised patients who underwent plastic surgery and maxillo-facial surgical procedures. Complications were reported in 169 cases (3.3%). One hundred and forty-one (2.77%) patients were classified as having minor complications, specifically: nodularity/induration 93 (1.83%), dysesthesia 14 (0.26%), hematoma 12 (0.23%), superficial infection 11 (0.21%), pain 7 (0.13%), poor cosmesis 3 (0.06%), and abnormal breast secretion 1 (0.02%), while 28 patients (0.55%) were classified as having major complications, specifically: deep infection 22 (0.43%), sepsis 3 (0.06%), abdominal hematoma 2 (0.04%), and pneumothorax 1 (0.02%). Application of cell therapy in venous leg ulcer is currently used only for patients not responding to the standard treatment. The review shows the lack of randomized clinical trials for application of adipose-derived stem cells among treatments for venous leg ulcer. Finally, adipose-derived stem cells implantation at the wound site promotes a new tissue formation rich in vascular structures and remodeling collagen. Conclusion Adipose-derived stem cells strategy represents a great opportunity for the treatment of chronic wounds, due to the simplicity of the technique and the application of cell treatment in the operating room immediately following debridement. However, clinical studies and data from randomized trials are currently lacking.

  9. Dutch Venous Ulcer guideline update.

    PubMed

    Maessen-Visch, M Birgitte; de Roos, Kees-Peter

    2014-05-01

    The revised guideline of 2013 is an update of the 2005 guideline "venous leg ulcer". In this special project four separate guidelines (venous leg ulcer, varicose veins, compression therapy and deep venous disorders) were revised and developed simultaneously. A meeting was held including representatives of any organisation involved in venous disease management including patient organizations and health insurance companies. Eighteen clinical questions where defined, and a new strategy was used to accelerate the process. This resulted in two new and two revised guidelines within one year. The guideline committee advises use of the C of the CEAP classification as well as the Venous Clinical Severity Score (VCSS) and a Quality of life (QoL) score in the assessment of clinical signs. These can provide insight into the burden of disease and the effects of treatment as experienced by the patient. A duplex ultrasound should be performed in every patient to establish the underlying aetiology and to evaluate the need for treatment (which is discussed in a separate guideline). The use of the TIME model for describing venous ulcers is recommended. There is no evidence for antiseptic or antibiotic wound care products except for a Cochrane review in which some evidence is presented for cadexomer iodine. Signs of infection are the main reason for the use of oral antibiotics. When the ulcer fails to heal the use of oral aspirin and pentoxifylline can be considered as an adjunct. For the individual patient, the following aspects should be considered: the appearance of the ulcer (amount of exudate) according to the TIME model, the influence of wound care products on moisturising the wound, frequency of changing compression bandages, pain and allergies. The cost of the dressings should also be considered. Education and training of patients t improves compliance with compression therapy but does not influence wound healing rates.

  10. Novel Anti-Microbial Peptide SR-0379 Accelerates Wound Healing via the PI3 Kinase/Akt/mTOR Pathway

    PubMed Central

    Tomioka, Hideki; Nakagami, Hironori; Tenma, Akiko; Saito, Yoshimi; Kaga, Toshihiro; Kanamori, Toshihide; Tamura, Nao; Tomono, Kazunori; Kaneda, Yasufumi; Morishita, Ryuichi

    2014-01-01

    We developed a novel cationic antimicrobial peptide, AG30/5C, which demonstrates angiogenic properties similar to those of LL-37 or PR39. However, improvement of its stability and cost efficacy are required for clinical application. Therefore, we examined the metabolites of AG30/5C, which provided the further optimized compound, SR-0379. SR-0379 enhanced the proliferation of human dermal fibroblast cells (NHDFs) via the PI3 kinase-Akt-mTOR pathway through integrin-mediated interactions. Furthermore SR-0379 promoted the tube formation of human umbilical vein endothelial cells (HUVECs) in co-culture with NHDFs. This compound also displays antimicrobial activities against a number of bacteria, including drug-resistant microbes and fungi. We evaluated the effect of SR-0379 in two different would-healing models in rats, the full-thickness defects under a diabetic condition and an acutely infected wound with full-thickness defects and inoculation with Staphylococcus aureus. Treatment with SR-0379 significantly accelerated wound healing when compared to fibroblast growth factor 2 (FGF2). The beneficial effects of SR-0379 on wound healing can be explained by enhanced angiogenesis, granulation tissue formation, proliferation of endothelial cells and fibroblasts and antimicrobial activity. These results indicate that SR-0379 may have the potential for drug development in wound repair, even under especially critical colonization conditions. PMID:24675668

  11. Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds

    PubMed Central

    Seow, Wei Yang; Salgado, Giorgiana; Lane, E. Birgitte; Hauser, Charlotte A. E.

    2016-01-01

    Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing. PMID:27600999

  12. Transparent crosslinked ultrashort peptide hydrogel dressing with high shape-fidelity accelerates healing of full-thickness excision wounds

    NASA Astrophysics Data System (ADS)

    Seow, Wei Yang; Salgado, Giorgiana; Lane, E. Birgitte; Hauser, Charlotte A. E.

    2016-09-01

    Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing.

  13. Skin-derived precursors possess the ability of differentiation into the epidermal progeny and accelerate burn wound healing.

    PubMed

    Bayati, Vahid; Abbaspour, Mohammad Reza; Neisi, Niloofar; Hashemitabar, Mahmoud

    2017-02-01

    Skin-derived precursors (SKPs) are remnants of the embryonic neural crest stem cells that reside in the dermis until adulthood. Although they possess a wide range of differentiation potentials, their differentiation into keratinocyte-like cells and their roles in skin wound healing are obscure. The present study aimed to investigate the differentiation of SKPs into keratinocyte-like cells and evaluate their role in healing of third degree burn wounds. To this aim, SKPs were differentiated into keratinocyte-like cells on tissue culture plate and collagen-chitosan scaffold prepared by freeze-drying. Their differentiation capability was detected by real-time RT-PCR and immunofluorescence. Thereafter, they were cultured on scaffold and implanted in a rat model of burn wound. Histopathological and immunohistochemical analyses were employed to examine the reconstituted skin. The research findings revealed that SKPs were able to differentiate along the epidermal lineage and this ability can be enhanced on a suitable scaffold. Additionally, the results indicated that SKPs apparently promoted wound healing process and accelerate its transition from proliferating stage to maturational phase, especially if they were differentiated into keratinocyte-like cells. Regarding the results, it is concluded that SKPs are able to differentiate into keratinocyte-like cells, particularly when they are cultured on collagen-chitosan scaffold. Moreover, they can regenerate epidermal and dermal layers including thick collagen bundles, possibly through differentiation into keratinocyte-like cells.

  14. Feasibility of an electrostimulation system treatment for wound healing: a case series of patients with chronic ulcers in Barbados.

    PubMed

    Ojeh, Nkemcho; Rose, Angela; Jackman, Selma; Applewhaite, Morvillia; Webster, Veronica

    2016-12-01

    Major advances have been made in the development of new therapies for chronic wounds. Fenzian™, an electrostimulation system (ES), has been clinically used for a variety of conditions. The ES was recently tested in the Barbadian population for tolerability and acceptability by asthma patients, with encouraging results. Barbados has an estimated 170 people with diabetes having some form of lower-extremity amputation annually. Here, we describe a case series of 21 chronic ulcer patients with diabetes recruited as inpatients (n = 10) and outpatients (n = 11) in a pilot study to evaluate the feasibility and acceptability of ES in the Barbadian population. Results showed statistically significant improvement among those in the inpatient- versus outpatient-recruited group for wound perimeter (P = 0·04), wound surface area (P = 0·03) and wound volume (P = 0·08). We also demonstrate that the improvement continued after cessation of ES treatment. Participants reported increased levels of pain at the end of treatment, and there was no statistically significant change in the reported quality of life. Our results showed greater improvements in reduction of ulcer size for participants from the inpatient- versus outpatient-recruited group.

  15. Acarbose Accelerates Wound Healing via Akt/eNOS Signaling in db/db Mice

    PubMed Central

    Yu, Jiawen; Sun, Yuannan; Ren, Guofei; Zhu, Jianjun

    2017-01-01

    Refractory wound is a dreaded complication of diabetes and is highly correlated with EPC dysfunction caused by hyperglycemia. Acarbose is a widely used oral glucose-lowering drug exclusively for T2DM. Previous studies have suggested the beneficial effect of acarbose on improving endothelial dysfunction in patients with T2DM. However, no data have been reported on the beneficial efficacy of acarbose in wound healing impairment caused by diabetes. We herein investigated whether acarbose could improve wound healing in T2DM db/db mice and the possible mechanisms involved. Acarbose hastened wound healing and enhanced angiogenesis, accompanied by increased circulating EPC number in db/db mice. In vitro, a reversed BM-EPC dysfunction was observed after the administration of acarbose in db/db mice, as reflected by tube formation assay. In addition, a significantly increased NO production was also witnessed in BM-EPCs from acarbose treated db/db mice, with decreased O2 levels. Akt inhibitor could abolish the beneficial effect of acarbose on high glucose induced EPC dysfunction in vitro, accompanied by reduced eNOS activation. Acarbose displayed potential effect in promoting wound healing and improving angiogenesis in T2DM mice, which was possibly related to the Akt/eNOS signaling pathway. PMID:28373902

  16. Transplantation of endothelial progenitor cells accelerates dermal wound healing with increased recruitment of monocytes/macrophages and neovascularization.

    PubMed

    Suh, Wonhee; Kim, Koung Li; Kim, Jeong-Min; Shin, In-Soon; Lee, Young-Sam; Lee, Jae-Young; Jang, Hyung-Suk; Lee, Jung-Sun; Byun, Jonghoe; Choi, Jin-Ho; Jeon, Eun-Seok; Kim, Duk-Kyung

    2005-01-01

    Endothelial progenitor cells (EPCs) act as endothelial precursors that promote new blood vessel formation and increase angiogenesis by secreting growth factors and cytokines in ischemic tissues. These facts prompt the hypothesis that EPC transplantation should accelerate the wound-repair process by facilitating neovascularization and the production of various molecules related to wound healing. In a murine dermal excisional wound model, EPC transplantation accelerated wound re-epithelialization compared with the transplantation of mature endothelial cells (ECs) in control mice. When the wounds were analyzed immunohistochemically, the EPC-transplanted group exhibited significantly more monocytes/macrophages in the wound at day 5 after injury than did the EC-transplanted group. This observation is consistent with enzyme-linked immunosorbent assay results showing that EPCs produced in abundance several chemoattractants of monocytes and macrophages that are known to play a pivotal role in the early phase of wound healing. At day 14 after injury, the EPC-transplanted group showed a statistically significant increase in vascular density in the granulation tissue relative to that of the EC-transplanted group. Fluorescence microscopy revealed that EPCs preferentially moved into the wound and were directly incorporated into newly formed capillaries in the granulation tissue. These results suggest that EPC transplantation will be useful in dermal wound repair and skin regeneration, because EPCs both promote the recruitment of monocytes/macrophages into the wound and increase neovascularization.

  17. Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity

    PubMed Central

    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Hajiaghaalipour, Fatemeh; Zahedifard, Maryam; Tayeby, Faezeh; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Purpose Curcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats. Materials and methods Twenty four rats were randomly divided into 4 groups: A) negative control (blank placebo, acacia gum), B) low dose of HECP, C) high dose of HECP, and D) positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm) were made on the neck area of each rat. Groups 1–4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg), HECP (200 mg/kg), and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson’s trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates. Results Macroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process by downregulating Bax and upregulating Hsp70 protein at the wound site. The formation of new blood vessel was observed in Masson’s trichrome staining of wounds treated with HECP (100 and 200 mg/kg). In addition, HECP administration caused a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation. Conclusion These findings suggested that HECP accelerated wound-healing process in rats via antioxidant activity, angiogenesis

  18. Topical Estrogen Accelerates Cutaneous Wound Healing in Aged Humans Associated with an Altered Inflammatory Response

    PubMed Central

    Ashcroft, Gillian S.; Greenwell-Wild, Teresa; Horan, Michael A.; Wahl, Sharon M.; Ferguson, Mark W. J.

    1999-01-01

    The effects of intrinsic aging on the cutaneous wound healing process are profound, and the resulting acute and chronic wound morbidity imposes a substantial burden on health services. We have investigated the effects of topical estrogen on cutaneous wound healing in healthy elderly men and women, and related these effects to the inflammatory response and local elastase levels, an enzyme known to be up-regulated in impaired wound healing states. Eighteen health status-defined females (mean age, 74.4 years) and eighteen males (mean age, 70.7 years) were randomized in a double-blind study to either active estrogen patch or identical placebo patch attached for 24 hours to the upper inner arm, through which two 4-mm punch biopsies were made. The wounds were excised at either day 7 or day 80 post-wounding. Compared to placebo, estrogen treatment increased the extent of wound healing in both males and females with a decrease in wound size at day 7, increased collagen levels at both days 7 and 80, and increased day 7 fibronectin levels. In addition, estrogen enhanced the strength of day 80 wounds. Estrogen treatment was associated with a decrease in wound elastase levels secondary to reduced neutrophil numbers, and decreased fibronectin degradation. In vitro studies using isolated human neutrophils indicate that one mechanism underlying the altered inflammatory response involves both a direct inhibition of neutrophil chemotaxis by estrogen and an altered expression of neutrophil adhesion molecules. These data demonstrate that delays in wound healing in the elderly can be significantly diminished by topical estrogen in both male and female subjects. PMID:10514397

  19. A prospective, randomised, controlled, multicentre clinical trial examining healing rates, safety and cost to closure of an acellular reticular allogenic human dermis versus standard of care in the treatment of chronic diabetic foot ulcers.

    PubMed

    Zelen, Charles M; Orgill, Dennis P; Serena, Thomas; Galiano, Robert; Carter, Marissa J; DiDomenico, Lawrence A; Keller, Jennifer; Kaufman, Jarrod; Li, William W

    2017-04-01

    Acellular dermal matrices can successfully heal wounds. This study's goal was to compare clinical outcomes of a novel, open-structure human reticular acellular dermis matrix (HR-ADM) to facilitate wound closure in non-healing diabetic foot ulcers (DFUs) versus DFUs treated with standard of care (SOC). Following a 2-week screening period in which DFUs were treated with offloading and moist wound care, patients were randomised to either SOC alone or HR-ADM plus SOC applied weekly for up to 12 weeks. At 6 weeks, the primary outcome time, 65% of the HR-ADM-treated DFUs healed (13/20) compared with 5% (1/20) of DFUs that received SOC alone. At 12 weeks, the proportions of DFUs healed were 80% and 20%, respectively. Mean time to heal within 12 weeks was 40 days for the HR-ADM group compared with 77 days for the SOC group. There was no incidence of increased adverse or serious adverse events between groups or any adverse events related to the graft. Mean and median graft costs to closure per healed wound in the HR-ADM group were $1475 and $963, respectively. Weekly application of HR-ADM is an effective intervention for promoting closure of non-healing DFUs.

  20. A unique combination of infrared and microwave radiation accelerates wound healing.

    PubMed

    Schramm, J Mark; Warner, Dave; Hardesty, Robert A; Oberg, Kerby C

    2003-01-01

    Light or electromagnetic radiation has been reported to enhance wound healing. The use of selected spectra, including infrared and microwave, has been described; however, no studies to date have examined the potential benefit of combining these spectra. In this study, a device that emits electromagnetic radiation across both the infrared and microwave ranges was used. To test the effects of this unique electromagnetic radiation spectrum on wound healing, two clinically relevant wound-healing models (i.e., tensile strength of simple incisions and survival of McFarlane flaps) were selected. After the creation of a simple full-thickness incision (n = 35 rats) or a caudally based McFarlane flap (n = 33 rats), animals were randomly assigned to one of three treatment groups: untreated control, infrared, or combined electromagnetic radiation. Treatment was administered for 30 minutes, twice daily for 18 days in animals with simple incisions, and 15 days in animals with McFarlane flaps. The wound area or flap was harvested and analyzed, blinded to the treatment regimens. A p value of less than 0.05 obtained by analysis of variance was considered to be statistically significant. Animals receiving combined electromagnetic radiation demonstrated increased tensile strength (2.62 N/mm2) compared with animals receiving infrared radiation (2.36 N/mm2) or untreated controls (1.73 N/mm2, p < 0.001). Animals with McFarlane flaps receiving combined electromagnetic radiation had increased flap survival (78.0 percent) compared with animals receiving infrared radiation (69.7 percent) and untreated controls (63.1 percent, p < 0.01). Thus, combined electromagnetic radiation provided a distinct advantage in wound healing that might augment current treatment regimens.

  1. Evaluation of an Oxygen-Diffusion Dressing for Accelerated Healing of Donor-Site Wounds

    DTIC Science & Technology

    2014-06-01

    of their wounds, compared with a similar occlusive dressing without oxygen.7 Hyperbaric oxy- gen therapy is thought to improve healing of chronic...wounds in humans,8 but requires visits to facilities with trained personnel and is limited by oxygen toxicity issues. Compared with hyperbaric oxygen...3rd, Fife CE, Gesell LB, Bennett M. Undersea Hyperbaric Medicine Society (UHMS) position statement: topical oxygen for chronic wounds. Undersea

  2. Proangiogenic activity of plant extracts in accelerating wound healing - a new face of old phytomedicines.

    PubMed

    Majewska, Iwona; Gendaszewska-Darmach, Edyta

    2011-01-01

    Angiogenesis, the formation of new capillaries from pre-existing vascular network, plays an important role in physiological and pathological processes such as embryonic development, wound healing, and development of atherosclerosis. Extension of the circulatory network is also considered to be one the most important factors during cancerogenesis. Inhibition of angiogenesis may lead to inhibition of tumor growth whereas stimulation may improve wound healing. Research achievements suggest the use of plants and their extracts as potential therapeutic agents with pro- or antiangiogenic activity. Since the anticancer and antiangiogenic properties of many phytomedicines have been amply reviewed elsewhere this paper will focus on the treatment of vascular insufficiency in wound healing. Globally accepted herbal drugs are thought to be safe and effective, however, there is a need for more evidence-based confirmation in controlled and validated trials. Among the most frequently studied proangiogenic phytochemicals are ginsenosides from Panax ginseng, beta-sitosterol from Aloe vera, calycosin from Radix Astragali, and extracts from Hippophae rhamnoides L. and Angelica sinensis.

  3. An innovative bi-layered wound dressing made of silk and gelatin for accelerated wound healing.

    PubMed

    Kanokpanont, Sorada; Damrongsakkul, Siriporn; Ratanavaraporn, Juthamas; Aramwit, Pornanong

    2012-10-15

    In this study, the novel silk fibroin-based bi-layered wound dressing was developed. Wax-coated silk fibroin woven fabric was introduced as a non-adhesive layer while the sponge made of sericin and glutaraldehyde-crosslinked silk fibroin/gelatin was fabricated as a bioactive layer. Wax-coated silk fibroin fabrics showed improved mechanical properties compared with the non-coated fabrics, but less adhesive than the commercial wound dressing mesh. This confirmed by results of peel test on both the partial- and full-thickness wounds. The sericin-silk fibroin/gelatin spongy bioactive layers showed homogeneous porous structure and controllable biodegradation depending on the degree of crosslinking. The bi-layered wound dressings supported the attachment and proliferation of L929 mouse fibroblasts, particularly for the silk fibroin/gelatin ratio of 20/80 and 0.02% GA crosslinked. Furthermore, we proved that the bi-layered wound dressings promoted wound healing in full-thickness wounds, comparing with the clinically used wound dressing. The wounds treated with the bi-layered wound dressings showed the greater extent of wound size reduction, epithelialization, and collagen formation. The superior properties of the silk fibroin-based bi-layered wound dressings compared with those of the clinically used wound dressings were less adhesive and had improved biological functions to promote cell activities and wound healing. This novel bi-layered wound dressing should be a good candidate for the healing of full-thickness wounds.

  4. Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a randomized, placebo-controlled trial.

    PubMed

    Falanga, V; Fujitani, R M; Diaz, C; Hunter, G; Jorizzo, J; Lawrence, P F; Lee, B Y; Menzoian, J O; Tretbar, L L; Holloway, G A; Hoballah, J; Seabrook, G R; McMillan, D E; Wolf, W

    1999-01-01

    Several small studies have indicated that the systemic administration of pentoxifylline may accelerate healing of venous leg ulcers. The goal of this study was to further evaluate these findings in a larger scale placebo controlled trial and to explore the effect of the dose of pentoxifylline on healing. The study used a prospective, randomized, double-blind, parallel group placebo controlled design in a multicenter outpatient setting. Patients with one or more venous ulcer were enrolled, with all patients receiving standardized compression bandaging for treatment for their ulcers. Patients were also randomized to receive either pentoxifylline 400 mg, pentoxifylline 800 mg (two 400 mg tablets), or placebo tablets three times a day for up to 24 weeks. The main outcome measure was time to complete healing of all leg ulcers, using life table analysis. The study was completed as planned in 131 patients. Patients receiving 800 mg three times a day of pentoxifylline healed faster than placebo (p = 0.043, Wilcoxon test). The median time to complete healing was 100, 83, and 71 days for placebo, pentoxifylline 400 mg, and pentoxifylline 800 mg three times a day, respectively. Over half of all patients were ulcer free at week 16 (placebo) and at week 12 in both pentoxifylline groups. Whereas the placebo group had only achieved complete healing in half of the cases by week 16, all of the subjects remaining in the group receiving the high dose of pentoxifylline had healed completely. Treatment with pentoxifylline was well tolerated with similar drop-out rates in all three treatment groups. Complete wound closure occurred at least 4 weeks earlier in the majority of patients treated with pentoxifylline by comparison to placebo. A higher dose of pentoxifylline (800 mg three times a day) was more effective than the lower dose. We conclude that pentoxifylline is effective in accelerating healing of leg ulcers.

  5. Transdermal deferoxamine prevents pressure-induced diabetic ulcers.

    PubMed

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W; Maan, Zeshaan N; Rennert, Robert C; Inayathullah, Mohammed; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V; Whitmore, Arnetha J; Walmsley, Graham G; Galvez, Michael G; Whittam, Alexander J; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C

    2015-01-06

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.

  6. Transdermal deferoxamine prevents pressure-induced diabetic ulcers

    PubMed Central

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W.; Maan, Zeshaan N.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V.; Whitmore, Arnetha J.; Galvez, Michael G.; Whittam, Alexander J.; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C.

    2015-01-01

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation. PMID:25535360

  7. Acoustic pressure wound therapy in the treatment of stage II pressure ulcers.

    PubMed

    Thomas, Raenell

    2008-11-01

    Pressure ulcers are localized skin injuries secondary to unrelieved pressure or friction. Patients with immobility issues are at increased risk for developing pressure ulcers. In 2004, stricter federal regulations for prevention and treatment of pressure ulcers in institutional settings--eg, long-term care facilities--were introduced. Effective, low-cost treatments for pressure ulcers are needed; acoustic pressure wound therapy (APWT), a noncontact, low-frequency, therapeutic ultrasound system, is one option. A retrospective case series of six long-term care patients (two men and one woman, age range 61 to 92 years), each with one Stage II pressure ulcer, is presented. Acoustic pressure wound therapy was provided as an adjunct to standard treatment that included balsam of Peru/castor oil/trypsin ointment, hydrogel, hydrocolloid dressings, silver dressings, and offloading. Outcomes (days to healing) were determined through changes in wound dimensions. Study participants each received APWT for 3 to 4 minutes three to four times weekly. In four of the six wounds, the average number of days to healing was 22. One of the two remaining patients discontinued treatment at 95% healed; treatment for the sixth patient was ongoing due to hospitalization that delayed APWT. In a long-term care setting, APWT added to standard of care may accelerate healing of Stage II pressure ulcers.

  8. Wireless electrical stimulation: an innovative powerful tool for the treatment of a complicated chronic ulcer.

    PubMed

    Castana, Ourania; Dimitrouli, Aekaterini; Argyrakos, Theodoros; Theodorakopoulou, Emilia; Stampolidis, Nektarios; Papadopoulos, Emmanouil; Pallantzas, Athanasios; Stasinopoulos, Ioannis; Poulas, Konstantinos

    2013-03-01

    High-voltage electrical stimulation has been long proposed as a method of accelerating the wound healing process. Its beneficial effect has been successfully evaluated in the treatment of a number of chronic ulcers and burns. We present here the implementation of a new wireless electrical stimulation technique for the treatment of a complicated chronic ulcer of the lower limb. The device is transferring charges to the wound, without any contact with it, creating a microcurrent that is able to generate the current of injury. The results suggest that this easy-to-use method is an effective therapeutic option for chronic ulcers.

  9. Loss of Gi G-Protein-Coupled Receptor Signaling in Osteoblasts Accelerates Bone Fracture Healing.

    PubMed

    Wang, Liping; Hsiao, Edward C; Lieu, Shirley; Scott, Mark; O'Carroll, Dylan; Urrutia, Ashley; Conklin, Bruce R; Colnot, Celine; Nissenson, Robert A

    2015-10-01

    G-protein-coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of G(i) -GPCR or activation of G(s) -GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of G(i) signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age-related bone loss in female mice. In addition, activation of G(s) signaling by expressing the G(s) -coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the G(i) and G(s) pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous G(i) signaling was inhibited by PTX, or to mice with activated G(s) signaling mediated by Rs1. Blockade of endogenous G(i) resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous G(i) signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that G(i) blockade and G(s) activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of G(s) and G(i) -GPCR activation may be important for optimizing fracture repair.

  10. PEDF promotes self-renewal of limbal stem cell and accelerates corneal epithelial wound healing.

    PubMed

    Ho, Tsung-Chuan; Chen, Show-Li; Wu, Ju-Yun; Ho, Mei-Ying; Chen, Lee-Jen; Hsieh, Jui-Wen; Cheng, Huey-Chuan; Tsao, Yeou-Ping

    2013-09-01

    Limbal epithelial stem cell (LSC) transplantation is a prevalent therapeutic method for patients with LSC deficiency. The maintenance of stem cell characteristics in the process of culture expansion is critical for the success of ocular surface reconstruction. Pigment epithelial-derived factor (PEDF) increased the numbers of holoclone in LSC monolayer culture and preserved the stemness of LSC in suspension culture by evidence of ΔNp63α, Bmi-1, and ABCG2 expression. BrdU pulse-labeling assay also demonstrated that PEDF stimulated LSCs proliferation. In air-lift culture of limbal equivalent, PEDF was capable of increasing the numbers of ΔNp63α-positive cells. The mitogenic effect of PEDF was found to be mediated by the phosphorylations of p38 MAPK and STAT3 in LSCs. Synthetic 44-mer PEDF (residues 78-121) was as effective as the full length PEDF in LSC expansion in suspension culture and limbal equivalent formation, as well as the activation of p38 MAPK and STAT3. In mice subjecting to mechanical removal of cornea epithelium, 44-mer PEDF facilitated corneal wound healing. Microscopically, 44-mer PEDF advanced the early proliferative response in limbus, increased the proliferation of ΔNp63α-positive cells both in limbus and in epithelial healing front, and assisted the repopulation of limbus in the late phase of wound healing. In conclusion, the capability of expanding LSC in cell culture and in animal indicates the potential of PEDF and its fragment (e.g., 44-mer PEDF) in ameliorating limbal stem cell deficiency; and their uses as therapeutics for treating corneal wound.

  11. Effects of weekly LED therapy at 625 nm on the treatment of chronic lower ulcers.

    PubMed

    Siqueira, Cláudia Patrícia Cardoso Martins; de Paula Ramos, Solange; Gobbi, Cynthia A A; Shigaki, Leonardo; Kashimoto, Roberto K; Venâncio, Emerson José; de Oliveira Toginho Filho, Dari; Castaldin, André G; Felinto, Alan S; Silva, Francisco Pereira; Silva, Ricardo B; Dias, Ivan Frederico Lupiano

    2015-01-01

    The aim of this study was to evaluate the effects of LED therapy associated with compression therapy on chronic venous leg ulcers (CVUs). The study included CVU patients (n = 17, eight men) who were eligible for Unna's boot treatment. Ulcers were treated on a weekly basis with either LED therapy (625 nm, 4 J/cm(2)) and an Unna's boot (LED ulcers, n = 14) or a placebo treatment and an Unna's boot (control ulcers, n = 14). The total surface area of the ulcers, the relative ulcer area, and the healing rate were recorded over a period of 30 weeks. Ulcer exudates were collected for determination of local tumor necrosis factor alpha (TNF-α) levels. The total area was not significantly different between the LED and control ulcers (P > 0.05, Mann-Whitney U test) throughout the study. However, the relative area indicated that non-healing treatment resistant ulcers (n = 6) persisted in the control group after 19 weeks (P < 0.05, Mann-Whitney U Test). No differences in median healing rate were observed (hazard ratio 0.89, CI 95%: 0.40-1.98) between LED (15 weeks) and control ulcers (19.5 weeks). No differences in TNF-α levels were detected (P > 0.05, Mann-Whitney U test). The results suggest that LED therapy improved the effectiveness of the Unna's boot since no refractory ulcer was observed in the LED group after 19 weeks. However, LED therapy did not alter the local secretion of TNF-α nor accelerate wound healing.

  12. G-CSF Administration after the Intraosseous Infusion of Hypertonic Hydroxyethyl Starches Accelerating Wound Healing Combined with Hemorrhagic Shock

    PubMed Central

    Huang, Hong; Liu, Jiejie; Hao, Haojie; Tong, Chuan; Ti, Dongdong; Liu, Huiling; Song, Haijing; Jiang, Chaoguang; Fu, Xiaobing; Han, Weidong

    2016-01-01

    Objective. To evaluate the therapeutic effects of G-CSF administration after intraosseous (IO) resuscitation in hemorrhagic shock (HS) combined with cutaneous injury rats. Methods. The rats were randomly divided into four groups: (1) HS with resuscitation (blank), (2) HS with resuscitation + G-CSF (G-CSF, 200 μg/kg body weight, subcutaneous injection), (3) HS with resuscitation + normal saline solution injection (normal saline), and (4) HS + G-CSF injection without resuscitation (Unres/G-CSF). To estimate the treatment effects, the vital signs of alteration were first evaluated, and then wound closure rates and homing of MSCs and EPCs to the wound skins and vasculogenesis were measured. Besides, inflammation and vasculogenesis related mRNA expressions were also examined. Results. IO infusion hypertonic hydroxyethyl starch (HHES) exhibited beneficial volume expansion roles and G-CSF administration accelerated wound healing 3 days ahead of other groups under hemorrhagic shock. Circulating and the homing of MSCs and EPCs at wound skins were significantly elevated at 6 h after G-CSF treatment. Inflammation was declined since 3 d while angiogenesis was more obvious in G-CSF treated group on day 9. Conclusions. These results suggested that the synergistical application of HHES and G-CSF has life-saving effects and is beneficial for improving wound healing in HS combined with cutaneous injury rats. PMID:26989687

  13. Stromal cell-derived factor-1 receptor CXCR4-overexpressing bone marrow mesenchymal stem cells accelerate wound healing by migrating into skin injury areas.

    PubMed

    Yang, Dazhi; Sun, Shijin; Wang, Zhengguo; Zhu, Peifang; Yang, Zailiang; Zhang, Bo

    2013-06-01

    Stromal cell-derived factor-1 (SDF-1) and its membrane receptor C-X-C chemokine receptor type 4 (CXCR4) are involved in the homing and migration of multiple stem cell types, neovascularization, and cell proliferation. This study investigated the hypothesis that bone marrow-derived mesenchymal stem cells (BMSCs) accelerate skin wound healing in the mouse model by overexpression of CXCR4 in BMSCs. We compared SDF-1 expression and skin wound healing times of BALB/c mice, severe combined immunodeficiency (SCID) mice, and immune system-deficient nude mice after (60)Co radiation-induced injury of their bone marrow. The occurrence of transplanted adenovirus-transfected CXCR4-overexpressing male BMSCs in the wound area was compared with the occurrence of untransfected male BALB/c BMSCs in (60)Co-irradiated female mice skin wound healing areas by Y chromosome marker analyses. The wound healing time of BALB/c mice was 14.00±1.41 days, whereas for the nude and SCID mice it was 17.16±1.17 days and 19.83±0.76 days, respectively. Male BMSCs could be detected in the surrounding areas of (60)Co-irradiated female BALB/c mice wounds, and CXCR4-overexpressing BMSCs accelerated the wound healing time. CXCR4-overexpressing BMSCs migrate in an enhanced manner to skin wounds in a SDF-1-expression-dependent manner, thereby reducing the skin wound healing time.

  14. Loss of epithelial hypoxia-inducible factor prolyl hydroxylase 2 accelerates skin wound healing in mice.

    PubMed

    Kalucka, Joanna; Ettinger, Andreas; Franke, Kristin; Mamlouk, Soulafa; Singh, Rashim Pal; Farhat, Katja; Muschter, Antje; Olbrich, Susanne; Breier, Georg; Katschinski, Dörthe M; Huttner, Wieland; Weidemann, Alexander; Wielockx, Ben

    2013-09-01

    Skin wound healing in mammals is a complex, multicellular process that depends on the precise supply of oxygen. Hypoxia-inducible factor (HIF) prolyl hydroxylase 2 (PHD2) serves as a crucial oxygen sensor and may therefore play an important role during reepithelialization. Hence, this study was aimed at understanding the role of PHD2 in cutaneous wound healing using different lines of conditionally deficient mice specifically lacking PHD2 in inflammatory, vascular, or epidermal cells. Interestingly, PHD2 deficiency only in keratinocytes and not in myeloid or endothelial cells was found to lead to faster wound closure, which involved enhanced migration of the hyperproliferating epithelium. We demonstrate that this effect relies on the unique expression of β3-integrin in the keratinocytes around the tip of the migrating tongue in an HIF1α-dependent manner. Furthermore, we show enhanced proliferation of these cells in the stratum basale, which is directly related to their attenuated transforming growth factor β signaling. Thus, loss of the central oxygen sensor PHD2 in keratinocytes stimulates wound closure by prompting skin epithelial cells to migrate and proliferate. Inhibition of PHD2 could therefore offer novel therapeutic opportunities for the local treatment of cutaneous wounds.

  15. Effectiveness of indonesian honey on the acceleration of cutaneous wound healing: an experimental study in mice.

    PubMed

    Haryanto, Haryanto; Urai, Tamae; Mukai, Kanae; Gontijo Filho, Paulo P; Suriadi, Suriadi; Sugama, Junko; Nakatani, Toshio

    2012-04-01

    The purpose of this study was to investigate the effectiveness of Indonesian honey in wound healing compared to Tegaderm hydrocolloid dressing and Manuka honey. Three groups of male mice were treated to produce 2 circular, full-thickness skin wounds on the dorsum. They were then randomly allocated to receive daily Indonesian honey, Manuka honey, or hydrocolloid (control). Macroscopic findings were observed from day 0 to 14 after wounding. Microscopic findings on days 3, 7, 11, and 14 after wounding were obtained. The ratios of wound areas for honey groups on day 3 were smaller than those of the control group. Wound areas of honey groups gradually decreased to almost the same wound area as the control group on day 14, while the control group wound area peaked on day 5 and rapidly decreased until day 14. On day 3, myofibroblasts and new blood capillaries in wound tissue of honey groups were observed, but were not seen in the control group. After day 7, microscopic findings were almost the same among the 3 groups. These results indicate that Indonesian honey is almost as effective for wound healing as Manuka honey and hydrocolloid dressing. .

  16. Loss of Epithelial Hypoxia-Inducible Factor Prolyl Hydroxylase 2 Accelerates Skin Wound Healing in Mice

    PubMed Central

    Kalucka, Joanna; Ettinger, Andreas; Franke, Kristin; Mamlouk, Soulafa; Singh, Rashim Pal; Farhat, Katja; Muschter, Antje; Olbrich, Susanne; Breier, Georg; Katschinski, Dörthe M.; Huttner, Wieland; Weidemann, Alexander

    2013-01-01

    Skin wound healing in mammals is a complex, multicellular process that depends on the precise supply of oxygen. Hypoxia-inducible factor (HIF) prolyl hydroxylase 2 (PHD2) serves as a crucial oxygen sensor and may therefore play an important role during reepithelialization. Hence, this study was aimed at understanding the role of PHD2 in cutaneous wound healing using different lines of conditionally deficient mice specifically lacking PHD2 in inflammatory, vascular, or epidermal cells. Interestingly, PHD2 deficiency only in keratinocytes and not in myeloid or endothelial cells was found to lead to faster wound closure, which involved enhanced migration of the hyperproliferating epithelium. We demonstrate that this effect relies on the unique expression of β3-integrin in the keratinocytes around the tip of the migrating tongue in an HIF1α-dependent manner. Furthermore, we show enhanced proliferation of these cells in the stratum basale, which is directly related to their attenuated transforming growth factor β signaling. Thus, loss of the central oxygen sensor PHD2 in keratinocytes stimulates wound closure by prompting skin epithelial cells to migrate and proliferate. Inhibition of PHD2 could therefore offer novel therapeutic opportunities for the local treatment of cutaneous wounds. PMID:23798557

  17. Transcutaneous electrical nerve stimulation (TENS) accelerates cutaneous wound healing and inhibits pro-inflammatory cytokines.

    PubMed

    Gürgen, Seren Gülşen; Sayın, Oya; Cetin, Ferihan; Tuç Yücel, Ayşe

    2014-06-01

    The purpose of this study was to evaluate transcutaneous electrical nerve stimulation (TENS) and other common treatment methods used in the process of wound healing in terms of the expression levels of pro-inflammatory cytokines. In the study, 24 female and 24 male adult Wistar-Albino rats were divided into five groups: (1) the non-wounded group having no incision wounds, (2) the control group having incision wounds, (3) the TENS (2 Hz, 15 min) group, (4) the physiological saline (PS) group and (5) the povidone iodine (PI) group. In the skin sections, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed with enzyme-linked immunosorbent assay and immunohistochemical methods. In the non-wounded group, the expression of IL-1β, IL-6, and TNF-α signaling molecules was weaker in the whole tissue; however, in the control group, significant inflammatory response occurred, and strong cytokine expression was observed in the dermis, granulation tissue, hair follicles, and sebaceous glands (P < 0.05). In the TENS group, the decrease in TNF-α, IL-1β, and IL-6 immunoreaction in the skin was significant compared to the other forms of treatment (P < 0.05). Distinctive decreases of pro-inflammatory cytokines observed in the dermis in the TENS group suggest that TENS shortened the healing process by inhibating the inflammation phase.

  18. Influence of different energy densities of laser phototherapy on oral wound healing

    PubMed Central

    Wagner, Vivian Petersen; Meurer, Luise; Martins, Marco Antonio Trevizani; Danilevicz, Chris Krebs; Magnusson, Alessandra Selinger; Marques, Márcia Martins; Filho, Manoel Sant’Ana; Squarize, Cristiane Helena

    2013-01-01

    Abstract. The aim of the present prospective study was to evaluate the impact of laser phototherapy (LPT) on the healing of oral ulcers. Different power densities were used on oral wounds in Wistar rats (n=72) randomly divided into three groups: control (0  J/cm2), 4  J/cm2 laser, and 20  J/cm2 laser. Ulcers (3 mm in diameter) were made on the dorsum of the tongue with a punch. Irradiation with an indium-gallium-aluminum-phosphide laser (660 nm; output power: 40 mW; spot size: 0.04  cm2) was performed once a day in close contact with the ulcer for 14 consecutive days. A statistically significant acceleration in healing time was found with wounds treated with 4  J/cm2 LPT. Moreover, striking differences were found in the ulcer area, healing percentage, degree of reepithelialization, and collagen deposition. The most significant changes occurred after 5 days of irradiation. Based on the conditions employed in the present study, LPT is capable of accelerating the oral mucosa wound-healing process. Moreover, faster and more organized reepithelialization and tissue healing of the oral mucosa were achieved with an energy density of 4  J/cm2 in comparison to 20  J/cm2. PMID:24337496

  19. Influence of different energy densities of laser phototherapy on oral wound healing

    NASA Astrophysics Data System (ADS)

    Wagner, Vivian Petersen; Meurer, Luise; Martins, Marco Antonio Trevizani; Danilevicz, Chris Krebs; Magnusson, Alessandra Selinger; Marques, Márcia Martins; Filho, Manoel Sant'Ana; Squarize, Cristiane Helena; Martins, Manoela Domingues

    2013-12-01

    The aim of the present prospective study was to evaluate the impact of laser phototherapy (LPT) on the healing of oral ulcers. Different power densities were used on oral wounds in Wistar rats (n=72) randomly divided into three groups: control (0 J/cm2), 4 J/cm2 laser, and 20 J/cm2 laser. Ulcers (3 mm in diameter) were made on the dorsum of the tongue with a punch. Irradiation with an indium-gallium-aluminum-phosphide laser (660 nm output power: 40 mW spot size: 0.04 cm) was performed once a day in close contact with the ulcer for 14 consecutive days. A statistically significant acceleration in healing time was found with wounds treated with 4 J/cm2 LPT. Moreover, striking differences were found in the ulcer area, healing percentage, degree of reepithelialization, and collagen deposition. The most significant changes occurred after 5 days of irradiation. Based on the conditions employed in the present study, LPT is capable of accelerating the oral mucosa wound-healing process. Moreover, faster and more organized reepithelialization and tissue healing of the oral mucosa were achieved with an energy density of 4 J/cm2 in comparison to 20 J/cm2.

  20. Liposome-encapsulated hemoglobin accelerates bronchial healing after pneumonectomy in the rat with or without preoperative radiotherapy.

    PubMed

    Takeichi, Haruka; Kawaguchi, Akira T; Murayama, Chieko; Koike, Junki; Iwazaki, Masayuki

    2014-08-01

    Liposome-encapsulated hemoglobin (LEH) has been reported to accelerate wound healing in the stomach and skin in an experimental setting. LEH was tested in bronchial anastomotic healing after radiation and pneumonectomy in the rat. Sprague-Dawley rats (n = 61) received preoperative radiation (20 Gy) to the chest and underwent left pneumonectomy with bronchial stump closure using the Sweet method 4 days later, when they were randomized to receive intravenous infusion of LEH with high O2 affinity (P50 O2  = 17 mm Hg, 10 mL/kg, n = 32) or saline (n = 29). Additional rats (n = 18) were treated in the same way without preoperative radiation. Bronchial anastomotic healing was evaluated 2 days after surgery by determining the bursting pressure and infiltration of neutrophils, monocytes, and macrophages. Bronchial bursting pressure was elevated in the rats receiving LEH both in the unirradiated group (LEH 212 ± 78 vs. saline 135 ± 63 mm Hg, P < 0.05) and in rats with preoperative radiation (LEH 162 ± 48 vs. saline 116 ± 56 mm Hg, P < 0.01). Moreover, the percentage of rats with bursting pressure <100 mm Hg tended to be smaller in the unirradiated group (LEH 1/9 [11.1%] vs. saline 4/9 [44.4%], NS) and was significantly reduced in irradiated animals (LEH 3/32 [9.4%] vs. saline 11/29 [38%], P < 0.05). There were no morphological differences except for macrophage infiltration to the anastomotic area, which was significantly prominent in the LEH-treated rats (P < 0.05) regardless of the presence or absence of preoperative irradiation (IR). The results suggest that LEH with high O2 affinity may improve mechanical strength and morphological findings in bronchial anastomosis in rats regardless of the presence or absence of preoperative IR. The irradiated rats later treated with LEH had equivalent or better bronchial healing than that of saline-treated naïve animals undergoing pneumonectomy alone.

  1. Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model

    PubMed Central

    Orihuela-Campos, Rita Cristina; Fukui, Makoto; Ito, Hiro-O

    2016-01-01

    The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses. PMID:26798423

  2. Hydrogen-Rich Water Intake Accelerates Oral Palatal Wound Healing via Activation of the Nrf2/Antioxidant Defense Pathways in a Rat Model.

    PubMed

    Tamaki, Naofumi; Orihuela-Campos, Rita Cristina; Fukui, Makoto; Ito, Hiro-O

    2016-01-01

    The wound healing process attempts to restore the integrity and function of the injured tissue. Additionally, proinflammatory cytokines, growth factors, and oxidative stress play important roles in wound healing. The aim of this study was to determine whether hydrogen-rich water intake induces the activation of the Nrf2/antioxidant defense pathway in rat palatal tissue, thereby reducing systemic oxidative stress and proinflammatory cytokine levels and promoting healing-associated genes. A circular excisional wound was created in the oral palatal region, and the wound healing process was observed. The rats were divided into two experimental groups in which either hydrogen-rich water or distilled water was consumed. In the drinking hydrogen-rich water, the palatal wound healing process was accelerated compared to that in the control group. As molecular hydrogen upregulated the Nrf2 pathway, systemic oxidative stresses were decreased by the activation of antioxidant activity. Furthermore, hydrogen-rich water intake reduced proinflammatory cytokine levels and promoted the expression of healing-associated factors in rat palatal tissue. In conclusion, hydrogen-rich water intake exhibited multiple beneficial effects through activation of the Nrf2/antioxidant defense pathway. The results of this study support the hypothesis that oral administration of hydrogen-rich water benefits the wound healing process by decreasing oxidative stress and inflammatory responses.

  3. Tri-potassium di-citrato bismuthate: a report of its pharmacological properties and therapeutic efficacy in peptic ulcer.

    PubMed

    Brogden, R N; Pinder, R M; Sawyer, P R; Speight, T M; Avery, G S

    1976-12-01

    Tri-potassium di-citrato bismuthate is a complex bismuth salt stable in colloidal form advocated for the treatment of peptic ulcer. Preliminary placebo-controlled trials in small numbers of ambulant patients with endoscopically proven peptic ulcer, strongly suggest that the compound accelerates the rate of healing of gastric and duodenal ulcer within 4 weeks of treatment. However, trials involving larger numbers of patients followed-up for longer periods are required before a clear verdict on the efficacy of tripotassium di-citrato bismuthate in gastric and duodenal ulcer can be given. There are no reliable data on the effect of the drug on ulcer recurrence rate. Side-effects are negligible and the drug could become an important therapeutic agent in peptic ulcer therapy if results of further study are conclusive. The drug causes dark discolouration of the stools and this should be borne in mind when considering the possibility of the presence of intestinal bleeding.

  4. Effect of Hydro-alcoholic Extract of Persian Oak (Quercus brantii) in Experimentally Gastric Ulcer

    PubMed Central

    Azizi, Shahrzad; Ghasemi Pirbalouti, Abdollah; Amirmohammadi, Mahdi

    2014-01-01

    Persian oak (Quercus brantii Lindl.) belongs the family Fagaceae, is a medicinal plant which seed flour is used to treat inflammatory and gastric ulcers by the tribes in south western Iran. The current study was done to evaluate the effect of hydro-alcoholic extract of Q. brantii seed flour for treatment of gastric ulcers induced by ethanol in Wistar rats. The hydro-alcoholic extract of Q. brantii was tested orally at doses of 250, 500, and 1000 mg/Kg, control group and standard drug (omperazole) on experimentally gastric ulceration. At the 3, 6, 9, and 14th days, ulcer index in mm2 and histopathological findings were evaluated. Results indicated the size of ulcers significantly reduced at 9, and 14 days after of Q. brantii extract treatment. Curative effect in the hydro-alcoholic induced gastric damage was 100% at 1000 mg/Kg and omeprazole, 99.8 % at 500 mg/Kg, and 95.4% at 250 mg/Kg after 14 days. Results of histopathological investigation showed the thickness of ulcerated mucosa was similar to the normal mucosa with 1000 mg/Kg of Q. brantii hydro-alcoholic extract after 14 days but in the groups treated by 250, and 500 mg/Kg, superficial erosions were visible in the central portion of the healed ulcers. In conclusion, the hydro-alcoholic extract of Q. brantii had active components (tannin = 8.2%) that accelerates ulcer healing and thus supported its traditional use. PMID:25276198

  5. Venous Ulcers

    PubMed Central

    Caprini, J.A.; Partsch, H.; Simman, R.

    2013-01-01

    Venous leg ulcers are the most frequent form of wounds seen in patients. This article presents an overview on some practical aspects concerning diagnosis, differential diagnosis and treatment. Duplex ultrasound investigations are essential to ascertain the diagnosis of the underlying venous pathology and to treat venous refluxes. Differential diagnosis includes mainly other vascular lesions (arterial, microcirculatory causes), hematologic and metabolic diseases, trauma, infection, malignancies. Patients with superficial venous incompetence may benefit from endovenous or surgical reflux abolition diagnosed by Duplex ultrasound. The most important basic component of the management is compression therapy, for which we prefer materials with low elasticity applied with high initial pressure (short-stretch bandages and Velcro-strap devices). Local treatment should be simple, absorbing and not sticky dressings keeping adequate moisture balance after debridement of necrotic tissue and biofilms are preferred. After the ulcer is healed compression therapy should be continued in order to prevent recurrence. PMID:26236636

  6. Laser Biostimulation Of Wound Healing In Arteriopatic Patients

    NASA Astrophysics Data System (ADS)

    Tallarida, G.; Baldoni, F.; Raimondi, G.; Massaro, M.; Peruzzi, G.; Bertolotti, M.; Ferrari, A.; Scudieri, F.

    1981-05-01

    Low-power laser irradiation has been employed in the attempt to accelerate the wound-healing of ischemic cutaneous ulcerations with threatening or manifest gangrene due to arteriosclerosis obliterans of the lower limbs. Irradiation was performed by using a low-power He-Ne gas laser of 6328 Å wavelength and was concentrated at the peripheral zone of the lesions. The preliminary results of the study indicate that laser stimulation might be new approach in the conservative menagement of the ischemic ulcers in patients with severe peripheral obstructive arteriopaties not suited for arterial reconstruction.

  7. Gelatin powders accelerate the resorption of calcium phosphate cement and improve healing in the alveolar ridge.

    PubMed

    Matsumoto, Goichi; Sugita, Yoshihiko; Kubo, Katsutoshi; Yoshida, Waka; Ikada, Yoshito; Sobajima, Satoshi; Neo, Masashi; Maeda, Hatsuhiko; Kinoshita, Yukihiko

    2014-05-01

    The aim of this study was to show the effectiveness of combining calcium phosphate cement and gelatin powders to promote bone regeneration in the canine mandible. We mixed gelatin powders with calcium phosphate cement to create a macroporous composite. In four beagle dogs, two saddle-type bone defects were created on each side of the mandible, and calcium phosphate cement alone or calcium phosphate cement containing composite gelatin powders was implanted in each of the defects. After a healing period of six months, mandibles were removed for µCT and histological analyses. The µCT and histological analyses showed that at experimental sites at which calcium phosphate cement alone had been placed new bone had formed only around the periphery of the residual calcium phosphate cement and that there had been little or no ingrowth into the calcium phosphate cement. On the other hand, at experimental sites at which calcium phosphate cement containing composite gelatin powders had been placed, we observed regenerated new bone in the interior of the residual calcium phosphate cement as well as around its periphery. The amount of resorption of calcium phosphate cement and bone regeneration depended on the mixing ratio of gelatin powders to calcium phosphate cement. New bone replacement was significantly better in the sites treated with calcium phosphate cement containing composite gelatin powders than in those treated with calcium phosphate cement alone.

  8. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    PubMed

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-09-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis.

  9. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    PubMed Central

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  10. Ascorbic Acid Promotes the Stemness of Corneal Epithelial Stem/Progenitor Cells and Accelerates Epithelial Wound Healing in the Cornea.

    PubMed

    Chen, Jialin; Lan, Jie; Liu, Dongle; Backman, Ludvig J; Zhang, Wei; Zhou, Qingjun; Danielson, Patrik

    2017-03-09

    High concentration of ascorbic acid (vitamin C) has been found in corneal epithelium of various species. However, the specific functions and mechanisms of ascorbic acid in the repair of corneal epithelium are not clear. In this study, it was found that ascorbic acid accelerates corneal epithelial wound healing in vivo in mouse. In addition, ascorbic acid enhanced the stemness of cultured mouse corneal epithelial stem/progenitor cells (TKE2) in vitro, as shown by elevated clone formation ability and increased expression of stemness markers (especially p63 and SOX2). The contribution of ascorbic acid on the stemness enhancement was not dependent on the promotion of Akt phosphorylation, as concluded by using Akt inhibitor, nor was the stemness found to be dependent on the regulation of oxidative stress, as seen by the use of two other antioxidants (GMEE and NAC). However, ascorbic acid was found to promote extracellular matrix (ECM) production, and by using two collagen synthesis inhibitors (AzC and CIS), the increased expression of p63 and SOX2 by ascorbic acid was decreased by around 50%, showing that the increased stemness by ascorbic acid can be attributed to its regulation of ECM components. Moreover, the expression of p63 and SOX2 was elevated when TKE2 cells were cultured on collagen I coated plates, a situation that mimics the in vivo situation as collagen I is the main component in the corneal stroma. This study shows direct therapeutic benefits of ascorbic acid on corneal epithelial wound healing and provides new insights into the mechanisms involved. © Stem Cells Translational Medicine 2017.

  11. Loss of CAR promotes migration and proliferation of HaCaT cells, and accelerates wound healing in rats via Src-p38 MAPK pathway.

    PubMed

    Su, Linlin; Fu, Lanqing; Li, Xiaodong; Zhang, Yue; Li, Zhenzhen; Wu, Xue; Li, Yan; Bai, Xiaozhi; Hu, Dahai

    2016-01-25

    The coxsackie and adenovirus receptor (CAR) is a cell adhesion molecule mostly localized to cell-cell contacts in epithelial and endothelial cells. CAR is known to regulate tumor progression, however, its physiological role in keratinocyte migration and proliferation, two essential steps in re-epithelialization during wound healing, has less been investigated. Here we showed that CAR was predominantly expressed in the epidermis of human skin, CAR knockdown by RNAi significantly accelerated HaCaT cell migration and proliferation. In addition, knockdown of CAR in vitro increased p-Src, p-p38, and p-JNK protein levels; however, Src inhibitor PP2 prevented the increase of p-Src and p-p38 induced by CAR RNAi, but not p-JNK, and decelerated cell migration and proliferation. More intriguingly, in vivo CAR RNAi on the skin area surrounding the wounds on rat back visually accelerated wound healing and re-epithelialization process, while treatment with PP2 or p38 inhibitor SB203580 obviously inhibited these effects. By contrast, overexpressing CAR in HaCaT cells significantly decelerated cell migration and proliferation. Above results demonstrate that suppression of CAR could accelerate HaCaT cell migration and proliferation, and promote wound healing in rat skin, probably via Src-p38 MAPK pathway. CAR thus might serve as a novel therapeutic target for facilitating wound healing.

  12. Loss of CAR promotes migration and proliferation of HaCaT cells, and accelerates wound healing in rats via Src-p38 MAPK pathway

    PubMed Central

    Su, Linlin; Fu, Lanqing; Li, Xiaodong; Zhang, Yue; Li, Zhenzhen; Wu, Xue; Li, Yan; Bai, Xiaozhi; Hu, Dahai

    2016-01-01

    The coxsackie and adenovirus receptor (CAR) is a cell adhesion molecule mostly localized to cell-cell contacts in epithelial and endothelial cells. CAR is known to regulate tumor progression, however, its physiological role in keratinocyte migration and proliferation, two essential steps in re-epithelialization during wound healing, has less been investigated. Here we showed that CAR was predominantly expressed in the epidermis of human skin, CAR knockdown by RNAi significantly accelerated HaCaT cell migration and proliferation. In addition, knockdown of CAR in vitro increased p-Src, p-p38, and p-JNK protein levels; however, Src inhibitor PP2 prevented the increase of p-Src and p-p38 induced by CAR RNAi, but not p-JNK, and decelerated cell migration and proliferation. More intriguingly, in vivo CAR RNAi on the skin area surrounding the wounds on rat back visually accelerated wound healing and re-epithelialization process, while treatment with PP2 or p38 inhibitor SB203580 obviously inhibited these effects. By contrast, overexpressing CAR in HaCaT cells significantly decelerated cell migration and proliferation. Above results demonstrate that suppression of CAR could accelerate HaCaT cell migration and proliferation, and promote wound healing in rat skin, probably via Src-p38 MAPK pathway. CAR thus might serve as a novel therapeutic target for facilitating wound healing. PMID:26804208

  13. Infrared laser therapy after surgically assisted rapid palatal expansion to diminish pain and accelerate bone healing.

    PubMed

    Abreu, Marcelo Emir Requia; Viegas, Vinicius Nery; Pagnoncelli, Rogerio Miranda; de Lima, Eduardo Martinelli Santayama; Farret, Alessandro Marchiori; Kulczynski, Fernando Zugno; Farret, Marcel Marchiori

    2010-01-01

    The aim of this study was to illustrate how gallium arsenite aluminum diode laser (824 nm) irradiation can reduce postsurgical edema and discomfort and accelerate sutural osseous regeneration after surgically assisted rapid palatal expansion (SARPE). An adult patient with an 8-mm transverse maxillary discrepancy was treated with SARPE. Infrared laser therapy was started on the 7th postoperative day, with a total of eight sessions at intervals of 48 hours. The laser probe spot had a size of 0.2827 cm2 and was positioned in contact with the following (bilateral) points: infraorbital foramen, nasal alar, nasopalatine foramen, median palatal suture at the height of the molars, and transverse palatine suture distal to the second molars. The laser was run in continuous mode with a power of 100 mW and a fluency of 1.5 J/cm2 for 20 seconds at each point. Subsequently, an absence of edema and pain was observed. Further, fast bone regeneration in the median palatal suture could be demonstrated by occlusal radiographs. These findings suggest that laser therapy can accelerate bone regeneration of the median palatal suture in patients who have undergone SARPE.

  14. Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds

    PubMed Central

    Skardal, Aleksander; Mack, David; Kapetanovic, Edi; Atala, Anthony; Jackson, John D.; Yoo, James

    2012-01-01

    Stem cells obtained from amniotic fluid show high proliferative capacity in culture and multilineage differentiation potential. Because of the lack of significant immunogenicity and the ability of the amniotic fluid-derived stem (AFS) cells to modulate the inflammatory response, we investigated whether they could augment wound healing in a mouse model of skin regeneration. We used bioprinting technology to treat full-thickness skin wounds in nu/nu mice. AFS cells and bone marrow-derived mesenchymal stem cells (MSCs) were resuspended in fibrin-collagen gel and “printed” over the wound site. At days 0, 7, and 14, AFS cell- and MSC-driven wound closure and re-epithelialization were significantly greater than closure and re-epithelialization in wounds treated by fibrin-collagen gel only. Histological examination showed increased microvessel density and capillary diameters in the AFS cell-treated wounds compared with the MSC-treated wounds, whereas the skin treated only with gel showed the lowest amount of microvessels. However, tracking of fluorescently labeled AFS cells and MSCs revealed that the cells remained transiently and did not permanently integrate in the tissue. These observations suggest that the increased wound closure rates and angiogenesis may be due to delivery of secreted trophic factors, rather than direct cell-cell interactions. Accordingly, we performed proteomic analysis, which showed that AFS cells secreted a number of growth factors at concentrations higher than those of MSCs. In parallel, we showed that AFS cell-conditioned media induced endothelial cell migration in vitro. Taken together, our results indicate that bioprinting AFS cells could be an effective treatment for large-scale wounds and burns. PMID:23197691

  15. Evaluating the effectiveness of a self-management exercise intervention on wound healing, functional ability and health-related quality of life outcomes in adults with venous leg ulcers: a randomised controlled trial.

    PubMed

    O'Brien, Jane; Finlayson, Kathleen; Kerr, Graham; Edwards, Helen

    2017-02-01

    Exercise that targets ankle joint mobility may lead to improvement in calf muscle pump function and subsequent healing. The objectives of this research were to assess the impact of an exercise intervention in addition to routine evidence-based care on the healing rates, functional ability and health-related quality of life for adults with venous leg ulcers (VLUs). This study included 63 patients with VLUs. Patients were randomised to receive either a 12-week exercise intervention with a telephone coaching component or usual care plus telephone calls at the same timepoints. The primary outcome evaluated the effectiveness of the intervention in relation to wound healing. The secondary outcomes evaluated physical activity, functional ability and health-related quality of life measures between groups at the end of the 12 weeks. A per protocol analysis complemented the effectiveness (intention-to-treat) analysis to highlight the importance of adherence to an exercise intervention. Intention-to-treat analyses for the primary outcome showed 77% of those in the intervention group healed by 12 weeks compared to 53% of those in the usual care group. Although this difference was not statistically significant due to a smaller than expected sample size, a 24% difference in healing rates could be considered clinically significant. The per protocol analysis for wound healing, however, showed that those in the intervention group who adhered to the exercise protocol 75% or more of the time were significantly more likely to heal and showed higher rates for wound healing than the control group (P = 0·01), that is, 95% of those who adhered in the intervention group healed in 12 weeks. The secondary outcomes of physical activity, functional ability and health-related quality of life were not significantly altered by the intervention. Among the secondary outcomes (physical activity, functional ability and health-related quality of life), intention-to-treat analyses did not support the

  16. Expression of natural antimicrobial peptide beta-defensin-2 and Langerhans cell accumulation in epidermis from human non-healing leg ulcers.

    PubMed

    Galkowska, Hanna; Olszewski, Waldemar L; Wojewodzka, Urszula

    2005-01-01

    Chronic wounds like venous calf and diabetic foot ulcers are frequently contaminated and colonized by bacteria and it remains unclear whether there is sufficient expression of defensins and recruitment of epidermal Langerhans cells in the margin of ulcer compared to normal skin. The aim of this study was to examine immunohistochemically the expression of beta-defensin-2 (hBD2), GM-CSF, VEGF growth factors and accumulation of CD1a+ Langerhans cells (LC) in epidermis from chronic skin ulcers and to compare it to normal skin from the corresponding areas. Studies were carried out in 10 patients with diabetic foot, 10 patients with varicous ulcers of the calf and 10 patients undergoing orthopedic surgery (normal skin for control). Biopsy specimens were immunostained using specific primary antibodies, LSAB+ kit based on biotin-avidin-peroxidase complex technique and DAB chromogen. Results were expressed as a mean staining intensity. Statistical analysis of staining showed significantly higher staining of hBD2 in both normal and ulcerated epidermis from foot sole skin compared to calf skin (normal and ulcerated, p < 0.05). Chronic ulcers showed the same expression of hBD2 as normal skin. There was significantly lower accumulation of CD1a+ LC in normal epidermis from foot sole skin compared to normal calf skin (p<0.05). Accumulation of CD1a+ LC and GM-CSF upregulation at the border area of diabetic foot ulcer and reduction of LC concentration at the margin of venous calf ulcer compared to normal skin were observed. It seems that normal calf and sole epidermis is, unlike in the mechanisms of innate immunity, influenced by the different keratinocyte turnover and bacterial flora colonizing these regions. Insufficient upregulation of hBD2 in both diabetic foot and venous calf ulcers may suggest the pathological role of this protein in the chronicity of ulcers.

  17. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: An in vitro study of fibroblast and keratinocyte scratch assays

    SciTech Connect

    Walter, M.N.M.; Wright, K.T.; Fuller, H.R.; MacNeil, S.; Johnson, W.E.B.

    2010-04-15

    We have used in vitro scratch assays to examine the relative contribution of dermal fibroblasts and keratinocytes in the wound repair process and to test the influence of mesenchymal stem cell (MSC) secreted factors on both skin cell types. Scratch assays were established using single cell and co-cultures of L929 fibroblasts and HaCaT keratinocytes, with wound closure monitored via time-lapse microscopy. Both in serum supplemented and serum free conditions, wound closure was faster in L929 fibroblast than HaCaT keratinocyte scratch assays, and in co-culture the L929 fibroblasts lead the way in closing the scratches. MSC-CM generated under serum free conditions significantly enhanced the wound closure rate of both skin cell types separately and in co-culture, whereas conditioned medium from L929 or HaCaT cultures had no significant effect. This enhancement of wound closure in the presence of MSC-CM was due to accelerated cell migration rather than increased cell proliferation. A number of wound healing mediators were identified in MSC-CM, including TGF-{beta}1, the chemokines IL-6, IL-8, MCP-1 and RANTES, and collagen type I, fibronectin, SPARC and IGFBP-7. This study suggests that the trophic activity of MSC may play a role in skin wound closure by affecting both dermal fibroblast and keratinocyte migration, along with a contribution to the formation of extracellular matrix.

  18. Hemoglobinopathies and Leg Ulcers.

    PubMed

    Alavi, Afsaneh; Kirsner, Robert S

    2015-09-01

    Major hemoglobinopathies, including sickle cell anemia, are becoming a global health issue. Leg ulcers are the most common cutaneous manifestation of sickle cell disease and an important contributor to morbidity burden in this population. Leg ulcers following sickling disorders are extremely painful, and hard to heal. The clinical evidence for the optimal management of these ulcers is limited. Treating the cause and the strategies to prevent sickling are the mainstay of treatment. The basic principles of wound bed preparation and compression therapy is beneficial in these patients.

  19. Platelets and wound healing.

    PubMed

    Nurden, Alan T; Nurden, Paquita; Sanchez, Mikel; Andia, Isabel; Anitua, Eduardo

    2008-05-01

    Platelets help prevent blood loss at sites of vascular injury. To do this, they adhere, aggregate and form a procoagulant surface favoring thrombin generation and fibrin formation. In addition, platelets express and release substances that promote tissue repair and influence processes such as angiogenesis, inflammation and the immune response. They contain large secretable pools of biologically active proteins, while newly synthesized active metabolites are also released. Although anucleate, activated platelets possess a spliceosome and can synthesize tissue factor and interleukin-1beta. The binding of secreted proteins within a developing fibrin mesh or to the extracellular matrix can create chemotactic gradients favoring the recruitment of stem cells, stimulating cell migration and differentiation, and promoting repair. The therapeutic use of platelets in a fibrin clot has a positive influence in clinical situations requiring rapid healing. Dental implant surgery, orthopaedic surgery, muscle and tendon repair, skin ulcers, hole repair in eye surgery and cardiac surgery are situations where the use of autologous platelets accelerates healing. We now review the ways in which platelets participate in these processes.

  20. 5. Accelerated Fracture Healing Targeting Periosteal Cells: Possibility of Combined Therapy of Low-Intensity Pulsed Ultrasound (LIPUS), Bone Graft, and Growth Factor (bFGF).

    PubMed

    Uchida, Kentaro; Urabe, Ken; Naruse, Koji; Mikuni-Takagaki, Yuko; Inoue, Gen; Takaso, Masashi

    2016-08-01

    We have studied the mechanism of fracture healing, and the effect of LIPUS, bone graft and growth factor on accelerating fracture healing. We present here the results of our research. To examine callus formation cells in fracture healing, we made marrow GFP chimera mice and a fracture model of marrow mesenchymal stem cell GFP chimera mice. It was demonstrated that periosteal cells were essential for callus formation. We focused on periosteal cells and examined the effect of LIPUS. In an in vitro experiment using a cultured part of the femur, LIPUS promoted ossification of the periosteal tissue. Further, LIPUS accelerated VEGF expression in the experiment using the femoral fracture model of mice. From these results, it was suggested that activation of periosteal cells might play a role in the fracture healing mechanism of LIPUS. Next, we discussed the possibility of combined therapy of LIPUS, bone graft and growth factor. Therapy involving the topical administration of bFGF using a controlled release system and bone graft could promote callus formation. In addition, LIPUS was able to promote membranaceous ossification after the bone graft. It was suggested that combined therapy of LIPUS, bone graft and bFGF could be a new option for treating fractures.

  1. Recombinant growth factor mixtures induce cell cycle progression and the upregulation of type I collagen in human skin fibroblasts, resulting in the acceleration of wound healing processes.

    PubMed

    Lee, Do Hyun; Choi, Kyung-Ha; Cho, Jae-We; Kim, So Young; Kwon, Tae Rin; Choi, Sun Young; Choi, Yoo Mi; Lee, Jay; Yoon, Ho Sang; Kim, Beom Joon

    2014-05-01

    Application of growth factor mixtures has been used for wound healing and anti-wrinkles agents. The aim of this study was to evaluate the effect of recombinant growth factor mixtures (RGFM) on the expression of cell cycle regulatory proteins, type I collagen, and wound healing processes of acute animal wound models. The results showed that RGFM induced increased rates of cell proliferation and cell migration of human skin fibroblasts (HSF). In addition, expression of cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)4, and Cdk2 proteins was markedly increased with a growth factor mixtures treatment in fibroblasts. Expression of type I collagen was also increased in growth factor mixtures-treated HSF. Moreover, growth factor mixtures-induced the upregulation of type I collagen was associated with the activation of Smad2/3. In the animal model, RGFM-treated mice showed accelerated wound closure, with the closure rate increasing as early as on day 7, as well as re-epithelization and reduced inflammatory cell infiltration than phosphate-buffered saline (PBS)-treated mice. In conclusion, the results indicated that RGFM has the potential to accelerate wound healing through the upregulation of type I collagen, which is partly mediated by activation of Smad2/3-dependent signaling pathway as well as cell cycle progression in HSF. The topical application of growth factor mixtures to acute and chronic skin wound may accelerate the epithelization process through these molecular mechanisms.

  2. Refractory duodenal ulcer.

    PubMed Central

    Bardhan, K D

    1984-01-01

    A refractory duodenal ulcer was arbitrarily defined as one that had failed to heal completely after treatment with cimetidine 1 g daily for three months. Of 66 patients with refractory duodenal ulcer, healing eventually occurred in 37 patients, after treatment for an average of 7.4 months. But 28 patients did not heal despite treatment for an average of 9.4 months; and one patient defaulted. In 41 patients the daily dose of cimetidine was increased to 2 g: the ulcers in 31 patients healed. In eight patients the daily dose was increased to 3 g and healing occurred in four patients. Eighteen patients required admission on 22 occasions because of severe symptoms despite treatment. Nine patients underwent surgery but in five the results were poor. Differences in clinical and endoscopic features between refractory and non-refractory ulcer patients were small. Acid and pepsin secretion were similar and gastrin concentrations normal. Blood levels of the drug and suppression of acid secretion were both satisfactory. Identification of refractory ulcer patients at the start of treatment was therefore not possible. Refractoriness could occur at any time during the course of the disease, previous treatment with cimetidine often having resulted in rapid healing, but subsequent relapses were also usually refractory. The cause of refractoriness remains unknown and the rather poor results of surgery in this series suggests that optimal management of these patients remains to be determined. Refractoriness probably indicates a changed natural history of the disease and in some patients a more poor prognosis. PMID:6428982

  3. Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes.

    PubMed

    Ansurudeen, Ishrath; Sunkari, Vivekananda Gupta; Grünler, Jacob; Peters, Verena; Schmitt, Claus Peter; Catrina, Sergiu-Bogdan; Brismar, Kerstin; Forsberg, Elisabete Alcantara

    2012-07-01

    Diabetes mellitus (DM) is a progressive disorder with severe late complications. Normal wound healing involves a series of complex and well-orchestrated molecular events dictated by multiple factors. In diabetes, wound healing is grossly impaired due to defective, and dysregulated cellular and molecular events at all phases of wound healing resulting in chronic wounds that fail to heal. Carnosine, a dipeptide of alanine and histidine and an endogenous antioxidant is documented to accelerate healing of wounds and ulcers. However, not much is known about its role in wound healing in diabetes. Therefore, we studied the effect of carnosine in wound healing in db/db mice, a mice model of Type 2 DM. Six millimeter circular wounds were made in db/db mice and analyzed for wound healing every other day. Carnosine (100 mg/kg) was injected (I.P.) every day and also applied locally. Treatment with carnosine enhanced wound healing significantly, and wound tissue analysis showed increased expression of growth factors and cytokines genes involved in wound healing. In vitro studies with human dermal fibroblasts and microvascular-endothelial cells showed that carnosine increases cell viability in presence of high glucose. These effects, in addition to its known role as an antioxidant and a precursor for histamine synthesis, provide evidence for a possible therapeutic use of carnosine in diabetic wound healing.

  4. A review of becaplermin gel in the treatment of diabetic neuropathic foot ulcers

    PubMed Central

    Fang, Robert C; Galiano, Robert D

    2008-01-01

    Diabetic neuropathic foot ulcers represent a serious health care burden to patients and to society. While the management of chronic diabetic foot ulcers has improved in recent years, it remains a frustrating problem for a variety of clinicians. This review examines the scientific underpinnings supporting the use of becaplermin (Regranex®; Ortho-McNeil Pharmaceutical, Raritan, NJ), or recombinant human platelet-derived growth factor (rhPDGF-BB), in diabetic forefoot wounds. An emphasis is placed upon proper medical and surgical care of diabetic foot wounds, as multiple studies have demonstrated that the success of this growth factor in accelerating healing is ultimately dependent on proper ulcer care. A focus on the cost-effectiveness of this form of therapy in the treatment of diabetic foot ulcers is also outlined. PMID:19707423

  5. Hallux ulceration in diabetic patients.

    PubMed

    ElMakki Ahmed, Mohamed; Tamimi, Abdulhakim O; Mahadi, Seif I; Widatalla, Abubakr H; Shawer, Mohamed A

    2010-01-01

    We undertook a prospective cohort study to assess risk factors associated with hallux ulceration, and to determine the incidence of healing or amputation, in consecutive patients with diabetes mellitus who were treated over the observation period extending from September 2004 to March 2005, at the Jabir Abu Eliz Diabetic Centre, Khartoum City, Sudan. There were 122 diabetic patients in the cohort (92 males and 30 females) with an overall mean age of 58 +/- 9 years. Fifty-three percent of patients had complete healing within 8 weeks and 43% healed within 20 weeks. The overall mean time to healing was 16 +/- 8 weeks. In 32 (26.2%) patients, osteomyelitic bone was removed, leaving a healed and boneless hallux. The hallux was amputated in 17 (13.9%) patients; in 2 (1.6%) patients it was followed by forefoot amputation and in 7 (5.7%) patients by below-the-knee amputation. In 90 (73.8%) patients the initial lesion was a blister. In conclusion, hallux ulceration is common in patients with diabetes mellitus and is usually preceded by a blister. Neuropathy, foot deformity, and wearing new shoes are common causative factors; and ischemia, osteomyelitis, any form of wound infection, and the size of the ulcer are main outcome determinants. Complete healing occurred in 103 (85%) of diabetic patients with a hallux ulcer. Vascular intervention is important relative to limb salvage when ischemia is the main cause of the ulcer.

  6. Preventing venous ulcer recurrence: a review.

    PubMed

    Vowden, Kathryn R; Vowden, Peter

    2006-03-01

    This review article examines the available evidence on both the primary and secondary prevention of venous ulceration, exploring both the individual, social and financial implications of system failures that allow patients to remain at increased risk of recurrent ulceration. The role of both venous disease assessment and corrective superficial venous surgery are discussed in the light of recently published randomised controlled studies on the role of superficial venous surgery as both an adjunct to ulcer healing and ulcer prevention.

  7. Hyperforin/HP-β-Cyclodextrin Enhances Mechanosensitive Ca2+ Signaling in HaCaT Keratinocytes and in Atopic Skin Ex Vivo Which Accelerates Wound Healing

    PubMed Central

    Takada, Hiroya; Yonekawa, Jun; Matsumoto, Masami; Sokabe, Masahiro

    2017-01-01

    Cutaneous wound healing is accelerated by mechanical stretching, and treatment with hyperforin, a major component of a traditional herbal medicine and a known TRPC6 activator, further enhances the acceleration. We recently revealed that this was due to the enhancement of ATP-Ca2+ signaling in keratinocytes by hyperforin treatment. However, the low aqueous solubility and easy photodegradation impede the topical application of hyperforin for therapeutic purposes. We designed a compound hydroxypropyl-β-cyclodextrin- (HP-β-CD-) tetracapped hyperforin, which had increased aqueous solubility and improved photoprotection. We assessed the physiological effects of hyperforin/HP-β-CD on wound healing in HaCaT keratinocytes using live imaging to observe the ATP release and the intracellular Ca2+ increase. In response to stretching (20%), ATP was released only from the foremost cells at the wound edge; it then diffused to the cells behind the wound edge and activated the P2Y receptors, which caused propagating Ca2+ waves via TRPC6. This process might facilitate wound closure, because the Ca2+ response and wound healing were inhibited in parallel by various inhibitors of ATP-Ca2+ signaling. We also applied hyperforin/HP-β-CD on an ex vivo skin model of atopic dermatitis and found that hyperforin/HP-β-CD treatment for 24 h improved the stretch-induced Ca2+ responses and oscillations which failed in atopic skin. PMID:28210627

  8. Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP+/− Mice and Accelerates Fracture Healing of Wild Mice

    PubMed Central

    Wang, Yinhe; Fang, Xin; Wang, Chun; Ding, Congzhu; Lin, Hua; Liu, Anlong; Wang, Lei; Cao, Yang

    2017-01-01

    Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone–related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/− mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods. Bone formation–related genes and protein expression levels were evaluated by real-time reverse transcriptase–polymerase chain reaction and Western blots. At two weeks PF, mineral density of callus, bony callus areas, mRNA levels of alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx-2), and protein levels of Runx-2 and insulin-like growth factor-1 decreased in PTHrP+/− mice compared with WT mice. At four weeks PF, total collagen-positive bony callus areas, osteoblast number, ALP-positive areas, and type I collagen-positive areas all decreased in PTHrP+/− mice. At both two and four weeks PF, tartrate-resistant acid phosphatase–positive osteoclast number and surface decreased a little in PTHrP+/− mice. The study indicates that exogenous PTHrP provided by subcutaneous injection could redress impaired bone fracture healing, leading to mutation of activated PTHrP by influencing callus areas, endochondral bone formation, osteoblastic bone formation, and bone turnover. PMID:28178186

  9. Spontaneous calcaneal fracture in patients with diabetic foot ulcer: Four cases report and review of literature

    PubMed Central

    Evran, Mehtap; Sert, Murat; Tetiker, Tamer; Akkuş, Gamze; Biçer, Ömer Sunkar

    2016-01-01

    Spontaneous calcaneal fractures in diabetic patients without obvious trauma may occur, sometimes accompanying diabetic foot ulcers. In the current study we report four cases who were hospitalized for diabetic foot ulcer with concomitant calcaneal fractures. There were four diabetic patients (one type 1 and three type 2) who registered with diabetic foot ulcers with coexisting calcaneal fractures, all of which were classified as Type A according to Essex Lopresti Calcaneal Fracture Classification. Two of the patients with renal failure were in a routine dialysis program, as well as vascular compromise and osteomyelitis in all of the patients. The diabetic foot ulcer of the 61 years old osteoporotic female patient healed with local debridement, vacuum assisted closure and then epidermal growth factor while the calcaneal fracture was then followed by elastic bandage. In two patients could not prevent progression of diabetic foot ulcers and calcaneal fractures to consequent below-knee amputation. The only patient with type 1 diabetes mellitus improved with antibiotic therapy and split thickness skin grafting, while the calcaneal fracture did not heal. In the current study we aimed to emphasize the spontaneous calcaneal fractures as possible co-existing pathologies in patients with diabetic foot ulcers. After all the medical treatment, amputation below knee had to be performed in 2 patients. It should be noted that other accompanying conditions such as impaired peripheral circulation, osteomyelitis, chronic renal failure, and maybe osteoporosis is a challenge of the recovery of calcaneal fractures and accelerate the progress to amputation in diabetic patients. PMID:27458594

  10. Manuka Honey Exerts Antioxidant and Anti-Inflammatory Activities That Promote Healing of Acetic Acid-Induced Gastric Ulcer in Rats

    PubMed Central

    Almasaudi, Saad B.; Al-Hindi, Rashad R.; Abdel-dayem, Umama A.; Ali, Soad S.; Saleh, Rasha M.; Al Jaouni, Soad K.

    2017-01-01

    Gastric ulcers are a major problem worldwide with no effective treatment. The objective of this study was to evaluate the use of manuka honey in the treatment of acetic acid-induced chronic gastric ulcers in rats. Different groups of rats were treated with three different concentrations of honey. Stomachs were checked macroscopically for ulcerative lesions in the glandular mucosa and microscopically for histopathological alterations. Treatment with manuka honey significantly reduced the ulcer index and maintained the glycoprotein content. It also reduced the mucosal myeloperoxidase activity, lipid peroxidation (MDA), and the inflammatory cytokines (TNF-α, IL-1β, and IL-6) as compared to untreated control group. In addition, honey-treated groups showed significant increase in enzymatic (GPx and SOD) and nonenzymatic (GSH) antioxidants besides levels of the anti-inflammatory cytokine IL-10. Flow cytometry studies showed that treatment of animals with manuka honey has normalized cell cycle distribution and significantly lowered apoptosis in gastric mucosa. In conclusion, the results indicated that manuka honey is effective in the treatment of chronic ulcer and preservation of mucosal glycoproteins. Its effects are due to its antioxidant and anti-inflammatory properties that resulted in a significant reduction of the gastric mucosal MDA, TNF-α, IL-1β, and IL-6 and caused an elevation in IL-10 levels. PMID:28250794

  11. Ulcer pain in patients with venous leg ulcers related to antibiotic treatment and compression therapy.

    PubMed

    Akesson, Nina; Oien, Rut Frank; Forssell, Henrik; Fagerström, Cecilia

    2014-09-01

    The aim of this study was to compare venous leg ulcer patients with and without ulcer pain to see whether ulcer pain affected the use of antibiotic treatment and compression therapy throughout healing. A total of 431 patients with venous leg ulcers were included during the study period. Every patient was registered in a national quality registry for patients with hard-to-heal leg, foot, and pressure ulcers. A high incidence of ulcer pain (57%) was found when the patients entered the study. Patients with ulcer pain had been treated more extensively with antibiotics both before and during the study period. Throughout healing there was a significant reduction of antibiotic use among patients in the 'no pain' group, from 44% to 23% (P=0.008). There was no significant difference between the two groups concerning compression therapy (85% vs. 88%), but 12% of patients in the 'pain' group did not get their prescribed compression compared with 6% of patients in the 'no pain' group. The groups did not differ significantly in terms of ulcer duration, ulcer size or healing time. This study shows a high incidence of ulcer pain, confirming that pain has a great impact on patients with venous leg ulcers. Results further suggest that the presence of ulcer pain increases the prescription of antibiotics but does not affect the use of compression therapy. Several advantages were found from using a national quality registry. The registry is a valuable clinical tool showing the importance of accurate diagnosis and effective treatment.

  12. Hierarchically micro-patterned nanofibrous scaffolds with a nanosized bio-glass surface for accelerating wound healing

    NASA Astrophysics Data System (ADS)

    Xu, He; Lv, Fang; Zhang, Yali; Yi, Zhengfang; Ke, Qinfei; Wu, Chengtie; Liu, Mingyao; Chang, Jiang

    2015-11-01

    A composite scaffold with a controlled micro-pattern, nano-sized fiber matrix and surface-modified nanobioglass component was successfully prepared for skin wound healing by combining the patterning electrospinning with pulsed laser deposition strategies, and the hierarchical micro/nano structures and nano-sized bioglass in the scaffolds could synergistically improve the efficiency and re-epithelialization of wound healing.A composite scaffold with a controlled micro-pattern, nano-sized fiber matrix and surface-modified nanobioglass component was successfully prepared for skin wound healing by combining the patterning electrospinning with pulsed laser deposition strategies, and the hierarchical micro/nano structures and nano-sized bioglass in the scaffolds could synergistically improve the efficiency and re-epithelialization of wound healing. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04802h

  13. Ugh! Ulcers

    MedlinePlus

    ... Going to the Doctor Medicines for Ulcers Ulcer Prevention "If you kids don't stop yelling, you'll give me an ulcer!" "Don't worry so much. You'll give yourself an ulcer." Have you ever heard people talk like this about ulcers? It ...

  14. Protective Effect of Flos Lonicerae against Experimental Gastric Ulcers in Rats: Mechanisms of Antioxidant and Anti-Inflammatory Action

    PubMed Central

    Kang, Jung-Woo; Yun, Nari; Han, Hae-Jung; Kim, Jeom-Yong; Kim, Joo-Young; Lee, Sun-Mee

    2014-01-01

    Flos Lonicerae is one of the oldest and most commonly prescribed herbs in Eastern traditional medicine to treat various inflammatory diseases. In the present study, we investigated the effects of ethyl acetate fraction of Flos Lonicerae (GC-7101) on experimental gastric ulcer models and its mechanisms of action in gastric ulcer healing. The pharmacological activity of GC-7101 was investigated in rats on HCl/EtOH, indomethacin, water immersion restraint stress induced acute gastric ulcer, and acetic-acid-induced subchronic gastric ulcer. To determine its gastroprotective mechanisms, gastric wall mucus secretion, mucosal PGE2, mucosal NO content, nuclear translocation of NF-κB, mRNA expression of inflammatory cytokines, lipid peroxidation and glutathione content, and superoxide dismutase and catalase activities were measured. GC-7101 significantly attenuated development of acute gastric ulcer and accelerated the healing of acetic-acid-induced subchronic gastric ulcer. In HCl/EtOH-induced gastric ulcer, GC-7101 markedly enhanced gastric wall mucus content which was accompanied by increased mucosal PGE2 and NO production. Furthermore, treatment of GC-7101 exhibited anti-inflammatory and antioxidant activities as evidenced by decreased myeloperoxidase activity, NF-κB translocation, inflammatory cytokines mRNA expression, and lipid peroxidation and increased glutathione content and superoxide dismutase and catalase activities. These results demonstrated that GC-7101 possesses strong antiulcerogenic effect by modulating oxidative stress and proinflammatory mediators. PMID:25610477

  15. The Four-Herb Chinese Medicine Formula Tuo-Li-Xiao-Du-San Accelerates Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats through Reducing Inflammation and Increasing Angiogenesis.

    PubMed

    Zhang, Xiao-Na; Ma, Ze-Jun; Wang, Ying; Li, Yu-Zhu; Sun, Bei; Guo, Xin; Pan, Cong-Qing; Chen, Li-Ming

    2016-01-01

    Impaired wound healing in diabetic patients is a serious complication that often leads to amputation or even death with limited effective treatments. Tuo-Li-Xiao-Du-San (TLXDS), a traditional Chinese medicine formula for refractory wounds, has been prescribed for nearly 400 years in China and shows good efficacy in promoting healing. In this study, we explored the effect of TLXDS on healing of diabetic wounds and investigated underlying mechanisms. Four weeks after intravenous injection of streptozotocin, two full-thickness excisional wounds were created with a 10 mm diameter sterile biopsy punch on the back of rats. The ethanol extract of TLXDS was given once daily by oral gavage. Wound area, histological change, inflammation, angiogenesis, and collagen synthesis were evaluated. TLXDS treatment significantly accelerated healing of diabetic rats and improved the healing quality. These effects were associated with reduced neutrophil infiltration and macrophage accumulation, enhanced angiogenesis, and increased collagen deposition. This study shows that TLXDS improves diabetes-impaired wound healing.

  16. Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol-chitosan hydrogel containing honey bee venom in diabetic rats.

    PubMed

    Amin, Mohamed A; Abdel-Raheem, Ihab T

    2014-08-01

    Diabetes is one of the leading causes of impaired wound healing. The objective of this study was to develop a bee venom-loaded wound dressing with an enhanced healing and anti-inflammatory effects to be examined in diabetic rats. Different preparations of polyvinyl alcohol (PVA), chitosan (Chit) hydrogel matrix-based wound dressing containing bee venom (BV) were developed using freeze-thawing method. The mechanical properties such as gel fraction, swelling ratio, tensile strength, percentage of elongation and surface pH were determined. The pharmacological activities including wound healing and anti-inflammatory effects in addition to primary skin irritation and microbial penetration tests were evaluated. Moreover, hydroxyproline, glutathione and IL-6 levels were measured in the wound tissues of diabetic rats. The bee venom-loaded wound dressing composed of 10 % PVA, 0.6 % Chit and 4 % BV was more swellable, flexible and elastic than other formulations. Pharmacologically, the bee venom-loaded wound dressing that has the same previous composition showed accelerated healing of wounds made in diabetic rats compared to the control. Moreover, this bee venom-loaded wound dressing exhibited anti-inflammatory effect that is comparable to that of diclofenac gel, the standard anti-inflammatory drug. Simultaneously, wound tissues covered with this preparation displayed higher hydroxyproline and glutathione levels and lower IL-6 levels compared to control. Thus, the bee venom-loaded hydrogel composed of 10 % PVA, 0.6 % Chit and 4 % BV is a promising wound dressing with excellent forming and enhanced wound healing as well as anti-inflammatory activities.

  17. Enhanced growth of endothelial precursor cells on PCG-matrix facilitates accelerated, fibrosis-free, wound healing: a diabetic mouse model.

    PubMed

    Kanitkar, Meghana; Jaiswal, Amit; Deshpande, Rucha; Bellare, Jayesh; Kale, Vaijayanti P

    2013-01-01

    Diabetes mellitus (DM)-induced endothelial progenitor cell (EPC) dysfunction causes impaired wound healing, which can be rescued by delivery of large numbers of 'normal' EPCs onto such wounds. The principal challenges herein are (a) the high number of EPCs required and (b) their sustained delivery onto the wounds. Most of the currently available scaffolds either serve as passive devices for cellular delivery or allow adherence and proliferation, but not both. This clearly indicates that matrices possessing both attributes are 'the need of the day' for efficient healing of diabetic wounds. Therefore, we developed a system that not only allows selective enrichment and expansion of EPCs, but also efficiently delivers them onto the wounds. Murine bone marrow-derived mononuclear cells (MNCs) were seeded onto a PolyCaprolactone-Gelatin (PCG) nano-fiber matrix that offers a combined advantage of strength, biocompatibility wettability; and cultured them in EGM2 to allow EPC growth. The efficacy of the PCG matrix in supporting the EPC growth and delivery was assessed by various in vitro parameters. Its efficacy in diabetic wound healing was assessed by a topical application of the PCG-EPCs onto diabetic wounds. The PCG matrix promoted a high-level attachment of EPCs and enhanced their growth, colony formation, and proliferation without compromising their viability as compared to Poly L-lactic acid (PLLA) and Vitronectin (VN), the matrix and non-matrix controls respectively. The PCG-matrix also allowed a sustained chemotactic migration of EPCs in vitro. The matrix-effected sustained delivery of EPCs onto the diabetic wounds resulted in an enhanced fibrosis-free wound healing as compared to the controls. Our data, thus, highlight the novel therapeutic potential of PCG-EPCs as a combined 'growth and delivery system' to achieve an accelerated fibrosis-free healing of dermal lesions, including diabetic wounds.

  18. Connective Tissue Ulcers

    PubMed Central

    Dabiri, Ganary; Falanga, Vincent

    2013-01-01

    Connective tissue disorders (CTD), which are often also termed collagen vascular diseases, include a number of related inflammatory conditions. Some of these diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), localized scleroderma (morphea variants localized to the skin), Sjogren’s syndrome, dermatomyositis, polymyositis, and mixed connective tissue disease. In addition to the systemic manifestations of these diseases, there are a number of cutaneous features that make these conditions recognizable on physical exam. Lower extremity ulcers and digital ulcers are an infrequent but disabling complication of long-standing connective tissue disease. The exact frequency with which these ulcers occur is not known, and the cause of the ulcerations is often multifactorial. Moreover, a challenging component of CTD ulcerations is that there are still no established guidelines for their diagnosis and treatment. The morbidity associated with these ulcerations and their underlying conditions is very substantial. Indeed, these less common but intractable ulcers represent a major medical and economic problem for patients, physicians and nurses, and even well organized multidisciplinary wound healing centers. PMID:23756459

  19. Hyperhomocysteinaemia and chronic venous ulcers.

    PubMed

    de Franciscis, Stefano; De Sarro, Giovambattista; Longo, Paola; Buffone, Gianluca; Molinari, Vincenzo; Stillitano, Domenico M; Gallelli, Luca; Serra, Raffaele

    2015-02-01

    Chronic venous ulceration (CVU) is the major cause of chronic wounds of lower extremities, and is a part of the complex of chronic venous disease. Previous studies have hypothesised that several thrombophilic factors, such as hyperhomocysteinaemia (HHcy), may be associated with chronic venous ulcers. In this study, we evaluated the prevalence of HHcy in patients with venous leg ulcers and the effect of folic acid therapy on wound healing. Eighty-seven patients with venous leg ulcers were enrolled in this study to calculate the prevalence of HHcy in this population. All patients underwent basic treatment for venous ulcer (compression therapy ± surgical procedures). Patients with HHcy (group A) received basic treatment and administered folic acid (1·2 mg/day for 12 months) and patients without HHcy (group B) received only basic treatment. Healing was assessed by means of computerised planimetry analysis. The prevalence of HHcy among patients with chronic venous ulcer enrolled in this study was 62·06%. Healing rate was significantly higher (P < 0·05) in group A patients (78·75%) compared with group B patients (63·33%). This study suggests a close association, statistically significant, between HHcy and CVU. Homocysteine-lowering therapy with folic acid seems to expedite wound healing. Despite these aspects, the exact molecular mechanisms between homocysteine and CVU have not been clearly defined and further studies are needed.

  20. Treatment of Diabetic Foot Ulcers through Systemic Effects of Extremely Low Frequency Electromagnetic Fields

    NASA Astrophysics Data System (ADS)

    Trejo-Núñez, A. D.; Pérez-Chávez, F.; García-Sánchez, C.; Serrano-Luna, G.; Cañendo-Dorantes, L.

    2008-08-01

    This study was designed to, investigate the healing effects of extremely low frequency electromagnetic fields (ELF-EMF) on diabetic foot ulcers and test two different exposure systems aimed at reducing the ELF-EMF exposure time of patients. In the first system the ELF-EMF were applied to the arm where only 3% of the total blood volume/min circulates at any given time. In the second system the ELF-EMF were applied to the thorax where more than 100% of the total blood volume/minute circulates at any given time. Twenty-six diabetic patients, with superficial neuropathic ulcers unresponsive to medical treatment were included in this preliminary report. In the first group (17 patients), the arm was exposed two hours twice a week to a extremely low frequency electromagnetic field of 0.45-0.9 mTrms, 120 Hz generated inside a solenoid coil of 10.1 cm by 20.5 cm long. In the second group the thorax of 7 patients was exposed 25 minutes twice a week to an electromagnetic field of 0.4-0.85 mTrms, 120 Hz generated in the center of a squared quasi-Helmholtz coil 52 cm by side. One patient was assigned to a placebo configuration of each exposure system with identical appearance as the active equipment but without magnetic field. Patients with deep ulcers, infected ulcers, cancer, or auto-immune disease were excluded. These preliminary results showed that the two exposure systems accelerate the healing process of neuropathic ulcers. Complete healing of the ulcer had a median duration of 90 days in both exposure systems. Therefore thorax exposure where more blood is exposed to ELF-EMF per unit of time was able to reduce 4.8 times the patient treatment time. In those patients assigned to the placebo equipment no healing effects were observed. This study will continue with a parallel, double blind placebo controlled protocol.

  1. Durability of healing from spray-applied cell therapy with human allogeneic fibroblasts and keratinocytes for the treatment of chronic venous leg ulcers: a 6-month follow-up.

    PubMed

    Kirsner, Robert S; Marston, William A; Snyder, Robert J; Lee, Tommy D; Cargill, D Innes; Zhang, Yuxin; Dickerson, Jaime E; Slade, Herbert B

    2013-01-01

    Patients who participated in a Phase 2 trial of HP802-247 for venous leg ulcers were invited to participate in this 24-week follow-up study to assess the durability of healing, document additional ulcer closures, and evaluate posttreatment safety. Consent was given by 90% (206/228), with 80% (183/228) completing all visits. Blinding was retained from the previous trial in which subjects had been randomized to vehicle or one of four cell therapy regimens. Visits were every 8 weeks. Among the 183 subjects, 43% (21/49) previously treated with cells and entering follow-up with an open wound achieved closure, compared with 35% (7/20) previously treated with vehicle, while 10% (11/106) and 17% (3/18), respectively, experienced reopening of a previously closed wound. Subjects previously treated with cells closed more open wounds than those previously treated with vehicle (OR 1.39, 95% CI 0.47-4.10; p = 0.739), and less subjects with a previously closed wound reopened (OR 0.65, CI 0.16-2.60; p = 0.821); however, these findings were not statistically significant. At the final visit, the difference in proportion of subjects with wounds closed continued to favor the best dose from the prior trial (83% closed vs. 58%, delta 25%). Follow-up beyond 12 weeks is necessary to evaluate the full benefit of this therapy, as treatment with cells may provide stimulus toward healing that persists for up to several weeks following the last application. The results show that the greater proportional benefit achieved by HP802-247 relative to standard care after 12 weeks of treatment persists over a meaningful timeframe.

  2. Venous ulcer: epidemiology, physiopathology, diagnosis and treatment.

    PubMed

    Abbade, Luciana P Fernandes; Lastória, Sidnei

    2005-06-01

    This review discusses the epidemiology, pathogenesis, diagnosis and current therapeutic options for venous ulcer. Venous ulcer is a severe clinical manifestation of chronic venous insufficiency (CVI). It is responsible for about 70% of chronic ulcers of the lower limbs. The high prevalence of venous ulcer has a significant socioeconomic impact in terms of medical care, days off work and reduced quality of life. Long-term therapeutics are needed to heal venous ulcers and recurrence is quite common, ranging from 54 to 78%. Thrombophlebitis and trauma with long-term immobilization predisposing to deep venous thrombosis are important risk factors for CVI and venous ulcer. The most recent theories about pathogenesis of venous ulcer have associated it with microcirculatory abnormalities and generation of an inflammatory response. Management of venous leg ulcers is based on understanding the pathogenesis. In recent years novel therapeutic approaches for venous ulcers have offered valuable tools for the management of patients with this disorder.

  3. Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Kant, Vinay; Gopal, Anu; Pathak, Nitya N; Kumar, Pawan; Tandan, Surendra K; Kumar, Dinesh

    2014-06-01

    Prolonged inflammation and increased oxidative stress impairs healing in diabetics and application of curcumin, a well known antioxidant and anti-inflammatory agent, could be an important strategy in improving impaired healing in diabetics. So, the present study was conducted to evaluate the cutaneous wound healing potential of topically applied curcumin in diabetic rats. Open excision skin wound was created in streptozotocin induced diabetic rats and wounded rats were divided into three groups; i) control, ii) gel-treated and iii) curcumin-treated. Pluronic F-127 gel (25%) and curcumin (0.3%) in pluronic gel were topically applied in the gel- and curcumin-treated groups, respectively, once daily for 19 days. Curcumin application increased the wound contraction and decreased the expressions of inflammatory cytokines/enzymes i.e. tumor necrosis factor-alpha, interleukin (IL)-1beta and matrix metalloproteinase-9. Curcumin also increased the levels of anti-inflammatory cytokine i.e. IL-10 and antioxidant enzymes i.e. superoxide dismutase, catalase and glutathione peroxidase. Histopathologically, the curcumin-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation and collagen deposition, and wounds were covered by thick regenerated epithelial layer. These findings reveal that the anti-inflammatory and antioxidant potential of curcumin caused faster and better wound healing in diabetic rats and curcumin could be an additional novel therapeutic agent in the management of impaired wound healing in diabetics.

  4. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology.

  5. Persistent nicorandil induced oral ulceration

    PubMed Central

    Healy, C M; Smyth, Y; Flint, S R

    2004-01-01

    Four patients with nicorandil induced ulceration are described, and the literature on the subject is reviewed. Nicorandil induced ulcers are very painful and distressing for patients. Clinically they appear as large, deep, persistent ulcers that have punched out edges. They are poorly responsive to topical steroids and usually require alteration of nicorandil treatment. The ulceration tends to occur at high doses of nicorandil and all four cases reported here were on doses of 40 mg per day or greater. In these situations reduction of nicorandil dose may be sufficient to promote ulcer healing and prevent further recurrence. However, nicorandil induced ulcers have been reported at doses as low as 10 mg daily and complete cessation of nicorandil may be required. PMID:15201264

  6. Application of Autologous Derived-Platelet Rich Plasma Gel in the Treatment of Chronic Wound Ulcer: Diabetic Foot Ulcer

    PubMed Central

    Akingboye, Akinfemi Ayobami; Giddins, Stephen; Gamston, Philip; Tucker, Arthur; Navsaria, Harshad; Kyriakides, Constantions

    2010-01-01

    Abstract: The treatment of chronic wounds remains problematic, despite new insight into the cellular and molecular basis of wound healing. Although the aetio-pathogenesis of chronic wounds is said to be multi-factorial, it is evident from literature that effective and adequate wound debridement has produced the most consistent effect in chronic wound treatment. There is a growing body of evidence that suggests that wound healing in chronic diabetic foot ulcers is growth factor dependent and that the therapeutic delivery of these growth factors to wounds topically, has the potential ability to accelerate wound healing in conjunction with conventional wound care. Autologous derived platelet concentrate is activated to release growth factors that are stored in the platelet granules. These secretory proteins include cytokines and growth factors such as transforming growth factor–beta, vascular endothelia growth factor, platelet derived growth factor, and so on. The enhancement of soft tissue healing by the application of autologous derived platelet rich plasma gel (APG) is supported by basic science and some clinical studies. This review article will attempt to provide a concise report of current concepts on the use of APG in treating chronic ulcers. PMID:20437788

  7. To evaluate the safety and efficiency of low level laser therapy (LLLT) in treating decubitus ulcers: a review

    NASA Astrophysics Data System (ADS)

    Ahmed, Ambereen

    2015-03-01

    Introduction: Pressure sores (decubitus ulcer) are a serious problem in health care management, especially for middleaged to older people who are bed-ridden. Although preventative measures are used, the condition remains common and development of novel, improved treatment methods are desirable. This article reviews the application of laser-based methods, previously shown to be effective in accelerating wound-healing in animal models and in the treatment of decubitus ulcers in humans. Methods: About 23 scientific articles on the effect of low level laser therapy (LLLT) on wound healing in animals and humans from 2000-2014 were reviewed. Additionally, results of several randomized controlled trials (RCTs) were reviewed, and compared with other treatment methods available. Results: Whilst carefully controlled, laboratory-based animal studies indicated that LLLT can reduce healing time for several types of injuries, however similar studies in humans failed to demonstrate consistent beneficial effects in the clinical setting. An acceleration of decubitus ulcer healing has been occasionally found, although limited to certain wavelengths and sometimes only in combination with other types of therapies. Indeed, some of the clinical articles indicated that certain laser wavelengths can have detrimental effects on time of healing. Conclusions: To date, there remains no convincing evidence that LLLT has consistent medical benefit in treating decubitus ulcers. Caution should be applied when considering LLLT since only certain wavelengths utilized have shown beneficial effects. It is concluded that, more RCTs are needed since, there is no clinical justification for LLLT, alone or in combination with other methods, in treating decubitus ulcers.

  8. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Cheng, Poh-Guat; Sabaratnam, Vikineswary; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats. PMID:24348715

  9. Polysaccharides-Rich Extract of Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst Accelerates Wound Healing in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Cheng, Poh-Guat; Phan, Chia-Wei; Sabaratnam, Vikineswary; Abdullah, Noorlidah; Abdulla, Mahmood Ameen; Kuppusamy, Umah Rani

    2013-01-01

    Ganoderma lucidum (M.A. Curtis:Fr.) P. Karst is a popular medicinal mushroom. Scientific reports had shown that the wound healing effects of G. lucidum were partly attributed to its rich polysaccharides. However, little attention has been paid to its potential effects on wounds associated with diabetes mellitus. In this study, we evaluated the wound healing activity of the hot aqueous extract of G. lucidum in streptozotocin-induced diabetic rats. The extract of G. lucidum was standardised based on chemical contents (w/w) of total polysaccharides (25.1%), ganoderic acid A (0.45%), and adenosine (0.069%). Six groups of six rats were experimentally wounded in the posterior neck region. Intrasite gel was used as a positive control and aqueous cream as the placebo. Topical application with 10% (w/w) of mushroom extract-incorporated aqueous cream was more effective than that with Intrasite gel in terms of wound closure. The antioxidant activity in serum of rats treated with aqueous extract of G. lucidum was significantly higher; whereas the oxidative protein products and lipid damage were lower when compared to those of the controls. These findings strongly support the beneficial effects of standardised aqueous extract of G. lucidum in accelerating wound healing in streptozotocin-induced diabetic rats.

  10. Demineralized Bone Matrix Add-On for Acceleration of Bone Healing in Atypical Subtrochanteric Femoral Fracture: A Consecutive Case-Control Study

    PubMed Central

    Kulachote, Noratep; Sirisreetreerux, Norachart; Chanplakorn, Pongsthorn; Fuangfa, Praman; Suphachatwong, Chanyut; Wajanavisit, Wiwat

    2016-01-01

    Background. Delayed union and nonunion are common complications in atypical femoral fractures (AFFs) despite having good fracture fixation. Demineralized bone matrix (DBM) is a successfully proven method for enhancing fracture healing of the long bone fracture and nonunion and should be used in AFFs. This study aimed to compare the outcome after subtrochanteric AFFs (ST-AFFs) fixation with and without DBM. Materials and Methods. A prospective study was conducted on 9 ST-AFFs patients using DBM (DBM group) during 2013-2014 and compared with a retrospective consecutive case series of ST-AFFs patients treated without DBM (2010–2012) (NDBM group, 9 patients). All patients were treated with the same standard guideline and followed up until fractures completely united. Postoperative outcomes were then compared. Results. DBM group showed a significant shorter healing time than NDBM group (28.1 ± 14.4 versus 57.9 ± 36.8 weeks, p = 0.04). Delayed union was found in 4 patients (44%) in DBM group compared with 7 patients (78%) in NDBM group (p > 0.05). No statistical difference of nonunion was demonstrated between both groups (DBM = 1 and NDBM = 2, p > 0.05). Neither postoperative infection nor severe local tissue reaction was found. Conclusions. DBM is safe and effective for accelerating the fracture healing in ST-AFFx and possibly reduces nonunion after fracture fixation. Trial registration number is TCTR20151021001. PMID:27022610

  11. Collagen Hydrogel Scaffold and Fibroblast Growth Factor-2 Accelerate Periodontal Healing of Class II Furcation Defects in Dog

    PubMed Central

    Momose, Takehito; Miyaji, Hirofumi; Kato, Akihito; Ogawa, Kosuke; Yoshida, Takashi; Nishida, Erika; Murakami, Syusuke; Kosen, Yuta; Sugaya, Tsutomu; Kawanami, Masamitsu

    2016-01-01

    Objective: Collagen hydrogel scaffold exhibits bio-safe properties and facilitates periodontal wound healing. However, regenerated tissue volume is insufficient. Fibroblast growth factor-2 (FGF2) up-regulates cell behaviors and subsequent wound healing. We evaluated whether periodontal wound healing is promoted by application of collagen hydrogel scaffold in combination with FGF2 in furcation defects in beagle dogs. Methods: Collagen hydrogel was fabricated from bovine type I collagen with an ascorbate-copper ion cross-linking system. Collagen hydrogel was mingled with FGF2 and injected into sponge-form collagen. Subsequently, FGF2 (50 µg)/collagen hydrogel scaffold and collagen hydrogel scaffold alone were implanted into class II furcation defects in dogs. In addition, no implantation was performed as a control. Histometric parameters were assessed at 10 days and 4 weeks after surgery. Result: FGF2 application to scaffold promoted considerable cell and tissue ingrowth containing numerous cells and blood vessel-like structure at day 10. At 4 weeks, reconstruction of alveolar bone was stimulated by implantation of scaffold loaded with FGF2. Furthermore, periodontal attachment, consisting of cementum-like tissue, periodontal ligament-like tissue and Sharpey’s fibers, was also repaired, indicating that FGF2-loaded scaffold guided self-assembly and then re-established the function of periodontal organs. Aberrant healing, such as ankylosis and root resorption, was not observed. Conclusion: FGF2-loaded collagen hydrogel scaffold possessed excellent biocompatibility and strongly promoted periodontal tissue engineering, including periodontal attachment re-organization. PMID:27583044

  12. Quercetin accelerated cutaneous wound healing in rats by increasing levels of VEGF and TGF-β1.

    PubMed

    Gopalakrishnan, A; Ram, M; Kumawat, S; Tandan, Sk; Kumar, D

    2016-03-01

    Quercetin (3,3',4',5,7-penthydroxyflavone)-induced biological effects have been beneficial in various disease conditions. In this study, wound healing potential of quercetin was evaluated in a time-dependent manner in open excision wounds in adult Wistar rats. Experimentally-wounded rats were divided into two groups namely, control and quercetin-treated. Wounds were photographed and the area was measured on the day of wounding and on days 3, 7, 11 and 14 post-wounding. The granulation/healing tissue was collected on days 3, 7, 11 and 14 post-wounding for cytokine/growth factor measurements and histology/immunohistochemistry studies. There was significant time-dependent increase in wound closure in quercetin-treated rats. Vascular endothelial growth factor and transforming growth factor-β1 expressions were significantly upregulated in quercetin-treated rats, whereas tumor necrosis factor-α level was markedly reduced. Interleukin- 10 levels and CD31 stained vessels were markedly higher on day 3 and on day 7, respectively, in quercetin-treated rats. In H & E stained sections, quercetin-treated group showed less inflammatory cells, more fibroblast proliferation, increased microvessel density, better reepithelialization and more regular collagen deposition, as compared to control. The results suggest that topical application of quercetin promotes wound healing by effectively modulating the cytokines, growth factors and cells involved in inflammatory and proliferative phases of healing.

  13. Intra-lesional injections of recombinant human epidermal growth factor promote granulation and healing in advanced diabetic foot ulcers: multicenter, randomised, placebo-controlled, double-blind study.

    PubMed

    Fernández-Montequín, José I; Valenzuela-Silva, Carmen M; Díaz, Odalys González; Savigne, William; Sancho-Soutelo, Natasha; Rivero-Fernández, Fidel; Sánchez-Penton, Pablo; Morejón-Vega, Lourdes; Artaza-Sanz, Heriberto; García-Herrera, Arístides; González-Benavides, Cecilio; Hernández-Cañete, Carlos M; Vázquez-Proenza, Alberto; Berlanga-Acosta, Jorge; López-Saura, Pedro A

    2009-12-01

    A multicenter, double-blind, placebo-controlled trial was carried out to evaluate the intra-lesional infiltration of recombinant epidermal growth factor (EGF) in Wagner's grade 3 or 4 diabetic foot ulcers (DFUs). Subjects (149) were randomised to receive EGF (75 or 25 microg) or placebo, three times per week for 8 weeks and standard good wound care. The main endpoint was granulation tissue covering > or = 50% of the ulcer at 2 weeks. It was achieved by 19/48 controls versus 44/53 in the 75 microg group [odds ratio (OR): 7.5; 95% confidence interval (CI): 2.9-18.9] and 34/48 in the 25 microg group (OR: 3.7; 1.6-8.7). Secondary outcome variables such as end-of-treatment complete granulation response (28/48 controls, 46/53 with 75 microg and 34/48 with 25 microg EGF), time-to-complete response (controls: 5 weeks; both EGF dose groups: 3 weeks), and wound closure after follow-up (25/48 controls, 40/53 with 75 microg and 25/48 with 25 microg EGF) were also treatment dependent. Multivariate analyses yielded that they were significantly enhanced by 75 microg EGF treatment and neuropathic versus ischemic ulcers. Most adverse events were mild and no drug-related severe adverse reactions were reported. It was concluded that recombinant human EGF (rhEGF) local injections offer a favourable risk-benefit balance in patients with advanced DFU.

  14. Hard to heal pressure ulcers (stage III-IV): efficacy of injected activated macrophage suspension (AMS) as compared with standard of care (SOC) treatment controlled trial.

    PubMed

    Zuloff-Shani, Adi; Adunsky, Abraham; Even-Zahav, Aviva; Semo, Haim; Orenstein, Arie; Tamir, Jeremy; Regev, Eli; Shinar, Eilat; Danon, David

    2010-01-01

    The objective of this study was to compare local injections of AMS with SOC treatments for stage III and IV pressure ulcers in elderly patients. It was designed as historically prospective 2-arms non-parallel open controlled trial, and conducted in a department of geriatric medicine and rehabilitation of a university affiliated tertiary hospital. We studied 100 consecutive elderly patients with a total of 216 stage III or IV pressure ulcers, 66 patients were assigned to the AMS group and had their wounds injected, while 38 patients were assigned to the SOC group. Primary outcome was rate of complete wound closure. Time to complete wound closure and 1-year mortality served as secondary outcomes. Statistical analyses were performed at both patient and wound levels. Percentage of completely closed wounds (wound level and patient level) were significantly better (p<0.001/p<0.001, respectively) in all patients in favor of AMS, as well as in the subset of diabetic patients (p<0.001/p<0.001). Similarly, AMS proved significantly better for the subset of those with leg ulcers and with baseline wounds ≤15 cm(2), compared with SOC. There were no statistically significant differences with regard to time to complete closure or 1-year mortality rates in the two groups. It is concluded that there is a significant difference in favor of stage III and IV wound closure rates by AMS, as compared with SOC treatments.

  15. The Pseudomonas aeruginosa quorum-sensing signal N-(3-oxododecanoyl) homoserine lactone can accelerate cutaneous wound healing through myofibroblast differentiation in rats.

    PubMed

    Nakagami, Gojiro; Minematsu, Takeo; Asada, Mayumi; Nagase, Takashi; Akase, Tomoko; Huang, Lijuan; Morohoshi, Tomohiro; Ikeda, Tsukasa; Ohta, Yasunori; Sanada, Hiromi

    2011-07-01

    Quorum sensing is a cell density-dependent gene regulation system in bacteria. N-(3-oxododecanoyl) homoserine lactone (3-oxo-C12-HSL) is used in the las quorum-sensing system in Pseudomonas aeruginosa, which is an opportunistic pathogen that causes many human diseases. Although many studies have investigated the sole effects of quorum sensing on several types of mammalian cells, including lung cells, little is known about the effects of quorum sensing on the cells associated with wound healing. To better understand the mechanism of bacterial wound infection, we investigated the effects of 3-oxo-C12-HSL on cells using a rat full-thickness wound-healing model. We found that the wound contraction was significantly increased at 24 h after the administration of 3-oxo-C12-HSL to the surface of granulation tissue. Differentiation of fibroblasts to myofibroblasts was induced in the in vivo wound-healing model and was confirmed in vitro using the rat fibroblastic cell line Rat-1. Cyclooxygenase (Cox)-2 expression was also induced in Rat-1 cells by 3-oxo-C12-HSL. This finding suggested that Cox-2 upregulation may be related to the inflammatory findings in the histological examinations, in which infiltrating polymorphonuclear neutrophils were observed at the wound site. Taken together, these results imply that mammals have a potential defense system against invading pathogens by responding to the presence of 3-oxo-C12-HSL and inducing the differentiation of fibroblasts to myofibroblasts as well as inflammation for accelerating wound healing.

  16. Comparison of laser and diode sources for acceleration of in vitro wound healing by low-level light therapy.

    PubMed

    Spitler, Ryan; Berns, Michael W

    2014-03-01

    Low-level light therapy has been shown to improve in vitro wound healing. However, well-defined parameters of different light sources for this therapy are lacking. The goal of this study was (1) to determine if the wavelengths tested are effective for in vitro wound healing and (2) to compare a laser and a light-emitting diode (LED) source at similar wavelengths. We show four wavelengths, delivered by either a laser or LED array, improved in vitro wound healing in A549, U2OS, and PtK2 cells. Improved wound healing occurred through increased cell migration demonstrated through scratch wound and transwell assays. Cell proliferation was tested by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-car-boxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay and was found generally not to be involved in the wound healing process. The laser and LED sources were found to be comparable when equal doses of light were applied. The biological response measured was similar in most cases. We conclude that the laser at 652 (5.57  mW/cm2, 10.02  J/cm2) and 806 nm (1.30  mW/cm2, 2.334  J/cm2) (full bandwidth 5 nm), and LED at 637 (5.57  mW/cm2, 10.02  J/cm2) and 901 nm (1.30  mW/cm2, 2.334  J/cm2) (full bandwidth 17 and 69 nm respectively) induce comparable levels of cell migration and wound closure.

  17. Neuropathic ulcers of the foot.

    PubMed

    Lang-Stevenson, A I; Sharrard, W J; Betts, R P; Duckworth, T

    1985-05-01

    We report a prospective study of the causes and treatment of 26 long-standing neuropathic ulcers of the foot in 21 patients. The most important causal factor, well illustrated by pressure studies, was the presence of a dynamic or static deformity leading to local areas of peak pressure on insensitive skin. All but one of the 26 ulcers had healed after an average of 10 weeks of treatment in a light, skin-tight plaster cast, with the prohibition of weight-bearing. Recurrent ulceration was prevented in all but one foot by early operation to correct the causative deformity; this was performed after the ulcer had healed and before allowing weight-bearing on the limb. Pressure studies after operation confirmed that pressure points had been relieved.

  18. Involvement of cyclooxygenase-1 and cyclooxygenase-2 activity in the therapeutic effect of ghrelin in the course of ethanol-induced gastric ulcers in rats.

    PubMed

    Warzecha, Z; Ceranowicz, P; Dembinski, M; Cieszkowski, J; Ginter, G; Ptak-Belowska, A; Dembinski, A

    2014-02-01

    Previous studies have shown that treatment with ghrelin exhibits protective and therapeutic effects in the gut. Aim of our present investigation was to examine the influence of ghrelin administration on the healing of ethanol-induced gastric ulcers and determine the role of cyclooxygenase-1 and cyclooxygenase-2 in this effect. Our studies were performed on male Wistar rats. Gastric ulcers were induced by intragastric administration of 75% ethanol. Ghrelin alone or in combination with cyclooxygenase inhibitors was administered twice, 1 and 13 hours after ethanol application. Cyclooxygenase-1 (COX-1) inhibitor (SC-560, 10 mg/kg/dose) or COX-2 inhibitor (celecoxib, 10 mg/kg/dose) were given 30 min prior to ghrelin. Twelve or 24 hours after administration of ethanol, rats were anesthetized and experiments were terminated. The study revealed that administration of ethanol induced gastric ulcers in all animals and this effect was accompanied by the reduction in gastric blood flow and mucosal DNA synthesis. Moreover induction of gastric ulcer by ethanol significantly increased mucosal expression of mRNA for COX-2, IL-1β and TNF-α. Treatment with ghrelin significantly accelerated gastric ulcer healing. Therapeutic effect of ghrelin was associated with significant reversion of the ulcer-evoked decrease in mucosal blood flow and DNA synthesis. Ghrelin administration also caused the reduction in mucosal expression of mRNA for IL-1β and TNF-α. Addition of SC-560 slightly reduced the therapeutic effect of ghrelin in the healing of ethanol-induced ulcer and the ulcer area in rats treated SC-560 plus ghrelin was significantly smaller than that observed in rats treated with saline or SC-560 alone. Pretreatment with celecoxib, a COX-2 inhibitor, abolished therapeutic effect of ghrelin. We concluded that treatment with ghrelin increases healing rate of gastric ulcers evoked by ethanol and this effect is related to improvement in mucosal blood flow, an increase in mucosal cell

  19. Randomised crossover trial of tripotassium dicitrato bismuthate versus high dose cimetidine for duodenal ulcers resistant to standard dose of cimetidine.

    PubMed

    Lam, S K; Lee, N W; Koo, J; Hui, W M; Fok, K H; Ng, M

    1984-07-01

    Of 212 patients with duodenal ulcer treated with four weeks of one gram daily cimetidine, 25 had ulcers which underwent no reduction in size despite treatment. The effects of tripotassium dicitrato bismuthate (TDB) tablet four times a day or cimetidine 1.6 g daily on the healing of these cimetidine resistant ulcers were compared in a randomised crossover trial. Ten of 12 patients on tripotassium dicitrato bismuthate and five of 13 patients on high dose cimetidine had complete healing (p less than 0.02). On crossing over, seven of the eight ulcers not healed by high dose cimetidine completely healed with TDB in another four weeks, and one of the two ulcers not healed by TDB healed with high dose cimetidine. Overall, TDB healed 85% of cimetidine resistant ulcers, whereas high dose cimetidine healed 40% (p less than 0.006). Tripotassium dicitrato bismuthate is recommended for cimetidine resistant duodenal ulcers.

  20. Local release of pioglitazone (a peroxisome proliferator-activated receptor γ agonist) accelerates proliferation and remodeling phases of wound healing.

    PubMed

    Sakai, Shigeki; Sato, Keisuke; Tabata, Yasuhiko; Kishi, Kazuo

    2016-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily known for its anti-inflammatory and macrophage differentiation effects, as well as its ability to promote fat cell differentiation and reduce insulin resistance. Pioglitazone (Pio) is a PPARγ agonist used clinically as an anti-diabetic agent for improving insulin sensitivity in patients with diabetes. The objective of this study was to develop a drug delivery system (DDS) for the local release of Pio to promote wound healing. Pio of low aqueous solubility was water-solubilized by micelles formed from gelatin grafted with L-lactic acid oligomers, and incorporated into a biodegradable gelatin hydrogel. An 8-mm punch biopsy tool was used to prepare two skin wounds on either side of the midline of 8-week-old mice. Wounds were treated by the hydrogels with (Pio-hydrogel group) or without (control group) Pio, and the wound area were observed 1, 4, 7, and 14 days after treatment. In addition, a protein assay and immunohistological stain were performed to determine the effects of the Pio-hydrogel on inflammation and macrophage differentiation. The Pio-hydrogels promote wound healing. Moreover, Western blotting analysis demonstrated that treatment with Pio-hydrogels resulted in decreased levels of the cytokines MIP-2 and TGF-β, and increased levels of glucose-regulating adiponectin. It is concluded that Pio-incorporated hydrogels promote the proliferation and remodeling phases of wound healing, and may prove to be effective as wound dressings.

  1. Effect of laser (λ 660 nm) and LED (λ 630 nm) photobiomodulation on formocresol-induced oral ulcers: a clinical and histological study on rodents.

    PubMed

    de Carvalho, Fabiola Bastos; Andrade, Aline Silva; Rasquin, Luis Cardoso; de Castro, Isabele Vieira; Cangussu, Maria Cristina Teixeira; Pinheiro, Antônio Luiz Barbosa; dos Santos, Jean Nunes

    2015-01-01

    The aim of this study was to evaluate, clinically and histologically, the influence of laser and LED photobiomodulation in the healing of formocresol-induced oral mucosa ulcers of rats. We used 60 Wistar rats in which oral ulcers were induced on the gingiva of the lower incisors. Forty-eight hours after inducing the ulcers, the animals were divided into three groups: laser, LED, and untreated. Animals from the laser group received irradiation with GaAlAs, 660 nm, CW, 40 mW, φ 4 mm(2), 4.8 J/cm(2). Animals from the LED group received irradiation with InGaAIP, 630 nm, 150 mW, 4.8 J/cm(2), 0.8 cm spot. Forty-eight hours after oral ulcer induction, both irradiations were applied in a punctuate manner in the center of the ulcer at 48-h interval until the end of the experimental period. The animals were killed at 3, 5, 7, and 11 days after day 0. The results of the clinical evaluation showed that the laser and LED phototherapies were able to accelerate the healing of formocresol-induced oral ulcers, which occurred first in the laser group (ANOVA, p < 0.05). Histologically, there was a slight variation between LED and laser therapy; therefore, the laser group proved to be effective in accelerating wound healing, especially at 5 days, whereas the LED group was more effective at the end of the experimental period. It was concluded that laser and LED photobiomodulation were effective in accelerating the healing of formocresol-induced oral ulcers in both clinical and histological aspects.

  2. Comparing the Healing Effects of Arnebia euchroma Ointment With Petrolatum on the Ulcers Caused by Fractional CO2 Laser: A Single-Blinded Clinical Trial

    PubMed Central

    Aliasl, Jale; Khoshzaban, Fariba; Barikbin, Behrooz; Naseri, Mohsen; Kamalinejad, Mohammad; Emadi, Fatemeh; Razzaghi, Zahra; Talei, Daryush; Yousefi, Maryam; Aliasl, Fatemeh; Barati, Maryam; Mohseni-Moghaddam, Parvaneh; Hasheminejad, Seyed Abbas; Esmailzad Nami, Hossein

    2014-01-01

    Background: Arnebia euchroma ointment (AEO) has been used in Iranian traditional medicine for burn wound healing. Objectives: The aim of this study is to evaluate wound healing efficacy of AEO in burn wounds after fractional Co2 laser. Patients and Methods: This split-face, single-blinded, single-center clinical study was performed in Shohada-e-Tajrish Hospital, Tehran, Iran. A total of 26 subjects with facial acne scar, who were to receive fractional CO2 laser resurfacing were recruited. After laser procedure, AEO was applied to one side of the face and petrolatum on the other side for wound healing. Digital photographs were taken from acne scar area before resurfacing and on each of the assessment sessions. Three researchers, who were unaware of the applied medications, assessed these digital photographs for erythema, edema, epithelial confluence, crusting/scabbing, and general wound appearance. Subject’s irritations such as dryness and itching were evaluated on the second, fifth, and seventh days. Results: Our study indicated higher epithelial confluence and general wound appearance scores (P = 0.045 for both) and less erythema and edema on fifth day in petrolatum (P = 0.009 and P = 0.034, respectively). The results showed less crusting and erythema (P = 0.016 and P = 0.035, respectively) and higher general wound appearance scores in petrolatum on the second day (P = 0.035 and P = 0.001, respectively). Dryness was the most common subjective complaint in both groups; however, it was more severe in AEO, especially on the second day (P = 0.023). Conclusions: Despite the healing effects of AEO in burn wounds, petrolatum was more effective than AEO in post-laser wound. PMID:25558382

  3. Medical therapy of peptic ulcer disease.

    PubMed

    McQuaid, K R; Isenberg, J I

    1992-04-01

    The gastric duodenal mucosa normally is protected from the damaging effects of gastric acid and pepsin by ill-defined mechanisms. Ulcers may arise when there is an imbalance between the aggressive and defensive factors that renders the mucosa susceptible to damage. A variety of factors have been identified that may favor the development of peptic ulcers, but no single pathophysiologic defect applies in all ulcer patients. In duodenal ulcers, gastric acid hypersecretion is observed in as many as one third of patients; however, most patients with duodenal ulcers secrete normal amounts of gastric acid. Decreased mucosal bicarbonate secretion may be important in at least some duodenal ulcer patients. Use of NSAIDs may cause either gastric or duodenal ulcers, probably through the inhibition of mucosal prostaglandin synthesis and disruption of mucosal defenses. Finally, a recently identified bacterium, H. pylori, causes a chronic gastritis that is found in the overwhelming majority of patients with duodenal ulcers and non-NSAID-associated gastric ulcers. This bacterium may play a pivotal role in ulcer pathogenesis and, especially, in ulcer recurrences. A number of drugs of proved efficacy are available for the treatment of acute duodenal and gastric ulcers. The H2 receptor antagonists administered once daily remain the mainstay of ulcer therapy because of their efficacy, ease of use, and excellent safety profile. More thorough and long-lasting acid inhibition is afforded by the H+/K(+)-ATPase inhibitor omeprazole. This agent also promotes more rapid ulcer healing, but in most patients, this minor advantage may not justify the higher cost. It is not known whether more rapid healing will translate into lower ulcer complication rates. Until further data are available, this drug may be preferable in patients with large or complicated ulcers. In patients with refractory ulcers, omeprazole is clearly superior to other available agents. Agents that promote mucosal defense

  4. Heberprot-P: a novel product for treating advanced diabetic foot ulcer.

    PubMed

    Berlanga, Jorge; Fernández, José I; López, Ernesto; López, Pedro A; del Río, Amaurys; Valenzuela, Carmen; Baldomero, Julio; Muzio, Verena; Raíces, Manuel; Silva, Ricardo; Acevedo, Boris E; Herrera, Luis

    2013-01-01

    Diabetic foot ulcer is a principal diabetic complication. It has been shown that diabetic patients have decreased growth factor concentrations in their tissues, particularly epidermal growth factor. Growth factor shortage impairs wound healing, which leads to chronic nonhealing wounds and sometimes eventual amputation. Ischemic diabetic foot ulcer is the most difficult to treat and confers the highest amputation risk. Injecting epidermal growth factor deep into the wound bottom and contours encourages a more effective pharmacodynamic response in terms of granulation tissue growth and wound closure. Epidermal growth factor injected into the ulcer matrix may also result in association with extracellular matrix proteins, thus enhancing cell proliferation and migration. Heberprot-P is an innovative Cuban product containing recombinant human epidermal growth factor for peri- and intra-lesional infiltration; evidence reveals it accelerates healing of deep and complex ulcers, both ischemic and neuropathic, and reduces diabetes-related amputations. Clinical trials of Heberprot-P in patients with diabetic foot ulcers have shown that repeated local infiltration of this product can enhance healing of chronic wounds safely and efficaciously. As a result, Heberprot-P was registered in Cuba in 2006, and in 2007 was included in the National Basic Medications List and approved for marketing. It has been registered in 15 other countries, enabling treatment of more than 100,000 patients. Heberprot-P is a unique therapy for the most complicated and recalcitrant chronic wounds usually associated with high amputation risk. Local injection in complex diabetic wounds has demonstrated a favorable risk-benefit ratio by speeding healing, reducing recurrences and attenuating amputation risk. Further testing and deployment worldwide of Heberprot-P would provide an opportunity to assess the product's potential to address an important unmet medical need.

  5. Biodegradable and plasma-treated electrospun scaffolds coated with recombinant Olfactomedin-like 3 for accelerating wound healing and tissue regeneration.

    PubMed

    Dunn, Louise L; de Valence, Sarra; Tille, Jean-Christophe; Hammel, Philippe; Walpoth, Beat H; Stocker, Roland; Imhof, Beat A; Miljkovic-Licina, Marijana

    2016-11-01

    Three-dimensional biomimetic scaffolds resembling the native extracellular matrix (ECM) are widely used in tissue engineering, however they often lack optimal bioactive cues needed for acceleration of cell proliferation, neovascularization, and tissue regeneration. In this study, the use of the ECM-related protein Olfactomedin-like 3 (Olfml3) demonstrates the importance and feasibility of fabricating efficient bioactive scaffolds without in vitro cell seeding prior to in vivo implantation. First, in vivo proangiogenic properties of Olfml3 were shown in a murine wound healing model by accelerated wound closure and a 1.4-fold increase in wound vascularity. Second, subcutaneous implantation of tubular scaffolds coated with recombinant Olfml3 resulted in enhanced cell in-growth and neovascularization compared with control scaffolds. Together, our data indicates the potential of Olfml3 to accelerate neovascularization during tissue regeneration by promoting endothelial cell proliferation and migration. This study provides a promising concept for the reconstruction of damaged tissue using affordable and effective bioactive scaffolds.

  6. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth.

    PubMed

    Staresinic, M; Sebecic, B; Patrlj, L; Jadrijevic, S; Suknaic, S; Perovic, D; Aralica, G; Zarkovic, N; Borovic, S; Srdjak, M; Hajdarevic, K; Kopljar, M; Batelja, L; Boban-Blagaic, A; Turcic, I; Anic, T; Seiwerth, S; Sikiric, P

    2003-11-01

    In studies intended to improve healing of transected Achilles tendon, effective was a stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419). Currently in clinical trials for inflammatory bowel disease (PLD-116, PL 14736, Pliva), it ameliorates internal and external wound healing. In rats, the right Achilles tendon transected (5 mm proximal to its calcaneal insertion) presents with a large tendon defect between cut ends. Agents (/kg b.w., i.p., once time daily) (BPC 157 (dissolved in saline, with no carrier addition) (10 microg, 10 ng or 10 pg) or saline (5.0 ml)), were firstly applied at 30 min after surgery, the last application at 24 h before autopsy. Achilles functional index (AFI) was assessed once time daily. Biomechanical, microscopical and macroscopical assessment was on day 1, 4, 7, 10 and 14. Controls generally have severely compromised healing. In comparison, pentadecapeptide BPC 157 fully improves recovery: (i) biomechanically, increased load of failure, load of failure per area and Young's modulus of elasticity; (ii) functionally, significantly higher AFI-values; (iii) microscopically, more mononuclears and less granulocytes, superior formation of fibroblasts, reticulin and collagen; (iv) macroscopically, smaller size and depth of tendon defect, and subsequently the reestablishment of full tendon integrity. Likewise, unlike TGF-beta, pentadecapeptide BPC 157, presenting with no effect on the growth of cultured cell of its own, consistently opposed 4-hydroxynonenal (HNE), a negative modulator of the growth. HNE-effect is opposed in both combinations: BPC 157+HNE (HNE growth inhibiting effect reversed into growth stimulation of cultured tendocytes) and HNE+BPC 157(abolished inhibiting activity of the aldehyde), both in the presence of serum and serum deprived conditions. In conclusion, these findings, particularly, Achilles tendon transection fully recovered in rats, peptide stability suitable delivery, usefully favor gastric

  7. Porous microspheres as promising vehicles for the topical delivery of poorly soluble asiaticoside accelerate wound healing and inhibit scar formation in vitro &in vivo.

    PubMed

    Zhang, Chen-Zhen; Niu, Jie; Chong, Yee-Song; Huang, Yan-Fen; Chu, Yang; Xie, Sheng-Yang; Jiang, Zhi-Hong; Peng, Li-Hua

    2016-12-01

    Asiaticoside is a natural compound possessing diverse pharmacological effects with great potential for clinical use. However, the low solubility and oil-water partition coefficient of asiaticoside lead to reduced effect and limited application. This study aims to construct a porous microsphere for the sustained release of asiaticoside to improve its absorption and enhance the therapeutic effects. Parameters of the formulations, including the drug to polymer ratio, solvent amounts of the inner and external phases, the stirring speed for preparation, and the drug entrapment efficiency were investigated and optimized. Particle size, morphology, pores structure, and Fourier transform infrared spectrum of the microsphere were characterized. The release kinetics and cellular uptake profiles of the asiaticoside-microspheres were examined. The therapeutic effects of asiaticoside-microspheres on wound healing and skin appendages regeneration were investigated in vitro & in vivo. Results showed that the optimized asiaticoside-microspheres possess spherical spongy structure with cylindrical holes. Asiaticoside can be loaded in the microsphere with high efficiency and released with sustained manner. The cellular uptake of asiaticoside from the microspheres was increased with 9.1 folds higher than that of free solution. Asiaticoside-microspheres expressed the strong promotion in the proliferation, migration of keratinocytes and wound scratching healing in vitro. More importantly, they significantly accelerated the re-epithelization, collagen synthesis and pro-angiogenesis in the rat full-skin wound healing. Porous microsphere was shown a novel carrier for the sustained delivery of poorly soluble asiaticoside, with absorption and therapeutic effects improved. Asiaticoside-microsphere is a promising topical preparation with excellent regenerative effects for the wound therapy.

  8. Secretome of Peripheral Blood Mononuclear Cells Enhances Wound Healing

    PubMed Central

    Haider, Thomas; Gschwandtner, Maria; Werba, Gregor; Barresi, Caterina; Zimmermann, Matthias; Golabi, Bahar; Tschachler, Erwin; Ankersmit, Hendrik Jan

    2013-01-01

    Non-healing skin ulcers are often resistant to most common therapies. Treatment with growth factors has been demonstrated to improve closure of chronic wounds. Here we investigate whether lyophilized culture supernatant of freshly isolated peripheral blood mononuclear cells (PBMC) is able to enhance wound healing. PBMC from healthy human individuals were prepared and cultured for 24 hours. Supernatants were collected, dialyzed and lyophilized (SECPBMC). Six mm punch biopsy wounds were set on the backs of C57BL/6J-mice and SECPBMC containing emulsion or controls were applied daily for three days. Morphology and neo-angiogenesis were analyzed by H&E-staining and CD31 immuno-staining, respectively. In vitro effects on diverse skin cells were investigated by migration assays, cell cycle analysis, and tube formation assay. Signaling pathways were analyzed by Western blot analysis. Application of SECPBMC on 6 mm punch biopsy wounds significantly enhanced wound closure. H&E staining of the wounds after 6 days revealed that wound healing was more advanced after application of SECPBMC containing emulsion. Furthermore, there was a massive increase in CD31 positive cells, indicating enhanced neo-angiogenesis. In primary human fibroblasts (FB) and keratinocytes (KC) migration but not proliferation was induced. In endothelial cells (EC) SECPBMC induced proliferation and tube-formation in a matrigel-assay. In addition, SECPBMC treatment of skin cells led to the induction of multiple signaling pathways involved in cell migration, proliferation and survival. In summary, we could show that emulsions containing the secretome of PBMC derived from healthy individuals accelerates wound healing in a mouse model and induce wound healing associated mechanisms in human primary skin cells. The formulation and use of such emulsions might therefore represent a possible novel option for the treatment of non-healing skin ulcers. PMID:23533667

  9. Secretome of peripheral blood mononuclear cells enhances wound healing.

    PubMed

    Mildner, Michael; Hacker, Stefan; Haider, Thomas; Gschwandtner, Maria; Werba, Gregor; Barresi, Caterina; Zimmermann, Matthias; Golabi, Bahar; Tschachler, Erwin; Ankersmit, Hendrik Jan

    2013-01-01

    Non-healing skin ulcers are often resistant to most common therapies. Treatment with growth factors has been demonstrated to improve closure of chronic wounds. Here we investigate whether lyophilized culture supernatant of freshly isolated peripheral blood mononuclear cells (PBMC) is able to enhance wound healing. PBMC from healthy human individuals were prepared and cultured for 24 hours. Supernatants were collected, dialyzed and lyophilized (SEC(PBMC)). Six mm punch biopsy wounds were set on the backs of C57BL/6J-mice and SEC(PBMC) containing emulsion or controls were applied daily for three days. Morphology and neo-angiogenesis were analyzed by H&E-staining and CD31 immuno-staining, respectively. In vitro effects on diverse skin cells were investigated by migration assays, cell cycle analysis, and tube formation assay. Signaling pathways were analyzed by Western blot analysis. Application of SEC(PBMC) on 6 mm punch biopsy wounds significantly enhanced wound closure. H&E staining of the wounds after 6 days revealed that wound healing was more advanced after application of SEC(PBMC) containing emulsion. Furthermore, there was a massive increase in CD31 positive cells, indicating enhanced neo-angiogenesis. In primary human fibroblasts (FB) and keratinocytes (KC) migration but not proliferation was induced. In endothelial cells (EC) SEC(PBMC) induced proliferation and tube-formation in a matrigel-assay. In addition, SEC(PBMC) treatment of skin cells led to the induction of multiple signaling pathways involved in cell migration, proliferation and survival. In summary, we could show that emulsions containing the secretome of PBMC derived from healthy individuals accelerates wound healing in a mouse model and induce wound healing associated mechanisms in human primary skin cells. The formulation and use of such emulsions might therefore represent a possible novel option for the treatment of non-healing skin ulcers.

  10. HDFx: a novel biologic immunomodulator accelerates wound healing and is suggestive of unique regenerative powers: potential implications for the warfighter and disaster victims.

    PubMed

    Altura, Burton M; Carella, Anthony; Gebrewold, Asefa

    2012-01-01

    Recently, we reported on the discovery of a new, conserved biologic protein (35-40 KDa), termed HDFx, that protects rats, guinea-pigs, mice, and rabbits against lethal hemorrhage, endotoxins, intestinal ischemic-shock, and traumatic injuries. It was found to stimulate several arms of the immune system. The present report demonstrates, for the first time, that HDFx accelerates wound healing in two different models (excision wound model; and incision wound model) in rats. The results shown, herein, indicate that HDFx produces greater rates of wound contraction, greater tensile strength, and more rapid healing than controls. Our new data also show that this biologic increases hydroxyproline content of granulation tissue coupled with a reduction in superoxide dismutase (SOD). In addition, we show that HDFx increases the levels of serum ascorbic acid and stimulates the mononuclear cells of the reticuloendothelial system (RES). Overall, these data suggest that HDFx may possess unique regenerative powers. We, thus, believe that HDFx can be of great potential use in diverse types of wounds which, otherwise, could result in difficult to treat infections and thus prevent sepsis and loss of body parts from amputations.

  11. Acceleration of bone formation during fracture healing by injectable collagen powder and human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase.

    PubMed

    Saito, Wataru; Uchida, Kentaro; Ueno, Masaki; Matsushita, Osamu; Inoue, Gen; Nishi, Nozomu; Ogura, Takayuki; Hattori, Shunji; Fujimaki, Hisako; Tanaka, Keisuke; Takaso, Masashi

    2014-09-01

    Growth factor delivered with implantable biomaterials has been used to both accelerate and ensure healing of open fractures in human patients. However, a major limitation of implantable biomaterials is the requirement for open surgical placement. Here, we developed an injectable collagen material-based bone formation system consisting of injectable collagen powder with fibril morphology and collagen triple helix conformation, and basic fibroblast growth factor (bFGF) fused to the collagen-binding domain (CBD) of Clostridium histolyticum collagenase. The affinity of the CBD towards collagen was confirmed by the results of collagen-binding assays. Moreover, the combination of the collagen binding-bFGF fusion protein (CB-bFGF) with injectable collagen powder induced bone formation at protein concentrations lower than those required for bFGF alone in mice fracture models. Taken together, these properties suggest that the CB-bFGF/collagen powder composite is a promising injectable material for bone repair in the clinical setting.

  12. Management of Chronic Pressure Ulcers

    PubMed Central

    2009-01-01

    Executive Summary In April 2008, the Medical Advisory Secretariat began an evidence-based review of the literature concerning pressure ulcers. Please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/tech/tech_mn.html to review these titles that are currently available within the Pressure Ulcers series. Pressure ulcer prevention: an evidence based analysis The cost-effectiveness of prevention strategies for pressure ulcers in long-term care homes in Ontario: projections of the Ontario Pressure Ulcer Model (field evaluation) Management of chronic pressure ulcers: an evidence-based analysis Objective The Medical Advisory Secretariat (MAS) conducted a systematic review on interventions used to treat pressure ulcers in order to answer the following questions: Do currently available interventions for the treatment of pressure ulcers increase the healing rate of pressure ulcers compared with standard care, a placebo, or other similar interventions? Within each category of intervention, which one is most effective in promoting the healing of existing pressure ulcers? Background A pressure ulcer is a localized injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure, or pressure in conjunction with shear and/or friction. Many areas of the body, especially the sacrum and the heel, are prone to the development of pressure ulcers. People with impaired mobility (e.g., stroke or spinal cord injury patients) are most vulnerable to pressure ulcers. Other factors that predispose people to pressure ulcer formation are poor nutrition, poor sensation, urinary and fecal incontinence, and poor overall physical and mental health. The prevalence of pressure ulcers in Ontario has been estimated to range from a median of 22.1% in community settings to a median of 29.9% in nonacute care facilities. Pressure ulcers have been shown to increase the risk of mortality among geriatric patients by

  13. Effects of beta-adrenoceptor drug stimulation on various models of gastric ulcer in rats.

    PubMed Central

    Esplugues, J.; Lloris, J. M.; Martí-Bonmatí, E.; Morcillo, E. J.

    1982-01-01

    1. Experiments were designed to evaluate the effect of the pharmacological activation of beta-adrenoceptors on various models of gastric ulcer in the rat. 2. Pretreatment with the beta-adrenoceptor stimulant drugs, isoprenaline or salbutamol, significantly inhibited stress-induced gastric ulcers. This anti-ulcer effect was abolished by propranolol but not by atenolol, suggesting that beta 2-adrenoceptors mediate this response. 3. In the pylorus-ligation model, salbutamol inhibited lesion formation and reduced the intragastric content of hydrogen ions, histamine and pepsin although the latter was only affected with the higher dose of salbutamol. 4. Salbutamol also prevented the ulcerogenic action on the gastric mucosa of an exogenously perfused artificial gastric juice, showing that the anti-ulcer effect is not necessarily dependent on acid inhibition. 5. Salbutamol also reduced the formation of acute ulcers induced by various iatrogenic means (histamine, polymyxin B, reserpine and indomethacin). 6. Long-term treatment with salbutamol accelerated the healing of experimental chronic gastric ulcer. 7. In anaesthetized rats, salbutamol produced a dose-related increase in mucosal blood flow which may contribute to its mode of action. 8. It is concluded that beta-adrenoceptor agonists exert preventive and curative effects on gastric damage induced in the rat. This effect seems specific and mediated through beta-adrenoceptor activation. PMID:6125225

  14. Peptic Ulcers

    MedlinePlus

    ... the stomach lining), peptic ulcer disease, and even stomach cancer later in life. In the past, having peptic ulcers meant living with a chronic condition for several years or even a lifetime. But ... pylori infection, and gastric ulcers, which may stem from other causes. It's ...

  15. Therapy of peptic ulcer with semax peptide.

    PubMed

    Ivanikov, I O; Brekhova, M E; Samonina, G E; Myasoedov, N F; Ashmarin, I P

    2002-07-01

    Experiments used is combination with traditional preparations (omeprasole, de-nol, and solcoseril), Semax peptide (Met-Glu-His-Phe-Pro-Gly-Pro) possessing nootropic and neuroprotective activity significantly promoted ulcer healing in patients with refractory peptic ulcers. On day 14 of treatment ulcer healing was observed in 89.5% patients receiving intranasal Semax (1% solution, 2-4 drops 3 times a day for 10 days) vs. 30.8% in the control group. Clinical studies of antiulcer activity of Semax in different combinations with usual antiulcer drugs are needed.

  16. Evidence-based chronic ulcer care and lower limb outcomes among Pacific Northwest veterans.

    PubMed

    Karavan, Mahsa; Olerud, John; Bouldin, Erin; Taylor, Leslie; Reiber, Gayle E

    2015-09-01

    Evidence-based ulcer care guidelines detail optimal components of care for treatment of ulcers of different etiologies. We investigated the impact of providing specific evidence-based ulcer treatment components on healing outcomes for lower limb ulcers (LLU) among veterans in the Pacific Northwest. Components of evidence-based ulcer care for venous, arterial, diabetic foot ulcers/neuropathic ulcers were abstracted from medical records. The outcome was ulcer healing. Our analysis assessed the relationship between evidence-based ulcer care by etiology, components of care provided, and healing, while accounting for veteran characteristics. A minority of veterans in all three ulcer-etiology groups received the recommended components of evidence-based care in at least 80% of visits. The likelihood of healing improved when assessment for edema and infection were performed on at least 80% of visits (hazard ratio [HR] = 3.20, p = 0.009 and HR = 3.54, p = 0.006, respectively) in patients with venous ulcers. There was no significant association between frequency of care components provided and healing among patients with arterial ulcers. Among patients with diabetic/neuropathic ulcers, the chance of healing increased 2.5-fold when debridement was performed at 80% of visits (p = 0.03), and doubled when ischemia was assessed at the first visit (p = 0.045). Veterans in the Pacific Northwest did not uniformly receive evidence-based ulcer care. Not all evidence-based ulcer care components were significantly associated with healing. At a minimum, clinicians need to address components of ulcer care associated with improved ulcer healing.

  17. [Peptic ulcer

    PubMed

    Carvalho, A S

    2000-07-01

    OBJECTIVE: To present a current review about pathogenesis, pathophysiology, diagnosis, and treatment of peptic ulcer disease in children, based on the reviewed publications and the author personal experience. METHODS: We revised the most relevant articles about peptic ulcer in children, published from the last 20 years. RESULTS: The gastroduodenal peptic ulcer is very common in adults, mostly in the developing countries. Although it is less frequent in children, the optical fibroendoscopy has improved the number of diagnosed cases. The peptic ulcer is classified as its etiology in primary and secondary. The secondary peptic ulcer is related to a subjacent disease or use of drugs, while the primary ulcer happens in the absence of underlying systemic diseases The primary duodenal ulcer is the most common presentation, and there are strong evidences of the H. pylori association in the etiology. Clinical presentation changes with age and ulcer type. Secondary ulcers are mostly acute and sometimes dramatic, while the primary ones have a chronic evolution mostly similar to patients with functional recurrent abdominal pain, but the presence of epigastric pain, feeding-related pain, vomiting, bleeding, familiar history for peptic ulcer, nocturnal pain, and male gender are strongly related to peptic ulcer. The acid antisecretory agents have great efficacy on relieving symptoms and solving ulcerate lesion, although the H. pylori eradication itself prevents primary duodenal ulcer recurrence. CONCLUSIONS: The primary peptic ulcer involve many factors in Its etiopathogenesis, being H. pylori the most important of them Although there isn t yet a ideal therapeutic course. The antibiotics play an important role in peptic ulcer and the H. pylori research must be done for na accurate diagnosis and treatment.

  18. Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats

    PubMed Central

    Xue, Xiao-Chang; Wu, Yong-Jie; Gao, Ming-Tang; Li, Wen-Guang; Zhao, Ning; Wang, Zeng-Lu; Bao, Chun-Jie; Yan, Zhen; Zhang, Ying-Qi

    2004-01-01

    AIM: To investigate the protective effects of gastric pentadecapeptide BPC 157 on acute and chronic gastric ulcers in rats and to compare the results in therapy of human gastric ulcers by different administration methods. METHODS: Gastric pentadecapeptide BPC 157 was administered (initial single or continuous administration) into rats either intragastrically or intramuscularly before (induced acute gastric ulcer) or after (induced chronic gastric ulcer) the applications of inducing agents, and each animal was sacrificed to observe the protective effects of BPC 157 on gastric ulcers. RESULTS: Both intramuscular (im) and intragastric (ig) administration of BPC 157 could apparently reduce the ulcer area and accelerate the healing of induced ulcer in different models and the effect of im administered BPC 157 was better than that of ig. The rats treated with higher dosages (400 ng/kg, 800 ng/kg) of BPC 157 (im and ig) showed significantly less lesion (P < 0.01 vs excipient or saline control), the inhibition ratio of ulcer formation varied between 45.7% and 65.6%, from all measurements except 400 ng/kg BPC 157 in pylorus ligation induced model (P < 0.05), in which the inhibition rate was 54.2%. When im administered (800 ng/kg BPC 157) in three models, the inhibition ratio of ulcer formation was 65.5%, 65.6% and 59.9%, respectively, which was better than that of famotidine (its inhibition rate was 60.8%, 57.2% and 34.3%, respectively). Continuous application of BPC 157 (in chronic acetate induced gastric ulcer) could accelerate rebuilding of glandular epithelium and formation of granulation tissue (P < 0.05 at 200 ng/kg and P < 0.01 at 400 ng/kg and 800 ng/kg vs excipient or saline control). CONCLUSION: Both im and ig administered gastric pentadecapeptide BPC 157 can apparently ameliorate acute gastric ulcer in rats and antagonize the protracted effect of acetate challenge on chronic ulcer. The effect of im administration of BPC 157 is better than that of ig, and the

  19. Sarcoidosis mimicking a venous ulcer: a case report.

    PubMed

    Joshi, Smita S; Romanelli, Paolo; Kirsner, Robert S

    2009-11-01

    Sarcoidosis--a chronic, multisystem disease of unknown etiology characterized by noncaseating granulomas--may cause ulcerative lesions, particularly in African American women. A case of ulcerative sarcoidosis mimicking a venous ulcer is presented. The patient is a 44-year-old African American hypertensive, obese woman with a nonhealing medially based lower leg ulcer of 3 years' duration clinically consistent with a venous ulcer. The ulcer did not heal with compression therapy and pentoxifylline. Subsequent biopsies showed granulomatous inflammation consistent with sarcoidosis. When intralesional triamcinolone was added to compression therapy, the ulcer resolved after 3 months. Given its propensity toward formation on the lower extremities and ulcerative and atrophic appearance, ulcerative sarcoidosis should be considered in the differential diagnosis of a venous ulcer refractory to standard therapy, especially in African American women.

  20. Recurring pressure ulcers: identifying the definitions. A National Pressure Ulcer Advisory Panel white paper.

    PubMed

    Tew, Cindy; Hettrick, Heather; Holden-Mount, Sarah; Grigsby, Rebekah; Rhodovi, Julie; Moore, Lyn; Ghaznavi, Amir M; Siddiqui, Aamir

    2014-01-01

    Currently, there is a lack of consensus regarding the accepted terminology pertaining to the pressure ulcer healing progression and recidivism. This lack of uniformity can negatively impact initiation of treatment pathways, completion of appropriate interventions, clinical documentation, medical coding, patient education, discharge planning and healthcare revenue through out the healthcare system. The purpose of this paper is to introduce a standard nomenclature as it pertains to pressure ulcer healing progression and any recidivism that may occur. The National Pressure Ulcer Advisory Panel has formulated a framework of terms regarding pressure ulcer progression. We also developed a clearer nomenclature for lack of progress and recidivism of pressure ulcers. This document should serve as a starting point for the discussion of the pressure ulcer care, research, and terminology.

  1. Quantitative Stain-Free and Continuous Multimodal Monitoring of Wound Healing In Vitro with Digital Holographic Microscopy

    PubMed Central

    Krausewitz, Philipp; Brückner, Markus; Ketelhut, Steffi; Domagk, Dirk; Kemper, Björn

    2014-01-01

    Impaired epithelial wound healing has significant pathophysiological implications in several conditions including gastrointestinal ulcers, anastomotic leakage and venous or diabetic skin ulcers. Promising drug candidates for accelerating wound closure are commonly evaluated in in vitro wound assays. However, staining procedures and discontinuous monitoring are major drawbacks hampering accurate assessment of wound assays. We therefore investigated digital holographic microscopy (DHM) to appropriately monitor wound healing in vitro and secondly, to provide multimodal quantitative information on morphological and functional cell alterations as well as on motility changes upon cytokine stimulation. Wound closure as reflected by proliferation and migration of Caco-2 cells in wound healing assays was studied and assessed in time-lapse series for 40 h in the presence of stimulating epidermal growth factor (EGF) and inhibiting mitomycin c. Therefore, digital holograms were recorded continuously every thirty minutes. Morphological changes including cell thickness, dry mass and tissue density were analyzed by data from quantitative digital holographic phase microscopy. Stimulation of Caco-2 cells with EGF or mitomycin c resulted in significant morphological changes during wound healing compared to control cells. In conclusion, DHM allows accurate, stain-free and continuous multimodal quantitative monitoring of wound healing in vitro and could be a promising new technique for assessment of wound healing. PMID:25251440

  2. Exosomes Derived from Human Endothelial Progenitor Cells Accelerate Cutaneous Wound Healing by Promoting Angiogenesis Through Erk1/2 Signaling

    PubMed Central

    Zhang, Jieyuan; Chen, Chunyuan; Hu, Bin; Niu, Xin; Liu, Xiaolin; Zhang, Guowei; Zhang, Changqing; Li, Qing; Wang, Yang

    2016-01-01

    Chronic skin wounds represent one of the most common and disabling complications of diabetes. Endothelial progenitor cells (EPCs) are precursors of endothelial cells and can enhance diabetic wound repair by facilitating neovascularization. Recent studies indicate that the transplanted cells exert therapeutic effects primarily via a paracrine mechanism and exosomes are an important paracrine factor that can be directly used as therapeutic agents for regenerative medicine. However, application of exosomes in diabetic wound repair has been rarely reported. In this study, we demonstrated that the exosomes derived from human umbilical cord blood-derived EPCs (EPC-Exos) possessed robust pro-angiogenic and wound healing effects in streptozotocin-induced diabetic rats. By using a series of in vitro functional assays, we found that EPC-Exos could be incorporated into endothelial cells and significantly enhance endothelial cells' proliferation, migration, and angiogenic tubule formation. Moreover, microarray analyses indicated that exosomes treatment markedly altered the expression of a class of genes involved in Erk1/2 signaling pathway. It was further confirmed with functional study that this signaling process was the critical mediator during the exosomes-induced angiogenic responses of endothelial cells. Therefore, EPC-Exos are able to stimulate angiogenic activities of endothelial cells by activating Erk1/2 signaling, which finally facilitates cutaneous wound repair and regeneration. PMID:27994512

  3. Allergic contact dermatitis to Plectranthus amboinicus masquerading as chronic leg ulcer.

    PubMed

    Chang, Shyue-Luen; Chang, Ya-Ching; Yang, Chin-Hsun; Hong, Hong-Shang

    2005-12-01

    This report discusses a case of a 69-year-old woman who developed chronic non-healing leg ulcers after long-term topical use of Plectranthus amboinicus. The ulcer was proven to be allergic contact dermatitis to P. amboinicus by a patch test. The ulcer healed after discontinuation of P. amboinicus. To the best of our knowledge, this is the first reported case of allergic contact dermatitis to P. amboinicus masquerading as chronic leg ulcer.

  4. Difference in Ulex europaeus agglutinin I-binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis.

    PubMed

    Okazaki, Hiroaki; Mizuno, Motowo; Nasu, Junichirou; Makidono, Chiho; Hiraoka, Sakiko; Yamamoto, Kazuhide; Okada, Hiroyuki; Fujita, Teizo; Tsuji, Takao; Shiratori, Yasushi

    2004-03-01

    Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay (P <.05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

  5. The Four-Herb Chinese Medicine Formula Tuo-Li-Xiao-Du-San Accelerates Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats through Reducing Inflammation and Increasing Angiogenesis

    PubMed Central

    Zhang, Xiao-na; Ma, Ze-jun; Wang, Ying; Li, Yu-zhu; Sun, Bei; Guo, Xin; Pan, Cong-qing; Chen, Li-ming

    2016-01-01

    Impaired wound healing in diabetic patients is a serious complication that often leads to amputation or even death with limited effective treatments. Tuo-Li-Xiao-Du-San (TLXDS), a traditional Chinese medicine formula for refractory wounds, has been prescribed for nearly 400 years in China and shows good efficacy in promoting healing. In this study, we explored the effect of TLXDS on healing of diabetic wounds and investigated underlying mechanisms. Four weeks after intravenous injection of streptozotocin, two full-thickness excisional wounds were created with a 10 mm diameter sterile biopsy punch on the back of rats. The ethanol extract of TLXDS was given once daily by oral gavage. Wound area, histological change, inflammation, angiogenesis, and collagen synthesis were evaluated. TLXDS treatment significantly accelerated healing of diabetic rats and improved the healing quality. These effects were associated with reduced neutrophil infiltration and macrophage accumulation, enhanced angiogenesis, and increased collagen deposition. This study shows that TLXDS improves diabetes-impaired wound healing. PMID:27057551

  6. Effect of pentoxifylline on treatment of lower limb ulcers in patients with thalassemia major.

    PubMed

    Angelides, N S; Angastiniotis, C; Pavlides, N

    1992-07-01

    The possible healing effect of deferoxamine and pentoxifylline on persisting lower limb ulcers was studied in 51 patients with thalassemia major. The results indicated that the regular use of deferoxamine at an intravenous dose of 20 mg/kg did not affect the healing progress and the recurrence rate of these ulcers significantly. On the contrary, the oral administration of pentoxifylline at a dose of 1,200 mg daily during the ulcer's healing time and at a low long-term maintenance dose of 400 mg daily during the ulcer-free intervals improved their healing ability impressively and diminished their recurrence rate significantly.

  7. Therapeutic Potential of Adipose-Derived SSEA-3-Positive Muse Cells for Treating Diabetic Skin Ulcers

    PubMed Central

    Kinoshita, Kahori; Kuno, Shinichiro; Ishimine, Hisako; Aoi, Noriyuki; Mineda, Kazuhide; Kato, Harunosuke; Doi, Kentaro; Kanayama, Koji; Feng, Jingwei; Mashiko, Takanobu; Kurisaki, Akira

    2015-01-01

    Stage-specific embryonic antigen-3 (SSEA-3)-positive multipotent mesenchymal cells (multilineage differentiating stress-enduring [Muse] cells) were isolated from cultured human adipose tissue-derived stem/stromal cells (hASCs) and characterized, and their therapeutic potential for treating diabetic skin ulcers was evaluated. Cultured hASCs were separated using magnetic-activated cell sorting into positive and negative fractions, a SSEA-3+ cell-enriched fraction (Muse-rich) and the remaining fraction (Muse-poor). Muse-rich hASCs showed upregulated and downregulated pluripotency and cell proliferation genes, respectively, compared with Muse-poor hASCs. These cells also released higher amounts of certain growth factors, particularly under hypoxic conditions, compared with Muse-poor cells. Skin ulcers were generated in severe combined immunodeficiency (SCID) mice with type 1 diabetes, which showed delayed wound healing compared with nondiabetic SCID mice. Treatment with Muse-rich cells significantly accelerated wound healing compared with treatment with Muse-poor cells. Transplanted cells were integrated into the regenerated dermis as vascular endothelial cells and other cells. However, they were not detected in the surrounding intact regions. Thus, the selected population of ASCs has greater therapeutic effects to accelerate impaired wound healing associated with type 1 diabetes. These cells can be achieved in large amounts with minimal morbidity and could be a practical tool for a variety of stem cell-depleted or ischemic conditions of various organs and tissues. PMID:25561682

  8. Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction

    PubMed Central

    Scioli, Maria Giovanna; Lo Giudice, Pietro; Bielli, Alessandra; Tarallo, Valeria; De Rosa, Alfonso; De Falco, Sandro; Orlandi, Augusto

    2015-01-01

    Background Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery. Methods and Results We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM) expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction. Conclusion PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction

  9. [Orthopaedic footwear against foot ulcers in diabetes].

    PubMed

    Bus, Sicco A

    2014-01-01

    In people with diabetes mellitus, foot ulcers are a major problem because they increase the risk of a foot infection and amputation and reduce quality of life. After a foot ulcer has healed, the risk of recurrence is high. Orthopaedic shoes and orthotics are often prescribed to high risk patients and aim to reduce the mechanical pressure on the plantar surface of the foot. Orthopaedic footwear that is modified to reduce pressure is not much more effective in preventing foot ulcer recurrence than orthopaedic footwear that did not undergo such modification, unless the shoes are worn as recommended. In that case, the risk of ulcer recurrence is reduced by 46%. In patients with a history of ulceration, compliance in wearing orthopaedic shoes at home is low, while these patients walk more inside the house than outside the house. Foot pressure measurements should be part of the prescription and evaluation of orthopaedic footwear for patients at high risk for foot ulceration.

  10. A Hydroxyurea-induced Leg Ulcer

    PubMed Central

    Hwang, Seon-Wook; Hong, Soon-Kwon; Kim, Sang-Hyun; Seo, Jong-Keun; Sung, Ho-Suk

    2009-01-01

    Hydroxyurea is a cytostatic agent that has recently become the drug of choice in the treatment of various myeloproliferative diseases. The cutaneous side effects of hydroxyurea include xerosis, hyperpigmentation, nail discoloration, and scaling. Leg ulcers have only rarely been reported in association with hydroxyurea treatment. A 75-year-old woman presented with leg ulcers, nail discoloration, and xerosis. The leg ulcers were refractory to conventional treatment. She had been taking oral hydroxyurea since being diagnosed with essential thrombocytosis in 2002. Hence, we suspected hydroxyurea-induced leg ulcers and discontinued her hydroxyurea treatment; the ulcers gradually healed thereafter. We present a rare case of hydroxyurea-induced leg ulcers in Korea. PMID:20548853

  11. Refractory peptic ulcer disease.

    PubMed

    Napolitano, Lena

    2009-06-01

    Refractory PUD is a diagnostic and therapeutic challenge. Optimal management of severe or refractory PUD requires a multidisciplinary team approach, using primary care providers, gastroenterologists, and general surgeons. Medical management has become the cornerstone of therapy. Identification and eradication of H pylori infection combined with acid reduction regimens can heal ulceration and also prevent recurrence. Severe, intractable or recurrent PUD and associated complications mandates a careful and methodical evaluation and management strategy to determine the potential etiologies and necessary treatment (medical or surgical) required.

  12. Cytoprotection with misoprostol: use in the treatment and prevention of ulcers.

    PubMed

    Ballinger, A

    1994-01-01

    Prostaglandins protect the gastric mucosa by decreasing gastric acid secretion, increasing mucus and bicarbonate production and maintaining mucosal blood flow. Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastroduodenal damage and this is due, at least in part, to inhibition of mucosal prostaglandin production. Misoprostol is a synthetic analogue of prostaglandin E1 which has been used in the healing of ulcers and prevention of peptic ulcers in patients taking NSAIDs. Misoprostol is of equal efficacy to H2 antagonists in the healing of ordinary peptic ulcers (not associated with NSAIDs). Misoprostol is superior to placebo in healing NSAID ulcers during continued NSAID treatment but there have been no comparative trials with other ulcer-healing drugs. Misoprostol, H2 antagonists and sucralfate are of similar efficacy in prevention of NSAID-associated duodenal ulcers but misoprostol is more effective in prevention of gastric ulcers. Misoprostol has not been compared to omeprazole in this situation.

  13. Randomised, double blind, multicentre, placebo controlled study of sulodexide in the treatment of venous leg ulcers.

    PubMed

    Coccheri, Sergio; Scondotto, Gaetano; Agnelli, Giancarlo; Aloisi, Daniele; Palazzini, Ernesto; Zamboni, Villiam

    2002-06-01

    Sulodexide, a highly purified glycosaminoglycan, was investigated for treatment of venous leg ulcers. Patients (n = 235) undergoing local treatment including wound care and compression bandaging, were randomised to receive either sulodexide or matching placebo for three months. Primary study endpoint was complete ulcer healing after 2 months; secondary endpoints were ulcer healing at 3 months and the time-course changes of ulcer areas. The proportion of patients with complete ulcer healing was higher with sulodexide at 2 months (p = 0.018) and 3 months. The "number needed to treat" to obtain one additional patient healed with sulodexide was 7 at 2 months and 5 at 3 months. The changes in ulcer surface area with time were significant for sulodexide only (p = 0.004). Fibrinogen significantly decreased in sulodexide patients (p = 0.006). In conclusion, sulodexide associated with local treatment proved to be effective and well tolerated in the management of venous leg ulcers.

  14. Healing or Not Healing.

    PubMed

    Padilla, Sabino; Sanchez, Mikel; Padilla, Ione; Orive, Gorka; Anitua, Eduardo

    2016-01-01

    Healing process might be considered as a byproduct of the mechanisms underlying the biological defense system consisting of hemostasis and clotting, the innate immune system, and fibrogenesis. But there is no biological process that does not potentially entail high costs through trade-offs with other life-history parameters and that might be seen as collateral damage. Depending on the balance among the robust and flexible modular defense system, which will be deployed in many different arrays, the structural outcome of the healing process will not resolve with a unitary outcome. Drawing on the regenerative potential of platelets, plasma biomolecules and fibrin matrix, several systems of producing autologous platelets-and plasma derived products (APPDPs) have been developed and aimed at enhancing the natural in vivo tissue regenerative capacity of damaged tissues. Despite the care with which the medical staff elaborate and apply autologous platelets-and plasma derived products, some pitfalls arise regarding the composition of autologous plasma-and platelet derived products, the modalities of their application, and the in vitro versus in vivo evaluations, all of which can deeply influence tissue healing - a process which is already unpredictable, without a unitary mechanism that might be deployed in many different structural and functional arrays which culminate in the tissue repair. A biological approach to the application of autologous platelets-and plasma derived products is crucial to obtaining optimum functional healing outcomes in addition to avoiding poor clinical results and reaching misleading conclusions.

  15. Using Light to Treat Mucositis and Help Wounds Heal

    NASA Technical Reports Server (NTRS)

    Ignatius, Robert W.; Martin, Todd S.; Kirk, Charles

    2008-01-01

    A continuing program of research and development is focusing on the use of controlled illumination by light-emitting diodes (LEDs) to treat mucositis and to accelerate healing of wounds. The basic idea is to illuminate the affected area of a patient with light of an intensity, duration, and wavelength (or combination of wavelengths) chosen to produce a therapeutic effect while generating only a minimal amount of heat. This method of treatment was originally intended for treating the mucositis that is a common complication of chemotherapy and radiation therapy for cancer. It is now also under consideration as a means to accelerate the healing of wounds and possibly also to treat exposure to chemical and radioactive warfare agents. Radiation therapy and many chemotherapeutic drugs often damage the mucosal linings of the mouth and gastrointestinal tract, leading to mouth ulcers (oral mucositis), nausea, and diarrhea. Hyperbaric-oxygen therapy is currently the standard of care for ischemic, hypoxic, infected, and otherwise slowlyhealing problem wounds, including those of oral mucositis. Hyperbaric-oxygen therapy increases such cellular activities as collagen production and angiogenesis, leading to an increased rate of healing. Biostimulation by use of laser light has also been found to be effective in treating mucositis. For hyperbaricoxygen treatment, a patient must remain inside a hyperbaric chamber for an extended time. Laser treatment is limited by laser-wavelength capabilities and by narrowness of laser beams, and usually entails the generation of significant amounts of heat.

  16. Increased vascular permeability, angiogenesis and wound healing induced by the serum of natural latex of the rubber tree Hevea brasiliensis.

    PubMed

    Mendonça, Ricardo José; Maurício, Vanessa Beatriz; Teixeira, Larissa de Bortolli; Lachat, João José; Coutinho-Netto, Joaquim

    2010-05-01

    Increases in vascular permeability and angiogenesis are crucial events to wound repair, tumoral growth and revascularization of tissues submitted to ischemia. An increased vascular permeability allows a variety of cytokines and growth factors to reach the damaged tissue. Nevertheless, the angiogenesis supply tissues with a wide variety of nutrients and is also important to metabolites clearance. It has been suggested that the natural latex from Hevea brasiliensis showed wound healing properties and angiogenic activity. Thus, the purpose of this work was to characterize its angiogenic activity and its effects on vascular permeability and wound healing. The serum fraction of the latex was separated from the rubber with reduction of the pH. The activity of the dialyzed serum fraction on the vascular permeability injected in subcutaneous tissue was assayed according Mile's method. The angiogenic activity was determined using a chick embryo chorioallantoic membrane assay and its effects on the wound-healing process was determined by the rabbit ear dermal ulcer model. The serum fraction showed evident angiogenic effect and it was effective in enhancing vascular permeability. In dermal ulcers, this material significantly accelerated wound healing. Moreover, the serum fraction boiled and treated with proteases lost these activities. These results are in accordance with the enhancement of wound healing observed in clinical trials carried out with a biomembrane prepared with the same natural latex.

  17. The role of nutrition for pressure ulcer management: national pressure ulcer advisory panel, European pressure ulcer advisory panel, and pan pacific pressure injury alliance white paper.

    PubMed

    Posthauer, Mary Ellen; Banks, Merrilyn; Dorner, Becky; Schols, Jos M G A

    2015-04-01

    Nutrition and hydration play an important role in preserving skin and tissue viability and in supporting tissue repair for pressure ulcer (PrU) healing. The majority of research investigating the relationship between nutrition and wounds focuses on PrUs. This white paper reviews the 2014 National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel, and Pan Pacific Pressure Injury Alliance Nutrition Guidelines and discusses nutrition strategies for PrU management.

  18. Platelet Rich Plasma: Efficacy in Treating Trophic Ulcers in Leprosy

    PubMed Central

    Anandan, V.; Jameela, W. Afthab; Saraswathy, P.

    2016-01-01

    Introduction Trophic ulcers secondary to leprosy pose a great stigma to the patients and remain a challenge to the treating dermatologists. The discovery of Platelet Rich Plasma (PRP) with its favourable role in wound healing is a boon for the patients. PRP introduces the growth factors directly into the wound and aids in rapid healing. Aim To study the efficacy and safety of PRP in the healing of trophic ulcers secondary to Hansen’s disease in a tertiary care centre in Southern India. Materials and Methods Based on inclusion and exclusion criteria, 50 patients were enrolled in the study. PRP was prepared by manual double spin method. After wound bed preparation, activated PRP was sprayed over the ulcer and occlusive dressings were applied. Same procedure was repeated every week until complete re-epithelisation or up to six sittings whichever occurred earlier. Results In our study, 46 patients (92%) showed complete healing. In 4 patients (8%), there was marked reduction in wound size with partial re-epithelization. In 88%, complete healing was seen after the fourth sitting. Mean time for ulcer healing was around 4.38 weeks. Conclusion PRP therapy leads to faster rate of induction of granulation tissue with rapid healing. Healing had no direct statistical correlation with the size, site and duration of ulcer, the leprosy spectrum and associated motor deformities. It is a simple, safe and cost effective in-office procedure, albeit requiring an optimal set-up and expertise. PMID:27891436

  19. [Drug-induced oral ulcerations].

    PubMed

    Madinier, I; Berry, N; Chichmanian, R M

    2000-06-01

    Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

  20. [Cycloferon in treating duodenal ulcers in rats].

    PubMed

    Bul'on, V V; Khnychenko, L K; Sapronov, N S; Kuznetsova, N N; Anikin, V B; arinenko, R Iu; Kovalenko, A L; Alekseeva, L E

    2001-01-01

    The possibility of using cycloferon (interferon inductor) for a complex treatment (in combination with the main drug solcoseryl possessing pronounced therapeutic properties) of duodenum ulcers was experimentally studied in male rats. The experiments showed a considerable difference in the interferon status of animals with model duodenum ulcers treated with cycloferon, solcoseryl, their combination, and placebo (control). The healing effect of solcoseryl administered in combination with cycloferon exceeded that of each component administered separately.

  1. PERSISTENT ULCER RESULTING FROM AN IXODID TICK BITE,

    DTIC Science & Technology

    ulcer) resembles acne vulgaris and impetigo, but differs from them by itching and also in that it does not heal rapidly. The nodule differs from tubercular-syphilis by absence of serpiginous development of the nodule. (Author)

  2. Managing chronic venous leg ulcers: time for a new approach?

    PubMed

    Brown, A

    2010-02-01

    Leg ulcer management focuses on healing, but if the wound does not respond to treatment, the patient may feel dejected and guilty. Centering the patient's life around treatment only makes matters worse. An alternative approach is needed.

  3. Case study: the treatment or palliative care of pressure ulcers.

    PubMed

    Hampton, S

    As nurse education increases there are reduced justifications for the existence of pressure ulcers. Patient assessment, along with rationalization of equipment and repositioning techniques, reduces the potential for pressure ulcer formation. Therefore, the future for pressure ulcer prevention will rely on nurse education and motivation. The patient featured in this case study suffered unnecessarily from pressure ulcers as, after her admission to a new nursing home where she was given the appropriate pressure-relieving and wound-dressing treatment, the ulcers were showing signs of healing.

  4. One week's anti-Helicobacter pylori treatment for duodenal ulcer.

    PubMed Central

    Logan, R P; Gummett, P A; Misiewicz, J J; Karim, Q N; Walker, M M; Baron, J H

    1994-01-01

    This open study tested whether eradication of Helicobacter pylori (H pylori) heals duodenal ulcers as well as decreasing recurrence. H pylori was detected in patients with endoscopic duodenal ulcers by histology, CLO-test, culture, and 13C-urea breath test (13C-UBT). Tripotassium dicitrato bismuthate (120 mg) and amoxycillin (500 mg) each four times daily, were given for seven days, with 400 mg metronidazole five times a day on days 5-7. The 13C-UBT was repeated immediately after treatment and endoscopy repeated within 21 days. After treatment unhealed ulcers were reinspected one month later and healed ulcers followed up by 13C-UBT alone for 12 months. Of 45 patients, 44 were available for follow up. Mean pretreatment excess delta 13CO2 excretion was 25.6 per mil, which fell to 2.4 per mil immediately after finishing treatment, indicating clearance of H pylori in every patient. At the second endoscopy (median interval 20 days from start of treatment) 33 of 44 (75%) duodenal ulcers had healed. Ten of the remaining 11 duodenal ulcers were smaller and those 10 healed in the next two weeks with no further treatment. Two patients' ulcers that initially healed with clearance of H pylori recurred three weeks later (both had metronidazole resistant H pylori). H pylori was eradicated in 28 of 44 (64%) patients (13C-UBT negative for median follow up 10.2 months). Overall 41 of 43 (93%, 95% confidence intervals 81%-99%) duodenal ulcers were healed at one month. This study suggests that one week of anti-H pylori triple treatment is effective in healing duodenal ulcers. PMID:8307442

  5. Ugh! Ulcers

    MedlinePlus

    ... sores, or ulcers, are caused. continue Who Has H. Pylori Infection? By testing someone's blood or bowel movements ( ... she has been exposed to and might have H. pylori . When tested, lots of people have H. pylori ...

  6. Ulcerative colitis

    MedlinePlus

    ... proctocolectomy - discharge Types of ileostomy Ulcerative colitis - discharge Review Date 8/14/2015 Updated by: Subodh K. ... gastroenterologist at Gastrointestinal Specialists of Georgia, Austell, GA. Review provided by VeriMed Healthcare Network. Internal review and ...

  7. Stomach ulcer

    MedlinePlus Videos and Cool Tools

    ... are absorbed in the small intestine. It produces acid and various enzymes that break down food into ... wall of the stomach is protected from the acid and enzymes by a mucous lining. Ulcers are ...

  8. Inflammation in chronic venous ulcers.

    PubMed

    Raffetto, J D

    2013-03-01

    Chronic venous ulcers (CVUs) occur in approximately 1% of the general population. Risk factors for chronic venous disease (CVD) include heredity, age, female sex and obesity. Although not restricted to the elderly, the prevalence of CVD, especially leg ulcers, increases with age. CVD has a considerable impact on health-care resources. It has been estimated that venous ulcers cause the loss of approximately two million working days and incur treatment costs of approximately $3 billion per year in the USA. Overall, CVD has been estimated to account for 1-3% of the total health-care budgets in countries with developed health-care systems. The pathophysiology of dermal abnormalities in CVU is reflective of a complex interplay that involves sustained venous hypertension, inflammation, changes in microcirculation, cytokine and matrix metalloproteinase (MMP) activation, resulting in altered cellular function and delayed wound healing.

  9. Clinical Features of Spontaneous Partial Healing During Mycobacterium ulcerans Infection

    PubMed Central

    Marion, Estelle; Chauty, Annick; Kempf, Marie; Le Corre, Yannick; Delneste, Yves; Croue, Anne; Marsollier, Laurent

    2016-01-01

    Background. Buruli ulcer, caused by Mycobacterium ulcerans, is a necrotizing skin disease leading to extensive cutaneous and subcutaneous destruction and functional limitations. Spontaneous healing in the absence of medical treatment occurs in rare cases, but this has not been well described in the literature. Methods. In a retrospective case study in an area of Benin where this disease is highly endemic, we selected 26 Buruli ulcer patients presenting features of spontaneous healing from a cohort of 545 Buruli ulcer patients treated between 2010 and 2013. Results. The 26 patients studied had a median age of 13.5 years and were predominantly male (1.4:1). Three groups of patients were defined on the basis of their spontaneous healing characteristics. The first group (12 patients) consisted of patients with an ulcer of more than 1 year′s duration showing signs of healing. The second (13 patients) group contained patients with an active Buruli ulcer lesion some distance away from a first lesion that had healed spontaneously. Finally, the third group contained a single patient displaying complete healing of lesions from a nodule, without treatment and with no relapse. Conclusions. We defined several features of spontaneous healing in Buruli ulcer patients and highlighted the difficulties associated with diagnosis and medical management. Delays in consultation contributed to the high proportion of patients with permanent sequelae and a risk of squamous cell carcinoma. Early detection and antibiotic treatment are the best ways to reduce impairments. PMID:26925431

  10. Misoprostol in peptic ulcer disease.

    PubMed

    Watkinson, G; Akbar, F A

    1987-01-01

    Misoprostol, a synthetic prostaglandin E1 (PGE1) methyl ester analog has potent antisecretory and cytoprotective effects on the gastric and duodenal mucosa which should make it an effective drug in the treatment of gastric and duodenal ulcer. In two multicenter, randomised, double-blind, controlled studies involving over 900 patients with endoscopically proven benign gastric ulcer and in six similar studies involving over 2000 patients with active duodenal ulcers, differing doses of misoprostol have been compared with either placebo therapy or with conventional doses of cimetidine. In these studies misoprostol 800 mcg daily given as two or four divided doses has been shown to produce rates of complete ulcer healing and pain relief which were significantly superior to placebo therapy and comparable to those achieved with cimetidine. Drug related adverse effects were infrequent. A dose related diarrhea occurred in a small proportion of patients which seldom necessitated suspension of therapy. Because of the known uterotropic effect of prostaglandins the drug should not be used in pregnant women or women of child bearing age unless they are using adequate contraceptive measures. No clinically significant adverse, hematological or biochemical effects have been reported. Two studies suggested that misoprostol reduced the adverse effect of smoking on the healing of duodenal ulcer. In addition, misoprostol has been shown to protect the gastro-duodenal mucosa from the damaging effects of alcohol and non-steroidal anti-inflammatory drugs. This action may prove of value in the treatment of ulcer patients who are inveterate smokers, alcohol users or who are compelled to consume non-steroidal anti-inflammatory drugs for pain relief from rheumatic and allied diseases.

  11. Treatment of sickle cell leg ulcers with pentoxifylline.

    PubMed

    Frost, M L; Treadwell, P

    1990-06-01

    A 58-year-old black man with leg ulcers of 43 years duration responded to pentoxifylline 400 mg tid in 8 months. The ability of pentoxifylline to increase erythrocyte flexibility and decrease blood viscosity was the basis for our use of this agent. Oral pentoxifylline may be a useful adjunct in healing sickle cell leg ulcers and preventing their recurrence.

  12. Diabetic foot ulcers. Pathophysiology, assessment, and therapy.

    PubMed Central

    Bowering, C. K.

    2001-01-01

    OBJECTIVE: To review underlying causes of diabetic foot ulceration, provide a practical assessment of patients at risk, and outline an evidence-based approach to therapy for diabetic patients with foot ulcers. QUALITY OF EVIDENCE: A MEDLINE search was conducted for the period from 1979 to 1999 for articles relating to diabetic foot ulcers. Most studies found were case series or small controlled trials. MAIN MESSAGE: Foot ulcers in diabetic patients are common and frequently lead to lower limb amputation unless a prompt, rational, multidisciplinary approach to therapy is taken. Factors that affect development and healing of diabetic patients' foot ulcers include the degree of metabolic control, the presence of ischemia or infection, and continuing trauma to feet from excessive plantar pressure or poorly fitting shoes. Appropriate wound care for diabetic patients addresses these issues and provides optimal local ulcer therapy with débridement of necrotic tissue and provision of a moist wound-healing environment. Therapies that have no known therapeutic value, such as foot soaking and topical antiseptics, can actually be harmful and should be avoided. CONCLUSION: Family physicians are often primary medical contacts for patients with diabetes. Patients should be screened regularly for diabetic foot complications, and preventive measures should be initiated for those at risk of ulceration. PMID:11398715

  13. Role of peroxisome proliferator-activated receptors alpha and gamma in gastric ulcer: An overview of experimental evidences

    PubMed Central

    Saha, Lekha

    2015-01-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three subtypes, PPARα, PPARβ/δ, and PPARγ, have been identified so far. PPARα is expressed in the liver, kidney, small intestine, heart, and muscle, where it activates the fatty acid catabolism and control lipoprotein assembly in response to long-chain unsaturated fatty acids, eicosanoids, and hypolipidemic drugs (e.g., fenofibrate). PPARβ/δ is more broadly expressed and is implicated in fatty acid oxidation, keratinocyte differentiation, wound healing, and macrophage response to very low density lipoprotein metabolism. This isoform has been implicated in transcriptional-repression functions and has been shown to repress the activity of PPARα or PPARγ target genes. PPARγ1 and γ2 are generated from a single-gene peroxisome proliferator-activated receptors gamma by differential promoter usage and alternative splicing. PPARγ1 is expressed in colon, immune system (e.g., monocytes and macrophages), and other tissues where it participates in the modulation of inflammation, cell proliferation, and differentiation. PPARs regulate gene expression through distinct mechanisms: Ligand-dependent transactivation, ligand-independent repression, and ligand-dependent transrepression. Studies in animals have demonstrated the gastric antisecretory activity of PPARα agonists like ciprofibrate, bezafibrate and clofibrate. Study by Pathak et al also demonstrated the effect of PPARα agonist, bezafibrate, on gastric secretion and gastric cytoprotection in various gastric ulcer models in rats. The majority of the experimental studies is on pioglitazone and rosiglitazone, which are PPARγ activators. In all the studies, both the PPARγ activators showed protection against the gastric ulcer and also accelerate the ulcer healing in gastric ulcer model in rats. Therefore, PPARα and PPARγ may be a target for gastric ulcer therapy

  14. Is the foot elevation the optimal position for wound healing of a diabetic foot?

    PubMed

    Park, D J; Han, S K; Kim, W K

    2010-03-01

    In managing diabetic foot ulcers, foot elevation has generally been recommended to reduce oedema and prevent other sequential problems. However, foot elevation may decrease tissue oxygenation of the foot more than the dependent position since the dependent position is known to increase blood flow within the arterial system. In addition, diabetic foot ulcers, which have peripheral vascular insufficiency, generally have less oedema than other wounds. Therefore, we argue that foot elevation may not be helpful for healing of vascularly compromised diabetic foot ulcers since adequate tissue oxygenation is an essential factor in diabetic wound healing. The purpose of this study was to evaluate the influence of foot height on tissue oxygenation and to determine the optimal foot position to accelerate wound healing of diabetic foot ulcers. This study included 122 cases (73 males and 47 females; two males had bilateral disease) of diabetic foot ulcer patients aged 40-93 years. Trans-cutaneous partial oxygen tension (TcpO(2)) values of diabetic feet were measured before and after foot elevation (n=21). Elevation was achieved by placing a foot over four cushions. We also measured foot TcpO(2) values before and after lowering the feet (n=122). Feet were lowered to the patient's tibial height, approximately 30-35 cm, beside a bed handrail. Due to the large number of lowering measurements, we divided them into five sub-groups according to initial TcpO(2.) Tissue oxygenation values were compared. Foot-elevation-lowered TcpO(2) values before and after elevation were 32.5+/-22.2 and 23.8+/-23.1 mmHg (p<0.01), respectively. Foot-lowering-augmented TcpO(2) values before and after lowering were 44.6+/-23.8 and 58.0+/-25.9 mmHg (p<0.01), respectively. The lower the initial TcpO(2) level, the more the TcpO(2) level increased. The foot lowering, rather than elevation, significantly augments TcpO(2) and may stimulate healing of diabetic foot ulcers.

  15. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds.

    PubMed

    Falanga, Vincent; Iwamoto, Satori; Chartier, Molly; Yufit, Tatyana; Butmarc, Janet; Kouttab, Nicholas; Shrayer, David; Carson, Polly

    2007-06-01

    The nonhematopoietic component of bone marrow includes multipotent mesenchymal stem cells (MSC) capable of differentiating into fat, bone, muscle, cartilage, and endothelium. In this report, we describe the cell culture and characterization, delivery system, and successful use of topically applied autologous MSC to accelerate the healing of human and experimental murine wounds. A single bone marrow aspirate of 35-50 mL was obtained from patients with acute wounds (n = 5) from skin cancer surgery and from patients with chronic, long-standing, nonhealing lower extremity wounds (n = 8). Cells were grown in vitro under conditions favoring the propagation of MSC, and flow cytometry and immunostaining showed a profile (CD29+, CD44+, CD105+, CD166+, CD34-, CD45-) highly consistent with published reports of human MSC. Functional induction studies confirmed that the MSC could differentiate into bone, cartilage, and adipose tissue. The cultured autologous MSC were applied up to four times to the wounds using a fibrin polymer spray system with a double-barreled syringe. Both fibrinogen (containing the MSC) and thrombin were diluted to optimally deliver a polymerized gel that immediately adhered to the wound, without run-off, and yet allowing the MSC to remain viable and migrate from the gel. Sequential adjacent sections from biopsy specimens of the wound bed after MSC application showed elongated spindle cells, similar to their in vitro counterparts, which immunostained for MSC markers. Generation of new elastic fibers was evident by both special stains and antibodies to human elastin. The application of cultured cells was safe, without treatment-related adverse events. A strong direct correlation was found between the number of cells applied (greater than 1 x 10(6) cells per cm2 of wound area) and the subsequent decrease in chronic wound size (p = 0.0058). Topical application of autologous MSC also stimulated closure of full-thickness wounds in diabetic mice (db

  16. Nutritional care in peptic ulcer

    PubMed Central

    VOMERO, Nathália Dalcin; COLPO, Elisângela

    2014-01-01

    Introduction Peptic ulcer is a lesion of the mucosal lining of the upper gastrointestinal tract characterized by an imbalance between aggressive and protective factors of the mucosa, having H. pylori as the main etiologic factor. Dietotherapy is important in the prevention and treatment of this disease. Aim To update nutritional therapy in adults' peptic ulcer. Methods Exploratory review without restrictions with primary sources indexed in Scielo, PubMed, Medline, ISI, and Scopus databases. Results Dietotherapy, as well as caloric distribution, should be adjusted to the patient's needs aiming to normalize the nutritional status and promote healing. Recommended nutrients can be different in the acute phase and in the recovery phase, and there is a greater need of protein and some micronutrients, such as vitamin A, zinc, selenium, and vitamin C in the recovery phase. In addition, some studies have shown that vitamin C has a beneficial effect in eradication of H. pylori. Fibers and probiotics also play a important role in the treatment of peptic ulcer, because they reduce the side effects of antibiotics and help reduce treatment time. Conclusion A balanced diet is vital in the treatment of peptic ulcer, once food can prevent, treat or even alleviate the symptoms involving this pathology. However, there are few papers that innovate dietotherapy; so additional studies addressing more specifically the dietotherapy for treatment of peptic ulcer are necessary. PMID:25626944

  17. VAC therapy to promote wound healing after surgical revascularisation for critical lower limb ischaemia.

    PubMed

    De Caridi, Giovanni; Massara, Mafalda; Greco, Michele; Pipitò, Narayana; Spinelli, Francesco; Grande, Raffaele; Butrico, Lucia; de Franciscis, Stefano; Serra, Raffaele

    2016-06-01

    Vacuum-assisted closure (VAC) therapy is a new emerging non-invasive system in wound care, which speeds up wound healing by causing vacuum, improving tissue perfusion and suctioning the exudates, and facilitating the removal of bacteria from the wound. The application of sub-atmospheric pressure on the lesions seems to alter the cytoskeleton of the cells on the wound bed, triggering a cascade of intracellular signals that increase the rate of cell division and subsequent formation of granulation tissue. The aim of this study is to analyse the results of VAC therapy used as an adjuvant therapy for the treatment of foot wounds in patients affected by critical limb ischaemia (CLI) (Rutherford 6 class) after distal surgical revascularisation, to promote and accelerate the healing of ulcers. Twenty-nine patients (20 males, 9 females; mean age 68·4) affected by CLI of Rutherford 6 class, after surgical revascularisation of the lower limb, underwent VAC therapy in order to speed up wound healing. Complete wound healing was achieved in 19 patients (65·51%), in an average period of 45·4 ± 25·6 days. VAC therapy is a valid aid, after surgical revascularisation, to achieve rapid healing of foot lesions in patients with CLI.

  18. Platelet-rich plasma (PRP) promotes fetal mesenchymal stem/stromal cell migration and wound healing process.

    PubMed

    Roubelakis, Maria G; Trohatou, Ourania; Roubelakis, Apostolos; Mili, Evgenia; Kalaitzopoulos, Ioannis; Papazoglou, Georgios; Pappa, Kalliopi I; Anagnou, Nicholas P

    2014-06-01

    Numerous studies have shown the presence of high levels of growth factors during the process of healing. Growth factors act by binding to the cell surface receptors and contribute to the subsequent activation of signal transduction mechanisms. Wound healing requires a complex of biological and molecular events that includes attraction and proliferation of different type of cells to the wound site, differentiation and angiogenesis. More specifically, migration of various cell types, such as endothelial cells and their precursors, mesenchymal stem/stromal cells (MSCs) or skin fibroblasts (DFs) plays an important role in the healing process. In recent years, the application of platelet rich plasma (PRP) to surgical wounds and skin ulcerations is becoming more frequent, as it is believed to accelerate the healing process. The local enrichment of growth factors at the wound after PRP application causes a stimulation of tissue regeneration. Herein, we studied: (i) the effect of autologous PRP in skin ulcers of patients of different aetiology, (ii) the proteomic profile of PRP, (iii) the migration potential of amniotic fluid MSCs and DFs in the presence of PRP extract in vitro, (iv) the use of the PRP extract as a substitute for serum in cultivating AF-MSCs. Considering its easy access, PRP may provide a valuable tool in multiple therapeutic approaches.

  19. Chronic leg ulceration in the community: changing the focus.

    PubMed

    Brown, Annemarie

    2010-09-01

    Compression therapy is considered the gold standard for healing chronic venous leg ulceration, and impressive healing rates are achievable for many patients. Unfortunately, this condition is chronic, characterized by frequent recurrences and, for some patients, ulcer healing may never occur. Within community services, commissioners of nursing services tend to focus on complete ulcer healing within a defined timescale as quality indicators. The challenge, therefore, will be for community nurses to demonstrate alternative but equally effective patient-centred outcome measures for nursing interventions when healing is delayed or does not occur. The current government health policy encourages active patient involvement in treatment, with an emphasis on self-care/management for patients with chronic conditions. Self-management interventions, such as the Expert Patient Programme (Department of Health, 2001) for chronic conditions, have been positively evaluated and have demonstrated considerable benefits for patients in terms of pain reduction and improved psychosocial wellbeing. This article briefly discusses the outcomes of such interventions and suggests that nurse-led self-care programmes could be adapted for leg ulcer patients in order to provide alternative outcome measures for nursing interventions when ulcer healing may not be achievable. This article also gives an overview of current innovations developed to encourage patient involvement and self-care in this client group.

  20. Nutritional Aspects of Gastrointestinal Wound Healing

    PubMed Central

    Mukherjee, Kaushik; Kavalukas, Sandra L.; Barbul, Adrian

    2016-01-01

    Significance: Although the wound healing cascade is similar in many tissues, in the gastrointestinal tract mucosal healing is critical for processes such as inflammatory bowel disease and ulcers and healing of the mucosa, submucosa, and serosal layers is needed for surgical anastomoses and for enterocutaneous fistula. Failure of wound healing can result in complications including infection, prolonged hospitalization, critical illness, organ failure, readmission, new or worsening enterocutaneous fistula, and even death. Recent Advances: Recent advances are relevant for the role of specific micronutrients, such as vitamin D, trace elements, and the interplay between molecules with pro- and antioxidant properties. Our understanding of the role of other small molecules, genes, proteins, and macronutrients is also rapidly changing. Recent work has elucidated relationships between oxidative stress, nutritional supplementation, and glucose metabolism. Thresholds have also been established to define adequate preoperative nutritional status. Critical Issues: Further work is needed to establish standards and definitions for measuring the extent of wound healing, particularly for inflammatory bowel disease and ulcers. In addition, a mounting body of evidence has determined the need for adequate preoperative nutritional supplementation for elective surgical procedures. Future Directions: A large portion of current work is restricted to model systems in rodents. Therefore, additional clinical and translational research is needed in this area to promote gastrointestinal wound healing in humans, particularly those suffering from critical illness, patients with enterocutaneous fistula, inflammatory bowel disease, and ulcers, and those undergoing surgical procedures. PMID:27867755

  1. Optimal management of digital ulcers in systemic sclerosis

    PubMed Central

    Abraham, Shawn; Steen, Virginia

    2015-01-01

    Raynaud’s phenomenon and digital ulcerations are two common clinical features seen in patients with systemic sclerosis. They are painful and lead to significant morbidity and altered hand function within this patient population. While currently there are no US Food and Drug Administration (FDA)-approved medications for the treatment of digital ulcerations in the United States, clinical trials have supported the use of pharmacologic and nonpharmacologic modalities in facilitating healing of existing digital ulcers and preventing formation of new ulcers. This article reviews the published data on these therapeutic options. PMID:26109864

  2. Wound healing: an overview of acute, fibrotic and delayed healing.

    PubMed

    Diegelmann, Robert F; Evans, Melissa C

    2004-01-01

    Acute wounds normally heal in a very orderly and efficient manner characterized by four distinct, but overlapping phases: hemostasis, inflammation, proliferation and remodeling. Specific biological markers characterize healing of acute wounds. Likewise, unique biologic markers also characterize pathologic responses resulting in fibrosis and chronic non-healing ulcers. This review describes the major biological processes associated with both normal and pathologic healing. The normal healing response begins the moment the tissue is injured. As the blood components spill into the site of injury, the platelets come into contact with exposed collagen and other elements of the extracellular matrix. This contact triggers the platelets to release clotting factors as well as essential growth factors and cytokines such as platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Following hemostasis, the neutrophils then enter the wound site and begin the critical task of phagocytosis to remove foreign materials, bacteria and damaged tissue. As part of this inflammatory phase, the macrophages appear and continue the process of phagocytosis as well as releasing more PDGF and TGF beta. Once the wound site is cleaned out, fibroblasts migrate in to begin the proliferative phase and deposit new extracellular matrix. The new collagen matrix then becomes cross-linked and organized during the final remodeling phase. In order for this efficient and highly controlled repair process to take place, there are numerous cell-signaling events that are required. In pathologic conditions such as non-healing pressure ulcers, this efficient and orderly process is lost and the ulcers are locked into a state of chronic inflammation characterized by abundant neutrophil infiltration with associated reactive oxygen species and destructive enzymes. Healing proceeds only after the inflammation is controlled. On the opposite end of the spectrum, fibrosis is characterized by

  3. Etiopathogenetic principles and peptic ulcer disease classification.

    PubMed

    Tytgat, G N J

    2011-01-01

    Ulceration corresponds to tissue loss, breaching the muscularis mucosae. When ulcers develop in the acid-peptic environment of the gastroduodenum, they are traditionally called peptic ulcer (PUD). Ulcers never develop spontaneously in a healthy gastroduodenal mucosa. Ulceration is the ultimate consequence of a disequilibrium between aggressive injurious factors and defensive mucosa-protective factors. The dominant aggressors are strong acid and high proteolytic (pepsin) activity in gastric secretions. The dominant defensors are the phospholipid surfactant layer, covering the mucus bicarbonate gel, the mucus bicarbonate layer covering the epithelium, the tight junctional structures between the epithelial cells, restricting proton permeability, and the epithelial trefoil peptides, contributing to healing after injury. Initially, acid-peptic aggression was considered the overwhelming cause of PUD, supported by the pioneering work of Schwartz, launching the dictum 'no acid, no ulcer'. This led to the universal therapy directed against intragastric acidity, also interfering with peptic activity when the pH was >4. The therapeutic sequence went from large doses of antacids to H(2)-receptor antagonists and finally to proton pump inhibitors (PPIs). The longer the intragastric pH was >3, the quicker ulcer healing was seen. Unfortunately, ulcers often recurred after stopping therapy, demanding maintenance therapy to keep the ulcers healed and to prevent the need for surgery (vagotomy, partial gastric resection). Later on, the emphasis gradually shifted to weakening/failing of the defensive factors, raising the vulnerability of the gastroduodenal mucosa to luminal secretions. Leading injurious mechanisms jeopardizing the mucosal integrity are numerous: infections, especially Helicobacter pylori, drug-induced injury, particularly acetylsalicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs), physicochemical and caustic injury, vascular disorders, interfering

  4. TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds.

    PubMed

    Qi, Yu; Jiang, Dongsheng; Sindrilaru, Anca; Stegemann, Agatha; Schatz, Susanne; Treiber, Nicolai; Rojewski, Markus; Schrezenmeier, Hubert; Vander Beken, Seppe; Wlaschek, Meinhard; Böhm, Markus; Seitz, Andreas; Scholz, Natalie; Dürselen, Lutz; Brinckmann, Jürgen; Ignatius, Anita; Scharffetter-Kochanek, Karin

    2014-02-01

    Proper activation of macrophages (Mφ) in the inflammatory phase of acute wound healing is essential for physiological tissue repair. However, there is a strong indication that robust Mφ inflammatory responses may be causal for the fibrotic response always accompanying adult wound healing. Using a complementary approach of in vitro and in vivo studies, we here addressed the question of whether mesenchymal stem cells (MSCs)-due to their anti-inflammatory properties-would control Mφ activation and tissue fibrosis in a murine model of full-thickness skin wounds. We have shown that the tumor necrosis factor-α (TNF-α)-stimulated protein 6 (TSG-6) released from MSCs in co-culture with activated Mφ or following injection into wound margins suppressed the release of TNF-α from activated Mφ and concomitantly induced a switch from a high to an anti-fibrotic low transforming growth factor-β1 (TGF-β1)/TGF-β3 ratio. This study provides insight into what we believe to be a previously undescribed multifaceted role of MSC-released TSG-6 in wound healing. MSC-released TSG-6 was identified to improve wound healing by limiting Mφ activation, inflammation, and fibrosis. TSG-6 and MSC-based therapies may thus qualify as promising strategies to enhance tissue repair and to prevent excessive tissue fibrosis.

  5. Improved Transplanted Stem Cell Survival in a Polymer Gel Supplemented With Tenascin C Accelerates Healing and Reduces Scarring of Murine Skin Wounds.

    PubMed

    Yates, Cecelia C; Nuschke, Austin; Rodrigues, Melanie; Whaley, Diana; Dechant, Jason J; Taylor, Donald P; Wells, Alan

    2017-01-24

    Mesenchymal stem cells (MSCs) remain of great interest in regenerative medicine because of their ability to home to sites of injury, differentiate into a variety of relevant lineages, and modulate inflammation and angiogenesis through paracrine activity. Many studies have found that despite the promise of MSC therapy, cell survival upon implant is highly limited and greatly reduces the therapeutic utility of MSCs. The matrikine tenascin C, a protein expressed often at the edges of a healing wound, contains unique EGF-like repeats that are able to bind EGFR at low affinities and induce downstream prosurvival signaling without inducing receptor internalization. In this study, we utilized tenascin C in a collagen/GAG-based polymer (TPolymer) that has been shown to be beneficial for skin wound healing, incorporating human MSCs into the polymer prior to application to mouse punch biopsy wound beds. We found that the TPolymer was able to promote MSC survival for 21 days in vivo, leading to associated improvements in wound healing such as dermal maturation and collagen content. This was most marked in a model of hypertrophic scarring, in which the scar formation was limited. This approach also reduced the inflammatory response in the wound bed, limiting CD3e+ cell invasion by approximately 50% in the early wound-healing process, while increasing the numbers of endothelial cells during the first week of wound healing as well. Ultimately, this matrikine-based approach to improving MSC survival may be of great use across a variety of cell therapies utilizing matrices as delivery vehicles for cells.

  6. A case series to describe the clinical characteristics of foot ulceration in patients with rheumatoid arthritis.

    PubMed

    Siddle, Heidi J; Firth, Jill; Waxman, Robin; Nelson, E Andrea; Helliwell, Philip S

    2012-03-01

    The aim of this study was to describe the clinical characteristics of foot ulceration in patients with rheumatoid arthritis (RA). Adults with RA and current foot ulceration but without diabetes were recruited. Clinical examination included assessment of RA disease activity, foot deformity, peripheral vascular disease, neuropathy and plantar pressures. Location, wound characteristics and time to healing were recorded for each ulcer. Participants completed the Health Assessment Questionnaire and Leeds Foot Impact Scale. Thirty-two cases with 52 current ulcers were recruited. Thirteen patients (41%) experienced more than one current ulcer: 5 (16%) had bilateral ulceration, 15 (47%) had previous ulceration at a current ulcer site. The majority (n = 33) of open ulcers were located over the dorsal aspect of the interphalangeal joints (n = 12), plantar aspect of the metatarsophalangeal joints (MTPJs) (n = 12) and medial aspect of first MTPJs (n = 9). In ulcerated limbs (n = 37), ankle brachial pressure index (ABPI) was <0.8 in 2 (5%); protective sensation was reduced in 25 (68%) and peak plantar pressures were >6 kg/cm(2) in 6 (16%). Mean ulcer size was 4.84 by 3.29 mm. Most ulcers (n = 42, 81%) were superficial; five (9.6%) were infected. Time to healing was available for 41 ulcers: mean duration was 28 weeks. Three ulcers remained open. In conclusion, foot ulceration in RA is recurrent and multiple ulcers are common. Whilst ulcers are small and shallow, time to achieve healing is slow, posing infection risk. Reduced protective sensation is common in affected patients. The prevalence of arterial disease is low but may be under estimated due to high intolerance of ABPI.

  7. [Influence of KU-1257 on the recurrence and relapse of acetic acid-induced chronic gastric ulcers in rats].

    PubMed

    Sekiguchi, H; Ohsawa, A; Kobayashi, F; Ohkubo, H; Taga, F

    1996-02-01

    The influence of KU-1257 on the recurrence and relapse of acetic acid ulcers in rats was investigated grossly and histologically in comparison with that of cimetidine. The ulcer was induced by topical application of glacial acetic acid at the junction of the corpus and antrum on the anterior wall of the stomach. The drug was administered from the 5th to the 153rd day after the ulcer induction and then discontinued to the 238th day. The healing rates of the control groups (control) rose until the 119th day after the ulcer induction, followed by ups and downs. The quality of healing in the regenerated mucosa and the granulation tissue of the healed ulcer was poor, resulting in the recurrence and relapse of ulcers. The recurrence and relapse of ulcers also occurred in the cimetidine groups (CIM). On the other hand, the KU-1257 groups (KU-1257) showed much lower recurrence and relapse rates of ulcers than the control and CIM groups. Moreover, KU-1257, unlike CIM, improved the quality of ulcer healing throughout the period of its administration and even after it was discontinued. These results suggest that KU-1257 improves the quality of ulcer healing, and this may contribute to the low recurrence and relapse rates of ulcers.

  8. Pharmacologic treatment of venous leg ulcers.

    PubMed

    Dormandy, J A

    1995-01-01

    In terms of prevalence, total cost and morbidity, venous leg ulcers are probably by far the most important type of ulcerations in the leg. The macrocirculatory defect leading to a raised ambulatory venous pressure is now accepted as a common initial pathologic pathway. Most current treatment modalities, such as surgery or external compression, are designed to control the macrovascular defect. However, it is the microcirculatory consequences of the venous hypertension that give rise to the trophic skin changes and ultimately to ulceration. At this microcirculatory level, pharmacotherapy may be a useful adjunct in the treatment of venous leg ulcers. The microcirculatory pathophysiologic changes include decreased fibrinolytic activity, elevated plasma fibrinogen, microcirculatory thrombi, and inappropriate activation of the white blood cells. The oxidative burst from the activated white cells probably plays a key role by releasing locally leukocyte-derived free radicals, proteolytic enzymes, cytokines, platelet-activating factor, and a number of other noxious mediators. An important additional component in recalcitrant venous ulcers is co-existing arterial disease, which is probably present in 15-20% of cases. Decreased arterial perfusion pressure will further aggravate the ischemic changes caused by the venous hypertension. Pentoxifylline downregulates leukocyte activation, reduces leukocyte adhesion, and also has fibrinolytic effects. A number of clinical studies have therefore been carried out to examine the clinical efficacy of pentoxifylline in treatment of venous leg ulcers. Probably the largest published placebo-controlled, double-blind randomized study was reported in 1990. In this study, 80 patients received either pentoxifylline 400 mg three times a day orally or matching placebo for 6 months or until their reference ulcer healed if this occurred sooner. Complete healing of the reference ulcer occurred in 23 of the 38 patients treated with pentoxifylline

  9. The effect of tri-potassium di-citrato bismuthate on the duodenal mucosa during ulceration. An ultrastructural study.

    PubMed

    Gregory, M A; Moshal, M G; Spitaels, J M

    1982-07-10

    The manner in which tri-potassium di-citrato bismuthate (TDB) promotes duodenal ulcer healing is not known. Endoscopic biopsy specimens were taken from the edges of duodenal ulcers from 5 patients before and after treatment with TDB. Using the bismuth contained within this drug as an electron-dense marker, the mode of action of TDB was determined by transmission electron microscopy. TDB was found to promote ulcer healing by adhering to the ulcerative mucosa, thereby providing an effective barrier to the substances which cause and maintain ulceration.

  10. [Evaluation of pressure ulcers area using the softwares Motic and AutoCAD®].

    PubMed

    Reis, Camila Letícia Dias dos; Cavalcante, Janaína Mortosa; Rocha Júnior, Edvar Ferreira da; Neves, Rinaldo Souza; Santana, Levy Aniceto; Guadagnin, Renato da Veiga; Brasil, Lourdes Mattos

    2012-01-01

    Pressure ulcer is a lesion that affects skin layers in some regions of the body and its healing can be followed up using image processing. The analysis of pressure ulcer area is relevant to evaluate its evolution and response to therapeutic procedures. Such areas can be evaluated through contour marking with the softwares Motic and AutoCAD®. In this study 35 volunteers computed areas from two grade III pressure ulcers using these instruments. It was possible to conclude that results are clinically equivalent and so can be considered to follow up healing evolution from pressure ulcers.

  11. Cyanoacrylate adhesive with conjunctival resection and superficial keratectomy in Mooren's ulcer.

    PubMed

    Agrawal, V; Kumar, A; Sangwan, V; Rao, G N

    1996-03-01

    Seventeen eyes of thirteen patients with Mooren's ulcer were treated with a combination therapy of local and systemic steroids, conjunctival resection, superficial keratectomy and application of cyanoacrylate tissue adhesive. The pathology was classified as acute, subacute and chronic. Ulcers were graded based on the extent of corneal thinning, degree and extent of ulceration, and amount of inflammation. Fourteen eyes (82.4%) healed completely with formation of a vascularised scars, while three eyes (17.6%) failed to respond to treatment and either went into phthisis bulbi or healed with gross tissue distortion. Our study suggests an early intervention of this therapy with cyanoacrylate tissue adhesive application for effective control of Mooren's ulceration.

  12. Ulcerative necrobiosis lipoidica successfully treated with photodynamic therapy: case report and literature review.

    PubMed

    Borgia, Francesco; Vaccaro, Mario; Cantavenera, Laura G; Aragona, Emanuela; Cannavò, Serafinella P

    2014-12-01

    Ulcerative necrobiosis lipoidica (NL) is a rare skin condition refractory to conventional therapies. We treated a forty-four year old woman affected by widespread ulcerative NL with 6 sessions of topical ALA-PDT at two weeks intervals. At the end of the treatment a dramatic improvement of the clinical features was observed, with complete healing of cutaneous ulcers and marked reduction of erythema in all the treated areas. The mechanism of action of PDT in ulcer healing is still unknown; however, it is possible to hypothesize a combination of anti-inflammatory effect, immunomodulatory activity and keratinocytes photoactivation.

  13. Red Deer Antler Extract Accelerates Hair Growth by Stimulating Expression of Insulin-like Growth Factor I in Full-thickness Wound Healing Rat Model.

    PubMed

    Yang, ZhiHong; Gu, LiJuan; Zhang, DongLiang; Li, Zheng; Li, JingJie; Lee, MiRa; Wang, ChunYan; Wang, Zhen; Cho, JeongHee; Sung, Changkeun

    2012-05-01

    In order to investigate and evaluate the effects of red deer antlers on hair growth in the full-thickness wound healing model, Sprague-Dawley rats were given incision wounds through the full thickness of their dorsal skin and deer antler was applied for 40 days. At specified intervals thereafter (4, 8, 16, 32 and 40 days), the animals were sacrificed and the wound site skins were excised, processed, and sectioned. At post-injury days 16, 32 and 40, longer and more active new hair appeared around the healing wound of antler-treated skin. Histological studies showed that the antler extract markedly increases the depth, size, and number of hair follicles. Expression of IGF-I (insulin-like growth factor) mRNA was detected by RT-PCR and real time RT-PCR. The result showed that the expression of IGF-I (days 16, 32, and 40) was obviously up-regulated in antler-treated skins compared to control skins. Similar results were seen in the ELISA analysis to quantify the IGF-I expression. These results support the notion that wound healing can cause hair growth by enhancing the expression of IGF-I. Deer antler extract appears to have the potential to promote hair growth and could be used in hair growth products.

  14. Skin ulceration due to cement.

    PubMed Central

    Robinson, S M; Tachakra, S S

    1992-01-01

    Despite legislation that requires manufacturers to inform the public about the dangers of contact with cement, severe ulceration from cement contact still occurs. We present a retrospective study of seven patients presenting to this department over a 2-year period. All were male and employed in the building trade, their injuries being sustained whilst at work. The injuries were to the lower limb, often multiple and required a median of seven visits before healing was complete. One required hospital admission and skin grafting. PMID:1449582

  15. The matricellular protein CCN1 promotes mucosal healing in murine colitis through IL-6.

    PubMed

    Choi, J S; Kim, K-H; Lau, L F

    2015-11-01

    The matricellular protein CCN1 (CYR61) is known to function in wound healing and is upregulated in colons of patients with Crohn's disease and ulcerative colitis, yet its specific role in colitis is unknown. Here we have used Ccn1(dm/dm) knockin mice expressing a CCN1 mutant unable to bind integrins α6β1 and αMβ2 as a model to probe CCN1 function in dextran sodium sulfate (DSS)-induced colitis. Ccn1(dm/dm) mice exhibited high mortality, impaired mucosal healing, and diminished interleukin-6 (IL-6) expression during the repair phase of DSS-induced colitis compared with wild-type mice, despite having comparable severity of initial inflammation and tissue injury. CCN1-induced IL-6 expression in macrophages through integrin αMβ2 and in fibroblasts through α6β1, and IL-6 promoted intestinal epithelial cell (IEC) proliferation. Administration of purified CCN1 protein fully rescued Ccn1(dm/dm) mice from DSS-induced mortality, restored IEC proliferation and enhanced mucosal healing, whereas delivery of IL-6 partially rectified these defects. CCN1 therapy accelerated mucosal healing and recovery from DSS-induced colitis even in wild-type mice. These findings reveal a critical role for CCN1 in restoring mucosal homeostasis after intestinal injury in part through integrin-mediated induction of IL-6 expression, and suggest a therapeutic potential for activating the CCN1/IL-6 axis for treating inflammatory bowel disease.

  16. IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice

    PubMed Central

    Kolumam, Ganesh; Wu, Xiumin; Lee, Wyne P.; Hackney, Jason A.; Zavala-Solorio, Jose; Gandham, Vineela; Danilenko, Dimitry M.; Arora, Puneet; Wang, Xiaoting; Ouyang, Wenjun

    2017-01-01

    Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. Mechanistically, when compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU. PMID:28125663

  17. Labral Healing

    PubMed Central

    Catan, Agustín; Vilaseca, Tomas; Arroquy, Damián; Carboni, Martín; Guiñazú, Jorge Eduardo; Orlowsky, Belén; Irigoitia, Nicolas; Chahla, Jorge

    2017-01-01

    Objectives: The purpouse of this study was to evaluate MRI images of labral repair after one year, trying to stablish MRI images as a reliable tool for the diagnosis of labral healing. Methods: One hundred and sixty-two patients presenting with femoroacetabular impingement that underwent an arthroscopic surgery were treated between 2012 and 2015. Of these, 124 met the selection criteria and were included in this study. Only patients with 12 months of follow up and labral repair were included. Patients with previous hip surgery were excluded. Coronal, sagittal and axial MRI cuts were evaluated by three independent observers, an arthroscopic hip surgery, a fellow in hip arthroscopic surgery and a musculoeskeletal radiologist. Results: on regard of our statistics 68% of the patients had labral healing images, 16% had no healing signals and 16% unsatisfactory images. Just in the 47% the observers had a 100% of agreement. Interobserver variation was: intraobserver agreement was 94% ( arthroscopic surgeon), 72 % (radiologist), 67 % (fellow). Conclusion: The main finding of this study was that a high inter and intraobserver variability was found when analysing the healing status of hip repaired labrums. Assessment of labrum healing after an arthroscopic repair should not only rely on imaging methods and therefore should be concurrently performed with a comprehensive physical examination.

  18. Pentadecapeptide BPC 157 and the esophagocutaneous fistula healing therapy.

    PubMed

    Cesarec, Vedran; Becejac, Tomislav; Misic, Marija; Djakovic, Zeljko; Olujic, Danijela; Drmic, Domagoj; Brcic, Luka; Rokotov, Dinko Stancic; Seiwerth, Sven; Sikiric, Predrag

    2013-02-15

    Esophagocutaneous fistulas are a failure of the NO-system, due to NO-synthase blockage by the NOS-blocker L-NAME consequently counteracted by l-arginine and gastric pentadecapeptide BPC 157 (l-arginine ulcer peptide, successful in inflammatory bowel disease trials, counteracting esophagitis, sphincter failure, gastrointestinal and skin ulcers, gastrocutaneous or colocutaneous fistulas. We treated rats with established cervical esophagocutaneous fistulas throughout four days (both open skin and esophageal defects, with significant leakage) with BPC 157 (parenterally and perorally) and L-NAME (blocking NO genesis) and l-arginine (NO-substrate) alone or in combination. RT-PCR investigated eNOS, iNOS, COX-2 mRNA levels in the fistulas. We evidenced a closely inter-related process of unhealed skin, esophageal defects, unhealed fistulas (up regulated eNOS, iNOS and COX2 mRNA levels), usually lethal, particularly NO-system related and therapy dependent. Generally, the course of fistula healing was accelerated either to a greater extent (with BPC 157 (in particular, less eNOS gene expression) completely counteracting L-NAME effects, in L-NAME+BPC 157 and L-NAME+l-arginine+BPC 157 groups), or to a lesser extent (with l-arginine). Conversely, the process was aggravated, rapidly and prominently (with L-NAME). In particular, BPC 157 was effective either given per-orally/intraperitoneally, in μg- and ng-regimens. Shortly, defects started to heal, with less fistula leakage and no mortality at day 4. Failure of pyloric and lower esophageal sphincter pressure was restored, with practically no esophagitis.

  19. [Non-Helicobacter pylori, Non-nonsteroidal Anti-inflammatory Drug Peptic Ulcer Disease].

    PubMed

    Chang, Young Woon

    2016-06-25

    Non-Helicobacter pylori, non-NSAID peptic ulcer disease (PUD), termed idiopathic PUD, is increasing in Korea. Diagnosis is based on exclusion of common causes such as H. pylori infection, infection with other pathogens, surreptitious ulcerogenic drugs, malignancy, and uncommon systemic diseases with upper gastrointestinal manifestations. The clinical course of idiopathic PUD is delayed ulcer healing, higher recurrence, higher re-bleeding after initial ulcer healing, and higher mortality than the other types of PUD. Genetic predisposition, older age, chronic mesenteric ischemia, cigarette smoking, concomitant systemic diseases, and psychological stress are considered risk factors for idiopathic PUD. Diagnosis of idiopathic PUD should systematically explore all possible causes. Management of this disease is to treat underlying disease followed by regular endoscopic surveillance to confirm ulcer healing. Continuous proton pump inhibitor therapy is an option for patients who respond poorly to the standard ulcer regimen.