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Sample records for accelerated ulcer healing

  1. 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.

  2. Traditional Japanese Formula Kigikenchuto Accelerates Healing of Pressure-Loading Skin Ulcer in Rats

    PubMed Central

    Kimura, Mari; Shibahara, Naotoshi; Hikiami, Hiroaki; Yoshida, Toshiko; Jo, Michiko; Kaneko, Maria; Nogami, Tatsuya; Fujimoto, Makoto; Goto, Hirozo; Shimada, Yutaka

    2011-01-01

    We evaluated the effect of kigikenchuto (KKT), a traditional Japanese formula, in a modified rat pressure-loading skin ulcer model. Rats were divided into three groups, KKT extract orally administered (250 or 500 mg/kg/day for 35 days) and control. KKT shortened the duration until healing. Immunohistochemically, KKT increased CD-31-positive vessels in early phase and increased α-smooth muscle actin-(α-SMA-) positive fibroblastic cells in early phase and decreased them in late phase of wound healing. By Western blotting, KKT showed the potential to decrease inflammatory cytokines (MCP-1, IL-1β, and TNF-α) in early phase, decrease vascular endothelial growth factor in early phase and increase it in late phase, and modulate the expression of extracellular protein matrix (α-SMA, TGF-β1, bFGF, collagen III, and collagen I). These results suggested the possibility that KKT accelerates pressure ulcer healing through decreases of inflammatory cytokines, increase of angiogenesis, and induction of extracellular matrix remodeling. PMID:21660308

  3. 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

  4. The probiotic mixture VSL#3 accelerates gastric ulcer healing by stimulating vascular endothelial growth factor.

    PubMed

    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 × 10(9) bacteria) or high (1.2 × 10(10) 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

  5. Polysaccharide-rich fraction of Termitomyces eurhizus accelerate healing of indomethacin induced gastric ulcer in mice.

    PubMed

    Chatterjee, Ananya; Khatua, Somanjana; Chatterjee, Sirshendu; Mukherjee, Shatavisa; Mukherjee, Atashi; Paloi, Soumitra; Acharya, Krishnendu; Bandyopadhyay, Sandip K

    2013-11-01

    The current study aims to determine the healing activity of water soluble polysaccharide-rich fraction of a wild mushroom, Termitomyces eurhizus (TEps) against the indomethacin induced gastric ulceration in mice model. Gastric tissue histology, myeloperoxidase (MPO) activity, cyclooxygenases (COX) 1 and 2 expression, prostaglandin E2 (PGE2) synthesis, and modulation of pro/anti inflammatory cytokines expression were studied for this purpose. Histological study shows that TEps (20 mg/kg) effectively healed the gastric ulceration. Based on biochemical results, the healing capacities of TEps could be attributed to reduction of MPO activity and protection of mucosal mucin content. Enhanced synthesis of PGE2 by modulation of COX-1 and COX-2 expression and a prominent shift of cytokines expression from pro (TNF-α, IL-1ß) to anti inflammatory (IL-10) side are also held responsible for ulcer healing. The preliminary study highlights the anti-ulcerogenic property of polysaccharide-rich fraction of Termitomyces eurhizus and opens an alternative cure for NSAID induced gastroduodenal diseases.

  6. Dehydrated Human Amnion/Chorion Grafts May Accelerate the Healing of Ulcers on Free Flaps in Patients With Venous Insufficiency and/or Lymphedema

    PubMed Central

    Friedman, Alex

    2016-01-01

    Objective: Ulceration of free flaps in patients with venous insufficiency and/or lymphedema is an uncommon but challenging problem. We hypothesized that dehydrated human amnion/chorion membrane (Epifix) grafts would accelerate healing of these challenging ulcers. Methods: Retrospective analysis of prospectively acquired data identified 8 lower extremity free flaps with ulcerations in the context of venous insufficiency and/or lymphedema. The first 4 were flaps that had been treated with conservative wound care to healing. The second group was treated conservatively initially but then converted to treatment with dehydrated human amnion/chorion membrane grafts. The primary endpoint was time to healing. Results: Comparison of Kaplan-Meier survival curves revealed a significant difference between the conservatively and dehydrated human amnion/chorion membrane–treated flap ulcers, favoring graft treatment (P = .0361). In those ulcers that healed, the average time to healing was 87 days for the conservative treatment group and 33 days for the dehydrated human amnion/chorion membrane treatment group (with an average of 1.7 grafts per ulcer). Conclusions: Dehydrated human amnion/chorion membrane may accelerate healing of ulcers on lower extremity free flaps in patient with lymphedema and/or venous disease in the treated leg.

  7. Dehydrated Human Amnion/Chorion Grafts May Accelerate the Healing of Ulcers on Free Flaps in Patients With Venous Insufficiency and/or Lymphedema

    PubMed Central

    Friedman, Alex

    2016-01-01

    Objective: Ulceration of free flaps in patients with venous insufficiency and/or lymphedema is an uncommon but challenging problem. We hypothesized that dehydrated human amnion/chorion membrane (Epifix) grafts would accelerate healing of these challenging ulcers. Methods: Retrospective analysis of prospectively acquired data identified 8 lower extremity free flaps with ulcerations in the context of venous insufficiency and/or lymphedema. The first 4 were flaps that had been treated with conservative wound care to healing. The second group was treated conservatively initially but then converted to treatment with dehydrated human amnion/chorion membrane grafts. The primary endpoint was time to healing. Results: Comparison of Kaplan-Meier survival curves revealed a significant difference between the conservatively and dehydrated human amnion/chorion membrane–treated flap ulcers, favoring graft treatment (P = .0361). In those ulcers that healed, the average time to healing was 87 days for the conservative treatment group and 33 days for the dehydrated human amnion/chorion membrane treatment group (with an average of 1.7 grafts per ulcer). Conclusions: Dehydrated human amnion/chorion membrane may accelerate healing of ulcers on lower extremity free flaps in patient with lymphedema and/or venous disease in the treated leg. PMID:27648116

  8. 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.

  9. Seasonal behaviour of healed duodenal ulcer.

    PubMed

    Gupta, A K; Pal, L S

    1998-04-01

    Incidence of peptic ulcer is more in people living at higher altitude and similarly relapse of healed duodenal ulcer is more in winter season. Seasonal behaviour of healed duodenal ulcer with or without maintenance therapy with H2 blockers was studied among subjects residing around Shimla (approximate altitude 7000 feet above mean sea level). Sixty-four subjects of endoscopically healed duodenal ulcer were alternatively advised placebo (32 subjects) and ranitidine 150 mg (32 subjects) at bed time as maintenance therapy for period of one year. Subjects were reviewed endoscopically and evaluated for H pylori by rapid urease test, every months or earlier if symptomatic. Relapse rate was analysed among 60 subjects at the end of one year. Cumulative relapse rate was found 60% in ranitidine group and 100% in placebo group. In ranitidine group percentage of relapse to number of endoscopic examinations was 21.4% throughout the year, but in placebo group during winter and spring season relapse was 87.5% of endoscopic examination whereas 57.2% during summer and fall season. Incidence of duodenal ulcer relapse without maintenance therapy was more in winter and spring season (October to March) as compared to summer and fall (April to September), whereas intermittent seasonal treatment is efficacious in prevention of duodenal ulcer relapse and also improves cost benefit ratio of ulcer treatment.

  10. Clopidogrel delays gastric ulcer healing in rats.

    PubMed

    Luo, Jiing-Chyuan; Huo, Teh-Ia; Hou, Ming-Chih; Lin, Hsiao-Yi; Li, Chung-Pin; Lin, Han-Chieh; Chang, Full-Young; Lee, Fa-Yauh

    2012-11-15

    Clopidogrel is not safe enough for the gastric mucosa in patients with high risk of peptic ulcer. This study aimed to explore if clopidogrel delays gastric ulcer healing and elucidate the involved mechanisms. Gastric ulcer was induced in rats and the ulcer size, mucosal epithelial cell proliferation of the ulcer margin, expression of growth factors [epidermal growth factor (EGF), basic fibroblast growth factor] and their receptors, and signal transduction pathways for cell proliferation were measured and compared between the clopidogrel-treated group and untreated controls. For the in vitro part, rat gastric mucosal epithelial cell line (RGM-1 cells) was used to establish EGF receptor over-expressed cells. Cell proliferation and molecular change under EGF treatment (10ng/ml) with and without clopidogrel (10(-6)M) were demonstrated. Ulcer size was significantly larger in the clopidogrel-treated group compared to the control and mucosal epithelial cell proliferation of the ulcer margin was significantly decreased in the clopidogrel-treated group (P<0.05). Clopidogrel (2mg and 10mg/kg/day) significantly decreased ulcer-induced gastric epithelial cell proliferation and ulcer-stimulated expressions of EGF receptor and phosphorylated extracellular signal-regulated kinase (PERK) at the ulcer margin (P<0.05). Clopidogrel (10(-6)M) also inhibited EGF-stimulated EGF receptor, PERK expression, and cell proliferation in RGM-1 cells (P<0.05), and caused much less inhibition of EGF-stimulated cell proliferation in EGF receptor over-expressed RGM-1 cells than in RGM-1 cells (22% vs. 32% reduction). In conclusion, clopidogrel delays gastric ulcer healing in rats via inhibiting gastric epithelial cell proliferation, at least by inhibition of the EGF receptor-ERK signal transduction pathway.

  11. Randomised controlled trial evaluating the efficacy of wrap therapy for wound healing acceleration in patients with NPUAP stage II and III pressure ulcer

    PubMed Central

    Mizuhara, Akihiro; Oonishi, Sandai; Takeuchi, Kensuke; Suzuki, Masatsune; Akiyama, Kazuhiro; Kobayashi, Kazuyo; Matsunaga, Kayoko

    2012-01-01

    Objectives To evaluate if ‘wrap therapy’ using food wraps, which is widely used in Japanese clinical sites, is not inferior when compared to guideline adhesion treatments. Design Multicentre, prospective, randomised, open, blinded endpoint clinical trial. Setting 15 hospitals in Japan. Patients 66 older patients with new National Pressure Ulcer Advisory Panel stage II or III pressure ulcers. Interventions Of these 66 patients, 31 were divided into the conventional treatment guidelines group and 35 into the wrap therapy group. Main outcome measures The primary end point was the period until the pressure ulcers were cured. The secondary end point was a comparison of the speed of change in the Pressure Ulcer Scale for Healing score. Results 64 of the 66 patients were analysed. The estimated mean period until healing was 57.5 days (95% CI 45.2 to 69.8) in the control group as opposed to 59.8 days (95% CI 49.7 to 69.9) in the wrap therapy group. By the extent of pressure ulcer infiltration, the mean period until healing was 16.0 days (95% CI 8.1 to 23.9) in the control group as opposed to 18.8 days (95% CI 10.3 to 27.2) in the wrap therapy group with National Pressure Ulcer Advisory Panel stage II ulcers, and 71.8 days (95% CI 61.4 to 82.3) as opposed to 63.2 days (95% CI 53.0 to 73.4), respectively, with stage III ulcers. There is no statistical significance in difference in Pressure Ulcer Scale for Healing scores. Conclusions It might be possible to consider wrap therapy as an alternative choice in primary care settings as a simple and inexpensive dressing care. Clinical Trial registration UMIN Clinical Trials Registry UMIN000002658. Summary protocol is available on https://upload.umin.ac.jp/cgi-bin/ctr/ctr.cgi?function=brows&action=brows&type=detail&recptno=R000003235&admin=0&language=J PMID:22223842

  12. Effect of ranitidine on healing of experimentally induced gastric ulcers in ponies.

    PubMed

    MacAllister, C G; Sangiah, S

    1993-07-01

    Thirty young ponies were examined endoscopically for evidence of gastric ulceration. Seven ponies had noninduced gastric ulcers present at the initial examination and were eliminated from the study. In an attempt to induce gastric ulcers experimentally, flunixin meglumine (1.1 mg/kg of body weight, IM, q 8 h) was administered for 7 days to the 23 ponies with endoscopically normal gastric mucosa. During the 7 days of flunixin administration, 11 ponies developed gastric ulcers that were appropriate for study. The 11 ponies were randomly allotted to 2 groups. Group-A (n = 5) and group-B (n = 6) ponies received ranitidine (4.4 mg/kg, PO, q 8 h) and corn syrup, respectively, until ulcers healed or for a maximum of 40 days. General anesthesia was induced every 3 to 5 days for visual evaluation of ulcer healing by use of a video endoscope. The earliest complete healing of gastric lesions observed in a corn syrup-treated pony was at 17 days. At 40 days, 3 of 5 and 3 of 6 ponies of the ranitidine and corn syrup-treated groups, respectively, had healed ulcers. Results of this study indicate that: noninduced gastric ulcers may be common in young ponies, flunixin meglumine may be effective in inducing gastric ulcers for gastric healing studies in young ponies, and ranitidine (4.4 mg/kg, q 8 h) is not significantly effective in accelerating healing of experimentally induced gastric ulcers in ponies under conditions of this study. PMID:8368605

  13. Attempts to accelerate wound healing.

    PubMed

    Kasuya, Akira; Tokura, Yoshiki

    2014-12-01

    Wound healing is a well-orchestrated process, where numerous factors are activated or inhibited in a sequence of steps. Immediately after the infliction of damage, the repair of wound stars. The initial step is an inflammatory change with activation of innate immunity, which is followed by proliferation phase, including fibroplasia, angiogenesis and re-epithelialization. Pathological impairment of wound healing process may lead to persistent ulceration as seen in diabetic patients. Various signaling pathways are involved in wound healing. TGFβ/Smad pathway is a representative and well known to participate in fibroplasia, however, its comprehensive effect on wound healing is controversial. Experimental and clinical remedies have been being tried to promote wound healing. Advancement of cell engineering allows us to use stem cells and living skin equivalents.

  14. 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

  15. Role of matrix metalloproteinases in non-healing venous ulcers.

    PubMed

    Amato, Bruno; Coretti, Guido; Compagna, Rita; Amato, Maurizio; Buffone, Gianluca; Gigliotti, Diego; Grande, Raffaele; Serra, Raffaele; de Franciscis, Stefano

    2015-12-01

    Chronic venous ulceration (CVU) of the lower limbs is a common condition affecting 1% of the adult population in Western countries, which is burdened with a high complication rate and a marked reduction in the quality of life often due to prolonged healing time. Several metalloproteinases (MMPs) such as MMP-9 together with neutrophil gelatinase-associated lipocalin (NGAL) appear to be involved in the onset and healing phases of venous ulcer, but it is still unclear how many biochemical components are responsible for prolonged healing time in those ulcers. In this study, we evaluate the role of MMP-1 and MMP-8 in long lasting and refractory venous ulcers. In a 2-year period we enroled 45 patients (28 female and 17 male, median age 65) with CVU. The enroled population was divided into two groups: group I were patients with non-healing ulcers (ulcers that had failed to heal for more than 2 months despite appropriate treatments) and group II were patients with healing ulcers (ulcers in healing phases). MMP-1 and MMP-8 were measured in fluids and tissues of healing and non-healing ulcers by means of enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. In particular the patterns of the collagenases MMP-1 and MMP-8 in healing wounds were distinct, with MMP-8 appearing in significantly greater amounts especially in the non-healing group. Our findings suggest that MMP-1, and MMP-8 are overexpressed in long lasting CVU. Therefore, this dysregulation may represent the main cause of the pathogenesis of non-healing CVU.

  16. Health literacy and diabetic foot ulcer healing.

    PubMed

    Margolis, David J; Hampton, Michelle; Hoffstad, Ole; Malay, D Scot; Thom, Stephen

    2015-01-01

    The adherence by patients to diabetic foot ulcer therapy is often difficult. The goal of this study was to begin to understand how a patient's health literacy affects their foot ulcer management decisions. Initially using a cross-sectional study design, we evaluated diabetics with foot ulcers within 4 weeks of being asked to participate in a longitudinal study. We assessed health literacy using measures of general health literacy, diabetes health literacy, diabetes self-efficacy, and diabetes numeracy. Individuals enrolled in the study had higher health literacy based on the Short Test of Functional Health Literacy in Adults [33.8 (SD 2.3) versus 27.3 (SD 9.6); p = 0.009] as compared to individuals who previously declined an invitation to enroll in the study. Furthermore, patients with lower Short Test of Functional Health Literacy in Adults scores had larger (p = 0.04) and older (p = 0.125) wounds (markers for poorer prognosis). Other measures of literacy showed similar results. In conclusion, those with diminished health literacy were less likely to enroll in an investigational study and had wounds that were less likely to heal.

  17. The effect of nitric oxide releasing cream on healing pressure ulcers

    PubMed Central

    Saidkhani, Vahid; Asadizaker, Marziyeh; Khodayar, Mohammad Javad; Latifi, Sayed Mahmoud

    2016-01-01

    Background: Pressure ulcer is one of the main concerns of nurses in medical centers around the world, which, if untreated, causes irreparable problems for patients. In recent years, nitric oxide (NO) has been proposed as an effective method for wound healing. This study was conducted to determine the effect of nitric oxide on pressure ulcer healing. Materials and Methods: In this clinical trial, 58 patients with pressure ulcer at hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences were homogenized and later divided randomly into two groups of treatment (nitric oxide cream; n = 29) and control (placebo cream; n = 29). In this research, the data collection tool was the Pressure Ulcer Scale for Healing (PUSH). At the outset of the study (before using the cream), the patients' ulcers were examined weekly in terms of size, amount of exudates, and tissue type using the PUSH tool for 3 weeks. By integrating these three factors, wound healing was determined. Data were analyzed using SPSS. Results: Although no significant difference was found in terms of the mean of score size, the amount of exudates, and the tissue type between the two groups, the mean of total score (healing) between the two groups was statistically significant (P = 0.04). Conclusions: Nitric oxide cream seems to accelerate wound healing. Therefore, considering its easy availability and cost-effectiveness, it can be used for treating pressure ulcers in the future. PMID:27186212

  18. Efficacy of Collagen Particles in Chronic Non Healing Ulcers

    PubMed Central

    Kumar, Yogesh; Kini, U Anand

    2015-01-01

    Introduction Chronic foot ulcers will lead to a significant and prolonged stress to the patients. Pain and discomfort that may be acute or continuous is the usual complaint in chronic non healing ulcers that may even exacerbate with change of the dressings. The end process in any wound healing is wound contracture and scar formation. Collagen plays an important role in this stage of wound healing. Collagen particles were used in chronic non healing ulcer management to prove their efficacy when compared with conventional dressing in a study conducted by us. Objective To compare the healing process in non healing ulcers using collagen particles with those of conventional method of dressing (betadine). Materials and Methods It was a non randomized, prospective study conducted for a period of October 2012 to October 2014 in hospitals belonging to Kasturba medical college. Non concurrent pre and post comparative study; between collagen group and conventional dressing group. A total of 110 patients with chronic ulcers were included; each group comprising 55 patients. Results There was a significant decrease in wound size with a mean difference of 37.29 in experimental group when compared to 14.29 in control group. Conclusion Collagen dressing is effective in management of chronic non healing ulcers when compared to conventional betadine dressing. It heals by forming an early granulation tissue and thus reducing the length of hospital stay. PMID:26266157

  19. Importance of luminal and mucosal zinc in the mechanism of experimental gastric ulcer healing.

    PubMed

    Opoka, W; Adamek, D; Plonka, M; Reczynski, W; Bas, B; Drozdowicz, D; Jagielski, P; Sliwowski, Z; Adamski, P; Brzozowski, T

    2010-10-01

    induction (day 0) and at day 3 but then it rose significantly at day 7 after ulcer induction. Treatment with zinc hydroaspartate (65 mg/kg-d i.g.), which significantly raised the gastric luminal and mucosal levels of Zn(2+), significantly accelerated ulcer healing at day 7 upon ulcer induction. The GBF, which reached a significantly higher value at the ulcer margin than the ulcer bed, was significantly increased in rats treated with zinc hydroaspartate compared with vehicle-controls. The gastric acid output was significantly inhibited in GF rats with gastric ulcer at day 3 then restored at day 14 followed by a significant rise in the plasma gastrin levels. Treatment with zinc hydroaspartate significantly inhibited gastric secretion and also significantly raised the plasma gastrin level when compared to vehicle-control rats. We concluded that 1) trace micronutrients such as Zn(2+) could be successfully measured in the gastric juice and gastric mucosa during ulcer healing; 2) compounds chelating of Zn(2+) can exert a beneficial influence on the ulcer healing via Zn(2+) mediated increase in gastric microcirculation, antisecretory activity and gastrin release, which may enhance the cell proliferation and differentiation during ulcer healing, ultimately exerting a trophic action on the ulcerated gastric mucosa.

  20. Heat treatment enhances healing process of experimental pseudomonas corneal ulcer.

    PubMed

    Nanbu, Patricia Naomi; Wakabayashi, Taketoshi; Yamashita, Ryoko; Hayashi, Hideo; Hisano, Setsuji; Oshika, Tetsuro

    2004-01-01

    We investigated the effects of hyperthermia on the healing process of experimental Pseudomonas corneal ulceration (PCU). Hartley guinea pigs were used to develop animal models of PCU. As a heat source, disposable chemical pocket warmers were applied. The healing process of PCU was compared between the heat-treated corneas and the control corneas. The severity of infection and the degree of angiogenesis were classified by a clinical scoring system. The animals were euthanized 14 days after infection and the corneas were submitted for histopathological examination. The expression of vascular endothelial growth factor (VEGF) was examined immunohistochemically. Comparative reverse transcription polymerase chain reaction was performed to measure the expression level of VEGF in the cornea. Hyperthermia significantly promoted corneal epithelization and neovascularization in the PCU model. Heat treatment significantly decreased the number of viable Pseudomonas organisms present in PCU. On immunohistochemistry, the heated cornea demonstrated more intense staining for VEGF. Comparative reverse transcription polymerase chain reaction showed upregulation of the expression level of VEGF mRNA in the heat-treated cornea. Hyperthermia accelerated the healing process of PCU with increased corneal neovascularization. Angiogenesis may play an important role in the PCU healing process, which is enhanced by the heat treatment. PMID:15292660

  1. 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.

  2. 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. PMID:23036453

  3. Nerve growth factor injected into the gastric ulcer base incorporates into endothelial, neuronal, glial and epithelial cells: implications for angiogenesis, mucosal regeneration and ulcer healing.

    PubMed

    Tanigawa, T; Ahluwalia, A; Watanabe, T; Arakawa, T; Tarnawski, A S

    2015-08-01

    A previous study has demonstrated that locally administered growth factors such as epidermal growth factor, basic fibroblast growth factor and hepatocyte growth factor can accelerate healing of experimental gastric ulcers in rats. That study indicates that locally administered growth factors can exert potent biological effects resulting in enhanced gastric ulcers healing. However, the fate of injected growth factors, their retention and localization to specific cellular compartments have not been examined. In our preliminary study, we demonstrated that local injection of nerve growth factor to the base of experimental gastric ulcers dramatically accelerates ulcer healing, increases angiogenesis - new blood vessel formation, and improves the quality of vascular and epithelial regeneration. Before embarking on larger, definitive and time sequence studies, we wished to determine whether locally injected nerve growth factor is retained in gastric ulcer's tissues and taken up by specific cells during gastric ulcer healing. Gastric ulcers were induced in anesthetized rats by local application of acetic acid using standard methods; and, 60 min later fluorescein isothiocyanate-labeled nerve growth factor was injected locally to the ulcer base. Rats were euthanized 2, 5 and 10 days later. Gastric specimens were obtained and processed for histology. Unstained paraffin sections were examined under a fluorescence microscope, and the incorporation of fluorescein isothiocyanate-labeled nerve growth factor into various gastric tissue cells was determined and quantified. In addition, we performed immunostaining for S100β protein that is expressed in neural components. Five and ten days after ulcer induction labeled nerve growth factor (injected to the gastric ulcer base) was incorporated into endothelial cells of blood vessels, neuronal, glial and epithelial cells, myofibroblasts and muscle cells. This study demonstrates for the first time that during gastric ulcer healing

  4. 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.

  5. Risk factors for healing of duodenal ulcer under antacid treatment: do ulcer patients need individual treatment?

    PubMed

    Massarrat, S; Müller, H G; Schmitz-Moormann, P

    1988-03-01

    In order to identify the risk factors affecting the healing of duodenal ulcer, a clinical trial with effective dose of antacid was carried out in 53 patients. Duration of ulcer history, number of relapses, duration of the last and present relapse, number, duration and severity of pain attacks in the present ulcer relapse, pain radiation to back, vomiting, appetite, smoking habit, intake of analgesics and previous haemorrhage were registered. Number of ulcers, ulcer depth, bublar narrowing, erosions, duodenitis at initial endoscopy and healing of ulcer were assessed by one endoscopist. Basic and peak acid output were measured. The extent of duodenitis on the site opposite the ulcer was determined by histological examination. Sixty per cent of the duodenal ulcers were healed after three weeks. By univariate analysis, the following factors affect the healing; pain radiation to back and pain duration during treatment (p less than 0.001), multiple or deep ulcers, narrowing of duodenal bulb (p less than 0.01), number of pain attacks and poor appetite (p less than 0.05). By the stepwise logistic regression model, the following factors were selected as predictors for healing of duodenal ulcer with 76% correct classification: pain radiation to back (p = 0.002), deep ulcer (p = 0.013), multiple ulcers (p = 0.028). Number of cigarettes/day (p less than 0.007) and male sex (p = 0.036). By this model, the prediction of healing could be accurately assessed in 78% in a new sample. Individual treatment should be carried out on the basis of these factors. PMID:3356359

  6. Pressure ulcers: a strategic plan to prevent and heal them.

    PubMed

    Levine, J M; Totolos, E

    1995-01-01

    Pressure ulcers are common in frail, disabled, or acutely ill older patients in the home, hospital, or nursing home. Prevention is the most important aspect of pressure ulcer care, and physician and nurse share in this responsibility. A nosocomial pressure ulcer adds significantly to mortality, morbidity, and hospital length-of-stay. Risk factor assessment scales can help identify patients who need prevention efforts, such as pressure relief, incontinence care, and nutritional supplements. When an ulcer does occur, careful documentation is required, including staging, size and depth description, and review of the interdisciplinary care plan. Knowledge of wound biology and cost-effectiveness should guide the choice of wound healing products.

  7. The healing of gastric ulcers by zinc sulphate.

    PubMed

    Frommer, D J

    1975-11-22

    A double-blind trial of zinc sulphate given by mouth (220 mg, three times a day) and placebo was undertaken in patients with benign gastric ulcers. The drug was given for a three-week period and the healing of the ulcers was estimated from results of barium-meal X-ray films taken immediately before and after this period. There were ten patients taking zinc sulphate and eight patients taking placebo. The two groups of patients were comparable in all respects, including initial ulcer size. Patients taking zinc sulphate had an ulcer healing rate three times that of patients treated with placebo. This difference was significant (P less than 0-05). Complete healing of ulcers occurred more frequently in the patients taking zinc sulphate than in patients treated with placebo. The placebo group contained more patients whose ulcers did not heal at all, than the group taking zinc sulphate. No side effects from zinc sulphate were noted. There was no evidence of zinc deficiency in any of the patients.

  8. Enhancement of gastric ulcer healing and angiogenesis by cochinchina Momordica seed extract in rats.

    PubMed

    Kang, Jung Mook; Kim, Nayoung; Kim, Bongcheol; Kim, Joo-Hyon; Lee, Bong-Yong; Park, Ji Hyun; Lee, Mi Kyoung; Lee, Hye Seung; Kim, Joo Sung; Jung, Hyun Chae; Song, In Sung

    2010-06-01

    Cochinchina momordica seed is the dried ripe seed of Momordica cochinchinensis, a perennial vine. The antiulcer effect of an extract from cochinchina momordica seeds (SK-MS10) was evaluated in a rat model of acetic acid-induced gastric ulcers. Gastric ulcers were produced by subserosal injection of acetic acid. SK-MS10 (200 mg/kg) or vehicle was administered orally once per day for 14 days after the acetic acid injection. The stomach was removed and the ulcer size measured at day 7 and 14 of the treatment. Expression of vascular endothelial growth factor (VEGF) was assessed by real-time RT-PCR and Western blot analysis. In addition, the microvasculature density (MVD) adjacent to the ulcer margin was examined by immunohistochemistry. The treatment with SK-MS10 for 7 and 14 days significantly accelerated ulcer healing and increased the expression of mRNA (at day 7) as well as VEGF protein (at day 14) compared to the vehicle-treated rats. The MVD for factor VIII was also higher in the SK-MS10 treatment group compared to the vehicle-treated rats; however, these differences were not statistically significant. These results suggest that SK-MS10 treatment accelerates the healing of gastric ulcers via upregulation of VEGF and angiogenesis in an acetic acid rat model. PMID:20514308

  9. Enhancement of gastric ulcer healing and angiogenesis by cochinchina Momordica seed extract in rats.

    PubMed

    Kang, Jung Mook; Kim, Nayoung; Kim, Bongcheol; Kim, Joo-Hyon; Lee, Bong-Yong; Park, Ji Hyun; Lee, Mi Kyoung; Lee, Hye Seung; Kim, Joo Sung; Jung, Hyun Chae; Song, In Sung

    2010-06-01

    Cochinchina momordica seed is the dried ripe seed of Momordica cochinchinensis, a perennial vine. The antiulcer effect of an extract from cochinchina momordica seeds (SK-MS10) was evaluated in a rat model of acetic acid-induced gastric ulcers. Gastric ulcers were produced by subserosal injection of acetic acid. SK-MS10 (200 mg/kg) or vehicle was administered orally once per day for 14 days after the acetic acid injection. The stomach was removed and the ulcer size measured at day 7 and 14 of the treatment. Expression of vascular endothelial growth factor (VEGF) was assessed by real-time RT-PCR and Western blot analysis. In addition, the microvasculature density (MVD) adjacent to the ulcer margin was examined by immunohistochemistry. The treatment with SK-MS10 for 7 and 14 days significantly accelerated ulcer healing and increased the expression of mRNA (at day 7) as well as VEGF protein (at day 14) compared to the vehicle-treated rats. The MVD for factor VIII was also higher in the SK-MS10 treatment group compared to the vehicle-treated rats; however, these differences were not statistically significant. These results suggest that SK-MS10 treatment accelerates the healing of gastric ulcers via upregulation of VEGF and angiogenesis in an acetic acid rat model.

  10. 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.

  11. 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

  12. 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.

  13. Healing times and prediction of wound healing in neuropathic diabetic foot ulcers: a prospective study.

    PubMed

    Zimny, S; Pfohl, M

    2005-02-01

    Time line of wound healing and prediction of healing times in diabetic foot ulcers is an important issue. Usually, the percentage of wounds healed within a defined period is used for characterization of wound healing. R=sqrtA/pi (R, radius; A, planimetric wound area; pi, constant 3.14), and the wound radius reduction was 0.39 mm/week which was previously established. The initial average wound area was 96.9+/-13.1 mm2 (mean+/-SEM), and 3.61+/-1.6 mm 2 after ten weeks with an average healing time of 75.9 (95 %-CI 71-81) days. Using the equation mentioned above and the calculated weekly wound radius reduction, the predicted healing time in the test group was 86.9 (95 %-CI 73-101) days. The predicted and the observed healing times were significantly correlated with each other (r=0.55, p=0.0002). Providing standard care, the time needed for wound healing can reliably be predicted in neuropathic diabetic foot ulcers. This may be a useful tool in daily clinical practice to predict wound healing and recognize ulcers who do not respond adequately to the treatment. PMID:15772900

  14. Efficacious Healing of Ulcerated Infantile Hemangiomas Using Topical Timolol

    PubMed Central

    Chang, Chun-Shin

    2016-01-01

    Summary: Infantile hemangiomas (IHs) are the most common benign pediatric soft-tissue tumors. Ulceration—the most frequent complication of IH—tends to heal poorly and is associated with pain, bleeding, infection, and scarring. Mainstay treatment modalities include propranolol (β-blocker) and corticosteroids, whose effectiveness is countered by a need for long-term medication and risk of systemic adverse effects and ulcer recurrence. A 3-month-old infant presented to us with a large, medial thigh-ulcerated IH that progressed despite 2 prior months of dressings and topical antimicrobials. Topical timolol 0.5% thrice daily was initiated, and significant healing was evident at 1 week, with complete healing at 1 month. Timolol was stopped after 3 months, and at 18 months after cessation of timolol, there was no ulcer recurrence. This novel therapy for ulcerated IH seems to have many advantages such as rapid efficacy with easy application, no systemic adverse effects and no long-term recurrence, and current literature describing similar advantages justifies the use of this treatment modality in infants. PMID:27014550

  15. Healing, antioxidant and cytoprotective properties of Indigofera truxillensis in different models of gastric ulcer in rats.

    PubMed

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

    2012-11-15

    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 PGE(2) 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.

  16. 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.

  17. 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.

  18. Degrees of acid suppression and ulcer healing: dosage considerations.

    PubMed

    Pounder, R E

    1991-01-01

    The human stomach has a normal circadian rhythm of intragastric acidity characterized by increasing acidity during the day and peaks in the early hours of the morning. Eating causes a transient decrease of intragastric acidity. Acid appears to be the permissive factor in peptic ulcer disease and to be responsible for symptoms; the patient with duodenal ulcer may secrete too much acid. Pharmacological control of gastric acid secretion will speed ulcer healing. Modern regimens, which typically use a bedtime dose of an H2-receptor antagonist, produce a pulse of decreased acidity. Intragastric acidity is decreased during the night and early morning, leaving a normal profile of acidity during the day and early evening. Higher or more frequent doses of an antisecretory agent can produce a more profound decrease of 24-h intragastric acidity. Theoretical problems associated with a sustained or profound decrease of 24-h intragastric acidity include the threat of enteric infection and infestation, potential bacterial overgrowth with possible N-nitrosamine formation, and drug-induced hypergastrinaemia. In light of these potential problems, for the management of simple peptic ulceration, it appears sensible to use the minimum intervention required. Bedtime H2-receptor blockade is one such regimen. The more potent antisecretory regimens can be used for difficult clinical problems such as the Zollinger-Ellison syndrome, intractable duodenal ulceration, and severe oesophagitis.

  19. Topical Administration of a Connexin43-based peptide Augments Healing of Chronic Neuropathic Diabetic Foot Ulcers: A Multicenter, Randomized Trial

    PubMed Central

    Grek, Christina L.; Prasad, G.M.; Viswanathan, Vijay; Armstrong, David G.; Gourdie, Robert G.; Ghatnekar, Gautam S.

    2015-01-01

    Nonhealing neuropathic foot ulcers remain a significant problem in individuals with diabetes. The gap-junctional protein connexin43 (Cx43) has roles in dermal wound healing and targeting Cx43 signaling accelerates wound reepithelialization. In a prospective, randomized, multi-center clinical trial we evaluated the efficacy and safety of a peptide mimetic of the C-terminus of Cx43, ACT1, in accelerating the healing of chronic diabetic foot ulcers (DFUs) when incorporated into standard of care protocols. Adults with DFUs of at least four weeks duration were randomized to receive standard of care with or without topical application of ACT1. Primary outcome was mean percent ulcer reepithelialization and safety variables included incidence of treatment related adverse events and detection of ACT1 immunogenicity. ACT1 treatment was associated with a significantly greater reduction in mean percent ulcer area from baseline to 12 weeks (72.1% vs. 57.1%; p = 0.03). Analysis of incidence and median time-to-complete-ulcer closure revealed that ACT1 treatment was associated with a greater percentage of participants that reached 100% ulcer reepitheliazation and a reduced median time-to-complete-ulcer closure. No adverse events reported were treatment related, and ACT1 was not immunogenic. Treatment protocols that incorporate ACT1 may present a therapeutic strategy that safely augments the reepithelialization of chronic DFUs. PMID:25703647

  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. The effects of ulcer size on the wound radius reductions and healing times in neuropathic diabetic foot ulcers.

    PubMed

    Zimny, S; Schatz, H; Pfohl, M

    2004-04-01

    The main problems in the treatment of diabetic foot ulcers are prolonged wound healing and not necessary amputations, which may sometimes be caused by the impression that the results of conservative treatment are somewhat unpredictable. The aim of this study was to determine the effects of ulcer size on the wound radius reduction and healing times using a previously established equation for wound healing in neuropathic diabetic foot ulcers. This prospective study evaluates wound healing in 120 diabetic patients with neuropathic foot ulcers who were grouped according to four different ulcer areas (A 100 150 200 mm (2)). Ulcer healing was assessed by planimetric measurement of the wound area every second week until wound healing. The time course of wound healing in the different groups was compared by the weekly wound radius reduction using the equation R = sqrt A/pi. The average healing time in group A was 70 (95 %-CI 64 - 77) days with a wound radius reduction of 0.42 mm/week (95 %-CI 0.28 - 0.56). In group B the average healing time was 79 (95 %-CI 75 - 82) days and the weekly wound radius reduction was 0.47 mm (95 %-CI 0.45 - 0.49). The average healing time in group C was 85 (95 %-CI 80 - 89) days with a wound radius reduction of 0.53 mm/week (95 %-CI 0.42 - 0.56). In group D the average healing time was 97 (95 %-CI 91 - 103) days. The weekly wound radius reduction was 0.57 mm (95 %-CI 0.49 - 0.81). Wound radius reductions and the time needed for healing are affected by the ulcer area, a measure of ulcer size, in neuropathic diabetic foot ulcers. The calculation of the weekly wound radius reduction for different ulcer areas may be a useful tool in daily clinical practice to identify ulcers who do not respond adequately to the treatment. PMID:15127323

  2. 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

  3. Acceleration Of Wound Healing Ny Photodynamic Therapy

    DOEpatents

    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.

  4. The Effect of a Connexin43-Based Peptide on the Healing of Chronic Venous Leg Ulcers: A Multicenter, Randomized Trial

    PubMed Central

    Ghatnekar, Gautam S; Grek, Christina L; Armstrong, David G; Desai, Sanjay C; Gourdie, Robert G

    2015-01-01

    The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury and during wound healing, and is abnormally upregulated at the epidermal wound margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic of the carboxyl-terminus of Cx43, accelerates fibroblast migration and proliferation, and wound reepithelialization. In a prospective, multicenter clinical trial conducted in India, adults with chronic VLUs were randomized to treatment with an ACT1 gel formulation plus conventional standard-of-care (SOC) protocols, involving maintaining wound moisture and four-layer compression bandage therapy, or SOC protocols alone. The primary end point was mean percent ulcer reepithelialization from baseline to 12 weeks. A significantly greater reduction in mean percent ulcer area from baseline to 12 weeks was associated with the incorporation of ACT1 therapy (79% (SD 50.4)) as compared with compression bandage therapy alone (36% (SD 179.8); P=0.02). Evaluation of secondary efficacy end points indicated a reduced median time to 50 and 100% ulcer reepithelialization for ACT1-treated ulcers. Incorporation of ACT1 in SOC protocols may represent a well-tolerated, highly effective therapeutic strategy that expedites chronic venous ulcer healing by treating the underlying ulcer pathophysiology through Cx43-mediated pathways. PMID:25072595

  5. Quality of healing of gastric ulcers: Natural products beyond acid suppression.

    PubMed

    Kangwan, Napapan; Park, Jong-Min; Kim, Eun-Hee; Hahm, Ki Baik

    2014-02-15

    Gastric ulcer is a chronic disease featured with unexpected complications, including bleeding, stenosis and perforation, as well as a high incidence of recurrence. Clinical treatments for gastric ulcer have allowed the rapid development of potent anti-ulcer drugs during the last several decades. Gastric ulcer healing is successful with conventional treatments including H2-receptor antagonists, and proton pump inhibitors (PPIs) have been essential for ulcer healing and prevention of complications. Additionally, Helicobacter pylori eradication therapy is effective in reducing ulcer recurrence and leads to physiological changes in the gastric mucosa which affect the ulcer healing process. However, in spite of these advancements, some patients have suffered from recurrence or intractability in spite of continuous anti-ulcer therapy. A new concept of the quality of ulcer healing (QOUH) was initiated that considers the reconstruction of the mucosal structure and its function for preventing ulcer recurrence. Although several gastroprotection provided these achievements of the QOUH, which PPI or other acid suppressants did not accomplish, we found that gastroprotection that originated from natural products, such as a newer formulation from either Artemisia or S-allyl cysteine from garlic, were very effective in the QOUH, as well as improving clinical symptoms with fewer side effects. In this review, we will introduce the importance of the QOUH in ulcer healing and the achievements from natural products.

  6. 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.

  7. Nutritional care to prevent and heal pressure ulcers.

    PubMed

    Singer, Pierre

    2002-09-01

    Pressure sores are a well-recognized problem, with an etiology that is multifactorial and not solely a consequence of pressure itself. Malnutrition is one of the factors involved, namely low calorie and protein intake. Mainly elderly patients, patients after hip fracture, but also patients after trauma, burns or extended surgery require additional nutritional support to reduce the possibility of pressure ulcers developing. Evidence has shown the efficacy of percutaneous endoscopic gastrostomy in elderly patients with malnutrition and dementia. Nutritional support should include sufficient calories, protein, fat, carbohydrates, vitamins and minerals. Arginine is the main amino acid required and is essential for collagen deposition and wound healing. Vitamin A and zinc should be added to nutritional support.

  8. Treatment of a non-healing diabetic foot ulcer with platelet-rich plasma.

    PubMed

    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.

  9. Hyperbaric Hyperoxia Accelerates Fracture Healing in Mice

    PubMed Central

    Kawada, Shigeo; Wada, Eiji; Matsuda, Ryoichi; Ishii, Naokata

    2013-01-01

    Increased oxygen tension influences bone metabolism. This study comprised two main experiments: one aimed to determine the bone mineral apposition and bone formation rates in vivo under hyperbaric hyperoxia (HBO), and the other aimed to evaluate the effects of exposure to HBO on fracture healing. In experiment 1, male mice were exposed to HBO [90 min/day at 90% O2 at 2 atmospheres absolute (ATA) for 5 days]. In experiment 2, an open femur fracture model was created in mice, followed by exposure to HBO 5 times/week (90 min/day at 90% O2 at 2 ATA) for 6 weeks after surgery. In experiment 1, HBO treatment significantly increased the mineral apposition and bone formation rates in the lumbar vertebra and femur and type 1 collagen alpha 1 and alkaline phosphatase mRNA expression in the lumbar vertebra. In experiment 2, at 2 weeks after fracture, the fracture callus was significantly larger in the HBO group than in the non-HBO group. Furthermore, at 4 and 6 weeks after fracture, radiographic findings showed accelerated fracture healing in the HBO group. At 6 weeks after fracture, femur stiffness and maximum load were significantly higher in the HBO group than in the non-HBO group. Urinary 8-hydroxy-2′-deoxyguanosine and plasma calcium concentrations were not significantly different between groups. These results suggest that exposure to HBO enhances bone anabolism and accelerates fracture healing without causing oxidative DNA damage or disruption of plasma calcium homeostasis. PMID:23967323

  10. The difficulty and the solution of compression therapy in a healed venous leg ulcer.

    PubMed

    Hampton, Sylvie

    2016-09-01

    Continuing preventative treatment once a venous ulcer is healed is fraught with dangers, with the most common problem being the inability of the wearer or their carer to apply compression therapy. A new novel compression modality has been introduced to solve the dilemma of applying compression once an injury has healed. This compression is also time-saving for practitioners who wish to heal leg ulcers. This will have an impact on the time restrictions of practice and district nurses-who have a 10-15 minute slot to dress and bandage their patients' venous ulcers. PMID:27594312

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Gastric emptying of combined liquid-solid meals in healed duodenal ulcer

    SciTech Connect

    Moore, J.G.; McIntyre, B.; Alazraki, N.

    1985-12-01

    The gastric emptying rates of combined liquid and solid radioisotopically labeled meals in 47 healed duodenal ulcer subjects and 17 healthy control subjects are compared. No significant differences were found between the groups in emptying slopes and the emptying half-times or in the percent retention values at any of the counting intervals for either the liquid or solid meals. These results are compatible with the observation that the rapid gastric emptying in many patients with duodenal ulcer is associated with the disease and that healing results in a return to normal gastric emptying rates. However, since gastric emptying rates during active ulceration were not determined in our patients, a more definitive interpretation awaits a study comparing emptying rates obtained during and after healing of active ulceration in the same patient.

  17. 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.

  18. 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. PMID:16785777

  19. 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

  20. A retrospective study using the pressure ulcer scale for healing (PUSH) tool to examine factors affecting stage II pressure ulcer healing in a Korean acute care hospital.

    PubMed

    Park, Kyung Hee

    2014-09-01

    Stage II pressure ulcers (PUs) should be managed promptly and appropriately in order to prevent complications. To identify the factors affecting Stage II PU healing and optimize care, the electronic medical records of patients with a Stage II PU in an acute care hospital were examined. Patient and ulcer characteristics as well as nutritional assessment variables were retrieved, and ulcer variables were used to calculate Pressure Ulcer Scale for Healing (PUSH) scores. The effect of all variables on healing status (healed versus nonhealed) and change in PUSH score for healing rate were compared. Records of 309 Stage II PUs from 155 patients (mean age 61.2 ± 15.2 [range 5-89] years, 182 [58.9%] male) were retrieved and analyzed. Of those, 221 healed and 88 were documented as not healed at the end of the study. The variables that were significantly different between patients with PUs that did and did not heal were: major diagnosis (P = 0.001), peripheral arterial disease (P = 0.007), smoking (P = 0.048), serum albumin ( <2.5 g/dL) (P = 0.002), antidepressant use (P = 0.035), vitamin use (P = 0.006), history of surgery (P <0.001), PU size (P = 0.003), Malnutrition Universal Screening Tool (MUST) score (P = 0.020), Braden scale score (P = 0.003), and mean arterial pressure (MAP, mm Hg) (P = 0.026). The Cox proportional hazard model showed a significant positive difference in PUSH score change -indicative of healing - when pressure-redistribution surfaces were used (P <0.001, HR = 2.317), PU size was small (≤3.0 cm2, P = 0.006, HR = 1.670), MAP (within a range of 52-112 mm Hg) was higher P = 0.010, HR = 1.016), and patients were provided multivitamins (P = 0.037, HR=1.431). The results of this study suggest strategies for healing Stage II PUs in the acute care setting should include early recognition of lower-stage PUs, the provision of static pressure-redistribution surfaces and multivitamins, and maintaining higher MAP may facilitate healing and prevent deterioration

  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. Effects of Purified Saccharomyces cerevisiae (1→3)-β-Glucan on Venous Ulcer Healing

    PubMed Central

    Medeiros, Sarah Dantas Viana; Cordeiro, Sara Lima; Cavalcanti, Jéssica Escorel Chaves; Melchuna, Karina Mendes; Lima, Aleida Maria da Silva; Filho, Irami Araújo; Medeiros, Aldo Cunha; Rocha, Keyla Borges Ferreira; Oliveira, Elizabeth Maia; Faria, Eduardo Dantas Baptista; Sassaki, Guilherme Lanzi; Rocha, Hugo Alexandre Oliveira; Sales, Valéria Soraya Farias

    2012-01-01

    Water-insoluble glucan was isolated from the baker’s yeast Saccharomyces cerevisiae. The yeast cells were treated with alkali and the residue then with acid. Chemical and NMR (1D and 2D) analyses showed that a linear (1→3)-β-glucan was purified that was not contaminated with other carbohydrates, proteins or phenolic compounds. The effects of the glucan on wound healing were assessed in human venous ulcers by histopathological analysis after 30 days of topical treatment. (1→3)-β-glucan enhanced ulcer healing and increased epithelial hyperplasia, as well as increased inflammatory cells, angiogenesis and fibroblast proliferation. In one patient who had an ulcer that would not heal for over 15 years, glucan treatment caused a 67.8% decrease in the area of the ulcer. This is the first study to investigate the effects of (1→3)-β-glucan on venous ulcer healing in humans; our findings suggest that this glucan is a potential natural biological response modifier in wound healing. PMID:22942695

  3. 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.

  4. [Treatment of trophic ulcers and non-healing wounds with CO2 laser].

    PubMed

    Koshelev, V N; Glukhov, E I; Barkhatov, L N

    1985-02-01

    The authors used high and low intensity CO2 lasers for the treatment of 140 patients with trophic ulcers and continuously non-healing wounds. Choice of the method of treatment, parameters of laser radiation are based on concrete values of indices of the regeneration processes in the wounds and ulcers. In 83,6% of patients there was a complete recovery of the wounds, in 16,4% the recovery was partial. PMID:3923679

  5. Influence of ulcer healing agents on ulcer relapse after discontinuation of acute treatment: a pooled estimate of controlled clinical trials.

    PubMed Central

    Dobrilla, G; Vallaperta, P; Amplatz, S

    1988-01-01

    Whether or not the incidence of ulcer relapse varies according to the drug used to produce initial healing is a controversial matter. We tackled this problem using data from 15 eligible trials from 25 published controlled trials in patients followed up for six to 12 months. Pooled estimates of differences in ulcer relapse incidence between patients initially healed with H2-antagonists and patients initially healed with non-H2-antagonist drugs were calculated. The overall incidence of relapse in patients healed with comparator drugs is 11 percentage units lower at six and 12 months, than that observed in H2-antagonist-healed patients. The confidence intervals are +/- 8% at six months and +/- 7% at 12 months. These data suggest the existence of a different effect on relapse incidence for the entire class of comparator drugs taken as a whole, compared with H2-antagonists. On considering the non-H2-antagonists singly, this conclusion holds good only in the case of tripotassium dicitrato bismuthate. PMID:2894337

  6. NorLeu3-Angiotensin (1-7) [DSC127] as a Therapy for the Healing of Diabetic Foot Ulcers

    PubMed Central

    Rodgers, Kathleen E.; Bolton, Laura L.; Verco, Shelagh; diZerega, Gere S.

    2015-01-01

    Significance: Diabetes is a disorder that is well known to delay wound repair resulting in the formation of colonized chronic wounds. Over their lifetime, diabetic patients have a 25% incidence of foot ulcers (DFUs), which contribute to increased risk of morbidity, including osteomyelitis and amputations, and increased burden to the healthcare system. Recent Advances: The only active product approved for the treatment of diabetic ulcers, Regranex®, is not widely used due to minimal proven efficacy and recent warnings added to the Instructions for Use. A novel topical agent that accelerates healing and increases the proportion of fully healed DFUs, DSC127 [aclerastide; active ingredient, NorLeu3-angiotensin (1-7) (NorLeu3-A(1-7))], is recruiting patients in Phase III clinical trials (NCT01830348 and NCT01849965). NorLeu3-A(1-7) is an analog of the naturally occurring peptide, angiotensin 1-7. The mechanisms of action include induction of progenitor proliferation, accelerated vascularization, collagen deposition, and re-epithelialization. Critical Issues: Current modalities for the treatment of DFUs include strict offloading, bandaging, debridement and, on a limited basis, application of Regranex. Novel potent therapies are needed to combat this significant burden to the diabetic patient and the healthcare system. Future Direction: Preclinical and clinical research shows that DSC127 is highly effective in the closure of diabetic wounds and is superior to Regranex in animal studies. Clinical development of DSC127 as a topical agent for the healing of DFU is underway. Further investigation into the mechanisms by which this product accelerates healing is warranted. PMID:26029484

  7. 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

  8. [Dynamic imaging of gastric ulcer healing using the most modern Morph-Software].

    PubMed

    Jaspersen, D; Keerl, R; Weber, R; Huppmann, A; Hammar, C H; Draf, W

    1996-06-01

    The presentation of gastric ulcer healing taken from video endoscopy as a dynamic process could not be realized till now. The documentation of the dynamic healing process shattered either on the patient's compliance or on the inconstancy of the image cut due to wobbling. The replay should be performed as a time lapse whereby the picture disturbances would become an essential part.-Instead of presenting a continuous film, instant takes of ulcer healing were processed. A dynamic effect was produced by computer-assisted production of intermediate pictures. A video was created in which short video sequences in definite time intervals were recorded endoscopically. Single stills-so-called original pictures-fitting together from each sequence were selected and spliced together. The missing intermediate pictures were made with a special computer technique according to the mathematical concept of interpolation. With this technique, the dynamic documentation of gastric ulcer healing in a 47-year-old male patient was performed. The technique enables an almost natural and real observation of ulcer healing and promises new physiological and patho-physiological knowledge in gastroenterologic endoscopy.

  9. 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.

  10. Metabolism of oral trefoil factor 2 (TFF2) and the effect of oral and parenteral TFF2 on gastric and duodenal ulcer healing in the rat

    PubMed Central

    Poulsen, S; Thulesen, J; Christensen, L; Nexo, E; Thim, L

    1999-01-01

    BACKGROUND—Trefoil factors (TFFs) are peptides produced by mucus-secreting cells in the gastrointestinal tract. A functional association between these peptides and mucus, leading to stabilisation of the viscoelastic gel overlying the epithelia, has been suggested. Both oral and parenteral administration of the peptides increase the resistance of the gastric mucosa.
AIM—To study the effect in rats of oral and parenteral porcine trefoil factor 2 (pTFF2) on the healing of gastric and duodenal ulcerations and to clarify the distribution and metabolism of orally administered pTFF2 in the gastrointestinal tract.
METHODS—Gastric ulcers were induced in female Sprague-Dawley rats by indomethacin and duodenal ulcers by mercaptamine. The rats were treated for up to seven days with oral or subcutaneous pTFF2. Ulcer size after treatment was assessed by stereomicroscopy after whole mount staining with periodic acid-Schiff stain. 125I-labelled pTFF2 was given orally to rats, and tissues were investigated by gamma counting of samples and by autoradiography of paraffin embedded sections.
RESULTS—pTFF2 accelerated gastric ulcer healing after both oral and subcutaneous administration. Duodenal ulcers were aggravated by both treatments. After oral administration of 125I-pTFF2, intact peptide was recovered from the superficial part of the mucus layer in the stomach; it passed through the small intestine but was degraded in the caecum. Only a minor part of the labelled pTFF2 entered the colon and was excreted in the faeces. Most of the label was excreted in the urine.
CONCLUSIONS—Oral as well as parenteral pTFF2 accelerates the healing of gastric ulceration and aggravates duodenal ulcers. Oral pTFF2 binds to the mucus layer of the stomach and the small intestine but does not reach the colonic mucosa.


Keywords: trefoil factors; spasmolytic polypeptide; ulcer healing; gastric ulcer; duodenal ulcer; rat PMID:10486358

  11. 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.

  12. Juxta CURES: compression for healing venous leg ulcers.

    PubMed

    Nugent, Lisa

    2013-09-01

    Clinicians are expected to show improved healing rates, reduction in recurrence rates and to demonstrate greater patient satisfaction. All patients should rightly expect a high standard of holistic care that supports both their physical and emotional needs. Keeping the patient engaged in the "healing process" has many beneficial outcomes, not least to their emotional wellbeing. Managing to heal the wounds within a realistic timeframe is the required outcome for all parties. This article demonstrates how a new compression device, Juxta CURES, has a positive impact on patients' quality of life, also benefiting the clinician while maintaining cost-saving efficiencies.

  13. Role of Negative Pressure Wound Therapy in Healing of Diabetic Foot Ulcers

    PubMed Central

    Nain, Prabhdeep Singh; Uppal, Sanjeev K.; Garg, Ramneesh; Bajaj, Kuljyot; Garg, Shirin

    2011-01-01

    Introduction: Foot disorders such as ulceration, infection and gangrene are the most common, complex and costly sequelae of diabetes mellitus.[1–3] Even for the most superficial wounds, treatment is often difficult with poor healing responses and high rates of complications. The purpose of this study is to compare the rate of ulcer healing with the negative pressure dressing technique to conventional moist dressings in the treatment of diabetic foot ulcers. Materials and Methods: The study was conducted on 30 patients, which were divided into two groups. One group received negative pressure dressing while other group received conventional saline moistened gauze dressing. Results were compared for rate of wound healing. Results: There was a statistically significant difference in the rate of appearance of granulation tissue between the two groups; with granulation tissue appearing earlier in the study group. The study group promised a better outcome (80% complete responders) as compared to the control group (60% complete responders). Conclusions: Negative pressure wound therapy has a definitive role in healing of diabetic foot ulcers. PMID:22022649

  14. 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. PMID:9252810

  15. Effects of vacuum-compression therapy on healing of diabetic foot ulcers: randomized controlled trial.

    PubMed

    Akbari, Asghar; Moodi, Hesam; Ghiasi, Fatemeh; Sagheb, Hamidreza Mahmoudzadeh; Rashidi, Homayra

    2007-01-01

    A single-blind, randomized controlled trial was conducted to evaluate vacuum-compression therapy (VCT) for the healing of diabetic foot ulcers. Eighteen diabetic patients with foot ulcers were recruited through simple nonprobability sampling. Subjects were randomly assigned to either an experimental or a control group. Before and after intervention, the foot ulcer surface area was estimated stereologically, based on Cavalieri's principle. The experimental group was treated with VCT in addition to conventional therapy for 10 sessions. The control group received only conventional therapy, including debridement, blood glucose control agents, systemic antibiotics, wound cleaning with normal saline, offloading (pressure relief), and daily wound dressings. The mean foot ulcer surface area decreased from 46.88 +/- 9.28 mm(2) to 35.09 +/- 4.09 mm(2) in the experimental group (p = 0.006) and from 46.62 +/- 10.03 mm(2) to 42.89 +/- 8.1 mm(2) in the control group (p = 0.01). After treatment, the experimental group significantly improved in measures of foot ulcer surface area compared with the control group (p = 0.024). VCT enhances diabetic foot ulcer healing when combined with appropriate wound care.

  16. "Toothbrush" the Feet: A Periodic Mechanical Stimulus for Healing of a Severe Chronic Leg Ulcer.

    PubMed

    Vounotrypidis, Periklis; Pappas, Periklis; Vrangalas, Vasilios; Pehlivanidis, Anthimos

    2015-09-01

    Chronic wounds develop when the sequence of healing events are disrupted, usually in patients with underlying diseases such as diabetes mellitus, venous insufficiency, peripheral artery disease, and neuropathies and they affect most often the lower extremities. We present a 68-year-old woman with plantar ulceration, lasting for approximately 18 months, resistant to healing with conventional therapy and various modalities we used. The patient had a long history of seronegative enteropathic arthritis, Crohn's disease, secondary fibrillar amyloidosis, multiplex neuropathy, and small vessel vasculitis, the latter being the trigger event for the ulceration of her right foot. Before the decision for a final surgical intervention, we implemented a mechanical periodic stimulus using a soft toothbrush, which resulted in the gradual and complete healing of the ulcer within a period of 6 weeks. Patient's history and previous treatments are presented along with the procedures that led to the healing of the chronic wound. This report supports the idea that periodic mechanical stimulus is of great importance for the healing process and this could be the mechanism of action of some other methods that have been described in the medical literature.

  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. 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.

  19. 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

  20. Accelerated wound closure of pressure ulcers in aged mice by chitosan scaffolds with and without bFGF.

    PubMed

    Park, Chan J; Clark, Sherrie G; Lichtensteiger, Carol A; Jamison, Russell D; Johnson, Amy J Wagoner

    2009-07-01

    Pressure ulcers are a significant healthcare concern, especially for elderly populations. Our work served to ameliorate the chronicity of these ulcers by addressing ischemia-reperfusion injury mediated by neutrophils and the concomitant loss of vasculature in these wounds. To this end, chitosan scaffolds loaded with basic fibroblast growth factor (bFGF) contained in gelatin microparticles were developed and tested for clinical relevance in an aged mouse model. Pressure ulcers were induced in aged mice, and efficacy of treatment was assessed. On days 3 and 7, both chitosan and chitosan-bFGF scaffolds significantly accelerated wound closure compared to gauze control. By day 10, all wounds achieved similar closure. Delivery and angiogenic function of bFGF was verified through ELISA and histology. Elevated neutrophil levels were observed in chitosan and chitosan-bFGF groups. Since neutrophil elastase contributes to the proteolytic environments of pressure ulcers, the effect of chitosan on elastase was assessed. In vitro, chitosan inhibited elastase activity. In vivo, elastase protein levels in wounds were reduced with chitosan-bFGF scaffolds by day 10. These results suggest that chitosan is an effective material for growth factor delivery and can help to heal chronic ulcers. Collectively, our data show that chitosan-bFGF scaffolds are effective in accelerating wound closure of pressure ulcers in aged animals.

  1. Low molecular weight heparin improves healing of chronic venous ulcers especially in the elderly.

    PubMed

    Serra, Raffaele; Buffone, Gianluca; Molinari, Vincenzo; Montemurro, Rossella; Perri, Paolo; Stillitano, Domenico M; Amato, Bruno; de Franciscis, Stefano

    2015-04-01

    Venous ulcers are common, especially in the elderly, accounting for more than 50% of all lower extremity ulcers with important socioeconomic problems. Improving extracellular matrix functioning, by heparin administration, seems to be a way to support wound healing. A total of 284 patients with venous ulcers were recruited in a 4-year period. All patients were subjected to the most appropriate treatment after considering their preference (compression therapy followed or not by vein surgery). Patients were randomised into two groups of 142 persons in each (group A and group B as cases and controls, respectively). Patients of group A, in addition to the basic treatment as described earlier, received administration of nadroparin 2850 IU/0.3 ml through subcutaneous injection once a day for 12 months, whereas group B patients received basic treatment alone. Healing was assessed by means of direct ulcer tracing with computerised planimetry. Group A showed a healing rate of 83·80% at 12 months, whereas that of group B was 60·56%. Results by age group surprisingly showed that the group of older patients took the most advantage from long-term treatment with low molecular weight heparin; this group also had lowest recurrence rate.

  2. 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.

  3. Increased Number of Langerhans Cells in the Epidermis of Diabetic Foot Ulcers Correlates with Healing Outcome

    PubMed Central

    Stojadinovic, Olivera; Yin, Natalie; Lehmann, Janin; Pastar, Irena; Kirsner, Robert S.; Tomic-Canic, Marjana

    2015-01-01

    Langerhans cells (LCs) are a specialized subset of epidermal dendritic cells. They represent one of the first cells of immunological barrier and play an important role during the inflammatory phase of acute wound healing. Despite considerable progress in our understanding of the immunopathology of diabetes mellitus and its associated co-morbidities such as diabetic foot ulcers (DFUs), considerable gaps in our knowledge exist. In this study, we utilized the human ex vivo wound model and confirmed the increased epidermal LCs at wound edges during early phases of wound healing. Next, we aimed to determine differences in quantity of LCs between normal human and diabetic foot skin and to learn if the presence of LCs correlates with the healing outcome in DFUs. We utilized immunofluorescence to detect CD207+ LCs in specimens from normal and diabetic foot skin and DFU wound edges. Specimens from DFUs were collected at the initial visit and 4 weeks at the time when the healing outcome was determined. DFUs that decreased in size by >50% were considered to be healing, while DFUs with a size reduction of <50% were considered non-healing. Quantitative assessment of LCs showed a higher number of LCs in healing when compared to non–healing DFU’s. Our findings provide evidence that LCs are present in higher number in diabetic feet than normal foot skin. Healing DFUs show a higher number of LCs compared to non-healing DFUs. These findings indicate that the epidermal immune barrier plays an important role in the DFU healing outcome and may offer new therapeutic avenues targeting LC in non-healing DFUs. PMID:24277309

  4. 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

  5. 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

  6. [Nutrition and chronic wound healing. A clinical case of a patient with a hard to heal venous leg ulcers].

    PubMed

    Lozano, Sandra Alexandre; Bonet, Carme Marquilles; Bou, Joan-Enric Torra I; Llobet Burgués, Marta

    2014-05-01

    The cronicity of a wound can be produced by the alteration of several factors. One of the agents that can produce a delay in the wound healing process is malnutrition. According with the evidence, nutrition is an important factor in chronic wound prevention and treatment. The prevalence of low extremity wounds increases in population aged 65 or more. As we became older, malnutrition risk is more relevant due to physiological changes related to ageing. We describe a clinical case of a torpid venous leg ulcer in an elder patient centering on nutrition assessment and management.

  7. 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.

  8. [Endoscopic nasobiliary and nasopancreatic drainage contributing to healing of duodenal ulcer perforation: a case report].

    PubMed

    Enokida, Kohei; Kikuyama, Masataka; Kurokami, Takafumi; Shirane, Naofumi; Aoyama, Haruna; Aoyama, Hiroyuki; Sato, Tatsunori; Taki, Yusuke

    2015-10-01

    A 75-year-old man with vomiting and right abdominal pain was admitted to the Department of Surgery in our hospital. With a diagnosis of perforated duodenal ulcer, he was treated conservatively. On the day 8 of hospitalization, his general condition worsened and he underwent surgery. During operation, the perforated duodenal ulcer and paraduodenal fluid collection was observed, and percutaneous drainage was accordingly established. After this procedure, renal dysfunction was exacerbated and he was transferred to our department for endoscopic treatment. On day 28 of hospitalization, nasobiliary and nasopancreatic drainage was administered. Renal dysfunction gradually improved, and healing of the perforated duodenal ulcer was recognized on day 93. On day 112, the patient was discharged. PMID:26440686

  9. Buccal mucosal ulcer healing effect of rhEGF/Eudispert hv hydrogel.

    PubMed

    Park, Jeong Sook; Yoon, Joon Il; Li, Hong; Moon, Dong Cheul; Han, Kun

    2003-08-01

    We have studied the effect of rhEGF on the buccal mucosal ulcer healing. rhEGF was rapidly degraded upon incubation with the hamster buccal mucosal homogenates; The degradation of rhEGF was significantly inhibited by sodium lauryl sulfate (SLS). Eudispert hv hydrogel and Polycarbophil 974P hydrogel were prepared for rhEGF delivery and their mucoadhesiveness was measured by the Instron method. The mucoadhesive force of Eudispert hv was significantly greater than that of Polycarbophil 974P. Moreover, rhEGF in Eudispert hv hydrogel remained stable for about 2 months. To evaluate the ulcer healing effect of rhEGF, the buccal mucosal ulcer was induced in golden hamsters using acetic acid. At 24 h after administration of rhEGF/Eudispert hv hydrogel, the ulcerous area was decreased compared with rhEGF solution and, as a result, the curative ratio was 36.8 +/- 5.68%. By the addition of SLS (0.5%) to Eudispert hv hydrogel, the curative ratio increased 1.5 times. The mechanism of the action was probably due to a combination of protection of the drug against proteases present in mucosa and prolongation of the release of rhEGF from the formulation at the site of action.

  10. Stimulation of angiogenesis by cilostazol accelerates fracture healing in mice.

    PubMed

    Herath, Steven C; Lion, Thorsten; Klein, Moritz; Stenger, David; Scheuer, Claudia; Holstein, Jörg H; Mörsdorf, Philipp; Rollmann, Mika F R; Pohlemann, Tim; Menger, Michael D; Histing, Tina

    2015-12-01

    Cilostazol, a selective phosphodiesterase-3 inhibitor, is known to control cyclic adenosine monophosphate (c-AMP) and to stimulate angiogenesis through upregulation of pro-angiogenic factors. There is no information, however, whether cilostazol affects fracture healing. We, therefore, studied the effect of cilostazol on callus formation and biomechanics during fracture repair. Bone healing was analyzed in a murine femur fracture stabilized with an intramedullary screw. Radiological, biomechanical, histomorphometric, histochemical, and protein biochemical analyses were performed at 2 and 5 weeks after fracture. Twenty-five mice received 30 mg/kg body weight cilostazol p.o. daily. Controls (n=24) received equivalent amounts of vehicle. In cilostazol-treated animals radiological analysis at 2 weeks showed an improved healing with an accelerated osseous bridging compared to controls. This was associated with a significantly higher amount of bony tissue and a smaller amount of cartilage tissue within the callus. Western blot analysis showed a higher expression of cysteine-rich protein 61 (CYR61), bone morphogenetic protein (BMP)-4, and receptor activator of NF-kappaB ligand (RANKL). At 5 weeks, improved fracture healing after cilostazol treatment was indicated by biomechanical analyses, demonstrating a significant higher bending stiffness compared to controls. Thus, cilostazol improves fracture healing by accelerating both bone formation and callus remodeling.

  11. Allogeneic Transplantation of an Adipose-Derived Stem Cell Sheet Combined With Artificial Skin Accelerates Wound Healing in a Rat Wound Model of Type 2 Diabetes and Obesity.

    PubMed

    Kato, Yuka; Iwata, Takanori; Morikawa, Shunichi; Yamato, Masayuki; Okano, Teruo; Uchigata, Yasuko

    2015-08-01

    One of the most common complications of diabetes is diabetic foot ulcer. Diabetic ulcers do not heal easily due to diabetic neuropathy and reduced blood flow, and nonhealing ulcers may progress to gangrene, which necessitates amputation of the patient's foot. This study attempted to develop a new cell-based therapy for nonhealing diabetic ulcers using a full-thickness skin defect in a rat model of type 2 diabetes and obesity. Allogeneic adipose-derived stem cells (ASCs) were harvested from the inguinal fat of normal rats, and ASC sheets were created using cell sheet technology and transplanted into full-thickness skin defects in Zucker diabetic fatty rats. The results indicate that the transplantation of ASC sheets combined with artificial skin accelerated wound healing and vascularization, with significant differences observed 2 weeks after treatment. The ASC sheets secreted large amounts of several angiogenic growth factors in vitro, and transplanted ASCs were observed in perivascular regions and incorporated into the newly constructed vessel structures in vivo. These results suggest that ASC sheets accelerate wound healing both directly and indirectly in this diabetic wound-healing model. In conclusion, allogeneic ASC sheets exhibit potential as a new therapeutic strategy for the treatment of diabetic ulcers.

  12. Healing of venous ulcers using compression therapy: Predictions of a mathematical model.

    PubMed

    Flegg, Jennifer A; Kasza, Jessica; Darby, Ian; Weller, Carolina D

    2015-08-21

    Venous Leg Ulceration (VLU) is a chronic condition for which healthcare systems worldwide face rising treatment costs. VLU can be due to sustained venous hypertension which causes the veins to become cuffed with fibrin, inhibiting the supply of nutrients to the wound site. For patients that cannot tolerate compression therapy with an inelastic short stretch (SS) bandage, the mainstay treatment, an elastic three layered (3L) bandage is an alternative. In this paper, a mathematical model is developed to investigate whether the healing of venous ulcers under SS and 3L bandages occurs at different rates and to postulate the reason for any difference. The two treatments were applied to a simplified wound geometry, under the assumption that the rate limiting step of healing is the supply of oxygen to the wounded tissue. Clinical data of wound size over time under the two treatments from Weller et al. (2012) was used to fit key, unknown, model parameters using a least squares approach. Numerical results are presented for the oxygen distribution within the wound space, using the fitted parameter values. The 3L bandage allows more oxygen flow into the wound than the SS bandage and, hence, the 3L bandage results in faster healing, however the difference is more significant for wounds of larger initial size. The model can be used as a predictive tool in a clinical setting to estimate the time to heal for a wound of a given initial size, treated with either a SS or 3L bandage.

  13. Healing of venous ulcers using compression therapy: Predictions of a mathematical model.

    PubMed

    Flegg, Jennifer A; Kasza, Jessica; Darby, Ian; Weller, Carolina D

    2015-08-21

    Venous Leg Ulceration (VLU) is a chronic condition for which healthcare systems worldwide face rising treatment costs. VLU can be due to sustained venous hypertension which causes the veins to become cuffed with fibrin, inhibiting the supply of nutrients to the wound site. For patients that cannot tolerate compression therapy with an inelastic short stretch (SS) bandage, the mainstay treatment, an elastic three layered (3L) bandage is an alternative. In this paper, a mathematical model is developed to investigate whether the healing of venous ulcers under SS and 3L bandages occurs at different rates and to postulate the reason for any difference. The two treatments were applied to a simplified wound geometry, under the assumption that the rate limiting step of healing is the supply of oxygen to the wounded tissue. Clinical data of wound size over time under the two treatments from Weller et al. (2012) was used to fit key, unknown, model parameters using a least squares approach. Numerical results are presented for the oxygen distribution within the wound space, using the fitted parameter values. The 3L bandage allows more oxygen flow into the wound than the SS bandage and, hence, the 3L bandage results in faster healing, however the difference is more significant for wounds of larger initial size. The model can be used as a predictive tool in a clinical setting to estimate the time to heal for a wound of a given initial size, treated with either a SS or 3L bandage. PMID:25957521

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

    PubMed

    Halter, F; Tarnawski, A S; Schmassmann, A; Peskar, B M

    2001-09-01

    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 gastrointestinal mucosa necessary for maintenance of mucosal integrity and ulcer healing.

  15. Experimental healing of preexisting gastric ulcers induced by hormones controlling food intake ghrelin, orexin-A and nesfatin-1 is impaired under diabetic conditions. A key to understanding the diabetic gastropathy?

    PubMed

    Szlachcic, A; Majka, J; Strzalka, M; Szmyd, J; Pajdo, R; Ptak-Belowska, A; Kwiecien, S; Brzozowski, T

    2013-10-01

    Hormonal peptides like ghrelin, orexin A (OXA) or nesfatin-1 not only regulate appetite, which is their basic biological function, but also contribute to mechanisms responsible for maintaining integrity of the gastric mucosa. Previous studies including those from our laboratory have revealed that their gastroprotective effect results from cooperation with other factors responsible for protection of the gastric mucosa, including prostaglandin (PG) synthesis pathway, nitric oxide (NO) and the sensory afferent fibres releasing the vasoactive neurotransmitters. The aim of the present study was to determine whether ghrelin, orexin-A (OX-A) or nesfatin-1 with their protective effect on the gastric mucosa, also can modify the healing of chronic gastric ulcers. Furthermore, an attempt was made to explain participation of these peptides in healing processes of chronic gastric ulcers with comorbid conditions for the human beings resulted from diabetes mellitus. In our study, a model of gastric ulcers caused by concentrated acetic acid to induce the chronic gastric ulcers was used, while the clinical condition corresponding to diabetes was induced by single injection of streptozotocin (STZ). We found that ghrelin, OX-A and nesfatin-1 accelerate dynamics of the acetic acid ulcers healing, confirmed by a reduction in the ulcer area and this effect was accompanied by an increase in gastric blood flow at the ulcer margin. Destruction of sensory afferent fibres with capsaicin or blocking of vanilloid receptors with capsazepine resulted in a significant reduction of ghrelin, OX-A and nesfatin-1-induced acceleration of ulcer healing. Similar results were obtained when an NO-synthase blocker, L-NNA was used in a combination with these peptides. Moreover, it was found that OX-A and nesfatin-1 failed to accelerate the healing process under diabetic condition because both these hormones induced reduction in the ulcer area and the increase in blood flow in normal, non-diabetic rats were

  16. Cost-effectiveness of becaplermin gel on wound healing of diabetic foot ulcers.

    PubMed

    Gilligan, Adrienne M; Waycaster, Curtis R; Motley, Travis A

    2015-01-01

    We sought to determine the long-term cost effectiveness (payer's perspective) of becaplermin gel plus good wound care (BGWC) vs. good wound care (GWC) alone in terms of wound healing and risk of amputation in patients with diabetic foot ulcers (DFUs). Outcomes data were derived from a propensity score-matched cohort from the Curative Health Services database between 1998 and 2004, which was followed for 20 weeks. A four-state Markov model was used to predict costs and outcomes of wound healing and risk of amputation for BGWC vs. GWC alone over 1 year in patients with DFU. The primary outcome was closed-wound weeks. Transition probabilities for healing and amputation were derived from the aforementioned propensity score-matched cohorts. Ulcer recurrence was estimated from the medical literature. Utilization for becaplermin was calculated using the dosing algorithm in the product labeling. Of 24,898 eligible patients, 9.6% received BGWC. Based on the model, patients treated with BGWC had substantially more closed-wound weeks compared with GWC (16.1 vs. 12.5 weeks, respectively). More patients receiving BGWC had healed wounds at 1 year compared with those receiving GWC (48.1% vs. 38.3%). Risk of amputation was lower in the BGWC cohort (6.8% vs. 9.8%). Expected annual direct costs for DFU were $21,920 for BGWC and $24,640 for GWC. BGWC was economically dominant over GWC, providing better outcomes at a lower cost in patients with DFU. Compared with GWC alone, BGWC is more effective in healing wounds and lowering amputation risk, thereby decreasing long-term costs for DFU.

  17. 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

  18. 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. PMID:26749197

  19. An Automatic Assessment System of Diabetic Foot Ulcers Based on Wound Area Determination, Color Segmentation, and Healing Score Evaluation

    PubMed Central

    Wang, Lei; Pedersen, Peder C.; Strong, Diane M.; Tulu, Bengisu; Agu, Emmanuel; Ignotz, Ron; He, Qian

    2015-01-01

    Background: For individuals with type 2 diabetes, foot ulcers represent a significant health issue. The aim of this study is to design and evaluate a wound assessment system to help wound clinics assess patients with foot ulcers in a way that complements their current visual examination and manual measurements of their foot ulcers. Methods: The physical components of the system consist of an image capture box, a smartphone for wound image capture and a laptop for analyzing the wound image. The wound image assessment algorithms calculate the overall wound area, color segmented wound areas, and a healing score, to provide a quantitative assessment of the wound healing status both for a single wound image and comparisons of subsequent images to an initial wound image. Results: The system was evaluated by assessing foot ulcers for 12 patients in the Wound Clinic at University of Massachusetts Medical School. As performance measures, the Matthews correlation coefficient (MCC) value for the wound area determination algorithm tested on 32 foot ulcer images was .68. The clinical validity of our healing score algorithm relative to the experienced clinicians was measured by Krippendorff’s alpha coefficient (KAC) and ranged from .42 to .81. Conclusion: Our system provides a promising real-time method for wound assessment based on image analysis. Clinical comparisons indicate that the optimized mean-shift-based algorithm is well suited for wound area determination. Clinical evaluation of our healing score algorithm shows its potential to provide clinicians with a quantitative method for evaluating wound healing status. PMID:26253144

  20. Primary gastric tuberculosis presenting as non-healing ulcer and mimicking Crohn's disease.

    PubMed

    Ishii, Naoki; Furukawa, Keiichi; Itoh, Toshiyuki; Fujita, Yoshiyuki

    2011-01-01

    A 39-year-old woman was referred to our hospital for treatment of a non-healing gastric ulcer. Esophagogastroduodenoscopy (EGD) revealed an erosion in the pyloric antrum and a longitudinal ulcer on the lesser curvature of the gastric body. The histopathologic examination of biopsy specimens revealed non-caseating epithelioid granulomas. Acid-fast staining did not reveal bacilli. The differential diagnosis included gastric tuberculosis, Crohn's disease, and sarcoidosis and empiric antituberculous therapy consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide was initiated. Gastric lesions were subsequently resolved and non-caseating epithelioid granulomas were not demonstrated on the post-treatment examination. Recurrence was not observed during the follow-up period of 53 months.

  1. Endothelin-1, an ulcer inducer, promotes gastric ulcer healing via mobilizing gastric myofibroblasts and stimulates production of stroma-derived factors.

    PubMed

    Nishida, Tsutomu; Tsuji, Shingo; Kimura, Arata; Tsujii, Masahiko; Ishii, Syuji; Yoshio, Toshiyuki; Shinzaki, Shinichiro; Egawa, Satoshi; Irie, Takanobu; Yasumaru, Masakazu; Iijima, Hideki; Murata, Hiroaki; Kawano, Sunao; Hayashi, Norio

    2006-05-01

    Endothelin (ET)-1 is a potent inducer of peptic ulcers. The roles of ET-1 in ulcer healing, however, have remained unclear, and these were investigated in mice. Gastric ulcers were induced in mice by serosal application of acetic acid. Three days later, mice were given a neutralizing ET-1 antibody or nonimmunized serum. The ulcer size, amount of fibrosis and myofibroblasts, and localization of ET-1 and ET(A/B) receptors were analyzed. To elucidate the mechanisms underlying the effects of ET-1, we examined the proliferation, migration, and release of growth and angiogenic factors in gastric myofibroblasts with or without ET-1. The expression of prepro-ET-1 (an ET-1 precursor) and ET-converting enzyme-1 was examined in gastric myofibroblasts using RT-PCR. Immunoneutralization of ET-1 delayed gastric ulcer healing. The areas of fibrosis and myofibroblasts were smaller in the anti-ET-1 antibody group than in the control. ET-1 was expressed in the gastric epithelium, myofibroblasts, and other cell types. ET(A) receptors, but not ET(B) receptors, were present in myofibroblasts. ET-1 increased proliferation and migration of gastric myofibroblasts. ET-1 stimulated the release of hepatocyte growth factor, VEGF, PGE(2), and IL-6 from gastric myofibroblasts. mRNA for prepro-ET-1 and ET-converting enzyme-1 was also expressed. ET-1 promotes the accumulation of gastric myofibroblasts and collagen fibrils at gastric ulcers. ET-1 also stimulates migration and proliferation of gastric myofibroblasts and enhances the release of growth factors, angiogenic factors, and PGE(2). Thus ET-1 has important roles not only in ulcer formation but also in ulcer healing via mobilizing myofibroblasts and inducing production of stroma-derived factors.

  2. 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.

  3. 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.

  4. 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

  5. Low molecular weight heparin seems to improve local capillary circulation and healing of chronic foot ulcers in diabetic patients.

    PubMed

    Jörneskog, G; Brismar, K; Fagrell, B

    1993-01-01

    Ten diabetic patients with peripheral arterial occlusive disease, peripheral polyneuropathy and chronic foot ulcers were given 2500 U low molecular weight heparin (Fragmin, Kabi-Pharmacia AB, Sweden) subcutaneously once a day during 8 weeks. The mean age was 63 (47-80) years and the mean duration of foot ulcers 8 (4-12) months. All patients had previously received conventional treatment during 12 weeks, without any noticeable improvement on ulcer healing. The ulcer area was measured, and the skin microcirculation of the forefoot and around the ulcers was investigated before, during and after treatment with Fragmin. The total skin microcirculation was measured by laser Doppler fluxmetry, the nutritional skin microcirculation by vital capillaroscopy and the macrocirculation by determination of the ankle/arm pressure ratio. The ulcer area decreased significantly in eight patients of which four healed the ulcers completely. Of the remaining two patients one deteriorated, whereas one showed a decrease of the ulcer area during treatment, but an increase when treatment was stopped. The macro- and total microcirculation were unchanged in all patients, whereas the nutritional capillary circulation improved in seven out of nine patients, concomitantly with clinical improvement. The biological zero value (a flow-independent part of the LD signal) was high in 4 patients before treatment, but decreased during treatment and remained low even after treatment with Fragmin.-The results indicate that Fragmin positively influences the healing process of chronic foot ulcers in diabetic patients, possibly by improving the capillary circulation in the ulcer margin, in spite of an unchanged arterial and total skin microcirculation of the region.

  6. 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.

  7. 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

  8. Nutrition, skin integrity, and pressure ulcer healing in chronically ill children: an overview.

    PubMed

    Rodriguez-Key, Margie; Alonzi, Allison

    2007-06-01

    Although information in the literature is scant, pediatric patients in long-term care are known to be at risk for pressure ulcers. Modifying adult guidelines and standards for well children has helped guide provision of care in the authors' pediatric long-term care and rehabilitation facility. In addition to standard comprehensive clinical and nutritional assessment protocols, patient growth and a history of prematurity, as well as the effect of chromosomal and neurological abnormalities, must be considered. Optimal protein intake is of particular concern in this population. Experience, along with necessary protocol adaptations, has offered insight into nutritional requirements and modifications needed for positive outcomes in pressure ulcer healing in chronically ill children. Better understanding of the role of nutrition in the assessment, treatment, and prevention of pressure ulcers is essential in any population. Research to increase understanding of the role of nutrition in maintaining skin integrity and optimizing repair in chronically ill children is needed to help clinicians improve care and outcomes.

  9. Gastroprotective and ulcer healing effects of essential oil of Hyptis martiusii Benth. (Lamiaceae).

    PubMed

    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

  10. Heparan sulfate glycosaminoglycan mimetic improves pressure ulcer healing in a rat model of cutaneous ischemia-reperfusion injury.

    PubMed

    Tong, Miao; Tuk, Bastiaan; Hekking, Ineke M; Pleumeekers, Mieke M; Boldewijn, Mireille B; Hovius, Steven E R; van Neck, Johan W

    2011-01-01

    Pressure ulcers are a major clinical problem, with a large burden on healthcare resources. This study evaluated the effects of the heparan sulfate glycosaminoglycan mimetic, OTR4120, on pressure ulceration and healing. Ischemia-reperfusion (I-R) was evoked to induce pressure ulcers by external clamping and then removal of a pair of magnet disks on rat dorsal skin for a single ischemic period of 16 hours. Immediately after magnet removal, rats received an intramuscular injection of OTR4120 weekly for up to 1 month. During the ischemic period, normal skin perfusion was reduced by at least 60% and at least 20-45% reperfused into the ischemic region after compression release. This model caused sustained skin incomplete necrosis for up to 14 days and led to grade 2-3 ulcers. OTR4120 treatment decreased the area of skin incomplete necrosis and degree of ulceration. OTR4120 treatment also reduced inflammation and increased angiogenesis. In OTR4120-treated ulcers, the contents of vascular endothelial growth factor, platelet-derived growth factor, and transforming growth factor beta-1 were increased. Moreover, OTR4120 treatment promoted early expression of alpha-smooth muscle actin and increased collagen biosynthesis. Long-term restoration of wounded tissue biomechanical strength was significantly enhanced after OTR4120 treatment. Taken together, we conclude that OTR4120 treatment reduces pressure ulcer formation and potentiates the internal healing bioavailability.

  11. High-mobility group box 1 inhibits gastric ulcer healing through Toll-like receptor 4 and receptor for advanced glycation end products.

    PubMed

    Nadatani, Yuji; Watanabe, Toshio; Tanigawa, Tetsuya; Ohkawa, Fumikazu; Takeda, Shogo; Higashimori, Akira; Sogawa, Mitsue; Yamagami, Hirokazu; Shiba, Masatsugu; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Takeuchi, Koji; Arakawa, Tetsuo

    2013-01-01

    High-mobility group box 1 (HMGB1) was initially discovered as a nuclear protein that interacts with DNA as a chromatin-associated non-histone protein to stabilize nucleosomes and to regulate the transcription of many genes in the nucleus. Once leaked or actively secreted into the extracellular environment, HMGB1 activates inflammatory pathways by stimulating multiple receptors, including Toll-like receptor (TLR) 2, TLR4, and receptor for advanced glycation end products (RAGE), leading to tissue injury. Although HMGB1's ability to induce inflammation has been well documented, no studies have examined the role of HMGB1 in wound healing in the gastrointestinal field. The aim of this study was to evaluate the role of HMGB1 and its receptors in the healing of gastric ulcers. We also investigated which receptor among TLR2, TLR4, or RAGE mediates HMGB1's effects on ulcer healing. Gastric ulcers were induced by serosal application of acetic acid in mice, and gastric tissues were processed for further evaluation. The induction of ulcer increased the immunohistochemical staining of cytoplasmic HMGB1 and elevated serum HMGB1 levels. Ulcer size, myeloperoxidase (MPO) activity, and the expression of tumor necrosis factor α (TNFα) mRNA peaked on day 4. Intraperitoneal administration of HMGB1 delayed ulcer healing and elevated MPO activity and TNFα expression. In contrast, administration of anti-HMGB1 antibody promoted ulcer healing and reduced MPO activity and TNFα expression. TLR4 and RAGE deficiency enhanced ulcer healing and reduced the level of TNFα, whereas ulcer healing in TLR2 knockout (KO) mice was similar to that in wild-type mice. In TLR4 KO and RAGE KO mice, exogenous HMGB1 did not affect ulcer healing and TNFα expression. Thus, we showed that HMGB1 is a complicating factor in the gastric ulcer healing process, which acts through TLR4 and RAGE to induce excessive inflammatory responses.

  12. Hyaluronidase Modulates Inflammatory Response and Accelerates the Cutaneous Wound Healing

    PubMed Central

    Fronza, Marcio; Caetano, Guilherme F.; Leite, Marcel N.; Bitencourt, Claudia S.; Paula-Silva, Francisco W. G.; Andrade, Thiago A. M.; Frade, Marco A. C.; Merfort, Irmgard; Faccioli, Lúcia H.

    2014-01-01

    Hyaluronidases are enzymes that degrade hyaluronan an important constituent of the extracellular matrix. They have been used as a spreading agent, improving the absorption of drugs and facilitating the subcutaneous infusion of fluids. Here, we investigated the influence of bovine testes hyaluronidase (HYAL) during cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the wound scratch assay that HYAL increased the migration and proliferation of fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell number by 20%. HYAL presented faster and higher reepithelialization in in vivo full-thickness excisional wounds generated on adult Wistar rats back skin already in the early phase at 2nd day post operatory compared to vehicle-control group. Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38% and 46% compared to 19% in the controls, respectively. Histological and biochemical analyses supported the clinical observations and showed that HYAL treated wounds exhibited increased granulation tissue, diminished edema formation and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL increased gene expression of peroxisome proliferator-activated receptors (PPAR) γ and PPAR β/δ, the collagen content in the early stages of healing processes as well as angiogenesis. Altogether these data revealed that HYAL accelerates wound healing processes and might be beneficial for treating wound disorders. PMID:25393024

  13. 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.

  14. High bacterial load in asymptomatic diabetic patients with neurotrophic ulcers retards wound healing after application of Dermagraft.

    PubMed

    Browne, A C; Vearncombe, M; Sibbald, R G

    2001-10-01

    Diabetic neuropathic foot ulcers are a major healthcare burden. These chronic wounds always have a bacterial load, and although normal flora is not harmful, increased tissue burden may impede healing before clinical signs of infection are evident. In this study, chronic noninfected diabetic neuropathic foot ulcers (those with adequate blood supply and pressure offloading) were assessed for bacterial burden immediately before the application of a skin substitute. Eight patients with diabetic neuropathic foot ulcers greater than 1 cm2 and free of necrotic tissue had 3-mm tissue biopsies taken from the ulcer base for quantitative bacteriology. Five of the eight patients (75%) had greater or equal to 10(5) colony forming units/gram organisms present despite the absence of clinical signs of infection. Wound healing rates were linked to bacterial load as determined from quantitative biopsy--no growth was associated with a wound healing rate of 0.2 cm per week, 10(5) to 10(6) colony forming units/gram was associated with a healing rate of 0.15 cm per week, and greater than 10(6) colony forming units/gram was associated with 0.05 cm/per week healing rate. High bacterial burden impeded healing both before and after the application of the skin substitute. The authors will change their clinical practice to assess all diabetic neuropathic foot ulcers using quantitative skin biopsies before applying skin substitutes. All patients will be treated with combination antibiotics and repeat biopsies obtained with decreased bacterial burden (< 10(6) colony forming units/gram) prior to using any bioengineered skin substitute or growth factor treatment.

  15. 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.

  16. Dipeptidyl peptidase 4 inhibition may facilitate healing of chronic foot ulcers in patients with type 2 diabetes.

    PubMed

    Marfella, Raffaele; Sasso, Ferdinando Carlo; Rizzo, Maria Rosaria; Paolisso, Pasquale; Barbieri, Michelangela; Padovano, Vincenzo; Carbonara, Ornella; Gualdiero, Pasquale; Petronella, Pasquale; Ferraraccio, Franca; Petrella, Antonello; Canonico, Raffaele; Campitiello, Ferdinando; Della Corte, Angela; Paolisso, Giuseppe; Canonico, Silvestro

    2012-01-01

    The pathophysiology of chronic diabetic ulcers is complex and still incompletely understood, both micro- and macroangiopathy strongly contribute to the development and delayed healing of diabetic wounds, through an impaired tissue feeding and response to ischemia. With adequate treatment, some ulcers may last only weeks; however, many ulcers are difficult to treat and may last months, in certain cases years; 19-35% of ulcers are reported as nonhealing. As no efficient therapy is available, it is a high priority to develop new strategies for treatment of this devastating complication. Because experimental and pathological studies suggest that incretin hormone glucagon-like peptide-1 may improves VEGF generation and promote the upregulation of HIF-1α through a reduction of oxidative stress, the study evaluated the effect of the augmentation of GLP-1, by inhibitors of the dipeptidyl peptidase-4, such as vildagliptin, on angiogenesis process and wound healing in diabetic chronic ulcers. Although elucidation of the pathophysiologic importance of these aspects awaits further confirmations, the present study evidences an additional aspect of how DPP-4 inhibition might contribute to improved ulcer outcome.

  17. 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.

  18. A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers.

    PubMed

    Bishop, J B; Phillips, L G; Mustoe, T A; VanderZee, A J; Wiersema, L; Roach, D E; Heggers, J P; Hill, D P; Taylor, E L; Robson, M C

    1992-08-01

    Chronic wounds such as venous stasis ulcers have become a socioeconomic problem. Even with successful initial management, the recurrence rate approaches 70%. With the advent of new wound healing agents, nonoperative attempts to heal these wounds appear indicated. This study reports a prospective randomized evaluator-blinded trial comparing two potential wound healing agents to an inert vehicle placebo. Eighty-six evaluable patients completed the trial. Silver sulfadiazine 1% in a cream proved to statistically reduce the ulcer size compared with a biologically active tripeptide copper complex 0.4% cream formulation or the placebo. There was no difference between the latter two treatments. Silver sulfadiazine has been shown to allow keratinocyte replication and to have antiinflammatory properties. In this trial its antibacterial action was not used since all ulcers had comparable bacterial levels (less than or equal to 10(5)/gm of tissue) before treatment. These results suggest that the silver sulfadiazine cream used in this study may facilitate healing in wounds healing largely by the process of epithelialization. PMID:1495150

  19. 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

  20. Research: Treatment Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial

    PubMed Central

    Armstrong, D G; Hanft, J R; Driver, V R; Smith, A P S; Lazaro-Martinez, J L; Reyzelman, A M; Furst, G J; Vayser, D J; Cervantes, H L; Snyder, R J; Moore, M F; May, P E; Nelson, J L; Baggs, G E; Voss, A C

    2014-01-01

    Aims Among people with diabetes, 10–25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and β-hydroxy-β-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes. Methods Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and β-hydroxy-β-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle–brachial index, and supplementation on healing was investigated. Results Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle–brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and β-hydroxy-β-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04–2.79) and 1.66 (95% CI 1.15–2.38) times more likely to heal. Conclusions While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and β-hydroxy-β-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and β-hydroxy-β-methylbutyrate in these high-risk subgroups might prove clinically valuable. PMID:24867069

  1. Effects of acetylsalicylic acid (ASA), ASA plus L-glutamine and L-glutamine on healing of chronic gastric ulcer in the rat.

    PubMed

    Okabe, S; Takeuchi, K; Honda, K; Takagi, K

    1976-01-01

    A chronic gastric ulcer model was produced in rats by the subserosal injection of 20% acetic acid solution (0.015 ml) in order to examine whether (1) acetylsalicylic acid (ASA) irritates the chronic gastric ulcer in active or healed or diminished stage, (2) L-glutamine, given together with ASA, inhibits the adverse effect of ASA. Oral ASA 200 mg/kg/day, given in two divided doses for 10 consecutive days, apparently delayed the healing of the gastric ulcer and irritated the healed ulcer to reulcerate. L-Glutamine, 1,500 mg/kg/day, which was given together with ASA in two divided doses, markedly protected the gastric ulcer both in active and healed stages from the deleterious activity of ASA. PMID:955326

  2. Myxopapillary ependymoma masquerading as subcutaneous sacrococcygeal non-healing ulcer: case report.

    PubMed

    Zaidi, Shaesta Naseem; AlKhalidi, Hisham; Al-Rikabi, Ammar Cherkees

    2014-01-01

    Ependymomas outside the confines of the cranium and spinal cord are rare. The occurrence of these tumors in an extradural, sacrococcygeal, or subcutaneous location may prove challenging, particularly in the absence of any obvious central nervous system connection. The origin of these tumors from sub.cutaneous sacrococcygeal ependymal rests is postulated on the basis of earlier reports. We describe 1 such rare extradural case of myxopapillary ependymoma in a 30-year-old female, which presented as a non-healing ulcer in the left gluteal area. It was initially diagnosed and was being treated as an infected epidermoid cyst. Clinical and histopathological features are described, and a brief review of published reports is presented. PMID:25266190

  3. [Healing process of uncomplicated sole ulcers in dairy cows kept in tie stalls: clinical description and blood chemical investigations].

    PubMed

    Lischer, C J; Dietrich-Hunkeler, A; Geyer, H; Schulze, J; Ossent, P

    2001-03-01

    A total of 74 dairy cows with 105 separate lesions were treated and the healing process was observed for half a year and the results compared with the biochemical data. The mean time for the formation of a closed layer of horn was 25 days for lesions with slight corium alterations, 33 days for moderate and 42 days for severe alterations. Thirty days after the initial treatment 68% of all lesions were completely covered by a solid layer of new horn. The further evaluation of the healing process was based on quality and rate of the new horn formation, recovery from lameness and sensitivity to hooftesters. Using these parameters the healing potential of exposed corium was judged one month after treatment with a scoring system. The 30-day-healing process was considered to be good in 61% and moderate to bad in 39% of the cows. The concentration of glucose, cholesterin, LDH and blood urea was increased in one third of the animals. Phosphorus and magnesium concentrations were lower than the reference values in 30%, and 26% of the animals, respectively. Cows with prolonged healing had higher levels of bilirubin, creatinkinase, LDH, ALT and AST than cows with a good healing process. Concentration of iron, vitamin A and biotin were significantly lower in cows with moderate to bad healing parameters than cows with a good healing potential. From these results it is suggested that biochemical blood parameters and the vitamin status might influence the healing of uncomplicated sole ulcers, respectively. PMID:11293931

  4. Diazoxide accelerates wound healing by improving EPC function.

    PubMed

    Li, Zhang-Peng; Xin, Ru-Juan; Yang, Hong; Jiang, Guo-Jun; Deng, Ya-Ping; Li, Dong-Jie; Shen, Fu-Ming

    2016-01-01

    Endothelial cell dysfunction is the primary cause of microvascular complications in diabetes. Diazoxide enables beta cells to rest by reversibly suppressing glucose-induced insulin secretion by opening ATP-sensitive K+ channels in the beta cells. This study investigated the role of diazoxide in wound healing in mice with streptozotocin (STZ)-induced diabetes and explored the possible mechanisms of its effect. Compared to the controls, mice with STZ-induced diabetes exhibited significantly impaired wound healing. Diazoxide treatment (30 mg/kg/d, intragastrically) for 28 days accelerated wound closure and stimulated angiogenesis in the diabetic mice. Circulating endothelial progenitor cells (EPCs) increased significantly in the diazoxide-treated diabetic mice. The adhesion, migration, and tube formation abilities of bone marrow (BM)-EPCs were impaired by diabetes, and these impairments were improved by diazoxide treatment. The expression of both p53 and TSP-1 increased in diabetic mice compared to that in the controls, and these increases were inhibited significantly by diazoxide treatment. In vitro, diazoxide treatment improved the impaired BM-EPC function and diminished the increased expression of p53 and TSP-1 in cultured BM-EPCs caused by high glucose levels. We conclude that diazoxide improved BM-EPC function in mice with STZ-induced diabetes, possibly via a p53- and TSP-1-dependent pathway. PMID:27100489

  5. 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. PMID:26967481

  6. 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.

  7. Association Between Microbial Bioburden and Healing Outcomes in Venous Leg Ulcers: A Review of the Evidence

    PubMed Central

    Tuttle, Marie S.

    2015-01-01

    Significance: Venous leg ulcers (VLUs) are susceptible to microbial invasion, and serious complications can result without the timely control of infection. Diagnosis of wound infection is primarily based on subjective clinical characteristics and patient-reported symptoms, and the treatment with antimicrobials has not consistently shown improvement in healing outcomes. This is a review of studies using bacterial cultures and/or new molecular-based methods associating microbial bioburden with healing outcomes in VLU patients, with the goal of guiding future studies to better determine significant patterns of microbial involvement in chronic wounds. Recent Advances: Studies reviewed here use cultivation-based identification of bacteria and next-generation sequencing of the bacterial 16S rRNA gene to gain insight into microbial bioburden in VLUs. Further application of sophisticated DNA sequencing and bioinformatic analyses has the potential to revolutionize our ability to further discern, with high resolution, complex microbial communities in chronic wounds. Critical Issues: Few previous studies of microbial bioburden in VLUs have incorporated the knowledge of clinical treatments, which includes close monitoring of patients' symptoms and responses to therapy. Thus, wound care practitioners are currently without evidence-based guidance for the diagnosis and treatment of wound infections. Future Directions: Clinically relevant breakthroughs are possible by combining advanced microbial detection techniques with improved study designs that reflect clinical practices. Well-designed longitudinal studies have great potential to lead to better evidence-based diagnosis of chronic wounds. A greater understanding of microbial bioburden in chronic wounds is likely to lead to better therapies that speed healing and prevent wound infection without risking the development of antimicrobial resistance. PMID:25566410

  8. Improved symptom relief and duodenal ulcer healing with lansoprazole, a new proton pump inhibitor, compared with ranitidine.

    PubMed Central

    Hawkey, C J; Long, R G; Bardhan, K D; Wormsley, K G; Cochran, K M; Christian, J; Moules, I K

    1993-01-01

    The purpose of this study was to compare duodenal ulcer healing, symptom relief, and safety of lansoprazole (a new proton pump inhibitor) given at doses of 30 mg and 60 mg, in the morning with ranitidine 300 mg at bedtime. Two hundred and eighty nine patients were enrolled over a 20 month period in a double blind randomised parallel group comparative study set in outpatient endoscopy units of six United Kingdom medical centres. Patients were randomised to receive lansoprazole 30 mg in the morning (n = 95), 60 mg in the morning (n = 96), or ranitidine 300 mg at bedtime (n = 98) for four weeks. Efficacy was assessed by gastroscopy at study entry and after two and four weeks of treatment. Symptom relief was monitored by patient diaries and physician review at two and four weeks. Both doses of lansoprazole resulted in significantly greater ulcer healing than ranitidine after two and four weeks. Respective healing rates on lansoprazole 30 mg, 60 mg, and ranitidine 300 mg were 78%, 80%, and 60% after two weeks and 93%, 97%, and 81% after four weeks. Patients on lansoprazole 30 mg (p = 0.002) and lansoprazole 60 mg (p = 0.026) also recorded greater relief of night time pain in the diary cards during the first seven days of treatment than those on ranitidine. Patients on lansoprazole 60 mg reported significantly better pain relief at their two week visit compared with those receiving ranitidine (p = 0.007). There were no differences between treatment groups in the occurrence or pattern of adverse drug reactions during the trial. It is concluded that for patients with duodenal ulcer, lansoprazole 30 mg or 60 mg is associated with faster ulcer healing and better symptom relief than ranitidine 300 mg at bedtime. There were no significant differences between lansoprazole 30 mg and 60 mg. These data indicate that lansoprazole should be used at a once daily dose of 30 mg for the treatment of duodenal ulcer. PMID:8244121

  9. Evaluation of effects of nutrition intervention on healing of pressure ulcers and nutritional states (randomized controlled trial).

    PubMed

    Ohura, Takehiko; Nakajo, Toshio; Okada, Shingo; Omura, Kenji; Adachi, Kayoko

    2011-01-01

    The objective of this study was to evaluate the effects of nutrition intervention on nutritional states and healing of pressure ulcers by standardizing or unified factors including nursing, care and treatment in a multicenter open randomized trial. Tube-fed patients with Stage III-IV pressure ulcers were selected. The control group (30 patients) received the same nutrition management as before participating in this trial, whereas the intervention group (30 patients) was given calories in the range of Basal Energy Expenditure (BEE) × 1.1 × 1.3 to 1.5. The intervention period was 12 weeks. The efficacy and safety were evaluated based on the nutritional states and the sizes of ulcers (length × width), and on the incidence of adverse events related to the study, respectively. The calories administered to the control and intervention groups were 29.1 ± 4.9 and 37.9 ± 6.5 kcal/kg/day, respectively. Significant interactions between the presence or absence of the intervention and the intervention period were noted for nutritional states (p<0.001 for body weight, p<0.05 for prealbumin). Similarly, the size of ulcers differed significantly between subjects in the intervention group and in the control group (p<0.001). The results suggest that nutrition intervention could directly enhance the healing process in pressure ulcer patients.

  10. 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.

  11. Ulcers

    MedlinePlus

    ... have one. Ulcers can also be caused by anti-inflammatory medicines. Although most people take these medicines without ... may damage the stomach lining and cause ulcers. Anti-inflammatory drugs include aspirin, ibuprofen (one brand name: Motrin), ...

  12. Milk Fat Globule–Epidermal Growth Factor 8 Is Decreased in Intestinal Epithelium of Ulcerative Colitis Patients and Thereby Causes Increased Apoptosis and Impaired Wound Healing

    PubMed Central

    Zhao, Qiu-jie; Yu, Yan-bo; Zuo, Xiu-li; Dong, Yan-yan; Li, Yan-qing

    2012-01-01

    Milk fat globule–epidermal growth factor 8 (MFG-E8) plays an important role in maintaining intestinal barrier homeostasis and accelerating intestinal restitution. However, studies of MFG-E8 expression in humans with ulcerative colitis are lacking. We examined MFG-E8 expression in colonic mucosal biopsies from ulcerative colitis patients and healthy controls (n = 26 each) by real-time quantitative polymerase chain reaction (PCR), Western blot analysis and immunohistochemistry. MFG-E8 mRNA and protein expression was lower in ulcerative colitis patients than in controls. MFG-E8 expression was inversely correlated with mucosal inflammatory activity and clinical disease activity in patients. MFG-E8 was present in human intestinal epithelial cells both in vivo and in vitro. Apoptosis induction was also detected in the intestinal epithelium of ulcerative colitis patients by terminal-deoxynucleoitidyl transferase mediated nick-end labeling assay. We used lentiviral vectors encoding human MFG-E8 targeting short hairpin RNA to obtain MFG-E8 knockdown intestinal epithelia cell clones. MFG-E8 knockdown could promote apoptosis in intestinal epithelial cell lines, accompanied by a decrease in level of the antiapoptotic protein B-cell lymphoma 2 (BCL-2) and induction of the proapoptotic protein BCL2-associated protein X (BAX). The addition of recombinant human MFG-E8 led to decreased BAX and cleaved caspase-3 levels and induction of BCL-2 level in intestinal epithelia cells. MFG-E8 knockdown also attenuated wound healing on scratch assay of intestinal epithelial cells. The mRNA level of intestinal trefoid factor 3, a pivotal factor in intestinal epithelial cell migration and restitution, was downregulated with MFG-E8 knockdown. In conclusion, we demonstrated that decreased colonic MFG-E8 expression in patients with ulcerative colitis may be associated with mucosal inflammatory activity and clinical disease activity through basal cell apoptosis and preventing tissue healing in

  13. Accelerated healing of cardiovascular textiles promoted by an RGD peptide.

    PubMed

    Tweden, K S; Harasaki, H; Jones, M; Blevitt, J M; Craig, W S; Pierschbacher, M; Helmus, M N

    1995-07-01

    Polytetrafluoroethylene (PTFE) and polyethylene terephthalate (Dacron polyester) fabrics are used extensively in cardiovascular devices, e.g. heart valve sewing cuffs and vascular prostheses. While devices containing these fabrics are generally successful, it is recognized that fabrics cause complications prior to tissue ingrowth due to their thrombogenic nature. A surface active synthetic peptide, called PepTite Coating (PepTite), which was modeled after the cell attachment domain of human fibronectin has been marketed as a biocompatible coating. This peptide stimulates cell attachment through the arginine-glycine-aspartic acid (RGD) sequence. Modification of medical implants with PepTite has been shown to promote ingrowth of surrounding cells into the material leading to better tissue integration, reduced inflammation and reduced fibrotic encapsulation. In this study, polyester and PTFE textiles were modified with PepTite. The effectiveness of this coating in enhancing wound healing was investigated in a simple vascular and cardiac valve model. Our results indicate that the RGD-containing peptide, PepTite, promoted the formation of an endothelial-like cell layer on both polyester and PTFE vascular patches in the dog model. PepTite was also found to promote the formation of a significantly thinner neointima (pannus) on polyester as compared to that on its uncoated control. These results were corroborated in the cardiac valve model in which a greater amount of thin pannus and less thrombus were seen on coated polyester sewing cuffs than on control uncoated cuffs. This research shows the promising tissue response to RGD coated textiles and the potential role of this peptide in material passivation via accelerated healing.

  14. A prospective, randomized, controlled study of hyperbaric oxygen therapy: effects on healing and oxidative stress of ulcer tissue in patients with a diabetic foot ulcer.

    PubMed

    Ma, Le; Li, Pingsong; Shi, Zehong; Hou, Tuanjie; Chen, Xiao; Du, Jin

    2013-03-01

    Although hyperbaric oxygen (HBO) therapy has been reported to help heal chronic foot ulcers in patients with diabetes mellitus (DM), production of HBO-related oxidative stress is a concern. To assess the therapeutic effect and oxidative stress of HBO, a 2-week, prospective, randomized, controlled clinical study was conducted from January 1, 2010 to January1, 2012 among 36 consecutively admitted patients with diabetic foot ulcers (DFU). Average patient age was 60.08 ± 5.97 years and average DM duration was 16.4 ± 11.3 years; 86.1% had type 2 DM, and 47.2% had Wagner grade-III foot ulcers. Patients randomized to the control group (n = 18) received standard care including offloading, wound debridement, and glucose control. HBO treatment group patients (n = 18) received standard care and twice-daily HBO sessions for 90 minutes at 2.5 atmospheres absolute (ATA) 5 days a week for 2 weeks. Transcutaneous oxygen pressure (TcPo2) at the edge of the ulcer and wound size were measured at baseline and after 7 and 14 days of treatment. Ulcer tissues were harvested on days 7 and 14 to determine oxidative stress by measuring malondialdehyde (MDA) and antioxidant enzyme (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GPx]) levels. Compared to baseline, TcPo2 in the HBO group increased on day 7 (477.8 ± 118.2 mm Hg versus 37.06 ± 5.23 mm Hg, P <0.01) and day 14 (501.1 ± 137.7 mm Hg versus 35.61 ± 4.85 mm Hg, P <0.01). Ulcer size reduction in the HBO group was greater than that of the control group (42.4% ± 20.0% versus 18.1% ± 6.5%, P <0.05). MDA levels, SOD, and CAT were all significantly higher in the HBO than in the control group on day 14 (P<0.05). The results of this study suggest HBO treatment for 2 weeks initiates a healing response in chronic DFUs, but the observed oxidative stress in local ulcer tissue may offset this effect long-term. Until needed additional research has been conducted, prolonged and/or inappropriate HBO treatment should

  15. Imaging in inflammatory bowel disease mucosal healing in ulcerative colitis: relevance for clinical outcomes.

    PubMed

    Schirbel, Anja; Sturm, Andreas

    2012-09-01

    There is growing evidence of the importance of mucosal healing (MH) in ulcerative colitis, but whether or not it should be a future primary treatment goal is still under intense discussion. Within the last decade many clinical trials have focused not only on response and remission rates but also on achievement of MH, while in clinical practice we still make treatment decisions on the basis of clinical symptoms. There is so far no internationally accepted definition of MH and the tools for assessment of MH vary from biomarkers to endoscopy with histological evaluation on the basis of several different scores and indices. This review will focus on present data dealing with methods to assess MH and the importance of MH for the future course of disease, the need for colectomy or risk of developing colorectal cancer and the patient's quality of life. Many questions remain: How and when do we best assess MH? How rapidly do we need to achieve MH? What is the optimal time point to discontinue treatment after achieving MH? Well defined prospective studies are needed to address these important questions. PMID:22664079

  16. Biotherapeutics in orthopaedic medicine: accelerating the healing process?

    PubMed

    Puleo, David

    2003-01-01

    Musculoskeletal injuries have a significant human and financial impact on society. In particular, fractures that lead to delayed union or even nonunion represent a serious clinical challenge for which few treatment options are available. The multiple surgical procedures often needed are associated with patient morbidity and reduced quality of life. Biotechnological advances have made possible a host of potential treatments for enhancing and accelerating the repair of bone. By stimulating the body's own healing mechanisms, clinical outcomes may be improved while also containing procedural costs. Biotherapeutics may take the form of proteins, genes or cells that can be used to treat the injury. Protein biotherapeutics have received the greatest attention. Using recombinant DNA techniques, growth factors that play important roles in bone development and repair are being produced. By delivering exogenous growth factors to the site of injury in an appropriate manner, bone formation can be stimulated. Although individual proteins have been the primary focus of investigation, combinations of biomolecules can have additive, and perhaps synergistic, effects. Alternatively, genes coding for osteotropic growth factors can be delivered to the site of injury. Expression of the gene effectively results in localised delivery of the growth factor. Delivery of cells having osteogenic potential can also result in bone formation. Furthermore, it may be possible to obtain additional benefits by combining biotherapeutic approaches, such as by introducing cells genetically modified to overexpress therapeutic proteins of interest. Although biotherapeutics have great potential for stimulating bone repair, only a limited number of treatments have been approved by governmental regulatory agencies for clinical use. Bone morphogenetic activity was initially described in 1965, but not until 2001 and 2002 did two protein biotherapeutics, utilising bone morphogenetic proteins 2 and 7, receive

  17. Knockout of Angiotensin AT2 receptors accelerates healing but impairs quality

    PubMed Central

    Faghih, Mahya; Hosseini, Sayed M.; Smith, Barbara; Ansari, Amir Mehdi.; Lay, Frank; Ahmed, Ali Karim; Inagami, Tedashi; Marti, Guy P.; Harmon, John W.; Walston, Jeremy D.; Abadir, Peter M.

    2015-01-01

    Wounds are among the most common, painful, debilitating and costly conditions in older adults. Disruption of the angiotensin type 1 receptors (AT1R), has been associated with impaired wound healing, suggesting a critical role for AT1R in this repair process. Biological functions of angiotensin type 2 receptors (AT2R) are less studied. We investigated effects of genetically disrupting AT2R on rate and quality of wound healing. Our results suggest that AT2R effects on rate of wound closure depends on the phase of wound healing. We observed delayed healing during early phase of wound healing (inflammation). An accelerated healing rate was seen during later stages (proliferation and remodeling). By day 12, fifty percent of AT2R−/− mice had complete wound closure as compared to none in either C57/BL6 or AT1R−/− mice. There was a significant increase in AT1R, TGFβ1 and TGFβ2 expression during the proliferative and remodeling phases in AT2R−/− mice. Despite the accelerated closure rate, AT2R−/− mice had more fragile healed skin. Our results suggest that in the absence of AT2R, wound healing rate is accelerated, but yielded worse skin quality. Elucidating the contribution of both of the angiotensin receptors may help fine tune future intervention aimed at wound repair in older individuals. PMID:26727887

  18. Inhibition of indoleamine 2,3-dioxygenase activity accelerates skin wound healing.

    PubMed

    Ito, Hiroyasu; Ando, Tatsuya; Ogiso, Hideyuki; Arioka, Yuko; Saito, Kuniaki; Seishima, Mitsuru

    2015-06-01

    Skin wound healing is a complex process involving several stages that include inflammation, proliferation, and remodeling. In the inflammatory phase, pro-inflammatory cytokines and chemokines are induced at the wound site and, they contribute to the development of wound healing. These cytokines also induce indoleamine 2,3-dioxygenase (IDO1) activity; this is the rate-limiting and first enzyme in the l-tryptophan (TRP)-l-kynurenine (KYN) pathway. This study examined the effect of IDO1 on the process of skin wound healing. The expression of the Ido1 mRNA was enhanced after creating a wound in wild-type (WT) mice. TRP concentration was simultaneously reduced at the wound site. The rate of wound healing in IDO1 knockout (IDO-KO) mice was significantly higher than that in WT mice. 1-Methyl-dl-tryptophan (1-MT), a potent inhibitor of IDO1, increased the rate of wound healing in WT mice. The administration of TRP accelerated wound healing in vivo and in an in vitro experimental model, whereas the rate of wound healing was not affected by the administration of KYN. The present study identifies the role of IDO1 in skin wound healing, and indicates that the local administration of 1-MT or TRP may provide an effective strategy for accelerating wound healing.

  19. Raman spectroscopy of endoscopic colonic biopsies from patients with ulcerative colitis to identify mucosal inflammation and healing

    PubMed Central

    Addis, James; Mohammed, Noor; Rotimi, Olorunda; Magee, Derek; Jha, Animesh; Subramanian, Venkataraman

    2016-01-01

    Raman spectroscopy was used to differentiate between mucosally healed (or quiescent) and inflamed colon tissue, as assessed endoscopically, in patients with ulcerative colitis. From the analysis of the Raman spectra of 60 biopsy tissue samples, clear differences were identified between the spectra of the quiescent and inflamed tissue. Three carotenoid peaks were found to be approximately twice as intense in the inflamed tissue. Two phospholipid peaks were found to be significantly lower in the inflamed tissue. Using multivariate statistical analysis, we show that these five peaks can be used to discriminate between endoscopically quiescent and inflamed tissue. We also correlated the Raman data with a histological assessment of the tissue. Four of the five peaks were found to be significantly different between the spectra of histologically healed (or quiescent) and histologically inflamed tissue. These findings indicate the ability of Raman spectroscopy to accurately classify colon tissue as either quiescent or inflamed, irrespective of whether an endoscopic or histological grading scheme is followed. We thus demonstrate that Raman spectroscopy could potentially be used as an early diagnosis tool for assessing the presence of mucosal healing or inflammation in patients with ulcerative colitis. PMID:27231640

  20. 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

  1. Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model

    PubMed Central

    2013-01-01

    Introduction Diabetic foot ulceration is the leading cause of amputation in people with diabetes mellitus. Peripheral vascular disease is present in the majority of patients with diabetic foot ulcers. Despite standard treatments there exists a high amputation rate. Circulating angiogenic cells previously known as early endothelial progenitor cells are derived from peripheral blood and support angiogenesis and vasculogenesis, providing a potential topical treatment for non-healing diabetic foot ulcers. Methods A scaffold fabricated from Type 1 collagen facilitates topical cell delivery to a diabetic wound. Osteopontin is a matricellular protein involved in wound healing and increases the angiogenic potential of circulating angiogenic cells. A collagen scaffold seeded with circulating angiogenic cells was developed. Subsequently the effect of autologous circulating angiogenic cells that were seeded in a collagen scaffold and topically delivered to a hyperglycemic cutaneous wound was assessed. The alloxan-induced diabetic rabbit ear ulcer model was used to determine healing in response to the following treatments: collagen seeded with autologous circulating angiogenic cells exposed to osteopontin, collagen seeded with autologous circulating angiogenic cells, collagen alone and untreated wound. Stereology was used to assess angiogenesis in wounds. Results The cells exposed to osteopontin and seeded on collagen increased percentage wound closure as compared to other groups. Increased angiogenesis was observed with the treatment of collagen and collagen seeded with circulating angiogenic cells. Conclusions These results demonstrate that topical treatment of full thickness cutaneous ulcers with autologous circulating angiogenic cells increases wound healing. Cells exposed to the matricellular protein osteopontin result in superior wound healing. The wound healing benefit is associated with a more efficient vascular network. This topical therapy provides a potential novel

  2. 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

  3. 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

  4. 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

  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

    2015-12-01

    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.

  6. 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. PMID:27314669

  7. Effect of myrrh (Commiphora molmol) on leukocyte levels before and during healing from gastric ulcer or skin injury.

    PubMed

    Haffor, Al-Said A

    2010-03-01

    Myrrh (Commiphora molmol) has been widely used as an anti-inflammatory and wound healing commercial product. As white blood cell (WBC)/leukocyte counts have been used as an indicator by clinicians to monitor progress of healing in patients, the purpose of this study was to examine effects of myrrh supplementation on blood WBC numbers before an injury and during healing. Male rats (7-8-wk-of-age) were randomly assigned to four groups. Group 1 (SIM) served as "skin injury treated + myrrh treatment (500 mg/kg/day)," Group 2 (SI) as "skin injury alone", Group 3 (GUM) as "gastric ulcer treated + myrrh treatment", and Group 4 (GU) as gastric ulcer only. Myrrh treatments (via drinking water) began 4 wk before induction of injury and continued for a 2 wk period post-injury. Baseline values for each WBC type were recorded before start of the myrrh treatments. Counts were performed again on Day 1 of the 5th wk (1-2 hr before injury) and post-injury on Days 4 and 7 of the 5th wk, and a final time on Day 4 of the 6th wk. Results showed that levels of all WBC types were significantly (P < 0.05) elevated before either injury in myrrh-treated rats (Groups 1 and 3) as compared with levels in rats in Groups 2 and 4. At all timepoints, there were neither significant differences between the values seen with rats in Groups 1 and 3, nor between those in Groups 2 and 4. Treatment with myrrh also induced an initial increase in WBC levels that persisted through the post-injury healing period. Levels of most cell types only increased in the Group 2 and 4 rats once the injury was induced, but then declined over the healing period. Since myrrh enhanced WBC levels before injury, we conclude that myrrh likely contains substances that could induce an apparent antigen-driven response. As the myrrh also helped maintain elevated WBC levels throughout the healing period, this implied it was also able to induce maturation/differentiation/activation of both myeloid and lymphoid cell types during the

  8. Angiogenesis in gastric mucosa: an important component of gastric erosion and ulcer healing and its impairment in aging.

    PubMed

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

    2014-12-01

    Angiogenesis (also referred to as neovascularization-formation of new blood vessels from existing vessels) is a fundamental process essential for healing of tissue injury and ulcers because regeneration of blood microvessels is a critical requirement for oxygen and nutrient delivery to the healing site. This review article updates the current views on angiogenesis in gastric mucosa following injury and during ulcer healing, its sequential events, the underlying mechanisms, and the impairment of angiogenesis in aging gastric mucosa. We focus on the time sequence and ultrastructural features of angiogenesis, hypoxia as a trigger, role of vascular endothelial growth factor signaling (VEGF), serum response factor, Cox2 and prostaglandins, nitric oxide, and importin. Recent reports indicate that gastric mucosa of aging humans and experimental animals exhibits increased susceptibility to injury and delayed healing. Gastric mucosa of aging rats has increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin, and other non-steroidal anti-inflammatory drugs because of structural and functional abnormalities including: reduced gastric mucosal blood flow, hypoxia, reduced expression of vascular endothelial growth factor and survivin, and increased expression of early growth response protein 1 (egr-1) and phosphatase and tensin homolog (PTEN). Until recently, postnatal neovascularization was assumed to occur solely through angiogenesis sprouting of endothelial cells and formation of new blood vessels from pre-existing blood vessels. New studies in the last decade have challenged this paradigm and indicate that in some tissues, including gastric mucosa, the homing of bone marrow-derived endothelial progenitor cells to the site of injury can also contribute to neovascularization by a process termed vasculogenesis.

  9. Angiogenesis in gastric mucosa: an important component of gastric erosion and ulcer healing and its impairment in aging.

    PubMed

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

    2014-12-01

    Angiogenesis (also referred to as neovascularization-formation of new blood vessels from existing vessels) is a fundamental process essential for healing of tissue injury and ulcers because regeneration of blood microvessels is a critical requirement for oxygen and nutrient delivery to the healing site. This review article updates the current views on angiogenesis in gastric mucosa following injury and during ulcer healing, its sequential events, the underlying mechanisms, and the impairment of angiogenesis in aging gastric mucosa. We focus on the time sequence and ultrastructural features of angiogenesis, hypoxia as a trigger, role of vascular endothelial growth factor signaling (VEGF), serum response factor, Cox2 and prostaglandins, nitric oxide, and importin. Recent reports indicate that gastric mucosa of aging humans and experimental animals exhibits increased susceptibility to injury and delayed healing. Gastric mucosa of aging rats has increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin, and other non-steroidal anti-inflammatory drugs because of structural and functional abnormalities including: reduced gastric mucosal blood flow, hypoxia, reduced expression of vascular endothelial growth factor and survivin, and increased expression of early growth response protein 1 (egr-1) and phosphatase and tensin homolog (PTEN). Until recently, postnatal neovascularization was assumed to occur solely through angiogenesis sprouting of endothelial cells and formation of new blood vessels from pre-existing blood vessels. New studies in the last decade have challenged this paradigm and indicate that in some tissues, including gastric mucosa, the homing of bone marrow-derived endothelial progenitor cells to the site of injury can also contribute to neovascularization by a process termed vasculogenesis. PMID:25521743

  10. Extracorporeal shockwave therapy in diabetic foot ulcers.

    PubMed

    Wang, Ching-Jen; Cheng, Jai-Hong; Kuo, Yur-Ren; Schaden, Wolfgang; Mittermayr, Rainer

    2015-12-01

    Diabetic foot ulcers (DFUs) are among the most common foot disorders with ulceration, infection, and gangrene that may ultimately lead to lower extremity amputation. The goals of treatment include the control of diabetes and proper shoe wear. An effective therapy and appropriate foot care are important in wound healing in DFUs. Recently, extracorporeal shockwave therapy (ESWT) was reported to significantly promote and accelerate the healing of complex soft tissue wounds as compared to the standard methods of treatment in DFUs. ESWT showed positive results in short-term and long-term outcomes in diabetic patients suffering from foot ulcers. In this article, we review the clinical results of ESWT in DFUs.

  11. Lansoprazole versus omeprazole for duodenal ulcer healing and prevention of relapse: a randomized, multicenter, double-masked trial.

    PubMed

    Dobrilla, G; Piazzi, L; Fiocca, R

    1999-08-01

    The aim of this randomized, multicenter, double-masked, parallel-group study was to compare the efficacy of lansoprazole with that of omeprazole monotherapy in duodenal ulcer healing and prevention of relapse. A total of 251 patients with duodenal ulcer were treated with either lansoprazole 30 mg/d (n = 167) or omeprazole 40 mg/d (n = 84). Patients with healed ulcers were then randomly allocated to 12 months of maintenance therapy with lansoprazole 15 mg/d (n = 74), lansoprazole 30 mg/d (n = 71), or omeprazole 20 mg/d (n = 73). Healing rates at 4 weeks (intent-to-treat analysis) were 93.9% (95% confidence interval [CI], 90.2% to 97.6%) with lansoprazole and 97.5% (95% CI, 93.7% to 100%) with omeprazole; there were no significant differences between groups. Endoscopic relapse rates after 6 months were 4.5% (95% CI, 0% to 10.6%) with lansoprazole 15 mg, 0% with lansoprazole 30 mg, and 6.3% (95% CI, 1.5% to 12.5%) with omeprazole 20 mg, compared with 3.3% (95% CI, 0% to 8.2%), 0%, and 3.5% (95% CI, 0% to 8.8%), respectively, at 12 months. Again, there were no significant differences between groups. The incidence of adverse events during acute treatment was 6.0% and 7.1% in the lansoprazole and omeprazole groups, respectively; during maintenance therapy, the incidences were 12.2% (lansoprazole 15 mg), 5.6% (lansoprazole 30 mg), and 11.0% (omeprazole 20 mg). Within treatment groups, pain was significantly ameliorated after the acute phase but not after maintenance therapy (P < 0.05); no differences were observed between groups. Gastrin values increased significantly after acute therapy (P < 0.05), persisted at these increased levels during maintenance therapy, and returned to normal after 6-month follow-up. Both lansoprazole and omeprazole were highly effective and well tolerated in the treatment of duodenal ulcer; relapse rates were similar for all doses studied. Thus no additional benefit is to be gained from using a proton-pump inhibitor at a dose > 15 mg

  12. 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

  13. Leprosy presenting as a non-healing ulcer and associated unusual myth.

    PubMed

    Yadav, Pravesh; Verma, Prashant; Singal, Archana

    2015-09-01

    A case of a 70 year old lady with borderline tuberculoid leprosy who presented with a chronic ulcer and associated myth has been illustrated. The need for awareness programmes focusing on these types. of myths has been stressed. PMID:26665366

  14. Leprosy presenting as a non-healing ulcer and associated unusual myth.

    PubMed

    Yadav, Pravesh; Verma, Prashant; Singal, Archana

    2015-09-01

    A case of a 70 year old lady with borderline tuberculoid leprosy who presented with a chronic ulcer and associated myth has been illustrated. The need for awareness programmes focusing on these types. of myths has been stressed.

  15. Formylpeptide receptors mediate rapid neutrophil mobilization to accelerate wound healing.

    PubMed

    Liu, Mingyong; Chen, Keqiang; Yoshimura, Teizo; Liu, Ying; Gong, Wanghua; Le, Yingying; Gao, Ji-Liang; Zhao, Jianhua; Wang, Ji Ming; Wang, Aimin

    2014-01-01

    Wound healing is a multi-phased pathophysiological process requiring chemoattractant receptor-dependent accumulation of myeloid cells in the lesion. Two G protein-coupled formylpeptide receptors Fpr1 and Fpr2 mediate rapid neutrophil infiltration in the liver of Listeria-infected mice by sensing pathogen-derived chemotactic ligands. These receptors also recognize host-derived chemotactic peptides in inflammation and injury. Here we report the capacity of Fprs to promote the healing of sterile skin wound in mice by initiating neutrophil infiltration. We found that in normal miceneutrophils rapidly infiltrated the dermis in the wound before the production of neutrophil-specific chemokines by the injured tissue. In contrast, rapid neutrophil infiltration was markedly reduced with delayed wound closure in mice deficient in both Fprs. In addition, we detected Fpr ligand activity that chemoattracted neutrophils into the wound tissue. Our study thus demonstrates that Fprs are critical for normal healing of the sterile skin wound by mediating the first wave of neutrophil infiltration.

  16. Regional implantation of autologous adipose tissue-derived cells induces a prompt healing of long-lasting indolent digital ulcers in patients with systemic sclerosis.

    PubMed

    Del Papa, Nicoletta; Di Luca, Gabriele; Sambataro, Domenico; Zaccara, Eleonora; Maglione, Wanda; Gabrielli, Armando; Fraticelli, Paolo; Moroncini, Gianluca; Beretta, Lorenzo; Santaniello, Alessandro; Sambataro, Gianluca; Ferraresi, Roberto; Vitali, Claudio

    2015-01-01

    Digital ulcers (DUs) are a rather frequent and invalidating complication in systemic sclerosis (SSc), often showing a very slow or null tendency to heal, in spite of the commonly used systemic and local therapeutic procedures. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. In the present study, we have tentatively treated long-lasting and poorly responsive to traditional therapy SSc-related DUs by implantation of autologous adipose tissue-derived cell (ATDC) fractions. Fifteen patients with SSc having a long-lasting DU in only one fingertip who were unresponsive to intensive systemic and local treatment were enrolled in the study. The grafting procedure consisted of the injection, at the basis of the corresponding finger, of 0.5-1 ml of autologous ATDC fractions, separated by centrifugation of adipose tissue collected through liposuction from subcutaneous abdominal fat. Time to heal after the procedure was the primary end point of the study, while reduction of pain intensity and of analgesic consumption represented a secondary end point. Furthermore, the posttherapy variation of the number of capillaries, observed in the nailfold video capillaroscopy (NVC) exam and of the resistivity in the digit arteries, measured by high-resolution echocolor-Doppler, were also taken into account. A rather fast healing of the DUs was reached in all of the enrolled patients (mean time to healing 4.23 weeks; range 2-7 weeks). A significant reduction of pain intensity was observed after a few weeks (p < 0.001), while the number of capillaries was significantly increased at 3- and 6-month NVC assessment (p < 0.0001 in both cases). Finally, a significant after-treatment reduction of digit artery resistivity was also recorded (p < 0.0001). Even with the limitations related to the small number of patients included and to the open-label design of the study, the observed strongly favorable outcome suggests that local grafting with ATDCs

  17. 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

  18. 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

  19. Role of platelet-rich plasma in acceleration of bone fracture healing.

    PubMed

    Simman, Richard; Hoffmann, Andrea; Bohinc, R Jordan; Peterson, Wylan C; Russ, Andrew J

    2008-09-01

    Platelet-rich plasma (PRP) is a common therapy for acceleration of maxillofacial and spinal fusion bone-graft healing. This study analyzes the therapeutic role of PRP during long-bone fracture healing evaluated Lewis rats. Following creation of unilateral open femur fractures, either 500 microL thrombin-activated PRP (PRP treated group) or 500 microL saline (control group) were applied once to the fracture site. Fracture healing was analyzed after 1 and 4 weeks. Following 4 weeks of fracture healing, radiographic analysis demonstrated higher callus to cortex width ratio (P < 0.05) in the PRP group (PRP: 1.65 +/- 0.06; control: 1.48 +/- 0.05). Three-point load bearing showed increased bone strength following PRP treatment (PRP: 60.85 +/- 6.06 Newton, control: 47.66 +/- 5.49 Newton). Fracture histology showed enhanced bone formation in the PRP group. Immunohistochemistry and Western-blotting demonstrated healing-associated changes in transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-2. Our results suggest that PRP accelerates bone fracture healing of rat femurs via modulation of TGF-beta1 and BMP-2 growth factor expression.

  20. 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

  1. 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

  2. Healing mechanisms of the hydroalcoholic extract and ethyl acetate fraction of green tea (Camellia sinensis (L.) Kuntze) on chronic gastric ulcers.

    PubMed

    Borato, Débora Gasparin; Scoparo, Camila Toledo; Maria-Ferreira, Daniele; da Silva, Luísa Mota; de Souza, Lauro Mera; Iacomini, Marcello; Werner, Maria Fernanda de Paula; Baggio, Cristiane Hatsuko

    2016-03-01

    Green tea is an infusion of unfermented leaves of Camellia sinensis (L.) Kuntze (Theaceae), traditionally used for the treatment of obesity, hypercholesterolemia, and gastric complaints. This study evaluated the mechanisms involved in the gastric ulcer healing of the hydroalcoholic extract from green tea (GEt), its ethyl acetate fraction, (GEAc) and epigallocatechin gallate (EGCG) using the model of acetic acid-induced gastric ulcer in rats. The chronic gastric ulcer was induced by application of 80 % acetic acid on serosal mucosa of rats. After 7 days of oral treatment with GEt and GEAc, the ulcer area, mucin content, inflammatory parameters (MPO and NAG), and antioxidant system (GSH and LOOH levels, SOD and GST activities) were evaluated. In vitro, the scavenging activity of GEt and GEAc were also measured. The antisecretory action was studied on the pylorus ligature method in rats. Oral treatment with GEt and GEAc reduced significantly the gastric ulcer area induced by acetic acid. The gastric ulcer healing was accompanied by increasing of mucin content, restoration of GSH levels and SOD activity, and reduction of MPO and LOOH levels. In addition, GEt and GEAc reduced the DPPH free radicals in vitro. Furthermore, the oral treatment of animals with GEt and GEAc did not alter the gastric acid secretion or cause signs of toxicity. Collectively, these results showed that GEt had a pronounced antiulcer effect, possibly through maintenance of mucin content and reduction of inflammation and oxidative stress. In addition, the compounds present in its ethyl acetate fraction could be responsible for the extract activity.

  3. 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.

  4. 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

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

    PubMed

    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; Brindley, Paul J; Loukas, Alex

    2015-10-01

    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

  6. 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

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

    PubMed

    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. PMID:25562608

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

    PubMed Central

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

    2015-01-01

    Abstract. 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. PMID:25562608

  9. Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway

    PubMed Central

    Yang, Rong-Hua; Qi, Shao-Hai; Shu, Bin; Ruan, Shu-Bin; Lin, Ze-Peng; Lin, Yan; Shen, Rui; Zhang, Feng-Gang; Chen, Xiao-Dong; Xie, Ju-Lin

    2016-01-01

    Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro. Importantly, Jag1 overexpression improves diabetic wound healing in vivo. These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound. PMID:27129289

  10. Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway.

    PubMed

    Yang, Rong-Hua; Qi, Shao-Hai; Shu, Bin; Ruan, Shu-Bin; Lin, Ze-Peng; Lin, Yan; Shen, Rui; Zhang, Feng-Gang; Chen, Xiao-Dong; Xie, Ju-Lin

    2016-08-01

    Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro Importantly, Jag1 overexpression improves diabetic wound healing in vivo These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound. PMID:27129289

  11. 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.

  12. 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

  13. 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.

  14. Enteral n-3 fatty acids and micronutrients enhance percentage of positive neutrophil and lymphocyte adhesion molecules: a potential mediator of pressure ulcer healing in critically ill patients.

    PubMed

    Theilla, Miriam; Schwartz, Betty; Zimra, Yael; Shapiro, Haim; Anbar, Ronit; Rabizadeh, Esther; Cohen, Jonathan; Singer, Pierre

    2012-04-01

    n-3 Fatty acids are recognised as influencing both wound healing and immunity. We assessed the impact of a fish oil- and micronutrient-enriched formula (study formula) on the healing of pressure ulcers and on immune function in critically ill patients in an intensive care unit. A total of forty patients with pressure ulcers and receiving nutritional support were enrolled (intervention group, n 20, received study formula; and a control group, n 20, received an isoenergetic formula). Total and differential leucocyte count and percentage of adhesion molecule positive granulocyte and lymphocyte cells (CD11a, CD11b, CD18 and CD49b) were measured on days 0, 7 and 14. Percentage of positive lymphocytes for CD54, CD49b, CD49d and CD8 were also measured on days 0, 7 and 14. The state of pressure ulcers was assessed by using the pressure ulcer scale for healing tool score on days 7, 14 and 28 of treatment. No between-group differences in patient demographics, anthropometry or diagnostic class were observed. Patients who received the study formula showed significant increases in the percentage of positive CD18 and CD11a lymphocytes and of CD49b granulocytes as compared to controls (P < 0·05). While the severity of pressure ulcers was not significantly different between the two groups on admission, severity increased significantly over time for the control group (P < 0·05), but not for the study group. The present study suggests that a fish oil- and micronutrient-enriched formula may prevent worsening of pressure ulcers and that this effect may be mediated by an effect on adhesion molecule expression.

  15. Insulin complexation with hydroxypropyl-beta-cyclodextrin: Spectroscopic evaluation of molecular inclusion and use of the complex in gel for healing of pressure ulcers.

    PubMed

    Valentini, Sóstenes Rosa; Nogueira, Ana Cláudia; Fenelon, Vanderson Carvalho; Sato, Francielle; Medina, Antonio N; Santana, Rosângela Getirana; Baesso, Mauro Luciano; Matioli, Graciette

    2015-07-25

    The pressure ulcer healing is a complex process and difficult to be achieved. Insulin is known to promote wound healing, and when complexed with cyclodextrin presents improved solubility, stability and biological activity. Complexation of insulin with hydroxypropyl-beta-cyclodextrin (HPβCD) was performed in this work through the coprecipitation method, providing the inclusion complex (HPβCD-I). The spectroscopic techniques used to analyze the complex were H(1) NMR, FT-Raman and FT-IR/ATR. A gel containing the HPβCD-I complex was prepared and a clinical study was conducted in patients with pressure ulcers. The spectroscopic techniques allowed to confirm the complex formation through the inclusion of aromatic amino acids, such as phenylalanine present in the HPβCD cavity. Data obtained from the FT-Raman and FT-IR/ATR techniques, combined with the H(1) NMR results, showed the effectiveness of these techniques in evaluating the inclusion complex of HPβCD with insulin. Clinical studies demonstrated tissue revitalization and a trend (p=0.06) for a significant difference between the healing effect of the control gel and that with HPβCD-I complex. The creation of the gel prepared with insulin and HPβCD-I complex and its use in patients with pressure ulcers appears to be promising in wound healing and its possible use in hospital care.

  16. Split thickness skin grafts for the treatment of non-healing foot and leg ulcers in patients with diabetes: a retrospective review

    PubMed Central

    Anderson, John J.; Wallin, Kelly J.; Spencer, Loren

    2012-01-01

    We retrospectively reviewed 107 diabetic patients who received a split thickness skin graft (STSG) for treatment of a non-healing diabetic foot or leg ulcer to describe healing times based on patient characteristics, comorbidities or complications. The minimum follow-up was 6 months from the time of STSG application. The mean time to healing among all patients was 5.1 weeks (3 to 16 weeks). The mean healing time for patients with complications was 12.0 weeks (10 to 16 weeks) while the mean healing time for those without complications was 4.9 weeks (3 to 10 weeks). Overall complication rate was 2.8%. Patients with a STSG take of less than 95% had a mean healing time of 7.9 weeks compared to 4.8 weeks for those with a STSG take of 100% (p<0.001). The use of autologous STSG for treatment of non-healing diabetic foot and leg wounds is a viable method for soft tissue closure and may present a low complication rate and a satisfactory rate of healing. PMID:22403742

  17. Split thickness skin grafts for the treatment of non-healing foot and leg ulcers in patients with diabetes: a retrospective review.

    PubMed

    Anderson, John J; Wallin, Kelly J; Spencer, Loren

    2012-01-01

    We retrospectively reviewed 107 diabetic patients who received a split thickness skin graft (STSG) for treatment of a non-healing diabetic foot or leg ulcer to describe healing times based on patient characteristics, comorbidities or complications. The minimum follow-up was 6 months from the time of STSG application. The mean time to healing among all patients was 5.1 weeks (3 to 16 weeks). The mean healing time for patients with complications was 12.0 weeks (10 to 16 weeks) while the mean healing time for those without complications was 4.9 weeks (3 to 10 weeks). Overall complication rate was 2.8%. Patients with a STSG take of less than 95% had a mean healing time of 7.9 weeks compared to 4.8 weeks for those with a STSG take of 100% (p<0.001). The use of autologous STSG for treatment of non-healing diabetic foot and leg wounds is a viable method for soft tissue closure and may present a low complication rate and a satisfactory rate of healing. PMID:22403742

  18. Healing.

    PubMed

    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

  19. Acceleration of skin wound healing with tragacanth (Astragalus) preparation: an experimental pilot study in rats.

    PubMed

    Fayazzadeh, Ehsan; Rahimpour, Sina; Ahmadi, Seyed Mohsen; Farzampour, Shahrokh; Sotoudeh Anvari, Maryam; Boroumand, Mohammad Ali; Ahmadi, Seyed Hossein

    2014-01-01

    Gum tragacanth is a natural complex mixture of polysaccharides and alkaline minerals extracted from species of Astragalus plant, which is found widely in arid regions of the Middle East. In a pilot experimental study we examined the effects of its topical application on wound healing in ten albino adult male rats. Two similar parasagittal elliptical full-thickness wounds (control vs. test samples) were created on the dorsum of each animal. Test group samples were fully covered by a thin layer of gum tragacanth daily. The extent of wound healing was evaluated by planimetric analysis on multiple occasions during the 10-day study period. On the 7th day of the study, the percent of wound closure was significantly higher in gum tragacanth-treated specimens compared to the control samples (87%±2% vs. 70%±4%, P<0.001). The majority of wounds in the test group were completely closed by the 10th day of the study. The difference in wound healing index measured by histological examination on day 10 of the study was also statistically meaningful between the two groups (0.624±0.097 vs. 0.255±0.063, P<0.05). The results of this study clearly showed the useful effects of topical application of gum tragacanth in acceleration of skin wound contraction and healing. More studies are encouraged to identify the implicating agents and precisely understand the mechanism by which they exert their wound healing effects.

  20. Reduced FOXO1 Expression Accelerates Skin Wound Healing and Attenuates Scarring

    PubMed Central

    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

    2015-01-01

    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. PMID:25010393

  1. FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer.

    PubMed

    Marion, Estelle; Jarry, Ulrich; Cano, Camille; Savary, Caroline; Beauvillain, Céline; Robbe-Saule, Marie; Preisser, Laurence; Altare, Frederic; Delneste, Yves; Jeannin, Pascale; Marsollier, Laurent

    2016-03-15

    Buruli ulcer, a debilitating disease, is caused by Mycobacterium ulcerans. The incidence of this neglected tropical disease is steadily increasing. As a rule, without treatment, skin ulcers occur and a lengthy healing process may be observed associated with severe functional disabilities. Mouse models are already available to study establishment of lesions or evaluation of therapy but a lack of a suitable animal model, mimicking all clinical stages, in particular the healing process, remains an obstacle to understand the pathophysiology of M. ulcerans infection. M. ulcerans was s.c. inoculated in three consanguine mouse strains, that is, BALB/c and C57BL/6, classically used to study mycobacterial infection, and FVB/N. Strikingly, FVB/N mice, although as sensitive as all other mouse strains with respect to M. ulcerans infection, presented a spontaneous healing after the ulcerative phase despite stable bacterial load, and mycolactone toxin was not detected in the healed tissues. The spontaneous healing process was accompanied by an activation of the innate immune system. The adaptive response initiated by FVB/N mice was not involved in the healing process and did not confer protection against M. ulcerans. Our work highlights the importance of innate immune responses to control M. ulcerans infection. This in vivo model of M. ulcerans infection now paves the way for new avenues of research toward the elucidation of critical stages of this disease, such as the characterization of the regulation of mycolactone production, a better understanding of the pathophysiology of M. ulcerans infection, and the development of new therapeutic strategies. PMID:26873988

  2. Novel combined approach in the management of non-healing solitary rectal ulcer syndrome - laparoscopic resection rectopexy and transanal endoscopic microsurgery.

    PubMed

    Ihnat, Petr; Martinek, Lubomir; Vavra, Petr; Zonca, Pavel

    2015-07-01

    Solitary rectal ulcer syndrome (SRUS) is an uncommon chronic disorder with a wide range of endoscopic findings, clinical presentations and characteristic histopathological features. There is no clear consensus regarding SRUS management, because of its poorly understood pathogenesis and frequent association with various pelvic floor disorders. Laparoscopic resection rectopexy and transanal endoscopic microsurgery (TEM) were used for the treatment of non-healing SRUS. The present paper reports a case of non-healing SRUS due to obstructive defecation syndrome based on combined pelvic floor disorders (rectocele, enterocele, internal rectal prolapse and dolichosigma) successfully managed by a novel combined mini-invasive approach which has never been previously reported in the literature (laparoscopic resection rectopexy and TEM). The new minimally invasive concept seems to be safe and feasible - laparoscopic resection rectopexy results in effective correction of the obstructive defecation syndrome, while TEM allows comfortable access for radical resection of a rectal ulcer.

  3. Novel combined approach in the management of non-healing solitary rectal ulcer syndrome – laparoscopic resection rectopexy and transanal endoscopic microsurgery

    PubMed Central

    Martinek, Lubomir; Vavra, Petr; Zonca, Pavel

    2015-01-01

    Solitary rectal ulcer syndrome (SRUS) is an uncommon chronic disorder with a wide range of endoscopic findings, clinical presentations and characteristic histopathological features. There is no clear consensus regarding SRUS management, because of its poorly understood pathogenesis and frequent association with various pelvic floor disorders. Laparoscopic resection rectopexy and transanal endoscopic microsurgery (TEM) were used for the treatment of non-healing SRUS. The present paper reports a case of non-healing SRUS due to obstructive defecation syndrome based on combined pelvic floor disorders (rectocele, enterocele, internal rectal prolapse and dolichosigma) successfully managed by a novel combined mini-invasive approach which has never been previously reported in the literature (laparoscopic resection rectopexy and TEM). The new minimally invasive concept seems to be safe and feasible – laparoscopic resection rectopexy results in effective correction of the obstructive defecation syndrome, while TEM allows comfortable access for radical resection of a rectal ulcer. PMID:26240632

  4. 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.

  5. Economic evaluation of noncontact normothermic wound therapy for treatment of pressure ulcers.

    PubMed

    Macario, Alex

    2002-06-01

    New adjunctive treatments for pressure ulcers have become available to complement standard care. The economic benefits of new advanced wound care treatments like noncontact normothermic wound therapy are related to: the costs of adequately providing standard care treatment, the baseline probability of healing a pressure ulcer to closure with standard care, the relative improvement in healing rates with the advanced wound care treatment and the acquisition cost of the advanced treatment. Healing data from preliminary clinical trials suggest that pressure ulcer healing in long-term care patients is accelerated two-fold with noncontact normothermic wound therapy. At this healing rate, noncontact normothermic wound therapy for stage III and IV pressure ulcer is an economically attractive intervention. Additional well-controlled clinical trials are necessary.

  6. 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.

  7. Potential Activity of 3-(2-Chlorophenyl)-1-phenyl-propenonein Accelerating Wound Healing in Rats

    PubMed Central

    Dhiyaaldeen, Summaya M.; Alshawsh, Mohammed A.; Salama, Suzy M.; Alwajeeh, Nahla S. I.

    2014-01-01

    Wound healing involves inflammation followed by granular tissue development and scar formation. In this study, synthetic chalcone 3-(2-Chlorophenyl)-1-phenyl-propenone (CPPP) was investigated for a potential role in enhancing wound healing and closure. Twenty-four male rats were divided randomly into 4 groups: carboxymethyl cellulose (CMC) (0.2 mL), Intrasite gel, and CPPP (25 or 50 mg/mL). Gross morphology, wounds treatment with the CPPP, and Intrasite gel accelerate the rate of wound healing compared to CMC group. Ten days after surgery, the animals were sacrificed. Histological assessment revealed that the wounds treated with CPPP showed that wound closure site contained little amount of scar and the granulation tissue contained more collagen and less inflammatory cells than wound treated with CMC. This finding was confirmed with Masson's trichrome staining. The antioxidant defence enzymes catalase (CAT) and superoxide dismutase (SOD) were significantly increased in the wound homogenates treated with CPPP (P < 0.05) compared to CMC treated group. However, in the CPPP treatment group, lipid peroxidation (MDA) was significantly decreased (P < 0.05), suggesting that the CPPP also has an important role in protection against lipid peroxidation-induced skin injury after ten days of treatment with CPPP, which is similar to the values of cytokines TGF-β and TNF-α in tissue homogenate. Finally the administration of CPPP at a dosage of 25 and 50 mg/kg was suitable for the stimulation of wound healing. PMID:24587992

  8. In Vivo Hypobaric Hypoxia Performed During the Remodeling Process Accelerates Bone Healing in Mice

    PubMed Central

    Durand, Marjorie; Collombet, Jean-Marc; Frasca, Sophie; Begot, Laurent; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

    2014-01-01

    We investigated the effects of respiratory hypobaric hypoxia on femoral bone-defect repair in mice because hypoxia is believed to influence both mesenchymal stromal cell (MSC) and hematopoietic stem cell mobilization, a process involved in the bone-healing mechanism. To mimic conditions of non-weight-bearing limb immobilization in patients suffering from bone trauma, our hypoxic mouse model was further subjected to hind-limb unloading. A hole was drilled in the right femur of adult male C57/BL6J mice. Four days after surgery, mice were subjected to hind-limb unloading for 1 week. Seven days after surgery, mice were either housed for 4 days in a hypobaric room (FiO2 at 10%) or kept under normoxic conditions. Unsuspended control mice were housed in either hypobaric or normoxic conditions. Animals were sacrificed on postsurgery day 11 to allow for collection of both contralateral and lesioned femurs, blood, and spleen. As assessed by microtomography, delayed hypoxia enhanced bone-healing efficiency by increasing the closing of the cortical defect and the newly synthesized bone volume in the cavity by +55% and +35%, respectively. Proteome analysis and histomorphometric data suggested that bone-repair improvement likely results from the acceleration of the natural bone-healing process rather than from extended mobilization of MSC-derived osteoprogenitors. Hind-limb unloading had hardly any effect beyond delayed hypoxia-enhanced bone-healing efficiency. PMID:24944208

  9. Blumea balsamifera Oil for the Acceleration of Healing of Burn Injuries.

    PubMed

    Fan, Zuo-Wang; Pang, Yu-Xin; Wang, Kai; Yu, Fu-Lai; Wang, Dan; Yang, Quan; Ma, Qing-Song; Li, Xiao-Ting; Zou, Jin; Zhang, Wen-Qing; Wu, Li-Fen

    2015-01-01

    Blumea balsamifera oil (BBO) is a main extract obtained from Blumea balsamifera (L.) DC (Ainaxiang) leaves, which are widely used as a traditional medicine by the Miao and Li Nations to promote skin trauma or burn injury healing. This study was initiated to investigate the healing efficacy in deep second-degree burn model in rats. The rats were treated by BBO for 21 consecutive days. The rate of healing, scabs dropped time and re-epithelialization time were observed every three days for 21 days after burn injury. The samples were collected from different treated rats by sacrificing the animals on the 1st, 2nd, 5th, 9th, 14th, and 21st day post-burn creation. Then, the water content of burn tissue was measured. Plasma interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) levels were evaluated, and the tissue expressions of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β) were determined along with skin histopathology. The results showed that the water content of tissue was significantly reduced, the scabs dropped time shortened, and healing accelerated after treatment with BBO in the burn injury rats. Furthermore, the expressions of growth factors were significantly increased in the tissue; however, the levels of inflammatory factors on plasma decreased. This study confirms the efficacy of BBO consumption on burn injuries. PMID:26393555

  10. Blumea balsamifera Oil for the Acceleration of Healing of Burn Injuries.

    PubMed

    Fan, Zuo-Wang; Pang, Yu-Xin; Wang, Kai; Yu, Fu-Lai; Wang, Dan; Yang, Quan; Ma, Qing-Song; Li, Xiao-Ting; Zou, Jin; Zhang, Wen-Qing; Wu, Li-Fen

    2015-09-17

    Blumea balsamifera oil (BBO) is a main extract obtained from Blumea balsamifera (L.) DC (Ainaxiang) leaves, which are widely used as a traditional medicine by the Miao and Li Nations to promote skin trauma or burn injury healing. This study was initiated to investigate the healing efficacy in deep second-degree burn model in rats. The rats were treated by BBO for 21 consecutive days. The rate of healing, scabs dropped time and re-epithelialization time were observed every three days for 21 days after burn injury. The samples were collected from different treated rats by sacrificing the animals on the 1st, 2nd, 5th, 9th, 14th, and 21st day post-burn creation. Then, the water content of burn tissue was measured. Plasma interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) levels were evaluated, and the tissue expressions of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β) were determined along with skin histopathology. The results showed that the water content of tissue was significantly reduced, the scabs dropped time shortened, and healing accelerated after treatment with BBO in the burn injury rats. Furthermore, the expressions of growth factors were significantly increased in the tissue; however, the levels of inflammatory factors on plasma decreased. This study confirms the efficacy of BBO consumption on burn injuries.

  11. Tuberculous granuloma: a rare cause of a non-healing ulcer.

    PubMed

    Graham, George Edward Alexander; Jones, Rupert; Derry, David

    2014-11-19

    A 78-year-old woman on ciclosporin for aplastic anaemia presented to her general practitioner with a 2 cm cystic swelling on the right side of her forehead. After a period of 8 months the lesion ruptured and, despite good wound care, failed to heal over a period of seven further months. Imaging demonstrated an invasive process and a biopsy was taken, which showed granulomatous inflammation that stained positively for mycobacteria. Further investigation with cross-sectional imaging revealed no other sites of disease. The only history of exposure to tuberculosis was 64 years prior to presentation. Differential diagnoses of mycetoma, autoimmune disease and non-tuberculous mycobacterial infection were considered, but culture confirmed tuberculosis. This case demonstrates an unusual presentation of isolated cutaneous tuberculosis in a patient with suppressed immune function.

  12. 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.

  13. 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.

  14. 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

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

    PubMed

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

    2014-10-09

    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.

  16. 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.

  17. Accelerated reepithelialization by triterpenes: proof of concept in the healing of surgical skin lesions.

    PubMed

    Metelmann, Hans-Robert; Brandner, Johanna M; Schumann, Hauke; Bross, Felix; Fimmers, Rolf; Böttger, Kerstin; Scheffler, Armin; Podmelle, Fred

    2015-01-01

    The acceleration of wound healing is a major surgical concern. A triterpene extract from birch bark (Betulae cortex) experimentally enhances keratinocyte differentiation in vitro and accelerates wound healing ex vivo. We conducted an open, blind-evaluated, controlled, prospective, randomized (1:1) phase II clinical trial in patients requiring split-thickness skin graft transplantation at two university hospitals in Germany. Donor sites on the upper legs were covered with a moist silicone-coated dressing. Oleogel-S10 ointment containing 10% birch bark extract was randomly applied to the distal or proximal half of the wound, with the other half serving as an intraindividual control, for 14 days after the skin graft surgery. The primary efficacy variable was faster reepithelialization as determined from macrophotographs by independent, blinded experts. Twenty-four patients were randomized and completed the trial. After the 14-day test period, the planned interim analysis revealed a highly significant (p < 0.0001) superiority of Oleogel-S10 in the primary efficacy variable and the trial was terminated early due to ethical concerns. The treatment side was also better reepithelialized and more similar to normal skin after 3 months. In conclusion, Oleogel-S10 significantly accelerated reepithelialization at split-thickness skin graft donor sites. Treatment with Oleogel-S10 was safe and well tolerated.

  18. Non-invasive low-intensity pulsed ultrasound accelerates bone healing in the rabbit.

    PubMed

    Pilla, A A; Mont, M A; Nasser, P R; Khan, S A; Figueiredo, M; Kaufman, J J; Siffert, R S

    1990-01-01

    The effect of ultrasound (US) on the rate of fibula osteotomy healing in 139 mature New Zealand white rabbits was assessed in this study. Bilateral midshaft fibular osteotomies were made using a 1-mm Gigli saw. US was noninvasively applied to one limb for 20 minutes daily, while the contralateral limb served as a control. A 2.5-cm PZT transducer was applied to both limbs, with the treated limb receiving a 200-microseconds burst of 1.5-MHz sine waves repeated at 1.0 kHz. The incident intensity was approximately 30 mW/cm2. Animals were killed at intervals between 14 and 28 days. Maximum strength increases (significant to p less than or equal to 0.01) ranged from 40 to 85% from postoperative day 14 to 23. On day 28, no significant difference in ultimate strength was noted. From day 17 through day 28, all US-treated fractures were as strong as intact bones (p less than or equal to 0.005). On the other hand, the ultimate strength of the control osteotomies attained intact values only by day 28. These results indicate that biomechanical healing is accelerated by a factor of nearly 1.7. This occurs with an overall acceleration of the healing curve in this fresh fracture model. If noninvasive low-intensity pulsed sine wave ultrasound can significantly accelerate bone repair in clinical application with an in-home treatment of 20 minutes daily, then US may be a useful adjunct for fracture care with a concomitant impact on patient morbidity.

  19. Beneficial effects of silver foam dressing on healing of wounds with ulcers and infection control of burn patients

    PubMed Central

    Yang, Bo; Wang, Xudong; Li, Zhonghua; Qu, Qi; Qiu, Yan

    2015-01-01

    Objective: To assess the beneficial effects of silver foam dressing on the healing of wounds with ulcers and infection control of burn patients. Methods: Eighty-four second-degree burn patients were selected and divided into a study group and a control group (n=42). After disinfection and cleaning, wound beds of the study group were covered with silver-containing soft-silicone foam dressing, and wound surfaces of the control group were wiped with 1% silver sulfadiazine cream (60 g/100 cm2). The two groups were checked weekly to observe wound healing progress and adverse reactions of the skin around wounds. Wound secretions were collected and subjected to bacterial culture. Related indices were recorded and quantified. Results: Thirty seven cases of the study group (88.1%) and 36 cases of the control group (85.7%) recovered to normal, and 3 (7.1%) and 2 cases (4.8%) in the two groups failed to recover. The recovery rates of the two groups were similar (P>0.05), but unrecovered patients in the study group had significantly higher proportions of repaired wounds (P<0.05). Wounds of the study group were healed significantly more rapidly than those of the control group (22.3±3.1 vs. 25.1±4.4, P<0.05). The study group had significantly higher proportions of repaired wounds from Day 7 to Day 21 (P<0.05), but the difference became less obvious with extended time to Day 28. The bacterial culture-positive (exceeding 105 organisms per gram of tissue) rates of both groups significantly reduced after treatment (Day 7 for the study group and Day 14 for the control group), and the rate of the study group was significantly lower at last (P<0.05). The study and control groups were observed 134 and 149 person-times respectively, with the normal wound-surrounding skin rates of 96.3% (129/134) and 88.6% (132/149) (P>0.05 except for on Day 14). Except for on Day 28, the study group had significantly lower pain scores than those of the control group (P<0.05), especially on Day 7 and

  20. 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.

  1. 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

  2. Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds.

    PubMed

    Popp, C; Kligman, A M; Stoudemayer, T J

    1995-01-01

    Pretreatment of skin with all-trans retinoic acid (tretinoin) has been shown to enhance wound healing. Previous studies have mainly used animal models to demonstrate this effect. We wanted to determine whether pretreatment could promote wound healing in severely photoaged dorsal forearm skin. Four elderly men with severely actinically damaged forearms were treated daily for 16 weeks. One arm was treated with 0.05-0.1% tretinoin cream (Retin A, Ortho), and the other with Purpose cream (Ortho) as a vehicle control. Four-millimetre punch biopsies were taken from both dorsal forearms prior to treatment. After 16 weeks, full-thickness 2-mm punch biopsies were taken from both sides. Serial photographs were taken, and healing of the wounds quantitatively assessed by image analysis. On the 11th day, the wounds were excised using a 4-mm biopsy punch. Biopsies were processed for light microscopy. After 16 weeks, the tretinoin-treated forearms showed moderate erythema and scaling. Polarized light photographs revealed multiple, red, vascularized foci and/or a diffuse network of small vessels. The histological effects were typical for tretinoin, i.e. compaction of the stratum corneum, epidermal acanthosis with correction of atypia, an increase in small vessels, and increased cellularity in the upper dermis. Purpose cream had no effect, either clinically or histologically. On the tretinoin-treated side, the wound areas were 35-37% smaller on days 1 and 4, and 47-50% smaller on days 6, 8, 11, compared with the controls. Clinically and histologically, reepithelialization occurred more rapidly. Thus tretinoin dramatically accelerated wound healing in photodamaged skin.

  3. 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

  4. 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.

  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. PDGF-BB does not accelerate healing in diabetic mice with splinted skin wounds.

    PubMed

    Park, Shin Ae; Raghunathan, Vijay Krishna; Shah, Nihar M; Teixeira, Leandro; Motta, Monica J; Covert, Jill; Dubielzig, Richard; Schurr, Michael; Isseroff, Roslyn Rivkah; Abbott, Nicholas L; McAnulty, Jonathan; Murphy, Christopher J

    2014-01-01

    Topical application of platelet-derived growth factor-BB (PDGF-BB) is considered to accelerate tissue repair of impaired chronic wounds. However, the vast literature is plagued with conflicting reports of its efficacy in animal models and this is often influenced by a wide array of experimental variables making it difficult to compare the results across the studies. To mitigate the confounding variables that influence the efficacy of topically applied PDGF-BB, we used a controlled full thickness splinted excisional wound model in db/db mice (type 2 diabetic mouse model) for our investigations. A carefully-defined silicone-splinted wound model, with reduced wound contraction, controlled splint and bandage maintenance, allowing for healing primarily by reepithelialization was employed. Two splinted 8 mm dorsal full thickness wounds were made in db/db mice. Wounds were topically treated once daily with either 3 µg PDGF-BB in 30 µl of 5% PEG-PBS vehicle or an equal volume of vehicle for 10 days. Body weights, wound contraction, wound closure, reepithelialization, collagen content, and wound bed inflammation were evaluated clinically and histopathologically. The bioactivity of PDGF-BB was confirmed by in vitro proliferation assay. PDGF-BB, although bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice using the splinted wound model. Considering that the predominant mechanism of wound healing in humans is by re-epithelialization, the most appropriate model for evaluating therapeutics is one that uses splints to prevent excessive wound contraction. Here, we report that PDGF-BB does not promote wound closure by re-epithelialization in a murine splinted wound model. Our results highlight that the effects of cytoactive factors reported in vivo ought to be carefully interpreted with critical consideration of the wound model used.

  7. Hyperbaric oxygen therapy stimulates colonic stem cells and induces mucosal healing in patients with refractory ulcerative colitis: a prospective case series

    PubMed Central

    Bekheit, Mohamed; Baddour, Nahed; Katri, Khaled; Taher, Yousry; El Tobgy, Khaled; Mousa, Essam

    2016-01-01

    Background Hyperbaric oxygen (HBO) is used as part of treatment in a variety of clinical conditions. Its use in the treatment of ulcerative colitis has been reported in few clinical reports. Objective We report the effect of HBO on refractory ulcerative colitis exploring one potential mechanism of action. Design A review of records of patients with refractory ulcerative colitis who received HBO was conducted. Clinical and histopathological scoring was utilised to evaluate the response to HBO therapy (HBOT). Results All patients manifested clinical improvement by the 40th cycle of HBOT. The median number of stool frequency dropped from seven motions/day (range=3–20) to 1/day (range=0.5–3), which was significant (z=−4.6, p<0.001). None of the patients manifested persistent blood passage after HBOT (z=−3.2, p=0.002). The severity index significantly improved after HBOT (z=−4.97, p<0.001). Histologically, a significant reduction of the scores of activity was recorded accompanied by a significant increase in the proliferating cell nuclear antigen labelling index of the CD44 cells of the colonic mucosa (p=0.001). Conclusions HBOT is effective in the setting of refractory ulcerative colitis. The described protocol is necessary for successful treatment. HBOT stimulates colonic stem cells to promote healing. PMID:27195128

  8. Effect of zinc sulphate on acetic acid-induced gastric ulceration in rats.

    PubMed

    Li, K M

    1990-09-01

    The effects of zinc sulphate on gastric ulcer healing rate and mucosal mucus content of acetic acid-induced ulceration in rats have been assessed. Daily treatment with zinc sulphate progressively accelerated ulcer healing in a dose-dependent manner with a significant increase observed on day 15 after ulcer induction in rats treated with 44 and 88 mg kg-1 zinc sulphate. A significant increase in gastric mucosal adherent mucus was also observed in those animals treated with 88 mg kg-1 zinc sulphate. The results suggest that a minimum treatment period of 15 days is needed for the zinc sulphate to be effective, and that zinc ions may promote gastric ulcer healing by enhancing mucus formation to prevent acid back-diffusion into the gastric mucosa.

  9. A prospective, randomized, controlled trial comparing the effects of noncontact, low-frequency ultrasound to standard care in healing venous leg ulcers.

    PubMed

    Gibbons, Gary W; Orgill, Dennis P; Serena, Thomas E; Novoung, Aksone; O'Connell, Jessica B; Li, William W; Driver, Vickie R

    2015-01-01

    Current scientific evidence suggests venous leg ulcers (VLUs) that do not respond to guideline-defined care may have a wound microenvironment that is out of physiological balance. A prospective, randomized, controlled, multicenter trial was conducted to compare percent wound size reduction, proportions healed, pain, and quality-of-life (QOL) outcomes in patients randomized to standard care (SC) alone or SC and 40 kHz noncontact, low-frequency ultrasound (NLFU) treatments 3 times per week for 4 weeks. One hundred, twelve (112) eligible participants with documented venous stasis, a VLU >30 days' duration, measuring 4 cm2 to 50 cm2, and demonstrated arterial flow were enrolled. Of these, 81 reduced <30% in size during the 2-week run-in study phase and were randomized (SC, n = 40; NLFU+SC, n = 41). Median age of participants was 59 years; 83% had multiple complex comorbidities. Index ulcers were 56% recurrent, with a median duration of 10.3 months (range 1 month to 204.5 months) and median ulcer area of 11.0 cm2 (range 3.7 cm2-41.3 cm2). All participants received protocol-defined SC compression (30-40 mm Hg), dressings to promote a moist wound environment, and sharp debridement at the bedside for a minimum of 1 time per week. Ulcer measurements were obtained weekly using digital planimetry. Pain and QOL scores were assessed at baseline and after 4 weeks of treatment using the Visual Analog Scale and the Short Form-36 Health Survey. After 4 weeks of treatment, average wound size reduction was 61.6% ± 28.9 in the NLFU+SC compared to 45% ± 32.5 in the SC group (P = 0.02). Reductions in median (65.7% versus 44.4%, P = 0.02) and absolute wound area (9.0 cm2 versus 4.1 cm2, P = 0.003) as well as pain scores (from 3.0 to 0.6 versus 3.0 to 2.4, P = 0.01) were also significant. NLFU therapy with guideline-defined standard VLU care should be considered for healing VLUs not responding to SC alone. The results of this study warrant further research on barriers to healing and the

  10. Ultrasound accelerates healing of normal wounds but not of ischemic ones.

    PubMed

    Altomare, Mariane; Nascimento, Adriana P; Romana-Souza, Bruna; Amadeu, Thaís P; Monte-Alto-Costa, Andréa

    2009-01-01

    To examine the influence of therapeutic ultrasound (US) on repair of standard and ischemic cutaneous lesions, full-thickness excisional wounds were made in rats and treated with a US 3 MHz, 0.5 W/cm(2) pulsed duty cycle. We used five experimental groups: control (received US powered off on the day of surgery, and on the second and fourth day), control US (received US on the day of surgery, and on the second and fourth day), ischemic (received US powered off on the day of surgery, and on the second and fourth day), ischemic US 3X (received US on the day of surgery, and on the second and fourth day) and ischemic US 5X (received US in the day of surgery, first, second, third and fourth day). The control US group showed acceleration in wound contraction 7 days after wounding, an increase in collagen density, and only focal inflammatory areas. Neo-epidermis formation was more advanced in the control US group than in the control one. Wound contraction was delayed in the ischemic group when compared with the control group as well as the ischemic US 3X group, was but slightly accelerated in the ischemic US 5X group when compared with the ischemic group 7 days after wounding. Reepithelialization was delayed in both ischemic US groups when compared with the ischemic group. The number of inflammatory cells was higher in both US ischemic groups. We conclude that US therapy accelerates wound healing in normal wounds and delays wound healing in ischemic wounds.

  11. 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.

  12. Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy.

    PubMed

    Eells, Janis T; Wong-Riley, Margaret T T; VerHoeve, James; Henry, Michele; Buchman, Ellen V; Kane, Mary P; Gould, Lisa J; Das, Rina; Jett, Marti; Hodgson, Brian D; Margolis, David; Whelan, Harry T

    2004-09-01

    Photobiomodulation by light in the red to near infrared range (630-1000 nm) using low energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound healing, improve recovery from ischemic injury in the heart and attenuate degeneration in the injured optic nerve. Recent evidence indicates that the therapeutic effects of red to near infrared light result, in part, from intracellular signaling mechanisms triggered by the interaction of NIR light with the mitochondrial photoacceptor molecule cytochrome c oxidase. We have demonstrated that NIR-LED photo-irradiation increases the production of cytochrome oxidase in cultured primary neurons and reverses the reduction of cytochrome oxidase activity produced by metabolic inhibitors. We have also shown that NIR-LED treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. Photobiomodulation improves wound healing in genetically diabetic mice by upregulating genes important in the promotion of wound healing. More recent studies have provided evidence for the therapeutic benefit of NIR-LED treatment in the survival and functional recovery of the retina and optic nerve in vivo after acute injury by the mitochondrial toxin, formic acid generated in the course of methanol intoxication. Gene discovery studies conducted using microarray technology documented a significant upregulation of gene expression in pathways involved in mitochondrial energy production and antioxidant cellular protection. These findings provide a link between the actions of red to near infrared light on mitochondrial oxidative metabolism in vitro and cell injury in vivo. Based on these findings and the strong evidence that mitochondrial dysfunction is involved in the pathogenesis of numerous diseases processes, we propose that NIR-LED photobiomodulation represents an innovative and non-invasive therapeutic approach for the treatment of tissue injury and disease processes in which mitochondrial

  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. PMID:27037778

  15. Osteogenic growth peptide accelerates bone healing during distraction osteogenesis in rabbit tibia.

    PubMed

    Zhao, Z-Y; Shao, L; Zhao, H-M; Zhong, Z-H; Liu, J-Y; Hao, C-G

    2011-01-01

    Distraction osteogenesis is a valuable treatment method that allows limb lengthening or reconstruction of large bone defects. However, its major disadvantage is the long period required for the consolidation of a distraction callus. Osteogenic growth peptide (OGP) stimulates endochondral bone formation in fracture callus, but its capacity to promote regenerate ossification during distraction osteogenesis has not been evaluated. This study investigated whether intravenously administered OGP accelerated bone healing during distraction osteogenesis in 36 male New Zealand White rabbits, randomized into two groups. The treatment group received OGP (200 ng/kg body weight) in phosphate-buffered saline (PBS), intravenously, each day; the control group received PBS alone. A 15-mm lengthening of the right lower leg was performed using the method of Ilizarov. Evidence from biomechanical, histological and radiographic evaluations demonstrated that systemic OGP treatment promoted optimal new bone formation during distraction osteogenesis in this rabbit model.

  16. Phase II clinical trial on effect of the long turmeric (Curcuma longa Linn) on healing of peptic ulcer.

    PubMed

    Prucksunand, C; Indrasukhsri, B; Leethochawalit, M; Hungspreugs, K

    2001-03-01

    The study examined patients who had symptoms indicating peptic ulcer. Forty-five patients, 24 males and 21 females, aged between 16-60 years were included in the study. Twenty-five patients, 18 males and 7 females, were endoscoped, their ulcers located in the duodenal bulb and gastric (angulus). The ulcer sizes varied between 0.5 to 1.5 cm in diameter. Capsule-filled turmeric was given orally in the dose of 2 capsules (300 mg each) five times daily, one half to an hour before meals, at 16.00 hours and at bedtime continuously. The result after 4 weeks of treatment showed that ulcers were absent in 48% or 12 cases (DU 9 and GU 3). Eighteen cases (DU 13 and GU 5) had absence of ulcer after 8 weeks of treatment. Nineteen cases (76%) (DU 14 and GU 5) did not have ulcers after 12 weeks of treatment. The rest, 20 cases were not found to have ulcers and some were not endoscoped. They appeared to have erosions, gastritis and dyspepsia. They received turmeric capsules for 4 weeks of treatment. The abdominal pain and discomfort satisfactorily subsided in the first and second week. They could take normal foods instead of soft meals. Blood chemistry and hematology of all 54 patients had no significant changes in hematological system, liver and renal functions both before and after treatment. PMID:11485087

  17. 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

  18. A prospective, randomized clinical study evaluating the effect of transdermal continuous oxygen therapy on biological processes and foot ulcer healing in persons with diabetes mellitus.

    PubMed

    Driver, Vickie R; Yao, Min; Kantarci, Alpdogan; Gu, Guosheng; Park, Nanjin; Hasturk, Hatice

    2013-11-01

    Hypoxia is a major factor in delayed wound healing. The aim of this prospective, randomized, clinical trial was to compare outcomes of treatment in persons with chronic diabetic foot ulcers (DFUs) randomly assigned to transdermal continuous oxygen therapy (TCOT) for 4 weeks as an adjunct to standard care (debridement, offloading, and moisture). Nine patients (age 58.6±7.1, range 38-73 years) received TCOT (treatment group) and eight patients (age 59.9±12.6, range 35-76 years) received standard care alone (control group). Most patients (12) were male, and all had a Wagner I or II foot ulcer for an average of 14 (control group) or 20 months (treatment group). Weekly wound measurements and wound tissue biopsies were obtained and wound fluid collected. Levels of pro-inflammatory cytokines and proteases in wound fluid samples were analyzed using Luminex-based multiplex assays. Tissue-resident macrophages were quantified by immunohistochemistry. At week 4, average wound size reduction was 87% (range 55.7% to 100%) in the treatment group compared to 46% (15% to 99%) in the control group (P <0.05). Changes in cytokine levels (IL-6, IL-8) and proteinases (MMP-1,-2,-9, TIMP-1) at weeks 2 to 4 in wound fluid correlated with clinical findings. CD68+ macrophage counts showed statistically significant reduction in response to TCOT compared to the control group (P <0.01). The results of this study show that TCOT may facilitate healing of DFUs by reversing the inflammatory process through reduction in pro-inflammatory cytokines and tissue-degrading proteases. Additional research to elucidate the effects of this treatment on complete healing and increase understanding about the role of wound fluid analysis is needed.

  19. Diabetic foot ulcer: assessment and management.

    PubMed

    Saraogi, Ravi Kant

    2008-02-01

    Diabetic foot ulcer is a rising health problem with rising prevalence of diabetes. It is the most important cause of non-traumatic foot amputations. Diabetic foot ulcers are primarily due to neuropathy and/or ischaemia, and are frequently complicated by infection. Up to 85% of all diabetic foot related problems are preventable through a combination of good foot care and appropriate education for patients and healthcare providers. The holistic care of diabetic foot ulcer patients requires a multidisciplinary team approach. Apart from blood sugar control, treatment of ulcer involves debridement, offloading, appropriate dressings, vascular maintenance and infection control. Use of adjunctive treatments such as various growth factors, skin replacement dressings and vacuum assisted closure will accelerate healing in selected cases.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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. PMID:25907598

  6. Nano-porous nitrocellulose liquid bandage modulates cell and cytokine response and accelerates cutaneous wound healing in a mouse model.

    PubMed

    Mu, Xiaofeng; Yu, Hao; Zhang, Caizhen; Chen, Xiufang; Cheng, Zhiyun; Bai, Ruyu; Wu, Xunxun; Yu, Qian; Wu, Chunlin; Diao, Yong

    2016-01-20

    Nitrocellulose liquid bandage (L-Bandage) is extensively used in hard-to-cover cuts and wounds management, owing to its flexibility, softness, transparency, and conformability. However, evidence supporting their mechanisms of action as wound dressing is scanty. This study introduces a novel nano-porous L-Bandage, and provides results from a mouse full-thickness wound model investigating its mechanism of action on wound healing. Different characteristics, such as porosity, mechanical properties and water vapor transmission rate (WVTR) were determined. The L-Bandage formed film had a porous network structure with mean diameter of 18 nm that could effectively prevent the bacterial invasion, and favorable properties of tensile strength, elongation, and WVTR. The L-Bandage treated wound exhibited accelerated healing, with reduced inflammations, enhanced wound re-epithelialization, contraction, granulation tissue formation, and rapid angiogenesis. Our data suggested that L-Bandage could serve as a promising wound dressing, because of its desirable properties for wound healing.

  7. Pyoderma gangrenosum and ulcerative colitis in the tropics.

    PubMed

    Alese, Olatunji B; Irabor, David O

    2008-01-01

    Pyoderma gangrenosum is a rare inflammatory skin condition, characterized by progressive and recurrent skin ulceration. There may be rapidly enlarging, painful ulcers with undermined edges and a necrotic, hemorrhagic base. Disorders classically associated with pyoderma gangrenosum include rheumatoid arthritis, inflammatory bowel disease, paraproteinemia and myeloproliferative disorders. There have been some reports of the occurrence of pyoderma gangrenosum in Africa, and in Nigeria, but only one specifically reported pyoderma gangrenosum in association with ulcerative colitis. We report on a 45-year-old man who presented with pyoderma gangrenosum associated with ulcerative colitis; the second report in Nigeria. The skin lesions were managed with daily honey wound dressings. Oral dapsone and prednisolone were started. The frequency of the bloody diarrhea decreased, and was completely resolved by the second week after admission. The ulcers also showed accelerated healing. The goal of therapy is directed towards the associated systemic disorder, if present.

  8. Ultrashort peptide nanofibrous hydrogels for the acceleration of healing of burn wounds.

    PubMed

    Loo, Yihua; Wong, Yong-Chiat; Cai, Elijah Z; Ang, Chuan-Han; Raju, Ashvin; Lakshmanan, Anupama; Koh, Alvin G; Zhou, Hui J; Lim, Thiam-Chye; Moochhala, Shabbir M; Hauser, Charlotte A E

    2014-06-01

    There is an unmet clinical need for wound dressings to treat partial thickness burns that damage the epidermis and dermis. An ideal dressing needs to prevent infection, maintain skin hydration to facilitate debridement of the necrotic tissue, and provide cues to enhance tissue regeneration. We developed a class of 'smart' peptide hydrogels, which fulfill these criteria. Our ultrashort aliphatic peptides have an innate tendency to self-assemble into helical fibers, forming biomimetic hydrogel scaffolds which are non-immunogenic and non-cytotoxic. These nanofibrous hydrogels accelerated wound closure in a rat model for partial thickness burns. Two peptide hydrogel candidates demonstrate earlier onset and completion of autolytic debridement, compared to Mepitel(®), a silicone-coated polyamide net used as standard-of-care. They also promote epithelial and dermal regeneration in the absence of exogenous growth factors, achieving 86.2% and 92.9% wound closure respectively, after 14 days. In comparison, only 62.8% of the burnt area is healed for wounds dressed with Mepitel(®). Since the rate of wound closure is inversely correlated with hypertrophic scar formation and infection risks, our peptide hydrogel technology fills a niche neglected by current treatment options. The regenerative properties can be further enhanced by incorporation of bioactive moieties such as growth factors and cytokines.

  9. A Quantitative, Pooled Analysis and Systematic Review of Controlled Trials on the Impact of Electrical Stimulation Settings and Placement on Pressure Ulcer Healing Rates in Persons With Spinal Cord Injuries.

    PubMed

    Liu, Liang; Moody, Julie; Gall, Angela

    2016-07-01

    Pressure ulcers (PrUs) are among the most common secondary complications following spinal cord injury (SCI). External electrical current applied to a wound is believed to mimic the body's natural bioelectricity and to restart and stimulate endogenous electrical fields to promote wound healing. A systematic review was conducted to critically appraise and synthesize updated evidence on the impact of electrical stimulation (ES) versus standard wound care (comprising cleansing, dressing, nutrition, and debridement as necessary) and/or sham stimulation on PrU healing rates in persons with SCIs. Medline, Embase, the Cumulative Index for Nursing and Allied Health Literature (CINAHL), PsycINFO, and Cochrane Central were searched using the terms spinal cord injury, electrical stimulation, and pressure ulcer in free text and MESH terms. Publications were limited to peer-reviewed, randomized controlled trials (RCTs) and non-RCTs (CCTs) published in English from 1985 to 2014. The methodological quality of the RCTs was evaluated using the Jadad scale; CCTs were assessed using the Downs and Black tool. Pooled analyses were performed to calculate the mean difference (MD) for continuous data, odds ratio (OR) for dichotomous data, and 95% confidence intervals (CI). A total of 8 trials were reviewed - 6 RCTs and 2 CCTs included a total of 517 SCI participants who had at least 1 PrU. The number of patients per study ranged from 7 to 150 and the number of wounds from 7 to 192. Comparison models included ES irrespective of current type and placement of electrodes against sham/no ES (7 trials), ES delivered by electrodes overlaid on the ulcer versus sham/no ES (4 trials), ES delivered by electrodes placed on intact skin around the ulcer versus sham/no ES (4 trials), ES delivered by electrodes overlaid on the wound bed versus placed on intact skin around the ulcer (1 trial), ES with pulsed current versus sham/no ES (6 trials), ES with constant current versus sham/no ES (2 trials), pulsed

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

    PubMed

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

    2016-09-12

    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.

  11. Green light emitting diodes accelerate wound healing: characterization of the effect and its molecular basis in vitro and in vivo.

    PubMed

    Fushimi, Tomohiro; Inui, Shigeki; Nakajima, Takeshi; Ogasawara, Masahiro; Hosokawa, Ko; Itami, Satoshi

    2012-01-01

    Because light-emitting diodes (LEDs) are low-coherent, quasimonochromatic, and nonthermal, they are an alternative for low level laser therapy, and have photobiostimulative effects on tissue repair. However, the molecular mechanism(s) are unclear, and potential effects of blue and/or green LEDs on wound healing are still unknown. Here, we investigated the effects of red (638 nm), blue (456 nm), and green (518 nm) LEDs on wound healing. In an in vivo study, wound sizes in the skin of ob/ob mice were significantly decreased on day 7 following exposure to green LEDs, and complete reepithelialization was accelerated by red and green LEDs compared with the control mice. To better understand the molecular mechanism(s) involved, we investigated the effects of LEDs on human fibroblasts in vitro by measuring mRNA and protein levels of cytokines secreted by fibroblasts during the process of wound healing and on the migration of HaCat keratinocytes. The results suggest that some cytokines are significantly increased by exposure to LEDs, especially leptin, IL-8, and VEGF, but only by green LEDs. The migration of HaCat keratinocytes was significantly promoted by red or green LEDs. In conclusion, we demonstrate that green LEDs promote wound healing by inducing migratory and proliferative mediators, which suggests that not only red LEDs but also green LEDs can be a new powerful therapeutic strategy for wound healing.

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

    PubMed

    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

  13. 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. PMID:24373522

  14. 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

  15. 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.

  16. Thymosin β4 Promotes Dermal Healing.

    PubMed

    Kleinman, H K; Sosne, G

    2016-01-01

    No agent has been identified that significantly accelerates the repair of chronic dermal wounds in humans. Thymosin beta 4 (Tβ4) is a small, abundant, naturally occurring regenerative protein that is found in body fluids and inside cells. It was found to have angiogenic and antiinflammatory activity and to be high in platelets that aggregate at the wound site. Thus we used Tβ4 initially in dermal healing. It has since been shown to have many activities important in tissue protection, repair, and regeneration. Tβ4 increases the rate of dermal healing in various preclinical animal models, including diabetic and aged animals, and is active for burns as well. Tβ4 also accelerated the rate of repair in phase 2 trials with patients having pressure ulcers, stasis ulcers, and epidermolysis bullosa wounds. It is safe and well tolerated and will likely have additional uses in the skin and in injured organs for tissue repair and regeneration. PMID:27450738

  17. Ulcerative Dermatitis in C57BL/6 Mice Exhibits an Oxidative Stress Response Consistent with Normal Wound Healing

    PubMed Central

    Williams, Lisa K; Csaki, Lauren S; Cantor, Rita M; Reue, Karen; Lawson, Greg W

    2012-01-01

    Ulcerative dermatitis (UD) is a common syndrome of unknown etiology that results in profound morbidity in C57BL/6 mice and lines on a C57BL/6 background. The lesions are due to severe pruritus-induced self-trauma, progressing from superficial excoriations to deep ulcerations. UD may be behavioral in origin, with ulcerative lesions resulting from self-mutilating behavior in response to unresolved inflammation or compulsion. Alternatively, abnormal oxidative damage may be a mechanism underlying UD. To evaluate whether UD behaves similarly to normal wounds, consistent with a secondary self-inflicted lesion, or is a distinct disorder with abnormal wound response, we evaluated expression levels of genes representing various arms of the oxidative stress response pathway UD-affected and unwounded C57BL/6J mice. No evidence indicated that UD wounds have a defect in the oxidative stress response. Our findings are consistent with an understanding of C57BL/6 UD lesions as typical rather than atypical wounds. PMID:22776048

  18. Ulcerative dermatitis in C57BL/6 mice exhibits an oxidative stress response consistent with normal wound healing.

    PubMed

    Williams, Lisa K; Csaki, Lauren S; Cantor, Rita M; Reue, Karen; Lawson, Greg W

    2012-06-01

    Ulcerative dermatitis (UD) is a common syndrome of unknown etiology that results in profound morbidity in C57BL/6 mice and lines on a C57BL/6 background. The lesions are due to severe pruritus-induced self-trauma, progressing from superficial excoriations to deep ulcerations. UD may be behavioral in origin, with ulcerative lesions resulting from self-mutilating behavior in response to unresolved inflammation or compulsion. Alternatively, abnormal oxidative damage may be a mechanism underlying UD. To evaluate whether UD behaves similarly to normal wounds, consistent with a secondary self-inflicted lesion, or is a distinct disorder with abnormal wound response, we evaluated expression levels of genes representing various arms of the oxidative stress response pathway UD-affected and unwounded C57BL/6J mice. No evidence indicated that UD wounds have a defect in the oxidative stress response. Our findings are consistent with an understanding of C57BL/6 UD lesions as typical rather than atypical wounds.

  19. Acceleration of diabetic wound healing by a cryopreserved living dermal substitute created by micronized amnion seeded with fibroblasts

    PubMed Central

    Zheng, Yongjun; Ji, Shizhao; Wu, Haibin; Tian, Song; Wang, Xingtong; Luo, Pengfei; Fang, He; Wang, Zhihong; Wang, Junjie; Wang, Zhongshan; Xiao, Shichu; Xia, Zhaofan

    2015-01-01

    Bioengineered dermal substitutes have been used for the treatment of diabetic ulcers in clinics and achieved satisfactory results. However, constructing traditional tissue engineered dermal substitutes with two-step method is high-cost, time-consuming and greatly decreases fibroblast proliferative activity because of repeated trypsinization. Inthisstudy, we created a 3D micronized amniotic membrane (mAM) and used it as a natural microcarrier for ex vivo culture and amplification of human dermal fibroblasts (HDF) combined with the rotary cell culture system (RCCS). This one-step mAM-RCCS method couldamplify HDF quickly and construct a dermal substitute HDF-mAM simultaneously. To facilitate the clinical application of mAM-RCCS, anoptimized storage method was used.Post-thawing HDF-mAM retained high cell viability, intact cell morphology and active peptide secretion. When transplanted to the wounds of db/db mice, cryopreserved HDF-mAM promoted vascularization and diabetic wound healing significantly. These results demonstrate the potential application of cryopreserved HDF-mAM as a living dermal substitutefor treating diabetic ulcers and other chronic wounds in clinics. PMID:26885266

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

    PubMed

    Li, Hongling; Cao, Cong; Huang, Ai; Man, Yi

    2015-01-01

    A recent paper in this journal, presented a novel method by topical application of growth factors in stimulating diabetic cutaneous wound healing that caught our attention. We believe that the experimental method in the article is efficient and creative, but it also has some controversies and shortcomings to be discussed. We noted that the authors used "Tegaderm" as a semiocclusive dressing film and stated that it exerted a "splinting effect" on the wound margins and controlled contraction. Indeed, the "Tegaderm" itself can serve as a dressing film to isolate the wound bed with outside environments while the "splinting effect" is mainly achieved by adding silicone splints around the wound. Considering the unique properties of silicone splints and "Tegaderm," our experimental group propose an alternative method named "combined-suturing" technique that is not only suturing the silicone splints but also securing the "Tegaderm" around the wound. The specific reasons and operative procedures are explained in detail in this letter. PMID:26457307

  1. Bacteriology of chronic leg ulcers.

    PubMed

    Lookingbill, D P; Miller, S H; Knowles, R C

    1978-12-01

    The quantitative bacteriology of 13 chronic leg ulcers was sequentially assessed by both swab and biopsy culture techniques, and the effect of either a 10% benzoyl peroxide lotion or placebo lotion was evaluated. There was good correlation between the swab and biopsy culture techniques in 12 of the 17 instances where simultaneous swabs and biopsies were done. Though the benzoyl peroxide did not favorably affect the bacterial flora, ulcer healing did appear to correlate with quantitative bacterial counts. THREE of five ulcers containing fewer than 10(5) organisms per gram of tissue or per centimeter of ulcer surface area healed, while none of eight ulcers containing more than 10(5) organisms healed. Quantitative bacteriological measurements can serve as useful tools in evaluating healing of leg ulcers.

  2. [Helicobacter pylori and gastric ulcer].

    PubMed

    Maaroos, H I

    1994-01-01

    In connection with longitudinal ulcer studies and the demonstration of Helicobacter pylori as the main cause of chronic gastritis, new aspects of gastric ulcer recurrences and healing become evident. This extends the possibilities to prognosticate the course of gastric ulcer and to use more effective treatment. PMID:7937016

  3. 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. PMID:24632085

  4. [Study of the glycosaminoglycan-glycosaminoglycan hydrolase system for evaluation of the healing dynamics in stomach and duodenal ulcer].

    PubMed

    Skobeleva, T V; Vasil'ev, Iu V; Kas'ianenko, V I

    2002-01-01

    When studying the state of metabolism of the main substance of the connective tissue (glycosaminoglycan (GAG) and one of gag-hydrolases) in case of stomach and duodenal ulcers in patients under in-patient clinic conditions, it was shown that the amount of GAG in the urine approximately doubles in both groups in the state of exacerbation, and the given index reduces to the norm in the state of remission with a insignificant fluctuation of the b-glucuronidase level in the blood serum. PMID:12503289

  5. 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.

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

    PubMed

    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.

  7. 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

    2015-01-01

    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.

  8. 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

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

    PubMed

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

    2016-09-07

    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.

  10. Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.

    PubMed

    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

    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

    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

  13. Effects of Hypochlorous Acid Solutions on Venous Leg Ulcers (VLU): Experience With 1249 VLUs in 897 Patients

    PubMed Central

    Bongiovanni, Cheryl M.

    2016-01-01

    In order to assess the impact of comorbidities and identify factors that accelerate the healing rate of venous leg ulcers we performed an extensive, retrospective analysis of our experience in a diverse population. From June, 2006 to June, 2014, 897 patients with 1249 venous leg ulcers were treated at Lake Wound Clinics. Treatment protocols utilized the standard regimen of wound cleaning, debridement and compression bandaging. Wound cleaning, autolytic debridement, packing and dressing of venous leg ulcers utilized aqueous solutions of hypochlorous acid (HCA) rather than the standard normal saline. This protocol caused all ulcers to close completely. Comorbidities that delayed healing included uncontrolled or poorly controlled diabetes mellitus, advanced peripheral artery occlusive disease (PAD), active smoking, use of steroid medications and/or street drugs, large initial ulcer size and significant depth. Other factors, including advanced age, recurrent venous ulceration, stasis dermatitis, lipodermatosclerosis, morbid obesity and infection with one or more multidrug resistant organisms did not delay closure. From this experience we conclude that venous leg ulcer care protocols that clean, debride, pack and dress with hypochlorous acid solutions can reduce the effects of some comorbidities while accelerating healing times. Additional benefits are described. PMID:27104143

  14. Therapeutic effects of connective tissue manipulation on wound healing and bacterial colonization count among patients with diabetic foot ulcer.

    PubMed

    Joseph, Leonard Henry; Paungmali, Aatit; Dixon, John; Holey, Liz; Naicker, Amaramalar Selvi; Htwe, Ohnmar

    2016-07-01

    This study investigated the therapeutic effects of connective tissue manipulation (CTM) in diabetic foot ulcer (DFU). A total of 20 participants (10 in CTM group and 10 in conventional treatment group (CG)) with DFU underwent the conventional DFU treatment. In addition, the CTM group received CTM twice per week for 6 weeks. The percentage wound area reduction (PWAR) and bacterial colonization count (BCC) in log10 colony-forming units (CFU) per ml wound fluid was evaluated at baseline and six weeks. Results showed a significant change in PWAR in CTM (p < 0.05, t = 3.82, Df = 9, CI L = 0.98 U = 3.81) and CG (p < 0.05, t = 2.97, Df = 9,CI L = 0.26 U = 1.98). Mean reduction of BCC showed a significant reduction (p < 0.05), with percentage of BCC reduction higher in CTM group (6.45%) than CG (3.55%). The findings suggest CTM as an effective adjunct therapy for DFU to enhance conventional treatments. PMID:27634091

  15. 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.

  16. Biofunctionalized electrospun silk mats as a topical bioactive dressing for accelerated wound healing.

    PubMed

    Schneider, A; Wang, X Y; Kaplan, D L; Garlick, J A; Egles, C

    2009-09-01

    Materials able to deliver topically bioactive molecules represent a new generation of biomaterials. In this article, we describe the use of silk mats, made of electrospun nanoscale silk fibers containing epidermal growth factor (EGF), for the promotion of wound healing processes. In our experiments, we demonstrated that EGF is incorporated into the silk mats and slowly released in a time-dependent manner (25% EGF release in 170h). We tested these materials using a new model of wounded human skin-equivalents displaying the same structure as human skin and able to heal using the same molecular and cellular mechanisms found in vivo. This human three-dimensional model allows us to demonstrate that the biofunctionalized silk mats, when placed on the wounds as a dressing, aid the healing by increasing the time of wound closure by the epidermal tongue by 90%. The preservation of the structure of the mats during the healing period as demonstrated by electronic microscopy, the biological action of the dressing, as well as the biocompatibility of the silk demonstrate that this biomaterial is a new and very promising material for medical applications, especially for patients suffering from chronic wounds.

  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. Trefoil peptide TFF2 (spasmolytic polypeptide) potently accelerates healing and reduces inflammation in a rat model of colitis

    PubMed Central

    Tran, C; Cook, G; Yeomans, N; Thim, L; Giraud, A

    1999-01-01

    BACKGROUND—The trefoil peptides are major secretory products of mucus cells of the gastrointestinal tract and show increased expression after inflammatory or ulcerative damage. Recombinant human TFF2 (spasmolytic polypeptide) has been shown to be cytoprotective, and enhances repair in models of gastric injury. 
AIMS—To test the healing effects of recombinant human (h)TFF2 in a rat model of chronic colitis. 
METHODS—Colitis was induced by intracolonic administration of dinitrobenzene sulphonic acid in ethanol. Mucosal repair was quantified macroscopically, microscopically by image analysis of tissue histology, and by measuring myeloperoxidase activity. 
RESULTS—Initial validation studies showed that maximal injury and inflammation occurred at the end of the first week after colitis induction (active phase), and that spontaneous healing was complete by eight weeks. Once daily intrarectal application of hTFF2 (2.5 mg/kg; approximately 0.5 mg/rat) for five days after maximal damage had been sustained, reduced both microscopic and macroscopic injury by 80% and inflammatory index by 50% compared with vehicle controls. In addition, endogenous concentrations of rat TFF2 and TFF3 (intestinal trefoil factor) were increased in the active phase of colitis and were reduced to basal levels by hTFF2 treatment. 
CONCLUSIONS—This study has shown that hTFF2 enhances the rate of colonic epithelial repair, and reduces local inflammation in a rat model of colitis, and suggests that luminal application of trefoil peptides may have therapeutic potential in the treatment of inflammatory bowel disease. 

 Keywords: trefoil peptide; TFF2; spasmolytic polypeptide; colitis; repair PMID:10205199

  19. 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

  20. Venous Ulcers.

    PubMed

    Caprini, J A; Partsch, H; Simman, R

    2012-09-01

    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.

  1. A comparative study between total contact casting and conventional dressings in the non-surgical management of diabetic plantar foot ulcers.

    PubMed

    Ganguly, Suparno; Chakraborty, Koustubh; Mandal, Pankaj Kumar; Ballav, Ambar; Choudhury, Subhankar; Bagchi, Subrata; Mukherjee, Satinath

    2008-04-01

    Of all non-traumatic amputations 50% occur in Diabetics, mostly as a final outcome of foot ulcers. A major biomechanical factor in the causation of foot ulcers in persons with diabetes mellitus is elevated peak plantar pressure. Offloading the ulcer area in the form of equalisation of pressure across the plantar surface can accelerate healing of the ulcer. Total contact casting is one such method of offloading, and this study attempts to investigate the advantages of the above method as compared to conventional dressings in the physiatric management of the depth--ischaemia grades 1A, 1B, 2A, 2B neuropathic plantar ulcers in a diabetic patient. The outcome measure was the time taken for complete resolution of the ulcers. Of the 29 patients in Category A treated with total contact casting involving a total of 39 foot ulcers, 36 healed, which was statistically significant (p < 0.05) as compared to 25 out of the 33 ulcers healing in Category B consisting of 26 patients treated by conventional dressings alone. Total contact casting is an effective, rapid, economical, ambulatory and outpatient--based method for the treatment of diabetic foot ulcers.

  2. 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.

  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. 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.

  5. 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.

  6. NeutroPhase(®) in chronic non-healing wounds.

    PubMed

    Crew, John; Varilla, Randell; Rocas, Thomas Allandale; Debabov, Dmitri; Wang, Lu; Najafi, Azar; Rani, Suriani Abdul; Najafi, Ramin Ron; Anderson, Mark

    2012-01-01

    Chronic non-healing wounds, such as venous stasis ulcers, diabetic ulcers, and pressure ulcers are serious unmet medical needs that affect a patient's morbidity and mortality. Common pathogens observed in chronic non-healing wounds are Staphylococcus including MRSA, Pseudomonas, Enterobacter, Stenotrophomonas, and Serratia spp. Topical and systemically administered antibiotics do not adequately decrease the level of bacteria or the associated biofilm in chronic granulating wounds and the use of sub-lethal concentrations of antibiotics can lead to resistant phenotypes. Furthermore, topical antiseptics may not be fully effective and can actually impede wound healing. We show 5 representative examples from our more than 30 clinical case studies using NeutroPhase(®) as an irrigation solution with chronic non-healing wounds with and without the technique of negative pressure wound therapy (NPWT). NeutroPhase(®) is pure 0.01% hypochlorous acid (i.e. >97% relative molar distribution of active chlorine species as HOCl) in a 0.9% saline solution at pH 4-5 and is stored in glass containers. NovaBay has three FDA cleared 510(k)s. Patients showed a profound improvement and marked accelerated rates of wound healing using NeutroPhase(®) with and without NPWT. NeutroPhase(®) was non-toxic to living tissues.

  7. 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

  8. Electrospun emodin polyvinylpyrrolidone blended nanofibrous membrane: a novel medicated biomaterial for drug delivery and accelerated wound healing.

    PubMed

    Dai, Xin-Yi; Nie, Wei; Wang, Yong-Chun; Shen, Yi; Li, Yan; Gan, Shu-Jie

    2012-11-01

    In this work, blended nanofibrous membranes were prepared by an electrospinning technique with polyvinylpyrrolidone (PVP) K90 as the filament-forming polymer, and emodin, an extract of polygonum cuspidate known as a medicinal plant, as the treatment drug. Detailed analysis of the blended nanofibrous membrane by scanning electron microscopy, Differential scanning calorimetry and X-ray diffraction revealed that emodin was well distributed in the ultrafine fibers in the form of amorphous nanosolid dispersions. Results from attenuated total reflectance Fourier transform infrared spectra suggested that the main interactions between PVP and emodin might be mediated through hydrogen bonding. In vitro dissolution tests proved that the blended nanofibrous membrane produced more desired release kinetics of the entrapped drug (emodin) as compared to the pure drug. Furthermore, wound healing test and histological evaluation revealed that the emodin loaded nanofibrous membrane to be more effective as a healing accelerator thereby proving potential strategies to develop composite drug delivery system as well as promising materials for future therapeutic biomedical applications.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis

    PubMed Central

    Bilic, R.; Simic, P.; Jelic, M.; Stern-Padovan, R.; Dodig, D.; van Meerdervoort, H. Pompe; Martinovic, S.; Ivankovic, D.; Pecina, M.

    2006-01-01

    We randomly assigned 17 patients with scaphoid non-union at the proximal pole to three treatment groups: (1) autologous iliac graft (n=6), (2) autologous iliac graft + osteogenic protein-1 (OP-1; n=6), and (3) allogenic iliac graft + OP-1 (n=5). Radiographic, scintigraphic, and clinical assessments were performed throughout the follow-up period of 24 months. OP-1 improved the performance of both autologous and allogenic bone implants and reduced radiographic healing time to 4 weeks compared with 9 weeks in group 1. Helical CT scans and scintigraphy showed that in OP-1-treated patients sclerotic bone was replaced by well-vascularised bone. The addition of OP-1 to allogenic bone implant equalised the clinical outcome with the autologous graft procedure. Consequently the harvesting of autologous graft can be avoided. PMID:16506027

  14. Peptic ulcer

    MedlinePlus

    ... I. bleed - peptic ulcer; H. pylori - peptic ulcer; Helicobacter pylori - peptic ulcer ... is infection of the stomach by bacteria called Helicobacter pylori ( H pylori ). Most people with peptic ulcers have ...

  15. 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

  16. 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

    2016-01-01

    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

  17. A poly-herbal formulation accelerates normal and impaired diabetic wound healing.

    PubMed

    Gupta, Asheesh; Upadhyay, Nitin K; Sawhney, R C; Kumar, Ratan

    2008-01-01

    In the present study, a poly-herbal formulation (PHF) was prepared by combining the aqueous lyophilized leaf extracts of Hippophae rhamnoides L. and Aloe vera L. and the ethanol rhizome extract of Curcuma longa L., in an optimized ratio (1 : 7 : 1). The efficacy of PHF treatment was studied in normal and impaired diabetic rats using a full-thickness cutaneous wound model. Topical PHF treatment increased cellular proliferation and collagen synthesis at the wound site in normal rats, as evidenced by the significant increase in DNA, total protein, hydroxyproline, and hexosamine contents in comparison with a positive control treated with a povidone-iodine ointment. The histological examinations and matrix metalloproteinases expression also correlated well with the biochemical findings, confirming the efficacy of PHF in normal wounds. In the streptozotocin-induced diabetic rats, PHF treatment increased hydroxyproline and hexosamine content. A faster wound contraction was also observed in PHF-treated normal and diabetic rats. The PHF also promoted angiogenesis as evidenced by an in vitro chick chorioallantoic membrane model and in vivo up-regulated vascular endothelial growth factor expression. The results suggest that PHF possesses significant wound healing potential in both normal as well as chronic diabetic wounds. PMID:19128249

  18. Thrombin receptor agonist Peptide immobilized in microspheres stimulates reparative processes in rats with gastric ulcer.

    PubMed

    Rusanova, A V; Makarova, A M; Strukova, S M; Markvicheva, E A; Gorbachyova, L R; Stashevskaya, K S; Vasil'eva, T V; Sidorova, E I; Bespalova, Zh D; Grandfils, Ch

    2006-07-01

    The effect of synthetic thrombin receptor (PAR1) agonist peptide encapsulated in microspheres made of lactic and glycolic acid copolymer on tissue reparation was studied in rats with acetate-induced ulcer. PAR1 agonist peptide was immobilized in biodegraded lactic and glycolic acid microspheres by double emulgation, the kinetics of peptide release was analyzed, and the dynamics of ulcer healing was studied in experimental (administration of microspheres with the peptide into the stomach) and two control groups (administration of saline or spheres without peptide). Thrombin receptor agonist peptide gradually released from lactic and glycolic acid microspheres into the stomach shortened the inflammation phase and shifted the proliferation phase to the earlier period, thus accelerating healing of experimental ulcers in rats. PMID:17369897

  19. Pressure ulcer-like presacral gummata in a patient with tertiary syphilis.

    PubMed

    Wollina, Uwe; Koch, André; Abdel-Naser, Mohammed Badawy; Schönlebe, Jacqueline

    2005-03-01

    Pressure ulcers are common among elderly patients. Here, we describe a case of tertiary syphilis with ulcerated gummata, appearing as a possible pressure ulcer. In such a case, wound management has to be accompanied by specific antibiosis to achieve healing.

  20. 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

  1. Diabetic Ulcer (Neurogenic Ulcer)

    MedlinePlus

    ... body's ability to fight infection and slows down wound healing. When to Seek Medical Care People can develop ... also medications that use growth factors to stimulate wound healing that your doctor may prescribe. Trusted Links MedlinePlus: ...

  2. Overexpression of vascular endothelial growth factor accelerates early vascularization and improves healing of genetically modified cultured skin substitutes.

    PubMed

    Supp, Dorothy M; Boyce, Steven T

    2002-01-01

    Cultured skin substitutes (CSS) lack a vascular plexus, leading to slower vascularization after grafting than split-thickness skin autograft. CSS containing keratinocytes genetically modified to overexpress vascular endothelial growth factor (VEGF) were previously shown to exhibit enhanced vascularization up to 2 weeks after grafting to athymic mice. The present study examines whether enhanced vascularization compared with controls persists after stable engraftment is achieved and analyzes VEGF expression, wound contraction, and engraftment. Control and VEGF-modified (VEGF+) CSS were grafted onto full-thickness wounds in athymic mice. VEGF expression was detected in VEGF+ CSS 14 weeks after grafting. Graft contraction was significantly lower in VEGF+ CSS compared with controls, suggesting more stable engraftment and better tissue development. Positive HLA-ABC staining, indicating persistence of human cells, was seen in 86.7% (13/15) of grafted VEGF+ CSS, compared with 58.3% (7/12) of controls. Differences in dermal vascularization between control and VEGF+ grafts were significant 1 week after surgery, but not at later times. However, the distribution of vessels was different, with more vessels in the upper dermis of VEGF+ grafts. These results suggest that VEGF overexpression in genetically modified CSS acts to accelerate early graft vascularization and can contribute to improved healing of full-thickness skin wounds.

  3. Vacuum-assisted therapy accelerates wound healing in necrotizing soft tissue infections: our experience in two intravenous drug abuse patients.

    PubMed

    Marinis, Athanasios; Voultsos, Mavroudis; Grivas, Paraskevas; Dikeakos, Panagiotis; Liarmakopoulos, Emmanouil; Paschalidis, Nikolaos; Rizos, Spyros

    2013-12-01

    Negative pressure wound therapy using vacuum-assisted closure (VAC) devices is currently a well established technique for managing complicated wounds. Such wounds occur after aggressive surgical debridement for necrotizing soft tissue infections (NSTI). In this report we present our experience in two intravenous drug abusers managed with VAC for NSTIs. The patients were 25 and 34 years old, HCV positive and presented with oedema of the upper femoral compartments and concomitant severe sepsis. Ultrasonography and computed tomography revealed severe cellulitis, fluid collection and necrosis of the affected fasciae and muscles. After emergent and subsequent aggressive surgical debridement during the first 48h, the VAC device was applied. Both patients had an uncomplicated postoperative course and a fast recovery from their multiorgan dysfunction. Suture closure of the wounds was achieved at the 25th and 38th postoperative days respectively and patients were discharged without any motor deficit. Negative pressure wound therapy is a modern therapeutic modality for treating complicated infected wounds. Moreover, it accelerates wound healing and primary closure, facilitating patient ambulation and recovery. A dedicated medical and nursing team is an important prerequisite for a successful outcome.

  4. 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.

  5. 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. PMID:27441766

  6. Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells.

    PubMed

    Collette, Nicole M; Yee, Cristal S; Hum, Nicholas R; Murugesh, Deepa K; Christiansen, Blaine A; Xie, LiQin; Economides, Aris N; Manilay, Jennifer O; Robling, Alexander G; Loots, Gabriela G

    2016-07-01

    Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 (Sostdc1(-/-)) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1(-/-) cortical bone measurements revealed larger bones with higher BMD, suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1(-/-) mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1(-/-) 5day calluses harbor >2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21days post fracture. These data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1(-/-) mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum.

  7. Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model.

    PubMed

    Bertone, A L; Pittman, D D; Bouxsein, M L; Li, J; Clancy, B; Seeherman, H J

    2004-11-01

    This study evaluated healing of rabbit bilateral ulnar osteotomies 6 and 8 weeks after surgery in response to percutaneous injection of transgenic adenoviral (Ad) bone morphogenetic protein-6 (BMP-6) vector or green fluorescent protein vector control (Ad-GFP) administered 7 days after surgery compared to untreated osteotomy controls. The amount, composition and biomechanical properties of the healing bone repair tissue were compared among groups and to historical data for intact rabbit ulnae obtained from similar studies at the same institution. Quantitative computed tomography was used to determine area, density and mineral content of the mineralized callus in the harvested ulnae. Maximum torque, torsional stiffness, and energy absorbed to failure were determined at 1.5 degrees /s. Calcified sections of excised ulnae (5 microm) were stained with Goldner's Trichrome and Von Kossa, and evaluated for callus composition, maturity, cortical continuity, and osteotomy bridging. Radiographic assessment of bone formation indicated greater mineralized callus in the ulnae injected with Ad-hBMP-6 as early as 1 week after treatment (2 weeks after surgery) compared to untreated osteotomy ulnae (p < 0.006) and Ad-GFP treated osteotomy ulnae (p < 0.002). Quantitative computed tomography confirmed greater bone area and bone mineral content at the osteotomy at 6 weeks in Ad-BMP-6 treated osteotomy as compared to untreated osteotomy ulnae (p < 0.001) and Ad-GFP treated osteotomy ulnae (p < 0.01). Ad-BMP-6 treated osteotomy ulnae were stronger (p < 0.001 and 0.003) and stiffer (p < 0.004 and 0.003) in torsion at 6 weeks than untreated osteotomy ulnae or Ad-GFP treated osteotomy ulnae, respectively. Maximum torque, torsional stiffness, and energy absorbed to failure were greater in Ad-BMP-6 treated osteotomy ulnae compared to their respective untreated contralateral osteotomy ulnae at 8 weeks [p < 0.03]. Maximum torque and torsional stiffness in the Ad-BMP-6 treated osteotomy ulnae

  8. 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

  9. Spontaneous calcaneal fracture in patients with diabetic foot ulcer: Four cases report and review of literature.

    PubMed

    Evran, Mehtap; Sert, Murat; Tetiker, Tamer; Akkuş, Gamze; Biçer, Ömer Sunkar

    2016-07-16

    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. 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.

  11. 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

  12. 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

  13. 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

  14. [Perforated gastroduodenal stress ulcer].

    PubMed

    Melinte, C; Dragomir, Cr

    2006-01-01

    Experimental and clinical data support the role of oxidative stress in the development of gastro-duodenal inflammatory lesions and peptic ulcer. Although quite common, stress ulcer remains a minor concern in the The authors review the literature data and perform a retrospective study on 205 personal cases of gastroduodenal ulcers, diagnosed and operated in the period 1986-2005. Of these, 58 (28.29%) were perforated ulcers, including 4 cases (6.8%) caused by various psychic traumas. All the patients presented symptoms and signs characteristic for perforated ulcer and were undoubtedly of psychogenic cause. The surgical treatment consisted in the closure of the perforation and peritoneal drainage. Besides medical treatment of peptic ulcer disease consisting of antisecretory drugs, antioxidants and sedatives were used. Postoperative follow-up showed a rapid and uneventful recovery in all cases. In conclusion, surgery is the mainstay of treatment in perforated ulcer, but additional stress therapy promotes healing and may reduce postoperative morbidity in cases with certain involvement of psychic trauma.

  15. 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.

  16. Low-intensity pulsed ultrasound accelerates rat femoral fracture healing by acting on the various cellular reactions in the fracture callus.

    PubMed

    Azuma, Y; Ito, M; Harada, Y; Takagi, H; Ohta, T; Jingushi, S

    2001-04-01

    Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture healing in both animal models and clinical trials, but the mechanism of action remains unclear. In fracture healing, various consecutive cellular reactions occurred until repair. We investigated whether the advanced effects of LIPUS depended on the duration and timing of LIPUS treatment in a rat closed femoral fracture model to determine the target of LIPUS in the healing process. Sixty-nine Long-Evans male rats that have bilateral closed femoral fractures were used. The right femur was exposed to LIPUS (30 mW/cm2 spatial and temporal average [SATA], for 20 minutes/day), and the left femur was used as a control. Rats were divided into four groups according to timing and duration of treatment (Ph-1, days 1-8; Ph-2, days 9-16; Ph-3, days 17-24; throughout [T], days 1-24 after the fracture). Animals were killed on day 25. After radiographs and microfocus X-ray computed tomography (muCT) tomograms were taken, the hard callus area (HCA), bone mineral content (BMC) at the fracture site, and mechanical torsion properties were measured, and histological analysis was conducted. Interestingly, the maximum torque of the LIPUS-treated femur was significantly greater than that of the controls in all groups without any changes in HCA and BMC. The multiviewing of three-dimensional (3D) muCT reconstructions and histology supported our findings that the partial LIPUS treatment time was able to accelerate healing, but longer treatment was more effective. These results suggest that LIPUS acts on some cellular reactions involved in each phase of the healing process such as inflammatory reaction, angiogenesis, chondrogenesis, intramembranous ossification, endochondral ossification, and bone remodeling.

  17. [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. PMID:16277953

  18. [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.

  19. 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.

  20. Novel pharmacologic approaches to the prevention and treatment of ulcerative colitis.

    PubMed

    Deng, Xiaoming; Szabo, Sandor; Khomenko, Tetyana; Tolstanova, Ganna; Paunovic, Brankica; French, Samuel W; Sandor, Zsuzsanna

    2013-01-01

    Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder of the colonic mucosa followed by poor quality of healing and recurring lesions. Recent studies demonstrated that the poor healing and chronic inflammation in colon of UC could be the result of microvascular dysfunction and endothelial barrier defect, resulting in sustained tissue hypoperfusion and ischemia in the colon. Long before angiogenesis became a popular research topic, our laboratory was the first to postulate that stimulation of angiogenesis alone might be sufficient to accelerate ulcer healing in the gastrointestinal tract. Our earlier studies demonstrated that therapy with genes or peptides of angiogenic growth factors, e.g., bFGF, PDGF and VEGF significantly accelerated healing of experimental duodenal ulcers (DU), while blockade of these angiogenic factors resulted in impaired healing of DU. However, unlike the angiogenesis in DU, increasing evidences from us and others indicate that angiogenesis plays a pathogenic role in UC, e.g., VEGF induces an abnormal "pathologic" angiogenesis which interferes with UC healing. Recently, another angiogenic factor, placental growth factor (PlGF), has also been suggested to be a marker of pathologic angiogenesis and may play a critical role in pathogenesis of UC. Although inhibition of pathologic angiogenesis by, e.g., anti-VEGF or -PlGF, was demonstrated to be a new approach to attenuate UC development, additional data of our and others showed that stimulating angiogenesis by administration of PDGF or bFGF significantly accelerated healing of UC. Also, activation of Rac1, a small GTPase, markedly improved VEGF-induced neovessel architecture defect and reduced vascular permeability (VP) in an angiogenic model. Thus, it seems that both angiogenic and anti-angiogenic therapies may be used in various stages of UC. More recently, we demonstrated that increased VP in colonic mucosa is an early and essential element in the initiation and progression of

  1. 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

  2. Application of autologous derived-platelet rich plasma gel in the treatment of chronic wound ulcer: diabetic foot ulcer.

    PubMed

    Akingboye, Akinfemi Ayobami; Giddins, Stephen; Gamston, Philip; Tucker, Arthur; Navsaria, Harshad; Kyriakides, Constantions

    2010-03-01

    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.

  3. 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.

  4. 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

  5. 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. PMID:24293065

  6. 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

  7. Multiple actions of Lucilia sericata larvae in hard-to-heal wounds: larval secretions contain molecules that accelerate wound healing, reduce chronic inflammation and inhibit bacterial infection.

    PubMed

    Cazander, Gwendolyn; Pritchard, David I; Nigam, Yamni; Jung, Willi; Nibbering, Peter H

    2013-12-01

    In Europe ≈15,000 patients receive larval therapy for wound treatment annually. Over the past few years, clinical studies have demonstrated the success of larvae of Lucilia sericata as debridement agents. This is based on a combination of physical and biochemical actions. Laboratory investigations have advanced our understanding of the biochemical mechanisms underlying the beneficial effects of larval secretions, including removal of dead tissue, reduction of the bacterial burden, and promotion of tissue regeneration. The present article summarizes our current understanding of the microbiological, immunological, and wound healing actions of larval therapy, and the molecules involved in these beneficial effects. Future studies will focus on the isolation, identification, and (pre)clinical testing of the effective molecules of L. sericata larvae. These molecules may be candidates for the development of new agents for the treatment of several infectious and inflammatory diseases, including chronic wounds.

  8. Multisystemic Sarcoidosis Presenting as Pretibial Leg Ulcers.

    PubMed

    Wollina, Uwe; Baunacke, Anja; Hansel, Gesina

    2016-09-01

    Sarcoidosis is a multisystemic disease of unknown etiology. Up to 30% of patients develop cutaneous manifestations, either specific or nonspecific. Ulcerating sarcoidosis leading to leg ulcers is a rare observation that may lead to confusions with other, more common types of chronic leg ulcers. We report the case of a 45-year-old female patient with chronic multisystemic sarcoidosis presenting with pretibial leg ulcers. Other etiology could be excluded. Histology revealed nonspecific findings. Therefore, the diagnosis of nonspecific leg ulcers in sarcoidosis was confirmed. Treatment consisted of oral prednisolone and good ulcer care. Complete healing was achieved within 6 months. Sarcoidosis is a rare cause of leg ulcers and usually sarcoid granulomas can be found. Our patient illustrates that even in the absence of sarcoid granulomas, leg ulcers can be due to sarcoidosis. PMID:27272316

  9. New molecules as drug candidates for the treatment of upper and lower GI tract ulcers.

    PubMed

    Szabo, Sandor; Tolstanova, Ganna

    2015-01-01

    Ulcers in the stomach, duodenum, ileum/jejunum and colon may look alike grossly and microscopically, but they have very different etiologies and pathogenesis. Unfortunately, there is virtually no etiologic treatment for any of these lesions which are also accompanied by limited or extensive inflammation. This article reviews four groups of new antiulcer drugs discovered and patented in our lab in Boston and Long Beach/Irvine (Table 1). Actually, the first group, pyrazole and its derivatives can be used for prevention, i.e., long lasting protection of gastric mucosa against alcohol- or NSAID-induced erosions. Dopamine seems to be a new etiologic treatment for both upper and lower GI tract ulcers. Angiogenic growth factors like bFGF or PDGF (daily administration as peptides orally or by rectal enemas, or as single or double-dose of gene therapy) accelerated the healing of gastroduodenal ulcers and UC, while VEGF seems to be effective only for upper GI tract ulcers. Last but not least, a novel group of angiogenic steroids which not only stimulate new blood vessel formation and granulation tissue production (essential elements of healing of ulcer types) but may also exert mild or prominent antiinflammatory action and seem to be ideal drugs for the treatment of IBD.

  10. [Aphthous ulcers and oral ulcerations].

    PubMed

    Vaillant, Loïc; Samimi, Mahtab

    2016-02-01

    Aphthous ulcers are painful ulcerations located on the mucous membrane, generally in the mouth, less often in the genital area. Three clinical forms of aphthous ulcers have been described: minor aphthous ulcers, herpetiform aphthous ulcers and major aphthous ulcers. Many other conditions presenting with oral bullous or vesiculous lesions orulcerations and erosions can be mistaken for aphthous ulcers. Currently, treatment of aphthous ulcers is palliative and symptomatic. Topical treatments (topical anesthetics, topical steroids and sucralfate) are the first line therapy. Recurrent aphthous stomatitis (RAS) is defined by the recurrence of oral aphthous ulcers at least 4 times per year. RAS is often idiopathic but can be associated with gastro-intestinal diseases (i.e. celiac disease, inflammatory bowel diseases), nutritional deficiencies (iron, folates...), immune disorders (HIV infection, neutropenia) and rare syndromes. Behçet's disease is a chronic, inflammatory, disease whose main clinical feature is recurrent bipolar aphthosis. Colchicine associated with topical treatments constitutes a suitable treatment of most RAS. Thalidomide is the most effective treatment of RAS but its use is limited by frequent adverse effects. Oral ulcers can be related to a wide range of conditions that constitute the differential diagnoses of aphthous ulcers. Oral ulcers are classified into three main groups: acute ulcers with abrupt onset and short duration, recurrent ulcers (mainly due to postherpetic erythema multiforme) and chronic ulcers (with slow onset and insidious progression). Acute oral ulcers are due to trauma, bacterial infections (including acute necrotizing ulcerative gingivitis), deep fungal infection, gastro-intestinal (namely inflammatory bowel disease) or systemic diseases. Chronic oral ulcers may be drug-induced, or due to benign or malignant tumors. Every oral solitary chronic ulcer should be biopsied to rule out squamous cell carcinoma. A solitary palatal ulcer

  11. Ciliary neurotrophic factor promotes the activation of corneal epithelial stem/progenitor cells and accelerates corneal epithelial wound healing.

    PubMed

    Zhou, Qingjun; Chen, Peng; Di, Guohu; Zhang, Yangyang; Wang, Yao; Qi, Xia; Duan, Haoyun; Xie, Lixin

    2015-05-01

    Ciliary neurotrophic factor (CNTF), a well-known neuroprotective cytokine, has been found to play an important role in neurogenesis and functional regulations of neural stem cells. As one of the most innervated tissue, however, the role of CNTF in cornea epithelium remains unclear. This study was to explore the roles and mechanisms of CNTF in the activation of corneal epithelial stem/progenitor cells and wound healing of both normal and diabetic mouse corneal epithelium. In mice subjecting to mechanical removal of corneal epithelium, the corneal epithelial stem/progenitor cell activation and wound healing were promoted by exogenous CNTF application, while delayed by CNTF neutralizing antibody. In cultured corneal epithelial stem/progenitor cells, CNTF enhanced the colony-forming efficiency, stimulated the mitogenic proliferation, and upregulated the expression levels of corneal epithelial stem/progenitor cell-associated transcription factors. Furthermore, the promotion of CNTF on the corneal epithelial stem/progenitor cell activation and wound healing was mediated by the activation of STAT3. Moreover, in diabetic mice, the content of CNTF in corneal epithelium decreased significantly when compared with that of normal mice, and the supplement of CNTF promoted the diabetic corneal epithelial wound healing, accompanied with the advanced activation of corneal epithelial stem/progenitor cells and the regeneration of corneal nerve fibers. Thus, the capability of expanding corneal epithelial stem/progenitor cells and promoting corneal epithelial wound healing and nerve regeneration indicates the potential application of CNTF in ameliorating limbal stem cell deficiency and treating diabetic keratopathy.

  12. 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.

  13. Approach to skin ulcers in older patients.

    PubMed Central

    Frank, Christopher

    2004-01-01

    OBJECTIVE: To provide family physicians with an approach to managing skin ulcers in older patients. SOURCES OF INFORMATION: Clinical practice guidelines and best practice guidelines were summarized to describe an evidence-based approach. MAIN MESSAGE; Preventing ulcers is important in frail older patients. Using guidelines can help prevent ulcers in institutions. Clarifying the cause and contributing factors is the first step in management. Pressure and venous ulcers are common in elderly people. Poor nutrition, edema, arterial insufficiency, and anemia often impair wound healing. Adequate debridement is important to decrease risk of infection and to promote healing. There are guidelines for cleaning ulcers. Choice of dressings depends on the circumstances of each wound, but dressings should provide a moist environment. Options for dressings are summarized. CONCLUSION: Family physicians can manage skin ulcers effectively by applying basic principles and using readily available guidelines. PMID:15648380

  14. Management of diabetic foot ulcers: evaluation of case studies.

    PubMed

    Torkington-Stokes, Rachel; Metcalf, Daniel; Bowler, Philip

    2016-08-11

    This article explores local barriers to diabetic foot ulcer healing, and describes the use of a dressing designed to manage exudate, infection and biofilm (AQUACEL® Ag+ dressing (AQAg+)) on recalcitrant diabetic foot ulcers. The authors consider four case studies that demonstrate how managing local barriers to wound healing with antimicrobial and anti-biofilm dressings in protocols of care can improve outcomes for patients.

  15. 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

  16. Medical and surgical treatment of chronic venous ulcers.

    PubMed

    Cooper, Michol A; Qazi, Umair; Bass, Eric; Zenilman, Jonathan; Lazarus, Gerald; Valle, M Frances; Malas, Mahmoud B

    2015-01-01

    Venous ulcer of the lower extremity is a common vascular condition and is associated with decreased quality of life, reduced mobility, and social isolation. Treatment of chronic venous ulcer (CVU) includes compression therapy, debridement of the ulcer when necessary, and wound care. Collagen and antimicrobial dressings can improve the proportion of ulcers healed compared with compression alone. Acellular skin equivalents are not superior to compression, but cellular human skin equivalents can promote more rapid healing, particularly in patients with longstanding ulcers. Current vascular surgical practice is to eliminate documented reflux or obstruction in patients with CVU that have failed a 3-month period of compression dressing, debridement, and local wound care. We found that surgical treatment of the superficial venous system can decrease the time to healing of CVUs compared with compression therapy alone, but does not increase the proportion of ulcers healed. PMID:27113282

  17. Medical and surgical treatment of chronic venous ulcers.

    PubMed

    Cooper, Michol A; Qazi, Umair; Bass, Eric; Zenilman, Jonathan; Lazarus, Gerald; Valle, M Frances; Malas, Mahmoud B

    2015-01-01

    Venous ulcer of the lower extremity is a common vascular condition and is associated with decreased quality of life, reduced mobility, and social isolation. Treatment of chronic venous ulcer (CVU) includes compression therapy, debridement of the ulcer when necessary, and wound care. Collagen and antimicrobial dressings can improve the proportion of ulcers healed compared with compression alone. Acellular skin equivalents are not superior to compression, but cellular human skin equivalents can promote more rapid healing, particularly in patients with longstanding ulcers. Current vascular surgical practice is to eliminate documented reflux or obstruction in patients with CVU that have failed a 3-month period of compression dressing, debridement, and local wound care. We found that surgical treatment of the superficial venous system can decrease the time to healing of CVUs compared with compression therapy alone, but does not increase the proportion of ulcers healed.

  18. 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

  19. 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

  20. Accelerated fracture healing in the geriatric, osteoporotic rat with recombinant human platelet-derived growth factor-BB and an injectable beta-tricalcium phosphate/collagen matrix.

    PubMed

    Hollinger, Jeffrey O; Onikepe, Andrew O; MacKrell, Jim; Einhorn, Thomas; Bradica, Gino; Lynch, Samuel; Hart, Charles E

    2008-01-01

    Aging and osteoporosis contribute to decreased bone mass and bone mineral density as well as compromised fracture healing rates and bone repair quality. Consequently, the purpose of this study was to determine if recombinant human platelet-derived growth factor-BB (rhPDGF-BB) delivered in an injectable beta-tricalcium phosphate/collagen matrix would enhance tibial fracture healing in geriatric (>2 years of age), osteoporotic rats. A total of 80 rats were divided equally among four groups: Fracture alone; Fracture plus matrix; Fracture plus matrix and either 0.3 mg/mL or 1.0 mg/mL rhPDGF-BB. At 3 and 5 weeks, rats were euthanized and treatment outcome was assessed histologically, radiographically, biomechanically, and by micro-CT. Results indicated rhPDGF-BB-treated fractures in osteoporotic, geriatric rats caused a statistically significant time-dependent increase in torsional strength 5 weeks after treatment. The healed fractures were equivalent in torsional strength to the contralateral, unoperated tibiae. Data from the study are the first, to our knowledge, to underscore rhPDGF-BB efficacy in an injectable beta-tricalcium phosphate/collagen matrix accelerated fracture repair in a geriatric, osteoporotic rat model.

  1. Gastric emptying abnormal in duodenal ulcer

    SciTech Connect

    Holt, S.; Heading, R.C.; Taylor, T.V.; Forrest, J.A.; Tothill, P.

    1986-07-01

    To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison of emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease.

  2. 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

  3. 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

  4. Ulcerative Colitis

    MedlinePlus

    Ulcerative colitis (UC) is a disease that causes inflammation and sores, called ulcers, in the lining of the rectum and colon. ... a group of diseases called inflammatory bowel disease. UC can happen at any age, but it usually ...

  5. Peptic Ulcer

    MedlinePlus

    A peptic ulcer is a sore in the lining of your stomach or your duodenum, the first part of your ... Comes and goes for several days or weeks Peptic ulcers happen when the acids that help you digest ...

  6. Mesenchymal Stromal Cells form Vascular Tubes when Placed in Fibrin Sealant and Accelerate Wound Healing in Vivo

    PubMed Central

    Mendez, Julio J.; Ghaedi, Mahboobe; Sivarapatna, Amogh; Dimitrievska, Sashka; Shao, Zhen; Osuji, Chinedum; Steinbacher, Derek M.; Leffell, David J.; Niklason, Laura E.

    2014-01-01

    Non-healing, chronic wounds are a growing public health problem and may stem from insufficient angiogenesis in affected sites. Here, we have developed a fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2. The ability for the MSCs to form tubular structures within the fibrin gels was directly dependent on the stoichiometric ratios of thrombin and fibrinogen and the resulting gel concentration, as well as on the presence of bFGF. Fibrin gel formulations that varied in stiffness were tested. ADSCs that are embedded in a stiff fibrin formulation express VE-cadherin and CD31 as shown by PCR, FACS and immunostaining. Confocal imaging analysis demonstrated that tubular structures formed, containing visible lumens, in the stiff fibrin gels in vitro. There was also a difference in the amounts of bFGF secreted by ADSCs grown in the stiffer gels as compared to softer gels. Additionally, hAT-MSCs gave rise to perfusable vessels that were VE-cadherin positive after subcutaneous injection into mice, whereas the softer fibrin formulation containing ADSCs did not. The application of ADSCs delivered in the stiff fibrin gels allowed for the wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, following 5 days of healing, the ADSCs remained within the fibrin gel and did not integrate into the granulation tissue of healing wounds in vivo. These data show that ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs. PMID:25433608

  7. 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.

  8. rhBMP-2 injected in a calcium phosphate paste (alpha-BSM) accelerates healing in the rabbit ulnar osteotomy model.

    PubMed

    Li, R H; Bouxsein, M L; Blake, C A; D'Augusta, D; Kim, H; Li, X J; Wozney, J M; Seeherman, H J

    2003-11-01

    This study evaluated the ability of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in an injectable calcium phosphate carrier (alpha-BSM) to accelerate healing in a rabbit ulna osteotomy model compared to untreated surgical controls. Healing was assessed by radiography, histology and biomechanics. Bilateral mid-ulnar osteotomies were created in 16 skeletally mature rabbits. One limb in each animal was injected with either 0.1 mg rhBMP-2/alpha-BSM (BMP) (N=8) or buffer/alpha-BSM (BSM) (N=8). Contralateral osteotomies served as untreated surgical controls (SXCT). Gamma scintigraphy showed 75%, 45% and 5% of the initial 125I-rhBMP-2 dose was retained at the osteotomy site at 3 h, 1 week and 3 weeks. The biological activity of rhBMP-2 (alkaline phosphatase activity from bioassay) extracted from alpha-BSM incubated in vitro up to 30 days at 37 degrees C was unchanged. Radiographs demonstrated complete bridging of the BMP limbs at 4 weeks whereas none of the BSM or SXCT limbs were bridged. Post-mortem peripheral quantitative computed tomography determined mineralized callus area was 62% greater in BMP limbs compared to SXCT limbs. Torsional stiffness and strength were 63% and 103% greater in BMP limbs compared to SXCT limbs. There was no difference in torsional properties between BSM and SXCT limbs. Failure occurred outside the osteotomy in four out of seven of the BMP limbs. All BSM and SXCT limbs failed through the osteotomy. Histology showed bony bridging of the osteotomy and no residual carrier in the BMP limbs. BSM and SXCT groups showed less mature calluses composed of primarily fibrocartilaginous tissue and immature bone in the osteotomy gap. These data indicate rhBMP-2 delivered in alpha-BSM accelerated healing in a rabbit ulna osteotomy model compared to BSM and SXCT groups.

  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. 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.

  11. Kruppel-like factor KLF4 facilitates cutaneous wound healing by promoting fibrocyte generation from myeloid-derived suppressor cells.

    PubMed

    Ou, Lingling; Shi, Ying; Dong, Wenqi; Liu, Chunming; Schmidt, Thomas J; Nagarkatti, Prakash; Nagarkatti, Mitzi; Fan, Daping; Ai, Walden

    2015-05-01

    Pressure ulcers (PUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Myeloid-derived suppressor cells (MDSCs) accumulate as a result of inflammation and promote cutaneous wound healing by mechanisms that are not fully understood. Recently, MDSCs have been shown to differentiate into fibrocytes, which serve as emerging effector cells that enhance cell proliferation in wound healing. We postulate that in wound healing MDSCs not only execute their immunosuppressive function to regulate inflammation but also stimulate cell proliferation once they differentiate into fibrocytes. In the current study, by using full-thickness and PU mouse models, we found that Kruppel-like factor 4 (KLF4) deficiency resulted in decreased accumulation of MDSCs and fibrocytes, and wound healing was significantly delayed. Conversely, KLF4 activation by the plant-derived product Mexicanin I increased the number of MDSCs and fibrocytes and accelerated the wound healing. Collectively, our study revealed a previously unreported function of MDSCs in cutaneous wound healing and identified Mexicanin I as a potential agent to accelerate PU wound healing.

  12. Flexible and rigid casting tape as a novel approach to offloading diabetic foot ulcers.

    PubMed

    Malone, M; Gannass, A Al; Bowling, F

    2011-07-01

    Offloading diabetic ulceration is a key component to the success in healing ulcers on the plantar aspect of the foot. New advances in offloading techniques allow for differing approaches in sometimes complex diabetic foot pathologies with associated ulceration. This case study looks at the use of flexible and rigid casting technique as part of the treatment in offloading plantar foot ulceration.

  13. Acceleration of tendon-bone healing in anterior cruciate ligament reconstruction using an enamel matrix derivative in a rat model.

    PubMed

    Kadonishi, Y; Deie, M; Takata, T; Ochi, M

    2012-02-01

    We examined whether enamel matrix derivative (EMD) could improve healing of the tendon-bone interface following reconstruction of the anterior cruciate ligament (ACL) using a hamstring tendon in a rat model. ACL reconstruction was performed in both knees of 30 Sprague-Dawley rats using the flexor digitorum tendon. The effect of commercially available EMD (EMDOGAIN), a preparation of matrix proteins from developing porcine teeth, was evaluated. In the left knee joint the space around the tendon-bone interface was filled with 40 µl of EMD mixed with propylene glycol alginate (PGA). In the right knee joint PGA alone was used. The ligament reconstructions were evaluated histologically and biomechanically at four, eight and 12 weeks (n = 5 at each time point). At eight weeks, EMD had induced a significant increase in collagen fibres connecting to bone at the tendon-bone interface (p = 0.047), whereas the control group had few fibres and the tendon-bone interface was composed of cellular and vascular fibrous tissues. At both eight and 12 weeks, the mean load to failure in the treated specimens was higher than in the controls (p = 0.009). EMD improved histological tendon-bone healing at eight weeks and biomechanical healing at both eight and 12 weeks. EMD might therefore have a human application to enhance tendon-bone repair in ACL reconstruction.

  14. [THERAPEUTIC GUIDE IN VENOUS ULCERS].

    PubMed

    López Herranz, Marta; Bas Caro, Pedro; García Jábega, Rosa Ma; García Carmona, Francisco Javier; Villalta García, Pedro; Postigo Mota, Salvador

    2014-11-01

    The treatment of venous ulcers and wounds in general, is a complex and important public health problem, with personal effects, family and health, without addressing the economic impact includes assistance, care of patients with ulcerative lesions. The increase in life expectancy, driven by improved socio-sanitary conditions that this aging population, facilitates the emergence of chronic diseases may be complicated by the presence of skin ulcers. There is no doubt that the best way to treat a skin ulcer is avoiding to occur, hence the importance of early diagnosis and risk factors act alone them. In relation to venous ulcers is crucial, provide local treatment, act on the cause, because if not, relapse is the norm in this type of injury. Currently, the moist wound healing, is an important step in solving earlier of these chronic wounds. This has meant that the pharmaceutical industry has been involved in researching and creating different types of dressings, having specific activity at different stages of venous ulcer healing, ie inflammatory phase, proliferative and remodeling. The proliferation of these products has been increasing over the years, not surprisingly, are described therapeutic 12 families that are applied in the management, care of these injuries. The fact of existing therapeutic options highlights the ineffectiveness of these products individually. Therefore, the nurse will not forget that the optimal treatment of venous ulcers, necessarily involves choosing the right product for every type and stage of the lesion. In this decision process, strongly influenced by the specific characteristics of each patient and injury, the nurse will take into account a lot of factors when choosing the product, not forgetting that an ulcer is not cured with a single therapeutic element, several products being used throughout the process to evolutionary venous ulcer until complete resolution.

  15. Management of finger ulcers in scleroderma.

    PubMed

    Ward, W A; Van Moore, A

    1995-09-01

    Twelve patients (15 hands) with documented scleroderma and chronic nonhealing digital ulcers were followed for their response to nonoperative and operative treatment. The patients were initially managed with nifedipine, biofeedback, digital xylocaine blockade, and silver sulfadiazine topical ointment and cessation of all vasoconstrictive agents. Ulcerations healed in 6 of 15 hands and remained healed at a 2-year follow-up examination. The remaining nine hands in seven patients failed nonoperative treatment and underwent a palmar digital sympathectomy. These chronic digital ulcerations healed within 6 weeks after surgery. After a 26- to 64-month follow-up period, six of the nine hands remained free of all digital ulcerations. Two patients (three hands) had partial recurrence of the ulceration. Digital sympathectomy can be an effective procedure for treating nonhealing digital ulcers in scleroderma patients after nonoperative treatment has failed. Significant vaso-occlusive disease is likely to be present in these patients, as demonstrated by arteriography. Our initial approach is cessation of all vasoconstricting agents, nifedipine biofeedback, and local antibiotic ointment. Wrist blocks with xylocaine and marcaine are offered if these modalities fail. If these methods do not result in healing of the ulcer within 12 weeks, then digital sympathectomy is considered.

  16. 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

  17. Adipose Stromal Cells Repair Pressure Ulcers in Both Young and Elderly Mice: Potential Role of Adipogenesis in Skin Repair

    PubMed Central

    Strong, Amy L.; Bowles, Annie C.; MacCrimmon, Connor P.; Frazier, Trivia P.; Lee, Stephen J.; Wu, Xiying; Katz, Adam J.; Gawronska-Kozak, Barbara; Bunnell, Bruce A.

    2015-01-01

    More than 2.5 million patients in the U.S. require treatment for pressure ulcers annually, and the elderly are at particularly high risk for pressure ulcer development. Current therapy for pressure ulcers consists of conservative medical management for shallow lesions and aggressive debridement and surgery for deeper lesions. The current study uses a murine model to address the hypothesis that adipose-derived stromal/stem cell (ASC) treatment would accelerate and enhance pressure ulcer repair. The dorsal skin of both young (2 months old [mo]) and old (20 mo) C57BL/6J female mice was sandwiched between external magnets for 12 hours over 2 consecutive days to initiate a pressure ulcer. One day following the induction, mice were injected with ASCs isolated from congenic mice transgenic for the green fluorescent protein under a ubiquitous promoter. Relative to phosphate-buffered saline-treated controls, ASC-treated mice displayed a cell concentration-dependent acceleration of wound closure, improved epidermal/dermal architecture, increased adipogenesis, and reduced inflammatory cell infiltration. The ASC-induced improvements occurred in both young and elderly recipients, although the expression profile of angiogenic, immunomodulatory, and reparative mRNAs differed as a function of age. The results are consistent with clinical reports that fat grafting improved skin architecture in thermal injuries; the authors of this published study have invoked ASC-based mechanisms to account for their clinical outcomes. Thus, the current proof-of-principle study sets the stage for clinical translation of autologous and/or allogeneic ASC treatment of pressure ulcers. Significance Adipose-derived stromal/stem cells (ASCs) promote the healing of pressure ulcer wounds in both young and old mice. ASCs enhance wound healing rates through adipogenic differentiation and regeneration of the underlying architecture of the skin. PMID:25900728

  18. Treatment with benzoyl peroxide of ulcers on legs within lesions of necrobiosis lipoidica diabeticorum.

    PubMed

    Hanke, C W; Bergfeld, W F

    1978-09-01

    A lotion of 20% benzoyl peroxide was applied to ulcers on legs from necrobiosis lipoidica diabeticorum. The ulcers healed rapidly and uneventfully, leaving firm, yellow scars. The efficacy and simplicity of use of topical benzoyl peroxide therapy is discussed.

  19. [Benzoyl peroxide for the treatment of leg ulcers (author's transl)].

    PubMed

    Ramelet, A A; van Melle, G

    1980-01-01

    40 leg ulcers were treated for 6 weeks by application twice a day of a 20% benzoyl peroxide lotion. Each ulcer was regularly measured and its bacterial flora was determined. Therapeutic results were very satisfactory: the average healing rate of the ulcers was 62.8% of the initial wound area after 4 weeks of treatment and 76.5% after 6 weeks of treatment. The bacterial flora of the ulcers changed during treatments, streptococci and staphylococci disappeared. Pseudomonas aeruginosa became abundant.

  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. PMID:26710090

  1. 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

  2. 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. PMID:16364130

  3. Combined application of low-intensity pulsed ultrasound and functional electrical stimulation accelerates bone-tendon junction healing in a rabbit model.

    PubMed

    Hu, Jianzhong; Qu, Jin; Xu, Daqi; Zhang, Tao; Qin, Ling; Lu, Hongbin

    2014-02-01

    The objective of this study was to elucidate the combined use of low-intensity pulsed ultrasound (LIPUS) and functional electrical stimulation (FES) on patella-patellar tendon (PPT) junction healing using a partial patellectomy model in rabbits. LIPUS was delivered continuously starting day 3 postoperative until week 6. FES was applied on quadriceps muscles to induce tensile force to the repaired PPT junction 5 days per week for 6 weeks since week 7 postoperatively. Forty rabbits with partial patellectomy were randomly divided into four groups: control, LIPUS alone, FES alone, and LIPUS + FES groups. At week 12, the PPT complexes were harvested for histology, radiographs, peripheral quantitative computed tomography, and biomechanical testing. There was better remodeling of newly formed bone and fibrocartilage zone in the three treatment groups compared with the control group. LIPUS and/or FES treatments significantly increased the area and bone mineral content of new bone. The failure load and ultimate strength of PPT complex were also highly improved in the three treatment groups. More new bone formed and higher tensile properties were showed in the LIPUS + FES group compared with the LIPUS or FES alone groups. Early LIPUS treatment and later FES treatment showed the additive effects of accelerating PPT junction healing.

  4. Dinitrosyl iron complexes with glutathione incorporated into a collagen matrix as a base for the design of drugs accelerating skin wound healing.

    PubMed

    Shekhter, Anatoly B; Rudenko, Tatyana G; Istranov, Leonid P; Guller, Anna E; Borodulin, Rostislav R; Vanin, Anatoly F

    2015-10-12

    Composites of a collagen matrix and dinitrosyl iron complexes with glutathione (DNIC-GS) (in a dose of 4.0 μmoles per item) in the form of spongy sheets (DNIC-Col) were prepared and then topically applied in rat excisional full-thickness skin wound model. The effects of DNIC-Col were studied in comparison with spontaneously healing wounds (SpWH) and wounds treated with collagen sponges (Col) without DNIC-GS. The composites induced statistically and clinically significant acceleration of complete wound closure (21±1 day versus 23±1 day and 26±1 day for DNIC-Col, Col and SpWH, respectively). Histological examination of wound tissues on days 4, 14, 18 and 21 after surgery demonstrated that this improvement was supported by enhanced growth, maturation and fibrous transformation of granulation tissue and earlier epithelization of the injured area in rats treated with DNIC-Col composites benchmarked against Col and SpWH. It is suggested that the positive effect of the new pharmaceutical material on wound healing is based on the release of NO from decomposing DNIC. This effect is believed to be potentiated by the synergy of DNIC and collagen.

  5. Osteogenic gene regulation and relative acceleration of healing by adenoviral-mediated transfer of human BMP-2 or -6 in equine osteotomy and ostectomy models.

    PubMed

    Ishihara, Akikazu; Shields, Kathleen M; Litsky, Alan S; Mattoon, John S; Weisbrode, Steven E; Bartlett, Jeffrey S; Bertone, Alicia L

    2008-06-01

    This study evaluated healing of equine metatarsal osteotomies and ostectomies in response to percutaneous injection of adenoviral (Ad) bone morphogenetic protein (BMP)-2, Ad-BMP-6, or beta-galactosidase protein vector control (Ad-LacZ) administered 14 days after surgery. Radiographic and quantitative computed tomographic assessment of bone formation indicated greater and earlier mineralized callus in both the osteotomies and ostectomies of the metatarsi injected with Ad-BMP-2 or Ad-BMP-6. Peak torque to failure and torsional stiffness were greater in osteotomies treated with Ad-BMP-2 than Ad-BMP-6, and both Ad-BMP-2- and Ad-BMP-6-treated osteotomies were greater than Ad-LacZ or untreated osteotomies. Gene expression of ostectomy mineralized callus 8 weeks after surgery indicated upregulation of genes related to osteogenesis compared to intact metatarsal bone. Expression of transforming growth factor beta-1, cathepsin H, and gelsolin-like capping protein were greater in Ad-BMP-2- and Ad-BMP-6-treated callus compared to Ad-LacZ-treated or untreated callus. Evidence of tissue biodistribution of adenovirus in distant organs was not identified by quantitative PCR, despite increased serum antiadenoviral vector antibody. This study demonstrated a greater relative potency of Ad-BMP-2 over Ad-BMP-6 in accelerating osteotomy healing when administered in this regimen, although both genes were effective at increasing bone at both osteotomy and ostectomy sites.

  6. The Presence of Oxygen in Wound Healing.

    PubMed

    Kimmel, Howard M; Grant, Anthony; Ditata, James

    2016-08-01

    Oxygen must be tightly governed in all phases of wound healing to produce viable granulation tissue. This idea of tight regulation has yet to be disputed; however, the role of oxygen at the cellular and molecular levels still is not fully understood as it pertains to its place in healing wounds. In an attempt to better understand the dynamics of oxygen on living tissue and its potential role as a therapy in wound healing, a substantial literature review of the role of oxygen in wound healing was performed and the following key points were extrapolated: 1) During energy metabolism, oxygen is needed for mitochondrial cytochrome oxidase as it produces high-energy phosphates that are needed for many cellular functions, 2) oxygen is also involved in the hydroxylation of proline and lysine into procollagen, which leads to collagen maturation, 3) in angiogenesis, hypoxia is required to start the process of wound healing, but it has been shown that if oxygen is administered it can accelerate and sustain vessel growth, 4) the antimicrobial action of oxygen occurs when nicotinamide adenine dinucleotide phosphate (NADPH)-linked oxygenase acts as a catalyst for the production of reactive oxygen species (ROS), a superoxide ion which kills bacteria, and 5) the level of evidence is moderate for the use of hyperbaric oxygen therapy (HBOT) for diabetic foot ulcers, crush injuries, and soft-tissue infections. The authors hypothesized that HBOT would be beneficial to arterial insufficiency wounds and other ailments, but at this time further study is needed before HBOT would be indicated. PMID:27560469

  7. [Venous ulcer].

    PubMed

    Böhler, Kornelia

    2016-06-01

    Venous disorders causing a permanent increase in venous pressure are by far the most frequent reason for ulcers of the lower extremity. With a prevalence of 1 % in the general population rising to 4 % in the elderly over 80 and its chronic character, 1 % of healthcare budgets of the western world are spent on treatment of venous ulcers. A thorough investigation of the underlying venous disorder is the prerequisite for a differenciated therapy. This should comprise elimination of venous reflux as well as local wound management. Chronic ulcers can successfully be treated by shave therapy and split skin grafting. Compression therapy is a basic measure not only in venous ulcer treatment but also in prevention of ulcer recurrence. Differential diagnosis which have to be considered are arterial ulcers, vasculitis and neoplasms. PMID:27405863

  8. Pressure ulcer prevention.

    PubMed

    Edlich, Richard F; Winters, Kathryne L; Woodard, Charles R; Buschbacher, Ralph M; Long, William B; Gebhart, Jocelynn H; Ma, Eva K

    2004-01-01

    has been compared to the standard hospital bed as well as to two other commercially available pressure relief mattresses. The most recent advance in pressure ulcer prevention is the development of the ALTERN8* seating system. This seating system provides regular periods of pressure relief and stimulation of blood flow to skin areas while users are seated. By offering the combination of pressure relief therapy and an increase in blood flow, the ALTERN8* reportedly creates an optimum pressure ulcer healing environment. Foam is the most commonly used material for pressure reduction and pressure ulcer prevention and treatment for the mobile individual. For those immobilized individuals who can achieve a passive standing position, a powered wheelchair that allows the individual to achieve a passive standing position is recommended. The beneficial effects of passive standing have been documented by comprehensive scientific studies. These benefits include reduction of seating pressure, decreased bone demineralization, increased blander pressure, enhanced orthostatic circulatory regulation, reduction in muscular tone, decrease in upper extremity muscle stress, and enhanced functional status in general. In the absence of these dynamic alternating pressure seating systems and mattresses, there are enormous medicolegal implications to the healthcare facility. Because there is not sufficient staff to provide pressure relief to rotate the patient every 2 hours in a hospital setting, with the exception of the intensive care unit, the immobile patient is prone to develop pressure ulcers. The cost of caring for these preventable pressure ulcers may now be as high as 60,000 dollars per patient. The occupational physical strain sustained by nursing personnel in rotating their patients has led to occupational back pain in nurses, a major source of morbidity in the healthcare environment.

  9. Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer.

    PubMed Central

    Bonnevie, O; Svendsen, L B; Holst-Christensen, J; Johansen, T S; Søltoft, J; Christiansen, P M

    1979-01-01

    In a double-blind randomised clinical trial a specific inhibition of peptic activity with a pentapeptide, pepstatin, had no significant advantage over placebo in the ulcer healing and symptomatology of duodenal ulcer. Thus, the inhibition of pepsin in human gastric juice does not appear to have a major influence on the healing of duodenal ulcer. PMID:385457

  10. Common Questions About Pressure Ulcers.

    PubMed

    Raetz, Jaqueline G M; Wick, Keren H

    2015-11-15

    Patients with limited mobility due to physical or cognitive impairment are at risk of pressure ulcers. Primary care physicians should examine at-risk patients because pressure ulcers are often missed in inpatient, outpatient, and long-term care settings. High-risk patients should use advanced static support surfaces to prevent pressure ulcers and air-fluidized beds to treat pressure ulcers. Physicians should document the size and clinical features of ulcers. Cleansing should be done with saline or tap water, while avoiding caustic agents, such as hydrogen peroxide. Dressings should promote a moist, but not wet, wound healing environment. The presence of infection is determined through clinical judgment; if uncertain, a tissue biopsy should be performed. New or worsening pain may indicate infection of a pressure ulcer. When treating patients with pressure ulcers, it is important to keep in mind the patient's psychological, behavioral, and cognitive status. The patient's social, financial, and caregiver resources, as well as goals and long-term prognosis, should also be considered in the treatment plan. PMID:26554282

  11. [Dyspepsia, Ulcer Disease – Helicobacter pylori, Gastroesophageal Reflux Disease].

    PubMed

    Wirth, Hans-Peter

    2016-06-01

    Prevalence of H. pylori (HP) is declining, whereas reflux disease and the proportion of non-steroidal antiinflammatory drugs (NSAR) to HP-induced ulcers increase. Eradication heals HP-ulcer disease, interrupts cancerous progression and can improve dyspeptic symptoms. NSAR-ulcers heal under proton pump inhibitor (PPI) therapy but tend to recur after reexposition. Anticoagulants and antiplatlet agents increase the risk additionally. PPI reduces NSAR-ulcer recurrence. Reflux patients with severe inflammation and complications often need long-term therapy. Barrett’s esophagus patients are at risk of esophageal adenocarcinoma.

  12. [Dyspepsia, Ulcer Disease – Helicobacter pylori, Gastroesophageal Reflux Disease].

    PubMed

    Wirth, Hans-Peter

    2016-06-01

    Prevalence of H. pylori (HP) is declining, whereas reflux disease and the proportion of non-steroidal antiinflammatory drugs (NSAR) to HP-induced ulcers increase. Eradication heals HP-ulcer disease, interrupts cancerous progression and can improve dyspeptic symptoms. NSAR-ulcers heal under proton pump inhibitor (PPI) therapy but tend to recur after reexposition. Anticoagulants and antiplatlet agents increase the risk additionally. PPI reduces NSAR-ulcer recurrence. Reflux patients with severe inflammation and complications often need long-term therapy. Barrett’s esophagus patients are at risk of esophageal adenocarcinoma. PMID:27269775

  13. [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.

  14. Laser-assisted skin closure (LASC) using a 815-nm diode laser system: determination of an optimal dose to accelerate wound healing

    NASA Astrophysics Data System (ADS)

    Capon, Alexandre; Mitchell, Valerie A.; Sumian, Chryslain C.; Gauthier, Beatrice; Mordon, Serge R.

    1999-01-01

    This study aimed to evaluate a 815 nm diode-laser system to assist wound closure. It was proposed to determine an optimal fluence being able to accelerate and improve heating process without thermal damage after laser irradiation. Male hairless rats with dorsal skin incisions were used for the study. Different fluences were screened (76 to 346 J/cm2) in a first phase with clinical examination at 3, 7, 15 and 21 days after surgery. Best results were obtained for a fluence of 145 J/cm2 and 3 sec time of exposure. A second phase was conducted to valid these parameters with histological study and determination of tensile strength at 3, 7, 15 and 21 days after surgery. LASC was 4 times faster to process than conventional suture. In the laser group with an optimal fluence of 145 J/cm2, healing was accelerated. The resulting scar was more indiscernible than in the control groups. Histological aspect was better with continuous epidermis and dermis at 3 days in most cases. Tensile strength was 30 to 58% greater than in control groups (1141 g/cm2 at 7 days in the laser group versus 856 g/cm2 and 724 g/cm2 in the control groups, p < 0.001).

  15. The role of stem cells in the treatment of diabetic foot ulcers.

    PubMed

    Blumberg, Sheila N; Berger, Alexandra; Hwang, Lisa; Pastar, Irena; Warren, Stephen M; Chen, Weiliam

    2012-04-01

    Diabetic foot ulcers (DFUs) are a significant and rapidly growing complication of diabetes and its effects on wound healing. Over half of diabetic patients who develop a single ulcer will subsequently develop another ulcer of which the majority will become chronic non-healing ulcers. One-third will progress to lower extremity amputation. Over the past decade, the outcomes for patients with DFUs ulcers have not improved, despite advances in wound care. Successful treatment of diabetic foot ulcers is hindered by the lack of targeted therapy that hones in on the healing processes dysregulated by diabetes. Stem cells are a promising treatment for DFUs as they are capable of targeting, as well as bypassing, the underlying abnormal healing mechanisms and deranged cell signaling in diabetic wounds and promote healing. This review will focus on existing stem cell technologies and their application in the treatment of DFUs.

  16. Evaluation of the effects of homologous platelet gel on healing lower extremity wounds in patients with diabetes.

    PubMed

    Shan, Gui-Qiu; Zhang, Ya-Ni; Ma, Jing; Li, Yan-Hui; Zuo, Da-Ming; Qiu, Jin-Lang; Cheng, Biao; Chen, Zheng-Liang

    2013-03-01

    The treatment of chronic diabetic wounds remains complicated, despite new insight into the cellular and molecular basis of wound healing and cutaneous regeneration. A growing body of clinical trials has shown that platelet release has a notable effectiveness on refractory ulcer healing. However, patients with chronic diabetic ulcers usually have poor general health, and the large-volume blood absence required to produce autologous platelet-rich plasma often causes adverse effects. To overcome the limitation, the homologous platelet gel (PG) from healthy donor was used for the treatment of chronic diabetic lower extremity wound in the study. We show here that homologous derived platelets significantly enhanced EVC304 cell and HaCaT cell proliferation and homologous PG was capable of prompting cell migration. Twenty-one patients with refractory diabetic lower extremity ulcers, who had no response to conventional treatments, were treated in this study. Our data indicated that homologous PG was effective for the enhancement and acceleration of diabetic lower extremity wounds healing. We propose that homologous PG appeared to enhance vascularization and epithelialization, which might induce a quicker healing process and and encourage controlled studies in future.

  17. Commercially available topical platelet-derived growth factor as a novel agent to accelerate burn-related wound healing.

    PubMed

    Travis, Taryn E; Mauskar, Neil A; Mino, Matthew J; Prindeze, Nick; Moffatt, Lauren T; Fidler, Philip E; Jordan, Marion H; Shupp, Jeffrey W

    2014-01-01

    The authors investigated whether the application of platelet-derived growth factor (PDGF) to donor site wounds would speed healing in a porcine model. In a red duroc pig model, three wounds that were 3 inches × 3 inches were created with a dermatome (0.06-inch depth) on one side of two different animals. These wounds were digitally and laser Doppler (LDI) imaged and biopsied immediately pre- and postwound creation and every 2 days for 2 weeks. A set of identical wounds were subsequently created on the opposite side of the same animals and treated with topical PDGF (becaplermin gel 0.01%, 4 g/wound) immediately on wounding. PDGF-treated wounds were imaged and biopsied as above. Digital images of wounds were assessed for epithelialization by clinicians using an ordinal scale. Perfusion units (PU) were evaluated by LDI. Wound healing was evaluated by hematoxylin and eosin histological visualization of an epithelium and intact basement membrane. First evidence of partial epithelialization was seen in control and PDGF-treated wounds within 7.7 ± 1.4 and 6.4 ± 1.1 days postwounding, respectively (P=.03). Completely epithelialized biopsies were seen in control and PDGF-treated wounds at 11.7 ± 2.6 and 9.6 ± 1.5 days, respectively (P=.02). Clinician evaluation of digital images showed that on day 9, control wounds were, on average, 48.3 ± 18.5% epithelialized vs 57.2 ± 20.2% epithelialized for PDGF-treated wounds. At day 16, control wounds showed an average of 72.9 ± 14.6% epithelialization and PDGF-treated wounds showed an average of 90 ± 11.8%epithelialization. Overall, PDGF-treated wounds had statistically significantly higher scores across all timepoints (P=.02). Average perfusion units as measured by LDI were similar for control and PDGF-treated wounds at time of excision (225 ± 81and 257 ± 100, respectively). On day 2 postwounding, average PU for control wounds were 803 and were 764 for PDGF-treated wounds. Control wounds maintained higher PU values

  18. Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats.

    PubMed

    El-Shinnawy, Nashwa A; Abd-Elmageid, Samira A; Alshailabi, Eda M A

    2014-05-01

    The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.

  19. Amniotic membrane can be a valid source for wound healing

    PubMed Central

    ElHeneidy, Hossam; Omran, Eman; Halwagy, Ahmed; Al-Inany, Hesham; Al-Ansary, Mirvat; Gad, Amr

    2016-01-01

    Amniotic membrane (AM) can promote proper epithelialization with suppression of excessive fibrosis by creating a supportive milieu for regeneration of chronic ulcer bed. Objective The objective of this study is to investigate whether AM scaffold can modulate the healing of a wound by promoting tissue reconstruction rather than promoting scar tissue formation. Subjects and methods AM was obtained and prepared and then applied to patients with chronic leg ulcers who were randomly divided into two different groups. Group I (control group) included eleven patients in whom ulcers were treated with conventional wound dressings that were changed daily for 8 weeks. Group II (study group) included 14 patients in whom the AM was placed in contact with the ulcer and held in place with a secondary dressing, which was changed daily. Follow-up was done to detect healing rate and detection of ulcer size, assessment of pain, and to take ulcer images (days 0, 7, 14, 21, 30, 45, and 60). Results In group I, all ulcers showed no reduction in their size, and ulcer floor remained the same. Healthy granulations were present in two ulcers (18.2%) and absent in nine ulcers (81.8%). There was no improvement of pain level in the eleven ulcers. In group II, complete healing of 14 ulcers occurred in 14–60 days with a mean of 33.3±14.7; healing rate range was 0.064–2.22 and the mean 0.896±0.646 cm2/day. Healthy granulations were present in 13 ulcers (92.9%) and absent in one ulcer (7.1%). Three ulcers (21.4%) were of mild severity (grade 1 ulcers) while eleven ulcers (78.6%) were of moderate severity (grade 2 ulcers). The healing rate was faster in ulcers of mild severity (1.7±0.438 cm2/day) in comparison to ulcers of moderate severity (0.673±0.498 cm2/day). Eleven cases (78.6%) showed improvement in their pain level on a scale from 0 to 10. Conclusion AM graft can be of value in wound healing. Further studies are needed to confirm these findings. PMID:27390533

  20. 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

  1. Thalidomide for mouth ulcers and wasting.

    PubMed

    Baker, R

    1995-12-01

    Thalidomide (Synovir), noted for causing severe birth defects when taken by pregnant women, can effectively and safely heal serious mouth ulcers (oral aphthous ulcers) in people with HIV infection. Interim results from a study supported by the National Institute of Allergy and Infectious Diseases (NIAID) show that ulcers healed in 14 of 23 people taking 200 mg/day oral thalidomide compared to only 1 of 22 people receiving placebo. Celgene Corporation is conducting a multicenter, double-blinded, placebo-controlled study of Synovir for the treatment of wasting syndrome. Participants will receive the drug for free, and will take one of three doses: 10, 50, or 200 mg. Interested parties should call the Healing Alternatives Foundation or the PWA Health group.

  2. Guilty as charged: bugs and drugs in gastric ulcer.

    PubMed

    Sontag, S J

    1997-08-01

    Gastric ulcer disease remains a cause of hemorrhage, perforation, outlet obstruction, and death. Recent advances in the understanding of peptic ulcer disease indicate that infection with Helicobacter pylori and ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) are the cause of almost all gastric and duodenal ulcers. Our therapy, therefore, is in a state of transition: the old acid-suppressive temporary therapy that allows frequent ulcer recurrences and complications is being replaced by curative therapies. The old therapy, by reducing gastric acid secretion or enhancing gastric mucosal defenses, inhibited the cofactors needed for ulcer development. Acid suppression relieved symptoms and healed ulcers, while defense enhancers, such as prostaglandin analogs healed and prevented acute NSAID-induced gastric ulcers. These benefits were maintained, however, only as long as acid-reducing agents or mucosal defense enhancers were continued. On the other hand, curative therapies (such as eradicating H. pylori infection and/or stopping the use of NSAIDs) eliminate the causes of ulcer. Curative combination regimens consisting of antibiotics, ranitidine bismuth citrate, bismuth, and proton pump inhibitors have been approved by the Food and Drug Administration. These new regimens can cure benign gastric ulcer. Unfortunately, we cannot always determine which gastric ulcers are benign, and concern about gastric cancer remains. All gastric ulcers therefore still require biopsy and histological examination. With new treatment regimens, the time may be rapidly approaching when ulcer disease will be "history."

  3. 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.

  4. Cure of peptic gastric ulcer associated with eradication of Helicobacter pylori. Finnish Gastric Ulcer Study Group.

    PubMed

    Seppälä, K; Pikkarainen, P; Sipponen, P; Kivilaakso, E; Gormsen, M H

    1995-06-01

    The effect of Helicobacter pylori eradication on ulcer healing and the relapse rate were investigated in a multicentre trial of 239 gastric ulcer patients. Patients with H pylori positive gastric ulcer were randomly assigned to one of three groups: (A) 10 days' treatment with metronidazole and eight weeks' treatment with colloidal bismuth subcitrate (CBS) (84 patients); (B) 10 days' treatment with metronidazole placebo and eight weeks with CBS (73 patients); or (C) ranitidine (82 patients). At 12 weeks in 210 patients, gastric ulcer was present in three (9%) of 35 H pylori negative patients, and in 45 (26%) of 175 H pylori positive patients (p < 0.05). Results after one year of follow up were available for 205 patients. Between 12 and 52 weeks, two (7%) ulcer relapses occurred in 29 H pylori negative patients and in 60 (47%) of 128 H pylori positive patients (p < 0.001). After two weeks of open triple therapy (CBS 120 mg four times daily, amoxicillin 500 mg four times daily, and metronidazole 400 mg three times daily), given to the patients with ulcer relapse, only one (an NSAID user) of 55 successfully treated patients had an ulcer relapse during the one year follow up. Healing of gastric ulcer is rapid and recurrence is infrequent after successful H pylori eradication. H pylori eradication changes the natural history of the gastric ulcer disease.

  5. Introducing and auditing a nurse-led leg ulcer service.

    PubMed

    Rotchell, L

    1999-05-01

    Leg ulcers have a significant impact on quality of life, and represent a major treatment cost for health services. Improved healing rates benefit patients and health service provision. Nurse-led clinics provide an appropriate setting for treatment.

  6. Ulcerative colitis - discharge

    MedlinePlus

    Inflammatory bowel disease - ulcerative colitis - discharge; Ulcerative proctitis - discharge; Colitis - discharge ... were in the hospital because you have ulcerative colitis. This is a swelling of the inner lining ...

  7. Epithelial-specific ETS-1 (ESE1/ELF3) regulates apoptosis of intestinal epithelial cells in ulcerative colitis via accelerating NF-κB activation.

    PubMed

    Li, Liren; Miao, Xianjing; Ni, Runzhou; Miao, Xiaobing; Wang, Liang; Gu, Xiaodan; Yan, Lijun; Tang, Qiyun; Zhang, Dongmei

    2015-06-01

    Epithelial-specific ETS-1 (ESE1), also named as ELF3, ERT and ESX, belonging to the ETS family of transcription factors, exerts multiple activities in inflammation, epithelial differentiation and cancer development. Previous data demonstrated that ESE1 synergizes with NF-κB to induce inflammation and drive tumor progress, and the nuclear translocation of ESE1 promotes colon cells apoptosis. However, the expression and biological functions of ESE1 in ulcerative colitis (UC) remain unclear. In this study, we reported for the first time that ESE1/ELF3 was over-expressed in intestinal epithelial cells (IECs) of patients with UC. In DSS-induced colitis mouse models, we observed the up-regulation of ESE1/ELF3 accompanied with the elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and NF-κB activation indicators [phosphorylated NF-κB p65 subunit (p-p65) and p-IκB] in colitis IECs. Increased co-localization of ESE1/ELF3 with active caspase-3 (and p-p65) in IECs of the DSS-induced colitis group further indicated the possible involvement of ESE1/ELF3 in NF-κB-mediated IEC apoptosis in UC. Employing the TNF-α-treated HT-29 cells as an IEC apoptosis model, we confirmed the positive correlation of ESE1/ELF3 with NF-κB activation and caspase-dependent IEC apoptosis in vitro. Immunoprecipitation and immunofluorescence assay revealed the physical interaction and increased nuclear translocation of ESE1/ELF3 and the NF-κB p65 subunit in TNF-α-treated HT-29 cells. Knocking ESE1/ELF3 down by siRNA significantly alleviated TNF-α-induced NF-κB activation and cellular apoptosis in HT-29 cells. Taken together, our data suggested that ESE1/ELF3 may promote the UC progression via accelerating NF-κB activation and thus facilitating IEC apoptosis.

  8. 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.

  9. 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.

  10. Anti-alpha-toxin monoclonal antibody and antibiotic combination therapy improves disease outcome and accelerates healing in a Staphylococcus aureus dermonecrosis model.

    PubMed

    Hilliard, Jamese J; Datta, Vivekananda; Tkaczyk, Christine; Hamilton, Melissa; Sadowska, Agnieszka; Jones-Nelson, Omari; O'Day, Terrence; Weiss, William J; Szarka, Szabolcs; Nguyen, Vien; Prokai, Laszlo; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2015-01-01

    Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. aureus disease in a mouse dermonecrosis model by neutralizing AT-mediated tissue necrosis and immune evasion. In the present study, MEDI4893*, an affinity-optimized version of 2A3, was characterized for therapeutic activity in the dermonecrosis model as a single agent and in combination with two frontline antibiotics, vancomycin and linezolid. MEDI4893* postinfection therapy was found to exhibit a therapeutic treatment window similar to that for linezolid but longer than that for vancomycin. Additionally, when combined with either vancomycin or linezolid, MEDI4893* resulted in reduced tissue damage, increased neutrophil and macrophage infiltration and abscess formation, and accelerated healing relative to those with the antibiotic monotherapies. These data suggest that AT neutralization with a potent MAb holds promise for both prophylaxis and adjunctive therapy with antibiotics and may be a valuable addition to currently available options for the treatment of S. aureus skin and soft tissue infections.

  11. Anti-alpha-toxin monoclonal antibody and antibiotic combination therapy improves disease outcome and accelerates healing in a Staphylococcus aureus dermonecrosis model.

    PubMed

    Hilliard, Jamese J; Datta, Vivekananda; Tkaczyk, Christine; Hamilton, Melissa; Sadowska, Agnieszka; Jones-Nelson, Omari; O'Day, Terrence; Weiss, William J; Szarka, Szabolcs; Nguyen, Vien; Prokai, Laszlo; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2015-01-01

    Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. aureus disease in a mouse dermonecrosis model by neutralizing AT-mediated tissue necrosis and immune evasion. In the present study, MEDI4893*, an affinity-optimized version of 2A3, was characterized for therapeutic activity in the dermonecrosis model as a single agent and in combination with two frontline antibiotics, vancomycin and linezolid. MEDI4893* postinfection therapy was found to exhibit a therapeutic treatment window similar to that for linezolid but longer than that for vancomycin. Additionally, when combined with either vancomycin or linezolid, MEDI4893* resulted in reduced tissue damage, increased neutrophil and macrophage infiltration and abscess formation, and accelerated healing relative to those with the antibiotic monotherapies. These data suggest that AT neutralization with a potent MAb holds promise for both prophylaxis and adjunctive therapy with antibiotics and may be a valuable addition to currently available options for the treatment of S. aureus skin and soft tissue infections. PMID:25348518

  12. Anti-Alpha-Toxin Monoclonal Antibody and Antibiotic Combination Therapy Improves Disease Outcome and Accelerates Healing in a Staphylococcus aureus Dermonecrosis Model

    PubMed Central

    Hilliard, Jamese J.; Datta, Vivekananda; Tkaczyk, Christine; Hamilton, Melissa; Sadowska, Agnieszka; Jones-Nelson, Omari; O'Day, Terrence; Weiss, William J.; Szarka, Szabolcs; Nguyen, Vien; Prokai, Laszlo; Suzich, JoAnn; Stover, C. Kendall

    2014-01-01

    Alpha-toxin (AT) is a major virulence determinant in Staphylococcus aureus skin and soft tissue infection models. We previously demonstrated that prophylactic administration of 2A3, an AT-neutralizing monoclonal antibody (MAb), prevents S. aureus disease in a mouse dermonecrosis model by neutralizing AT-mediated tissue necrosis and immune evasion. In the present study, MEDI4893*, an affinity-optimized version of 2A3, was characterized for therapeutic activity in the dermonecrosis model as a single agent and in combination with two frontline antibiotics, vancomycin and linezolid. MEDI4893* postinfection therapy was found to exhibit a therapeutic treatment window similar to that for linezolid but longer than that for vancomycin. Additionally, when combined with either vancomycin or linezolid, MEDI4893* resulted in reduced tissue damage, increased neutrophil and macrophage infiltration and abscess formation, and accelerated healing relative to those with the antibiotic monotherapies. These data suggest that AT neutralization with a potent MAb holds promise for both prophylaxis and adjunctive therapy with antibiotics and may be a valuable addition to currently available options for the treatment of S. aureus skin and soft tissue infections. PMID:25348518

  13. Platelet-Rich Fibrin Promotes an Accelerated Healing of Achilles Tendon When Compared to Platelet-Rich Plasma in Rat

    PubMed Central

    Dietrich, Franciele; L. Duré, Gustavo; P. Klein, Caroline; F. Bampi, Vinícius; V. Padoin, Alexandre; D. Silva, Vinícius; Braga-Silva, Jefferson

    2015-01-01

    BACKGROUND Autologous platelet concentrate has been used to improve the function and regeneration of injured tissues. Tendinopathies are common in clinical practice, although long-term treatment is required. On the basis of lead time, we compared the effect of using platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in repairing rat Achilles tendon. METHODS The effectiveness of using PRP and PRF was evaluated after 14 and 28 postoperative days by histological analysis. The quantification of collagen types I and III was performed by Sirius red staining. Qualitatively, the data were verified with hematoxylin-eosin (H&E) staining. RESULTS In Sirius red staining, no significant treatment differences were found between groups. Statistical difference was observed only between PRP (37.2% collagen) and the control group (16.2%) 14 days after treatment. Intra-groups compared twice showed a difference for collagen I (27.8% and 47.7%) and III (66.9% and 46.0%) in the PRF group. The control group showed differences only in collagen I (14.2% and 40.9%) and no other finding was observed in the PRP group. In H&E staining, PRF showed a better cellular organization when compared to the other groups at 28 days. CONCLUSION Our study suggests that PRF promotes accelerated regeneration of the Achilles tendon in rats, offering promising prospects for future clinical use. PMID:26284178

  14. [Lipschütz acute genital ulcer].

    PubMed

    Kluger, N; Garcia, C; Guillot, B

    2009-10-01

    Lipschütz acute genital ulcer is a rare distinctive cause of nonvenereal acute genital ulcers that occurs particularly in adolescents described in 1913. We report here a typical case that occurred in a 24-year-old virgin woman who developed flu-like symptoms and painful genital ulcers that healed spontaneously within a week and without any infection (Epstein Barr Virus, toxoplasmosis, salmonella). The physiopathogeny remains unknown. However, there are body of evidences pointing out a possible link to several nonvenereal infections, including mainly Epstein-Barr virus acute infection. This rare benign but disabling entity should be known by gynecologists.

  15. [Contact eczema in patients with leg ulcers].

    PubMed

    Degreef, H; Dooms-Goossens, A; Gladys, K

    1986-01-01

    Patients with leg ulcers or varicose eczema suffer much more often from contact eczema due to the local application of pharmaceutical preparations than patients suffering from other dermatological problems (even those of eczematous origin). This contact allergy may concern not only the active ingredient but also the excipient, the preservative, or even the perfume. In all cases of leg ulcers, of varicose eczema, but also of badly healed ulcers, epicutaneous tests should be carried out with all the components of the pharmaceutical preparations concerned. Moreover, the pharmaceutical industry really must perfect non-allergenic preparations.

  16. Gastric cancer detection in gastric ulcer disease.

    PubMed Central

    Mountford, R A; Brown, P; Salmon, P R; Alvarenga, C; Neumann, C S; Read, A E

    1980-01-01

    A retrospective study has been performed of all cases of gastric ulcer diagnosed or investigated within the Endoscopy Unit of the Department of Medicine, Bristol, over a three year period (1974-76). The average length of follow-up was two years. Two hundred and sixty five cases of gastric ulcer were studied of which 37 proved to be malignant (14%). Presenting complaints of anorexia, weight loss, nausea and/or vomiting, and multiple (greater than 3) symptoms, were commoner in the malignant ulcer group. Ulcer site and the presence of coexisting duodenal ulceration were largely unhelpful in deciding the status of an ulcer. Malignant ulcers tended to be large (greater than 1 cm diameter). Radiology was highly unreliable in distinguishing benign from malignant ulcers. Visual inspection at endoscopy was more reliable, but associated with a tendency to over-diagnose malignancy. False positive biopsies were uncommon (two cases). Three cases of clinically unsuspected superficial gastric carcinoma were revealed. Repeated endoscopy and biopsy of all gastric ulcers until they are completely healed is advised. Images Fig. 5 Fig. 6 PMID:7364322

  17. 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

  18. Improving outcome of pressure ulcers with nutritional interventions: a review of the evidence.

    PubMed

    Thomas, D R

    2001-02-01

    Pressure ulcers and malnutrition frequently co-exist in frail patients. Nutritional parameters have been correlated with development and with healing in chronic pressure ulcers, leading to suggestions that improving nutritional status can prevent or treat pressure ulcers. Despite a strong association, a causal relationship of poor nutritional status to development of pressure ulcers has not been established. Support for a causal relationship would include evidence that nutritional interventions improve general nutritional status, acute wound healing, or chronic wound healing. The data suggesting that nutritional intervention can improve clinical outcome are limited. No study has demonstrated that improvement in nutritional status can prevent pressure ulcers. There is at least suggestive evidence that improvement in nutritional status can improve outcome in pressure ulcer healing.

  19. Wormwood (Artemisia absinthium) suppresses tumour necrosis factor alpha and accelerates healing in patients with Crohn's disease - A controlled clinical trial.

    PubMed

    Krebs, Simone; Omer, Talib N; Omer, Bilal

    2010-04-01

    Suppression of tumour necrosis factor alpha (TNF-alpha) and other interleukins by wormwood (Artemisia absinthium) extracts were reported recently in in vitro studies. The aim of the present study was to find out if this effect can be also be observed in Crohn's Disease (CD) patients where TNF-alpha appears to play an important role. In a controlled trial, 10 randomly selected patients suffering from CD were given in addition to their basic CD therapy 3x750mg dried powdered wormwood for 6 weeks. Ten patients, also randomly selected who met the inclusion criteria served as control group. Minimum score of 200 on Crohn's Disease Activity Index (CDAI) was required at baseline for inclusion in each group. Patients who received infliximab or similar were excluded from the trial. TNF-alpha level in serum were measured at baseline, and after three and six weeks. During this period all concomitant CD medications was maintained at the baseline dose levels. Average serum TNF-alpha level fell from 24.5+/-3.5pg/ml at baseline to 8.0+/-2.5pg/ml after six weeks. The corresponding levels in the control group were 25.7+/-4.6 (week 0), and 21.1+/-3.2 (week 6). On the clinical side, CDAI scores fell from 275+/-15 to below 175+/-12 in wormwood group with remission of symptoms in eight patients (CDAI score below 170 or reduction by 70 points), compared to only two in the placebo group (CDAI of placebo group 282+/-11 at baseline and 230+/-14 on week 6). IBDQ also reflected accelerated clinical response with wormwood. Of clinical significance were the findings that wormwood also improved mood of the CD patients, as reflected in Hamilton's Depression Scale. These findings provide a base to test wormwood in clinical conditions thought to be mediated by increased production of pro-inflammatory cytokines such as TNF-alpha.

  20. The pivotal role of offloading in the management of neuropathic foot ulceration.

    PubMed

    Wu, Stephanie C; Crews, Ryan T; Armstrong, David G

    2005-12-01

    Lower extremity amputations among persons with diabetes are generally preceded by neuropathic foot ulcerations. Healing of diabetic ulcerations in a timely manner is of central importance in any plan for amputation prevention. With sufficient vascular supply, appropriate débridement, and infection control, the primary mode of healing a diabetic neuropathic foot ulcer is pressure dispersion. The total contact cast has been deemed by many to be the gold standard in offloading; however, modification of a standard removable cast walker to ensure patient compliance may be as efficacious in healing diabetic foot ulcers as the total contact cast. Combining an effective, easy to use offloading device that ensures patient compliance with advanced wound healing modalities may form a formidable team in healing ulcers and potentially averting lower limb amputations.

  1. 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

  2. Role of peroxisome proliferator-activated receptors alpha and gamma in gastric ulcer: An overview of experimental evidences.

    PubMed

    Saha, Lekha

    2015-11-01

    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

  3. 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

  4. 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

  5. [Innovations in the treatment of gastroduodenal ulcers].

    PubMed

    Bernier, J J

    1983-05-14

    It has long been known that gastroduodenal ulcers may heal spontaneously; this is the placebo effect in which the healing rate ranges from 20% at 2 weeks to 80% at 8 weeks. Two or three weeks can be gained by using cimetidine or ranitidine, with healing rates of 42% at 2 weeks and 85% at 6 weeks. Ranitidine probably has less side-effects than cimetidine. A new drug, omeprozole, appears to be much more potent but is not yet available. A vagolytic drug with specific affinity to the stomach (pirenzepine), as well as low-dosage bismuth bi-citrate and gastric mucosa protectors (sucralfate) are now returning in force. PMID:6304676

  6. Peptic Ulcers

    MedlinePlus

    ... is a good alternative to NSAIDs for most childhood conditions. Signs and Symptoms Although peptic ulcers are rare in kids, if your child has any of these signs and symptoms, call your doctor: burning pain in the abdomen between the breastbone and the belly button (the ...

  7. [Ulcerative colitis].

    PubMed

    Lopetuso, Loris; Gasbarrini, Antonio

    2016-06-01

    Inflammatory bowel disease (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing inflammatory disorders of the digestive tract resulting from dysregulated immune responses toward environmental factors in genetically predisposed individuals. This review focus on what is the state of the art of UC pathophysiology, diagnosis, and treatment and how any future findings could drive our clinical practice. PMID:27362722

  8. In Vivo Wound Healing Studies.

    PubMed

    2016-01-01

    Wound healing has emerged as a major treatment issue which has provoked the development of drugs that can improve the healing process. Studies using plant drugs have revealed many interesting results about existing commercial drugs. Effective wound healing leads to the restoration of tissue integrity and occurs through a highly organized multistage. Use of plant-derived medicines against excision, incision, and dead space models accelerates the wound healing process, which is briefly discussed in a manner to be followed easily during experimental sessions.

  9. In Vivo Wound Healing Studies.

    PubMed

    2016-01-01

    Wound healing has emerged as a major treatment issue which has provoked the development of drugs that can improve the healing process. Studies using plant drugs have revealed many interesting results about existing commercial drugs. Effective wound healing leads to the restoration of tissue integrity and occurs through a highly organized multistage. Use of plant-derived medicines against excision, incision, and dead space models accelerates the wound healing process, which is briefly discussed in a manner to be followed easily during experimental sessions. PMID:26939282

  10. Lipschütz genital ulceration associated with mumps.

    PubMed

    Chanal, Johan; Carlotti, Agnès; Laude, Hélène; Wallet-Faber, Nadège; Avril, Marie-Françoise; Dupin, Nicolas

    2010-01-01

    Lipschütz ulcers are characterised by a first flare of non-sexually related acute genital ulcers (AGU) occurring in adolescent girls. Epstein-Barr primary infection is the most frequently reported aetiology but other infectious agents are probably implicated. We report the first case of mumps associated with an AGU in a 21-year-old girl. She presented a bilateral parotitis with genital ulcers, and serology confirmed she had mumps. As in our case, most Lipschütz ulcers heal spontaneously within a couple of weeks and the diagnosis should be reconsidered in case of recurrence.

  11. Saliva and wound healing.

    PubMed

    Brand, Henk S; Veerman, Enno C I

    2013-01-01

    Wounds in the oral cavity heal faster and with less scarring than wounds in other parts of the body. One of the factors implicated in this phenomenon is the presence of saliva, which promotes the healing of oral wounds in several ways. Saliva creates a humid environment, which improves the survival and functioning of inflammatory cells that are crucial for wound healing. Furthermore, saliva contains a variety of proteins that play a role in the various stages of the intraoral wound healing. Tissue factor, present in salivary exosomes, accelerates the clotting of blood dramatically. The subsequent proliferation of epithelial cells is promoted by growth factors in saliva, especially epidermal growth factor. The importance of secretory leucocyte protease inhibitor is demonstrated by the observation that in the absence of this salivary protein, oral wound healing is considerably delayed. Members of the salivary histatin family promote wound closure in vitro by enhancing cell spreading and cell migration. Cell proliferation is not enhanced by histatin. Cyclization of histatin increased its biological activity approximately 1,000-fold compared to linear histatin. These studies suggest that histatins could potentially be used for the development of new wound healing medications.

  12. Enteral nutrition in the prevention and treatment of pressure ulcers in adult critical care patients.

    PubMed

    Cox, Jill; Rasmussen, Louisa

    2014-12-01

    Prevention and healing of pressure ulcers in critically ill patients can be especially challenging because of the patients' burden of illness and degree of physiological compromise. Providing adequate nutrition may help halt the development or worsening of pressure ulcers. Optimization of nutrition can be considered an essential ingredient in prevention and healing of pressure ulcers. Understanding malnutrition in critical care patients, the effect of nutrition on wound healing, and the application of evidence-based nutritional guidelines are important aspects for patients at high risk for pressure ulcers. Appropriate screenings for nutritional status and risk for pressure ulcers, early collaboration with a registered dietician, and administration of appropriate feeding formulations and micronutrient and macronutrient supplementation to promote wound healing are practical solutions to improve the nutritional status of critical care patients. Use of nutritional management and enteral feeding protocols may provide vital elements to augment nutrition and ultimately result in improved clinical outcomes.

  13. Cutaneous leishmaniasis "chiclero's ulcer" in subtropical Ecuador.

    PubMed

    Calvopiña, Manuel; Martinez, Leonardo; Hashiguchi, Yoshihisa

    2013-08-01

    An 18-year-old female presented with a severe ulcerative lesion on her right ear of 6 weeks duration. Her right ear was edematous and erythematous with a large, painless ulcerative lesion covering a third of the pinna and satellite papular lesions on the posterior. She was diagnosed with chiclero's ulcer. A skin smear stained with Diff-quik showed abundant Leishmania parasites. Chiclero's ulcer is a rare clinical presentation and is typically severe and difficult to treat. Physicians in Ecuador recommend administering prolonged intramuscular Glucantime. Side effects are common and can be severe resulting in low patient compliance. Because of preferences of the patient and the large volume needed for her weight, we recommended topical treatment with a lotion of Glucantime mixed half and half with white Merthiolate. After applying this lotion to the lesion 3 to 4 times a day for 6 weeks, the lesion healed.

  14. Chronic leg ulcers in Werner's syndrome.

    PubMed

    Yeong, E K; Yang, C C

    2004-01-01

    We report two siblings suffered from Werner's syndrome, which is a rare premature aging disorder caused by genetic mutations. They developed premature aging during adolescence with loss and graying of hair, short stature, baldness, atrophic skin, thin extremities, flat feet, 'bird' face and cataracts. Multiple chronic ulcers were noted over the feet in both patients. Healing was prolonged because of atrophic subcutaneous tissue, poor perfusion, impaired fibroblast activity and the loss of normal foot architecture. Treatment of the ulcers was challenging, as flap options were limited over the lower third of the leg and skin grafting was not easy as there was a lack of healthy granulations. However, we have successfully closed the ulcers with Integra artificial skin and ultra-thin split thickness skin grafting with the scalp as donor site. The main purpose of this paper is to alert physicians to this syndrome when treatments are being planned for patients with chronic leg ulcers.

  15. Primary squamous cell carcinoma with mucormycosis in a diabetic foot ulcer.

    PubMed

    Mandal, Palash Kumar; Bhattacharyya, Nirmal Kumar; Mookerjee, Sekhar Kumar; Chaudhuri, Bhaskarnarayan

    2013-02-01

    The diabetic foot ulcer is one of the major complications of diabetes mellitus leading to prolonged hospital stay. Non-healing foot ulcers in diabetes may be due to peripheral neuropathy and/or vasculopathy. Non-healing occurs following a trivial trauma due to loss of local immunity and increased infection by bacteria and fungus. Candida and mucormycosis are common fungal infection in diabetic foot ulcer. Squamous cell carcinoma in any non-healing ulcer is a common occurrence. But squamous cell carcinoma in non-healing diabetic foot ulcer is rarely reported. Here, mucormycosis in a diabetic foot ulcer which turned into squamous cell carcinoma is reported in a 62-year-old male with poor glycaemic control for last 21 years who presented with a non-healing ulcer of 8 months' duration over dorsum of left forefoot. Microbiological examination revealed presence of mucormycosis infection and histopathology of ulcer showed infiltrating well-differentiated squamous cell carcinoma. The clinicians and pathologists should be aware of these combinations because only eradication of mucormycosis may not cure the ulcer, rather presence of squamous cell carcinoma may be ignored that may be an immediate threat to the patient's life.

  16. 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. PMID:22052587

  17. Cutaneous Wound Healing After Treatment with Plant-Derived Human Recombinant Collagen Flowable Gel

    PubMed Central

    Roth, Sigal; Amzel, Tal; Harel-Adar, Tamar; Tamir, Eran; Grynspan, Frida; Shoseyov, Oded

    2013-01-01

    Chronic wounds, particularly diabetic ulcers, represent a main public health concern with significant costs. Ulcers often harbor an additional obstacle in the form of tunneled or undermined wounds, requiring treatments that can reach the entire wound tunnel, because bioengineered grafts are typically available only in a sheet form. While collagen is considered a suitable biodegradable scaffold material, it is usually extracted from animal and human cadaveric sources, and accompanied by potential allergic and infectious risks. The purpose of this study was to test the performance of a flowable gel made of human recombinant type I collagen (rhCollagen) produced in transgenic tobacco plants, indicated for the treatment of acute, chronic, and tunneled wounds. The performance of the rhCollagen flowable gel was tested in an acute full-thickness cutaneous wound-healing rat model and compared to saline treatment and two commercial flowable gel control products made of bovine collagen and cadaver human skin collagen. When compared to the three control groups, the rhCollagen-based gel accelerated wound closure and triggered a significant jumpstart to the healing process, accompanied by enhanced re-epithelialization. In a cutaneous full-thickness wound pig model, the rhCollagen-based flowable gel induced accelerated wound healing compared to a commercial product made of bovine tendon collagen. By day 21 post-treatment, 95% wound closure was observed with the rhCollagen product compared to 68% closure in wounds treated with the reference product. Moreover, rhCollagen treatment induced an early angiogenic response and induced a significantly lower inflammatory response than in the control group. In summary, rhCollagen flowable gel proved to be efficacious in animal wound models and is expected to be capable of reducing the healing time of human wounds. PMID:23259631

  18. [Digital ulcers in systemic scleroderma].

    PubMed

    Belz, D; Hunzelmann, N; Moinzadeh, P

    2014-11-01

    Digital ulcers (DU's) are one of the main symptoms of systemic scleroderma and occur in approximately 60% of all scleroderma patients. Due to possible complications such as infections, gangrene or amputation, they require regular medical attention and a good wound treatment by doctors and nursing staff. A definition of DU's has not yet been established. In 2009 the European League Against Rheumatism (EULAR) published guidelines for the treatment of DU's. An improvement of the healing of active ulcers has been described with Iloprost. Bosentan significantly reduced the frequency of occurrence of new DU's. In some small studies PDE-5 inhibitors appear helpful. Further studies with other therapeutic approaches will follow in the next few years. PMID:25336296

  19. Gastric ulcer treatment: cure of Helicobacter pylori infection without subsequent acid-suppressive therapy: is it effective?

    PubMed

    van Zanten, Sander Veldhuyzen; van der Knoop, Bloeme

    2008-06-01

    Whether it is a requirement to continue with anti-secretory therapy following anti-Helicobacter therapy in H. pylori positive gastric ulcers is an important question. As gastric ulcers tend to heal more slowly than duodenal ulcers, may be asymptomatic or only causing mild symptoms and success at curing H. pylori with current fist line therapies is 80% at best, clinicians will likely err on the side of caution and continue acid suppressive therapy to ensure healing of gastric ulcers. This is certainly recommended when dealing with bleeding ulcers.

  20. Anti-ulcer Activity.

    PubMed

    2016-01-01

    This chapter explains the procedure of ethanol-induced ulcer to check the protective effect of drugs over induced ulcer in rats. Ulcer is defined as the erosion in the lining of the stomach or duodenum and is caused by the disruptions of the gastric mucosal defence and repair systems. Ulceration of stomach is called gastric ulcer and that of duodenum is called duodenal ulcer and together peptic ulcer. In clinical practice, peptic ulcer is one of the most prevalent gastrointestinal disorders, which commonly occurs in developed countries.

  1. [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. PMID:22911414

  2. [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.

  3. Magnet Healing?

    NASA Astrophysics Data System (ADS)

    Finegold, Leonard

    2000-03-01

    Many people are convinced that static magnets—applied to their skin—will heal ills, and many businesses sell such magnets. The biophysics of such healing was reviewed [1] together with the general biophysics of static fields. Birds and insects do use the earth’s magnetic field for navigation. While insect and frog egg development can clearly be influenced by high fields (7 T and 17 T respectively), there is no experimental evidence that small magnetic fields (of less than 0.5 T) might heal, and much evidence that they cannot heal. A puzzle to the physics community is: How to show laypersons that simple magnets (very probably) do not heal, however attractive that idea might be. [1] L. Finegold, The Physics of "Alternative Medicine": Magnet Therapy, The Scientific Review of Alternative Medicine 3:26-33 (1999).

  4. Archetypal healing.

    PubMed

    Jones, D; Churchill, J E

    1994-01-01

    With emphasis on healing versus curing, the authors draw from a wide assortment of treatment methods for psychospiritual relief of pain in the terminally ill. These archetypal methods include: life-review therapy; ministry of presence; clinical hypnosis; myths, symbols, rituals, and community; creative therapies. In life-review therapy, the ill person shares his/her life story with the provider much like the healing rituals of the ancient storyteller did in his community. In the ministry of presence, the caregiver focuses on sharing his vulnerability, not his professional skills. Clinical hypnosis emphasizes the naturalness and simplicity of accessing the unconscious along with problem areas of the hypnoclinician. Myths, symbols, rituals, and community serve as nurturing agents in the intervention of pain, while creative therapies such as music, drama, crafts, and art continue to be powerful healing instruments. Archetypal healing produces relief of pain in the caregiver, as well as the ill, with emphasis on healing versus curing. PMID:8117487

  5. Applied felted foam for plantar pressure relief is an efficient therapy in neuropathic diabetic foot ulcers.

    PubMed

    Zimny, S; Meyer, M F; Schatz, H; Pfohl, M

    2002-10-01

    The application of felted foam is a promising method for plantar pressure reduction in the ulcer region of neuropathic diabetic foot ulcers, but the knowledge of its impact on the wound healing and healing times in foot ulcers compared to conventional methods of pressure relief is sparse. The aim of this study was to assess the effects on the wound healing of felted foam dressings for plantar pressure reduction in the therapy of neuropathic foot ulcers. This prospective cohort study evaluates healing times and wound healing in 61 diabetic patients with neuropathic foot ulcerations. Ulcer healing was assessed by planimetric measurement of the wound area at beginning of the study and after 10 weeks and at least until wound healing. The patients were consecutively enrolled in the study, 27 patients were randomized to the felted foam therapy, and 34 patients were randomized to conventional therapy. In the felted foam group, the initial average wound area was 110.8 +/- 14.4 mm 2 (mean +/- SE), and 2.1 +/- 0.5 mm 2 after ten weeks (p < 0.0001), with an average healing time of 79.6 (95%-CI 75-84) days. In the conventional therapy group, the initial average wound area was 119.2 +/- 13.8 mm 2, and 3.4 +/- 0.7 mm 2 after ten weeks (p < 0.0001). The average healing times was 83.2 (95%-CI 77-90) days. Both with respect to the wound healing process and the healing times, the felted foam technique appears to be as effective as conventional plantar ulcer treatment. We conclude that the felted foam technique is an useful alternative in the therapy of the neuropathic diabetic foot syndrome, especially in patients who are not able to avoid weight-bearing reliably.

  6. A non-randomised, controlled clinical trial of an innovative device for negative pressure wound therapy of pressure ulcers in traumatic paraplegia patients.

    PubMed

    Srivastava, Rajeshwar N; Dwivedi, Mukesh K; Bhagat, Amit K; Raj, Saloni; Agarwal, Rajiv; Chandra, Abhijit

    2016-06-01

    The conventional methods of treatment of pressure ulcers (PUs) by serial debridement and daily dressings require prolonged hospitalisation, associated with considerable morbidity. There is, however, recent evidence to suggest that negative pressure wound therapy (NPWT) accelerates healing. The commercial devices for NPWT are costly, cumbersome, and electricity dependent. We compared PU wound healing in traumatic paraplegia patients by conventional dressing and by an innovative negative pressure device (NPD). In this prospective, non-randomised trial, 48 traumatic paraplegia patients with PUs of stages 3 and 4 were recruited. Patients were divided into two groups: group A (n = 24) received NPWT with our NPD, and group B (n = 24) received conventional methods of dressing. All patients were followed up for 9 weeks. At week 9, all patients on NPD showed a statistically significant improvement in PU healing in terms of slough clearance, granulation tissue formation, wound discharge and culture. A significant reduction in wound size and ulcer depth was observed in NPD as compared with conventional methods at all follow-up time points (P = 0·0001). NPWT by the innovative device heals PUs at a significantly higher rate than conventional treatment. The device is safe, easy to apply and cost-effective.

  7. Incidence and management of ulcers in diabetic Charcot feet.

    PubMed

    Larsen, K; Fabrin, J; Holstein, P E

    2001-09-01

    This study followed 115 patients with diabetes--who between them had 140 feet with Charcot's arthropathy--over six to 114 months (median: 48). A total of 43 patients (37%) developed ulcers in 53 feet. Their treatment was multifactorial. An offloading regimen was adopted, with the use of crutches and therapeutic sandals with soft, individually moulded insoles, followed by adjusted or bespoke shoes. Recalcitrant ulcers were treated with surgery in 16 patients (37%). Antibiotics were needed by 21 patients (49%). The incidence of ulceration was 17% per year. The median time interval between the acute component of Charcot's arthropathy and ulcer development was 36 months (range: 0-120 months). In seven patients, the ulcer developed during the acute phase. In 12 patients the ulcers were localised to the rockerbottom deformity in the mid-foot region, but in 31 patients other regions were affected. Dynamic footprint analysis was used to help adjust the offloading shoe/insole on the rockerbottom deformity. Such ulcers took twice as long to heal as other ulcers. Surgical treatment comprised: major amputation (two patients), arthrodesis for unstable ankle (three patients), toe amputations (seven patients), resection of the rockerbottom deformity (one patient) and other revisions (three patients). One patient died with an unhealed ulcer. There is a four-fold risk of ulcers in diabetic Charcot deformity compared with the overall risk of foot ulcers in diabetic feet. Healing was achieved in 40 patients (93%). The surgical intervention rate of 37% in ulcer cases in Charcot feet was low compared with the literature.

  8. [Pathophysiological aspects of wound healing in normal and diabetic foot].

    PubMed

    Maksimova, N V; Lyundup, A V; Lubimov, R O; Melnichenko, G A; Nikolenko, V N

    2014-01-01

    The main cause of long-term healing of ulcers in patients with diabetic foot is considered to be direct mechanical damage when walking due to reduced sensitivity to due to neuropathy, hyperglycemia, infection and peripheral artery disease. These factors determine the standard approaches to the treatment of diabeticfoot, which include: offloading, glycemic control, debridement of ulcers, antibiotic therapy and revascularization. Recently, however, disturbances in the healing process of the skin in diabetes recognized an additional factor affecting the timing of healing patients with diabetic foot. Improved understanding and correction of cellular, molecular and biochemical abnormalities in chronic wound in combination with standard of care for affords new ground for solving the problem of ulcer healing in diabetes.

  9. Wound Healing and Care

    MedlinePlus

    ... heal through natural scar formation. continue The Healing Process Before healing begins, the body gears up to ... dry at all times to help the healing process. As the body does its healing work on ...

  10. How wounds heal

    MedlinePlus

    ... How scrapes heal; How puncture wounds heal; How burns heal; How pressure sores heal; How lacerations heal ... from germs. Not all wounds bleed. For example, burns, some puncture wounds, and pressure sores do not ...

  11. 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.

  12. Use of a strontium-enriched calcium phosphate cement in accelerating the healing of soft-tissue tendon graft within the bone tunnel in a rabbit model of anterior cruciate ligament reconstruction.

    PubMed

    Kuang, G M; Yau, W P; Lu, W W; Chiu, K Y

    2013-07-01

    We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft-bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL-bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft.

  13. Comparing the efficacies of alginate, foam, hydrocolloid, hydrofiber, and hydrogel dressings in the management of diabetic foot ulcers and venous leg ulcers: a systematic review and meta-analysis examining how to dress for success.

    PubMed

    Saco, Michael; Howe, Nicole; Nathoo, Rajiv; Cherpelis, Basil

    2016-01-01

    Diabetic foot ulcers and venous leg ulcers are chronic wounds frequently encountered by dermatologists. Choosing appropriate wound dressings can effectively promote wound healing and potentially reduce morbidity and financial burden experienced by patients. The objective of our systematic review and meta-analysis was to evaluate wound healing efficacies of synthetic active dressings in diabetic foot ulcer and venous leg ulcer management. For data collection, PubMed, Embase, Cochrane Library, CINAHL, and clinicaltrials.gov online databases were searched from database inception to 10 May 2015. Fixed and random effects modeling were used to calculate pooled risk ratios for complete ulcer healing from pairwise dressing comparisons. The results of our review showed moderate-quality level evidence that hydrogels were more effective in healing diabetic foot ulcers than basic wound contact dressings (RR 1.80 [95% CI, 1.27-2.56]). The other dressing comparisons showed no statistically significant differences between the interventions examined in terms of achieving complete diabetic foot ulcer healing. Non-adherent dressings were more cost-effective than hydrofiber dressings for diabetic foot ulcers in terms of mean total cost per patient of the dressings themselves. All venous leg ulcer pairwise dressing comparisons showed equivalent dressing efficacies in terms of promoting complete ulcer healing. Overall, most synthetic active dressings and traditional wound dressings are equally efficacious in treating diabetic foot ulcers and venous leg ulcers. For treating diabetic foot ulcers, hydrogels are more efficacious than basic wound contact dressings, and non-adherent dressings are more cost-effective than hydrofiber dressings. Ultimately, dressing choice should be tailored to the wound and the patient. PMID:27617934

  14. 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.

  15. [Round table discussion. Ulcer - vagus - gastrin].

    PubMed

    1976-03-01

    1. Both gastrin and the vagus nerve play a part in the pathogenesis of the duodenal ulcer. Which of these two factors is of greater significance--this problem is still subject to discussion as is the question whether other factors such as duodenal neutralization are more important than hitherto assumed. 2. At this time no reliable and harmless drugs that speed up the healing of duodenal ulcers and prevent relapses are yet available. Candidates for this are H2 receptor blockers, prostaglandines and possibly substances resembling secretin. 3. Only some of the participants considered it necessary to do endoscopic and radiological follow-ups in duodenal ulcers. 4. Proximal gastric vagotomy for the treatment of duodenal ulcers is still undergoing clinical trials. At present this method should only be used by surgeons with a special interest in gastric surgery who also dispose of the technology and the staff for careful postoperative checks on these patients. The advantages of proximal gastric vagotomy consist in sparing truncation, low mortality and good functional results. 5. In gastric ulcers--contrary to duodenal ones--malignancy should always be suspected. If medical treatment does not lead to complete remission within a few months, surgery must be performed. 6. Many surgeons still prefer resection to vagotomy and excision in the management of gastric ulcers.

  16. [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.

  17. [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. PMID:27312831

  18. Short-term multimodal phototherapy approach in a diabetic ulcer patient.

    PubMed

    Chandrasekaran, Baskaran; Chettri, Remon; Agrawal, Neha; Sathyamoorthy, Chandrakumar

    2012-06-01

    Foot ulcers increase morbidity and mortality in diabetic patients. Due to poor healing factors, surgical wound healing is questionable in diabetic patients. We report a patient with insulin-dependent diabetes mellitus, sensory neuropathy and microangiopathy, who had an infected stump of the right three middle digits and subsequent transmetatarsal amputation. The infected postoperative ulcer was treated with complex phototherapy, including laser and ultraviolet C (UVC) radiations. A total of 23 sessions of low-intensity laser therapy and UVC irradiation were administered over a five-week period. The infected surgical wound healed completely. During the three-month follow-up period, there was no recurrence of the ulcer, although the patient's metabolic profile remained unstable. Multimodal therapy combining UVC and laser may constitute a useful and side-effect-free alternative treatment modality for the induction of wound healing post metatarsal amputation in patients with unhealed diabetic ulcers. PMID:22711049

  19. Treatment of ulcers with ablative fractional lasers.

    PubMed

    Morton, Laurel M; Dover, Jeffrey S; Phillips, Tania J; Krakowski, Andrew C; Uebelhoer, Nathan S

    2015-03-01

    Chronic, nonhealing ulcers are a frustrating therapeutic challenge and investigation of innovative therapies continues to be an important research pursuit. One unique and newly applied intervention is the use of ablative fractional lasers. This technology has recently been employed for the treatment of hypertrophic, disfiguring and function-limiting scars, and was first shown to induce healing of chronic wounds in patients with persistent ulcers and erosions within traumatic scars. Recent reports suggest it may be applicable for other types of chronic wounds as well. The mechanism of action for this modality remains to be elucidated but possible factors include laser-induced collagen remodeling, photomicrodebridement and disruption of biofilms, and induction of a proper wound healing cascade.

  20. Low-intensity pulsed ultrasound accelerated bone-tendon junction healing through regulation of vascular endothelial growth factor expression and cartilage formation.

    PubMed

    Lu, Hongbin; Qin, Ling; Cheung, Winghoi; Lee, Kwongman; Wong, Wannar; Leung, Kwoksui

    2008-08-01

    The purpose of this study was to use our established partial patellectomy rabbit model to study the effects of low-intensity pulsed ultrasound (LIPUS) on patella-patellar tendon (PPT) junction repair through hypothesized pathways including regulation of vascular endothelial growth factor (VEGF) and chondrogenesis. Standard partial patellectomy was conducted in sixty-four 18 wk-old rabbits that were subsequently divided into LIPUS and control group. The PPT complex was harvested at week 2, 4, 8 and 16 postoperatively (n = 8 for each time point) for preparation of sagittal sections that were evaluated for angiogenesis by analyzing VEGF expression and chondrogenesis. Results showed differences in the pattern of VEGF expression between LIPUS and control groups during the entire healing process, i.e., significant differences in the average percentage of VEGF expression found in between the LIPUS and the control groups. At postoperative week 4, the chondrocytes and osteoblasts in woven bone expressed significantly more VEGF in the LIPUS group than that in the control group (35.6% +/- 7.0% versus 28.0% +/- 4.6%, p < 0.05). Compared with the control group, the development of cartilaginous metaplasia was found more advanced in the scar tissue next to the articular cartilage of the remaining patella in the LIPUS group that was expressed with VEGF in the chondrocytes (38.8% +/- 12.3%). However, the specimens in the control group just showed the similar cartilaginous metaplasia region until postoperative week 8. Histomorphometry revealed thicker fibrocartilage zone and larger cartilaginous metaplasia field at PPT healing interface in LIPUS group compared with those of the control group at week 8 and 16. In conclusion, this was the first quantitative study to demonstrate that LIPUS improved B-T junction healing through regulation of VEGF expression in early healing phase and subsequent chondrogenesis.

  1. Amino acids from Mytilus galloprovincialis (L.) and Rapana venosa molluscs accelerate skin wounds healing via enhancement of dermal and epidermal neoformation.

    PubMed

    Badiu, Diana L; Luque, Rafael; Dumitrescu, Elena; Craciun, Anca; Dinca, Danut

    2010-02-01

    Wound healing consists of re-epithelialization, contraction and formation of granulation and scar tissue. Amino acids from proteins are involved in these events, but their exact roles are not well understood. The present study was undertaken to investigate the anti-inflammatory effects of some amino acids from two molluscs, Mytilus galloprovincialis (L.) (Mediterranean mussel) and Rapana venosa (hard shell-clam) employed in induced skin burn injuries in Wistar rats. The treatment was evaluated in terms of essential amino acids composition which rendered the extracts very efficient in healing skin burns. The healing process was examined by periodic acid Schiff's, Verhoeff's Van Gieson and immunohistochemistry stains for collagen IV, CD 34 and CD 117 antibodies. According to the obtained results, as expressed by histological studies, the most abundant blood vessels, collagen fibres, basal and stem cells were found only for treated animals with amino acids from Rapana venosa extracts. The rich composition of amino acids from the two molluscs merits consideration as therapeutic agents in the treatment of skin burns.

  2. Astragulus polysaccharide-loaded fibrous mats promote the restoration of microcirculation in/around skin wounds to accelerate wound healing in a diabetic rat model.

    PubMed

    Yang, Ye; Wang, Fei; Yin, Dengke; Fang, Zhaohui; Huang, Lu

    2015-12-01

    Tissue engineering scaffolds (TES) can carry numerous biomacromolecules and cells, and they have been widely used in diabetic skin wound healing with positive effects. However, the bioactive retention of biomacromolecules and cells during fabrication and storage is still a factor restricting their use. Moreover, impaired blood supply in/around poorly healing diabetic skin wounds has not been considered. In the present study, a bioactive natural substance of Astragalus polysaccharide (APS), which has stable and confirmed effects on endothelial protection, was embedded into fibrous TES by electrospinning. The administration of APS-loaded TES on the skin wound in a diabetic rat model led to a dose-dependent promotion in skin blood flow around wounds and an increase in endoglin expression and microvessel density in regenerated skin tissues. Furthermore, the higher loading of APS in TES led to faster collagen synthesis, appendage and epidermal differentiation, and wound closure. In summary, the combination of APS with TES is a potentially novel therapeutic strategy for diabetic skin wound healing, as it not only mimics the ultrastructure of extracellular matrixes but also restores skin microcirculation.

  3. Stem Cell-Mediated Accelerated Bone Healing Observed with In Vivo Molecular and Small Animal Imaging Technologies in a Model of Skeletal Injury

    PubMed Central

    Lee, Sheen-Woo; Padmanabhan, Parasuraman; Ray, Pritha; Gambhir, Sanjiv Sam; Doyle, Timothy; Contag, Christopher; Goodman, Stuart B.; Biswal, Sandip

    2014-01-01

    Adult stem cells are promising therapeutic reagents for skeletal regeneration. We hope to validate by molecular imaging technologies the in vivo life cycle of adipose-derived multipotent cells (ADMCs) in an animal model of skeletal injury. Primary ADMCs were lentivirally transfected with a fusion reporter gene and injected intravenously into mice with bone injury or sham operation. Bioluminescence imaging (BLI), [18F]FHBG (9-(fluoro-hydroxy-methyl-butyl-guanine)-micro-PET, [18F]Fluoride ion micro-PET and micro-CT were performed to monitor stem cells and their effect. Bioluminescence microscopy and immunohistochemistry were done for histological confirmation. BLI showed ADMC’s traffic from the lungs then to the injury site. BLI microscopy and immunohistochemistry confirmed the ADMCs in the bone defect. Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7 (p <0.05). Systemically administered ADMC’s traffic to the site of skeletal injury and facilitate bone healing, as demonstrated by molecular and small animal imaging. Molecular imaging technologies can validate the usage of adult adipose tissue-derived multipotent cells to promote fracture healing. Imaging can in the future help establish therapeutic strategies including dosage and administration route. PMID:18752273

  4. Recurrent oral ulcers--an overview.

    PubMed

    Gaffar, A

    2001-01-01

    Recurrent oral ulcers (ROUs) are the most common oral mucosal disease. The etiology of ROUs is complex. The factors include mechanical trauma, genetics, stress, smoking, and viral and bacterial infections. Treatment modalities depend on the differential diagnosis of ROUs and could consist of antimicrobial agents, anti-inflammatory agents, immunomodulators, or over-the-counter medications. New therapy available in the form of a coating polymer, Colgate ORABASE Soothe.N.Seal, is clinically proven to provide rapid relief and healing of ROUs.

  5. Diabetic foot ulcer management: the podiatrist's perspective.

    PubMed

    Turns, Martin

    2013-12-01

    Diabetic foot complications result from two broad pathologies-neuropathic and neuro-ischaemic feet. It is important for diabetic patients to have at least a yearly review of foot ulcer risk factors, and they should have a corresponding risk classification agreed based on this assessment. Diabetic foot ulcer assessment should include a wound classification tool, which can give an indication of wounds at greater risk of non-healing or amputation. The treatment of diabetic foot ulcers should be part of a comprehensive care plan that should also include treatment of infection, frequent debridement (if deemed appropriate by a skilled specialist clinician), biomechanical offloading, blood glucose control and treatment of comorbidities. Clinicians should base dressing selection on the wound's location, size and depth, amount of exudate, presence of infection or necrosis and the condition of the surrounding tissue.

  6. Treatment of cutaneous ulcers with benzoyl peroxide.

    PubMed Central

    Pace, W. E.

    1976-01-01

    Benzoyl peroxide, a powerful organic oxidizing agent, was applied topically according to a carefully developed technique to cutaneous ulcers of different types. The healing time was shortened greatly by the rapid development of healthy granulation tissue and the quick ingrowth of epithelium. Exceptionally large pressure ulcers with deep cavities, undercut edges and sinus tracts were sucessfully treated, as were stasis ulcers of long duration resistant to all other therapy. There were only 13 treatment failures among the 133 cases. The slow, sustained release of oxygen by benzoyl peroxide was though to be responsible for the success. The only complications were contact irritant dermatitis in 3% and contact allergic dermatitis in 2% of patients treated. Images FIG. 2 FIG. 3 FIG. 4 PMID:1000442

  7. [Pressure ulcers and undernutrition--screening and assessment of nutritional status].

    PubMed

    Tran, C; Roulet, M; Guex, E; Coti Bertrand, P

    2008-03-01

    Acquired pressure ulcer is associated with significant human, economic and functional consequences. Its prevalence varies between 3 and 23% in a community hospital and between 7 and 54% in an elderly home residency. Pressure ulcer healing is a complex process which involves numerous cellular and molecular mechanisms. An altered nutritional status is a contributing factor in the development of pressure ulcers and the delay in pressure ulcer healing. The key to management of undernutrition is screening and early intervention. According to the gravity of undernutrition, various degrees of intervention will be required. Systematic oral supplementation with various nutrients may provide benefit in the prevention of pressure ulcers, but further studies have to be completed in human subjects prior to being recommended for the treatment of pressure ulcers.

  8. [Ulcer surgery - what remains?].

    PubMed

    Hölscher, A H; Bollschweiler, E; Mönig, S P

    2006-06-01

    Ulcer surgery today concentrates on the complications of chronic ulcer disease, especially ulcer perforation and endoscopically uncontrollable ulcer bleeding. In this case the laparoscopic or open closure of the gastroduodenal defect or local hemostasis of the bleeding ulcer by laparotomy are the main aims of surgery. Elective operations due to recurrent gastric or duodenal ulcers have become rare. An indication for gastric ulcer resistant to conservative therapy could be persisting suspicion of malignancy whereas in duodenal ulcer gastric outlet obstruction represents a reason for surgery. If these indications are confirmed the classic procedures of gastric resection like Billroth I and Billroth II are performed whereas vagotomy is no longer used. Altogether ulcer surgery has become very safe although it is practiced quite rarely.

  9. 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. PMID:23220707

  10. Managing pressure ulcers and moisture lesions with new hydrocolloid technology.

    PubMed

    Linthwaite, Adele; Bethell, Elaine

    In efforts to reduce the number of avoidable pressure ulcers in a large trust, a number of initiatives have taken place to increase staff awareness about the importance of preventing and treating pressure ulcers and moisture lesions. New documentation, the use of the 'Think Pink' folders and a social media campaign have all proved successful in seeing the number of avoidable pressure ulcers reported within the trust reduce. As part of this initiative an evaluation took place of a new hydrocolloid dressing. This proved effective at reducing healing times, reducing dressing spend and facilitating regular inspection of the affected areas. PMID:27126753

  11. Platelet-Rich Plasma Combined With Skin Substitute for Chronic Wound Healing: A Case Report

    PubMed Central

    Knox, Rebecca L.; Hunt, Allen R.; Collins, John C.; DeSmet, Marie; Barnes, Sara

    2006-01-01

    Abstract: Contemporary management of chronic wounds focuses on improving natural healing and individualization of treatment. Incorporating multiple therapies has become increasingly common. Of interest are autologous growth factors, which are especially important in chronic wound healing and may contribute to tissue formation and epithelialization. Autologous platelet concentrate or platelet-rich plasma (PRP) is a concentration of at least five autologous growth factors and has been shown to accelerate wound healing and may have infection-fighting properties. Chronic wound healing is complicated by both decreased growth factor availability and infection, making PRP use valuable in these types of wounds. In this report, the use of PRP therapy alone and in combination with a bioengineered skin substitute as a platelet-rich tissue graft in a chronic, non-healing wound is detailed. Over 27 weeks, the patient received multiple therapies in attempts to heal a severe decubitus ulcer of the sacrum. The introduction of PRP therapy at Week 14 led to a 26% reduction in wound depth over 4 weeks. At Week 19, PRP therapy was combined with a powdered skin substitute to create a platelet-rich tissue graft. The combination brought dramatic results, eliminating wound tunneling and reducing the wound dimensions from 6.2 cm long × 6.7 cm wide × 2.7 cm deep to 5.0 cm long × 6.0 cm wide × 1.4 cm deep. The promising observations from this case report indicate that further study on the combining of PRP therapy and skin substitutes is necessary. PMID:17089514

  12. Effect of sucralfate on gastric emptying in duodenal ulcer patients

    SciTech Connect

    Petersen, J.M.; Caride, V.J.; Prokop, E.K.; Troncale, F.; McCallum, R.W.

    1985-05-01

    Duodenal ulcer (DU) patients may have accelerated gastric emptying (GE) suggesting that there is an increase in unbuffered gastric acid reaching the duodenum contributing to DU disease. Aluminum-containing antacids were shown to delay GE. The authors' aim was to investigate whether another aluminum-containing compound, Sucralfate, affects GE in normal and DU patients. Nine normal volunteers and 10 patients with documented DU disease were studied. For each test the subject ingested a meal composed of chicken liver Tc-99m-S-C mixed with beef stew and eaten with 4 oz. of water labelled with 100..mu..Ci of III-in-DTPA. On two separate days, subjects received 1 gram of Sucralfate (190 mg of aluminum per gram) or placebo in a randomized double-blind fashion one hour prior to the test meal. GE of liquids and solids in normal subjects was not significantly changed by Sucralfate. Sucralfate in the DU patients significantly slowed liquid emptying in the initial 40 min and solid food throughout the study compared to placebo (p<0.05). This paper summarizes that; GE of solids but not liquids is accelerated in DU patients compared to normal subjects; and sucralfate delays GE of both liquid and solid components of a meal in DU patients but has no effect on GE in normals. The authors conclude that a slowing of gastric emptying possibly mediated by aluminum ions, may be one mechanism by which Sucralfate enhances healing and decreases recurrence of DU.

  13. [Indications for surgical treatment of hard scarring gastric ulcers].

    PubMed

    Durleshter, V M; Korochanskaia, N V; Serikova, S N

    2014-01-01

    It was done the comparative analysis of the morphofunctional state of the upper gastrointestinal tract between 350 patients with effective conservative treatment and 104 patients with hard scarring gastric ulcers. The analysis identified the predictors of ineffective medical treatment and led to deliver the indications for timely surgical treatment. It was identified the next indications for planned organ-preserving surgical treatment of patients with hard scarring gastric ulcers: penetrating and non-healing ulcers with large or gigantic size in case of the adequate medical therapy, high-grade dysplasia and colonic metaplasia of the gastric epithelium in the borders or fundus of the ulcer,ulcers combination with fixed cardio-fundal or fundo-corporal hiatal hernias; hypotonic-hypokinetic type of the gastric and duodenal activity with the development of gastrostasis and pronounced duodenogastric reflux.

  14. Role of Histologic Inflammation in the Natural History of Ulcerative Colitis.

    PubMed

    Patil, Deepa T; Moss, Alan C; Odze, Robert D

    2016-10-01

    The goals of therapy for ulcerative colitis have moved from symptom improvement to mucosal healing, and finally histologic resolution. The natural history of histologic inflammation in ulcerative colitis progresses from initial cellular infiltration to architectural disruption and recovery on medical therapy. Many studies have linked histologic changes to clinical outcomes, providing prognostic value to histologic abnormalities. This review covers all these components. PMID:27633592

  15. Emergency ulcer surgery.

    PubMed

    Lee, Constance W; Sarosi, George A

    2011-10-01

    The rate of elective surgery for peptic ulcer disease has been declining steadily over the past 3 decades. During this same period, the rate of emergency ulcer surgery rose by 44%. This means that the gastrointestinal surgeon is likely to be called on to manage the emergent complications of peptic ulcer disease without substantial experience in elective peptic ulcer disease surgery. The goal of this review is to familiarize surgeons with our evolving understanding of the pathogenesis, epidemiology, presentation, and management of peptic ulcer disease in the emergency setting, with a focus on peptic ulcer disease-associated bleeding and perforation.

  16. Noninfectious genital ulcers.

    PubMed

    Kirshen, Carly; Edwards, Libby

    2015-12-01

    Noninfectious genital ulcers are much more common than ulcers arising from infections. Still, it is important to take a thorough history of sexual activity and a sexual abuse screen. A physical exam should include skin, oral mucosa, nails, hair, vulva, and vaginal mucosa if needed. The differential diagnosis of noninfectious genital ulcers includes: lipschütz ulcers, complex aphthosis, Behçet's syndrome, vulvar metastatic Crohn's disease, hidradenitis suppurativa, pyoderma gangrenosum, pressure ulcers, and malignancies. It is important to come to the correct diagnosis to avoid undue testing, stress, and anxiety in patients experiencing genital ulcerations.

  17. Conservative management of ulcerated haemangioma--twenty years experience.

    PubMed

    Pandey, Anand; Gangopadhyay, Ajay Narayan; Sharma, Shiv Prasad; Kumar, Vijayendra; Gopal, Saroj Chooramani; Gupta, Dinesh Kumar

    2009-02-01

    Ulceration is the most common complication of haemangioma and occurs in 5-15% of cases. The present study was carried out to evaluate the clinical features of ulcerated haemangioma and efficacy of the management protocol adopted by us over a period of 20 years. All patients with ulcerated haemangioma were evaluated on the basis of age at presentation, sex, rural or urban distribution and site of haemangioma. Treatment included application of topical antibiotic and systemic antibiotic and analgesic for pain. The total number of patients was 608. The male to female ratio was 1: 2.28. The rural:urban distribution was 2.43:1. The most common site of involvement was head and neck. Mean age of patients was 5.60 +/- 2.44 months. Mean size of haemangioma and ulceration was 47.30 +/- 20.67 cm(2) and 7.49 +/- 4.52 cm(2), respectively. The mean time for ulcer healing was 40.06 +/- 19.41 days. Ulcer size of more than 10 cm(2) took more time to heal. Response to treatment was satisfactory. Ulcerated haemangioma usually occurs before completion of 1 year of age; hence, every patient with haemangioma needs careful attention. Adequate treatment and regular follow up brings satisfactory response in the patients.

  18. Healing in the irradiated wound

    SciTech Connect

    Miller, S.H.; Rudolph, R. )

    1990-07-01

    Poor or nonhealing of irradiated wounds has been attributed to progressive obliterative endarteritis. Permanently damaged fibroblasts may also play an important part in poor healing. Regardless of the cause, the key to management of irradiated skin is careful attention to prevent its breakdown and conservative, but adequate, treatment when wounds are minor. When wounds become larger and are painful, complete excision of the wound or ulcer is called for and coverage should be provided by a well-vascularized nonparasitic distant flap.16 references.

  19. Wound size measurement of lower extremity ulcers using segmentation algorithms

    NASA Astrophysics Data System (ADS)

    Dadkhah, Arash; Pang, Xing; Solis, Elizabeth; Fang, Ruogu; Godavarty, Anuradha

    2016-03-01

    Lower extremity ulcers are one of the most common complications that not only affect many people around the world but also have huge impact on economy since a large amount of resources are spent for treatment and prevention of the diseases. Clinical studies have shown that reduction in the wound size of 40% within 4 weeks is an acceptable progress in the healing process. Quantification of the wound size plays a crucial role in assessing the extent of healing and determining the treatment process. To date, wound healing is visually inspected and the wound size is measured from surface images. The extent of wound healing internally may vary from the surface. A near-infrared (NIR) optical imaging approach has been developed for non-contact imaging of wounds internally and differentiating healing from non-healing wounds. Herein, quantitative wound size measurements from NIR and white light images are estimated using a graph cuts and region growing image segmentation algorithms. The extent of the wound healing from NIR imaging of lower extremity ulcers in diabetic subjects are quantified and compared across NIR and white light images. NIR imaging and wound size measurements can play a significant role in potentially predicting the extent of internal healing, thus allowing better treatment plans when implemented for periodic imaging in future.

  20. Consensus opinion of a North American Working Group regarding the classification of digital ulcers in systemic sclerosis.

    PubMed

    Baron, Murray; Chung, Lorinda; Gyger, Geneviève; Hummers, Laura; Khanna, Dinesh; Mayes, Maureen D; Pope, Janet E; Shah, Ami A; Steen, Virginia D; Steele, Russell; Tatibouet, Solène; Herrick, Ariane; Müller-Ladner, Ulf; Hudson, Marie

    2014-02-01

    The objectives of this study were to develop a standard classification of digital ulcers (DUs) in systemic sclerosis (SSc) for use in observational or therapeutic studies and to assess the reliability of these definitions as well as of the measurement of ulcer area. Ten North American rheumatologists with expertise in SSc reviewed multiple photos of DUs, examined four SSc subjects with DUs, and came to a consensus on the definitions for digital, active, healed, and indeterminate ulcers. These ten raters then examined the right hand of ten SSc subjects twice and the left hand once to classify ulcers and to measure ulcer area. Weighted and Fleiss kappa were used to calculate intra- and interrater agreement on classification of ulcers, and intraclass correlation coefficient (ICC) was used to assess agreement on ulcer area. Because the traditional ICC calculations relied on a small number of ulcers, ICCs were recalculated using the results of linear mixed models to evaluate the variance components of observations on all the data. Intrarater kappa for classifying DU as not an ulcer/healed ulcer versus active/indeterminate ulcer was substantial (0.76), and interrater kappa was moderate (0.53). The ICC for ulcer area using the linear mixed models was moderate both for intrarater (0.57) and interrater (0.48) measurements. A consensus for the classification of DUs in SSc was developed, and after a training session, rheumatologists with expertise in SSc are able to reliably classify DUs and to measure ulcer area.

  1. Acute genital ulcers

    PubMed Central

    Delgado-García, Silvia; Palacios-Marqués, Ana; Martínez-Escoriza, Juan Carlos; Martín-Bayón, Tina-Aurora

    2014-01-01

    Acute genital ulcers, also known as acute vulvar ulcers, ulcus vulvae acutum or Lipschütz ulcers, refer to an ulceration of the vulva or lower vagina of non-venereal origin that usually presents in young women, predominantly virgins. Although its incidence is unknown, it seems a rare entity, with few cases reported in the literature. Their aetiology and pathogenesis are still unknown. The disease is characterised by an acute onset of flu-like symptoms with single or multiple painful ulcers on the vulva. Diagnosis is mainly clinical, after exclusion of other causes of vulvar ulcers. The treatment is mainly symptomatic, with spontaneous resolution in 2 weeks and without recurrences in most cases. We present a case report of a 13-year-old girl with two episodes of acute ulcers that fit the clinical criteria for Lipschütz ulcers. PMID:24473429

  2. Peptic Ulcer Disease

    MedlinePlus

    ... stomach and duodenum to diagnose or treat disease. Erosion – a very shallow sore, similar to an abrasion ... Ulcer – an open sore. Ulcers are deeper than erosions. Author(s) and Publication Date(s) Sean P. Caufield, MD, ...

  3. Ulcer emergencies (image)

    MedlinePlus

    Peptic ulcers may lead to emergency situations. Severe abdominal pain with or without evidence of bleeding may indicate a perforation of the ulcer through the stomach or duodenum. Vomiting of a substance that resembles coffee grounds, ...

  4. Acute genital ulcers.

    PubMed

    Delgado-García, Silvia; Palacios-Marqués, Ana; Martínez-Escoriza, Juan Carlos; Martín-Bayón, Tina-Aurora

    2014-01-28

    Acute genital ulcers, also known as acute vulvar ulcers, ulcus vulvae acutum or Lipschütz ulcers, refer to an ulceration of the vulva or lower vagina of non-venereal origin that usually presents in young women, predominantly virgins. Although its incidence is unknown, it seems a rare entity, with few cases reported in the literature. Their aetiology and pathogenesis are still unknown. The disease is characterised by an acute onset of flu-like symptoms with single or multiple painful ulcers on the vulva. Diagnosis is mainly clinical, after exclusion of other causes of vulvar ulcers. The treatment is mainly symptomatic, with spontaneous resolution in 2 weeks and without recurrences in most cases. We present a case report of a 13-year-old girl with two episodes of acute ulcers that fit the clinical criteria for Lipschütz ulcers.

  5. Helicobacter pylori infection and duodenal ulcer disease.

    PubMed

    Tytgat, G N; Noach, L A; Rauws, E A

    1993-03-01

    H. pylori is undoubtedly the dominant factor in the multifactorial peptic ulcer diathesis. We should not ignore the other contributing factors but rather try to identify how they interact with the organism and initiate the ulcerative process. The interplay of acid attack and mucosal defence is modulated by genetics, gender, blood group, smoking, age, and various physiologic considerations, which include acid output. These and other considerations probably explain the discrepancy between the high frequency of H. pylori infection in the population and the comparatively small proportion of individuals who develop a DU. Most agents used in DU are aimed at reducing acid secretion and achieve healing by minimizing acid attack. Such treatments, however, have no effect on H. pylori status and do not remedy the underlying gastroduodenitis. The mucosa therefore remains ill and vulnerable. After cessation of acid suppressive therapy, ulcer relapse is likely. Goodwin has likened the inflamed mucosa to a leaking roof, in which temporary dryness (healing) is assured if the rain (acid) is removed but permanent protection can be achieved only by mending the roof through healing of the mucosa. Therefore, therapy that fails to address the role of H. pylori in the causation of the mucosal inflammation, which predisposes to ulceration, is likely to confer only short-term benefit. Eradication of the infection has been shown beyond doubt to markedly alter the natural history of the disease, a number of series showing no recurrence at the end of 1 year, compared with a natural recurrence of > 70%. The economic savings after not only eradication but even suppression of H. pylori in DU disease have been estimated to be enormous. Despite these striking findings indicating H. pylori inflammation as the dominant factor in the DU diathesis and the possibilities of cure after H. pylori eradication, a large proportion of the medical community is still not willing to accept the consequences

  6. What's new: Management of venous leg ulcers: Approach to venous leg ulcers.

    PubMed

    Alavi, Afsaneh; Sibbald, R Gary; Phillips, Tania J; Miller, O Fred; Margolis, David J; Marston, William; Woo, Kevin; Romanelli, Marco; Kirsner, Robert S

    2016-04-01

    Leg ulcerations are a common problem, with an estimated prevalence of 1% to 2% in the adult population. Venous leg ulcers are primarily treated in outpatient settings and often are managed by dermatologists. Recent advances in the diagnosis and treatment of leg ulcers combined with available evidence-based data will provide an update on this topic. A systematized approach and the judicious use of expensive advanced therapeutics are critical. Specialized arterial and venous studies are most commonly noninvasive. The ankle brachial pressure index can be performed with a handheld Doppler unit at the bedside by most clinicians. The vascular laboratory results and duplex Doppler findings are used to identify segmental defects and potential operative candidates. Studies of the venous system can also predict a subset of patients who may benefit from surgery. Successful leg ulcer management requires an interdisciplinary team to make the correct diagnosis, assess the vascular supply, and identify other modifiable factors to optimize healing. The aim of this continuing medical education article is to provide an update on the management of venous leg ulcers. Part I is focused on the approach to venous ulcer diagnostic testing.

  7. Clinical Examination and Treatment of a Leg Ulcer Caused by a Stingray Puncture.

    PubMed

    Fino, Pasquale; Onesti, Maria Giuseppina; Felli, Antonina; Scuderi, Nicolò

    2015-06-01

    The most frequent causes of leg ulcers include venous incompetency (superficial and deep), arterial insufficiency, trauma, vasculitis, and neoplasm. Leg ulcers from injury by stingrays are quite rare. In this case report, we describe a leg ulcer caused by a stingray sting complicated by infection, which healed completely without surgery. In addition, since there few cases in the literature describing such traumas, we performed a comprehensive review of the literature. Important is the fact that the wound healing was complete without resorting to surgery, but only with a correct targeted antibiotic therapy and the use of a collagenase, which has the particularity of having hyaluronic acid as a component. PMID:24879461

  8. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats

    PubMed Central

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-01-01

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways. PMID:27271793

  9. A new option for endovascular treatment of leg ulcers caused by venous insufficiency with fluoroscopically guided sclerotherapy

    PubMed Central

    Garcarek, Jerzy; Falkowski, Aleksander; Rybak, Zbigniew; Jargiello, Tomasz; Łokaj, Marek; Czapla, Norbert

    2015-01-01

    Introduction Ulcers of lower legs are the most bothersome complication of chronic venous insufficiency (CVI). Aim To assess the effectiveness of endovascular fluoroscopically guided sclerotherapy for the treatment of venous ulcers. Material and methods Thirty-eight limbs in 35 patients with crural venous ulcers were treated with guided sclerotherapy under the control of fluoroscopy. Patients with non-healing ulcers in the course of chronic venous insufficiency, with and without features of past deep vein thrombosis, were qualified for the study. Doppler ultrasound and dynamic venography with mapping of venous flow were performed. Ambulatory venous pressure measurements, leg circumference and varicography were performed just before and following the procedure. Results In 84% of cases, ulcers were treated successfully and healed. Patients with post-thrombotic syndrome (n = 17) healed in 13 (76.5%) cases, whereas patients without post-thrombotic syndrome (n = 21) healed in 19 (90.5%) cases. The mean time of healing of an ulcer for all patients was 83 days (in the first group it was 121 days and in the second group 67 days). Recurrence of an ulcer was observed in 10 limbs: 6 cases in the first group and 4 cases in the second group. Occurrence of deep vein thrombosis associated with the procedure was not observed. Temporary complications were reported but none giving a serious clinical outcome. Conclusions Endovascular fluoroscopically guided sclerotherapy can be an alternative method of treatment of venous ulcers, especially in situations when surgical procedures or other options of treatment are impossible. PMID:26649090

  10. [Healing "booster" dressings].

    PubMed

    Fromantin, Isabelle; Téot, Luc; Meaume, Sylvie

    2011-09-01

    The relationship between the dressing and the wound is vital to clinical effectiveness. The more-or-less standard wound-surface coverings have been replaced with initial dressings, referred to as modern dressings, which contain an oily and sticky compound. They provide a moist medium by applying the basic mechanistic principles (liquid absorption and release). Other types of products and techniques modify the behaviour of wound cells by acting directly through irritation, biochemical stimulation or genetic modification of the cells, which accelerates the healing process.

  11. A systematic approach for the diagnosis and treatment of idiopathic peptic ulcers.

    PubMed

    Chung, Chen-Shuan; Chiang, Tsung-Hsien; Lee, Yi-Chia

    2015-09-01

    An idiopathic peptic ulcer is defined as an ulcer with unknown cause or an ulcer that appears to arise spontaneously. The first step in treatment is to exclude common possible causes, including Helicobacter pylori infection, infection with other pathogens, ulcerogenic drugs, and uncommon diseases with upper gastrointestinal manifestations. When all known causes are excluded, a diagnosis of idiopathic peptic ulcer can be made. A patient whose peptic ulcer is idiopathic may have a higher risk for complicated ulcer disease, a poorer response to gastric acid suppressants, and a higher recurrence rate after treatment. Risk factors associated with this disease may include genetic predisposition, older age, chronic mesenteric ischemia, smoking, concomitant diseases, a higher American Society of Anesthesiologists score, and higher stress. Therefore, the diagnosis and management of emerging disease should systematically explore all known causes and treat underlying disease, while including regular endoscopic surveillance to confirm ulcer healing and the use of proton-pump inhibitors on a case-by-case basis.

  12. Validation of binding of SE-75 labeled sucralfate to sites of gastrointestinal ulceration

    SciTech Connect

    Maurer, A.H.; Knight, L.C.; Kollman, M.; Krevsky, B.; Pleet, D.; D'Ercole, F.; Siegel, J.A.; Fisher, R.S.; Malmud, L.S.

    1985-05-01

    This study was performed to determine if and for how long sucralfate (SU) binds selectively to sites of gastro-intestinal (GI) ulceration. Se-Su was prepared by sulfating sucrose with tracer Se-75 and precipitating it as the basic Al salt. All patients (pts) had endoscopy to confirm the presence of either: esophagitis (n=5), gastritis (GA) (n=5), gastric ulcers (GU) (n=5), duodenal ulcers (DU) (n=5), or no ulceration (NU) (n=5). Following an overnight fast the pts swallowed 1 gm with 100 ..mu..Ci of Se-SU and were imaged continuously over 24 hours or until no activity remained in the upper GI tract. Pts with GU visually demonstrated focal SU binding at the ulcers for an average of 3.9 +- 1.1 hrs. with a mean GET of 68 +- 25 min. Mean GET for pts with DU was prolonged, 171 +- 63 min, however focal binding at duodenal ulcers was not seen. All pts with GA had diffuse retention of SU in the stomach with a mean GET of 118 +- 34 min. Focal binding of SU at all sites of esophagitis was seen with a T-1/2 of 65 +- 32 min at the ulcerations. In conclusion these data support the theory that the mechanism of ulcer healing with SU is related to its ability to adhere to the ulcer site forming a protective barrier. In addition Se-SU is a potential ulcer imaging agent which can be used to noninvasively assess healing.

  13. [Systematic review of nutritional support in pressure ulcer].

    PubMed

    de Luis, D; Aller, R

    2007-07-01

    Pressure ulcer is an area of localised damage to the skin and underlying tissue caused by pressure, shear, friction and/or combination of these things. Prevalence of this entity is between 3 and 66%, depending of the patients and the pathology. Pressure ulcer is associated with an increased risk of morbidity and mortality. One of the most important risk factors to develop a pressure ulcer is nutritional status. We can use different interventional strategies, first of all (primary intervention) before the patient has developed a ulcer and secondly, the treatment of a established ulcer (secondary prevention). In the most important primary prevention study with 662 patients, two oral nutritional supplements per day were given to the patients. The incidence of pressure ulcer was 40% (118/295) in the interventional group and 48% (181/377) in control group. A relative risk to develop a pressure ulcer with supplementation of 0.83 (CI95%: 0.70 a 0.99). In the studies with secondary prevention, when we analyze in an individual way the different nutrients, zinc has not demonstrated the utility in an independent way. Vitamin C shows contradictory data in two randomized clinical trial with the same dose (500 mg each 12 hours). Recently, some randomized clinical trials have demonstrated an improvement in healing rates with enhanced enteral formulas (zinc, arginine, vitamin C). Oral supplementation without taking account micronutrients decreases risk of pressure ulcer. However, studies of secondary prevention due to heterogeneity have not let clear conclusions. However, enteral enhanced formula could improve ulcer healing.

  14. E2F1 Hinders Skin Wound Healing by Repressing Vascular Endothelial Growth Factor (VEGF) Expression, Neovascularization, and Macrophage Recruitment

    PubMed Central

    Zeng, Ning; Wang, Haiping; Deng, Pei; Xu, Yi; Feng, Youping; Zeng, Hong; Yang, Hongxia; Hou, Kai; Wang, Andrew; Parthasarathy, Keshav; Goyal, Samaksh; Qin, Gangjian; Wu, Min

    2016-01-01

    Background Refractory surface of wound and dermal chronic ulcer are largely attributed to poor neovascularization. We have previously shown that E2F1 suppresses VEGF expression in the ischemic heart, and that genetic deletion of E2F1 leads to better cardiac recovery. However, whether E2F1 has a role in dermal wound healing is currently not known. Methods and Results Skin wounds were surgically induced in E2F1-null (E2F1–/–) mice and WT littermates. E2F1–/– displayed an accelerated wound healing including wound closure, dermal thickening and collagen deposition, which was associated with an increased endothelial cell proliferation and greater vessel density in the border zone of the wound. Furthermore, more macrophages were recruited to the skin lesions and the level of VEGF expression was markedly higher in E2F1–/– than in WT mice. Conclusions E2F1 hinders skin wound healing by suppressing VEGF expression, neovascularization, and macrophage recruitment. Strategies that target E2F1 may enhance wound healing. PMID:27490344

  15. Squamous cell carcinoma developed on chronic venous leg ulcer.

    PubMed

    Sîrbi, Adelina Gabriela; Florea, Marius; Pătraşcu, Virgil; Rotaru, Maria; Mogoş, Dan Gabriel; Georgescu, Claudia Valentina; Mărgăritescu, Nicolae Dragoş

    2015-01-01

    Chronic venous leg ulcers (VLU), especially long-lasting non-healing ulcers, are among the risk factors for squamous cell carcinoma (SCC). Malignant transformation of a VLU is a rare finding and the relative risk of carcinomatous transformation is quite low (about 5.8). SCC arising in the context of a VLU has a particularly aggressive behavior. A 76-year-old male patient with no relevant medical familial history, with chronic venous insufficiency CEAP C6 for 10 years [recurrent leg ulcers with favorable outcome (healing) after specific local and systemic treatment], showing for about three years one ulcerated lesion located on the anterior upper third of the right calf non-responsive to specific treatment, which subsequently increased their size and merged. Biopsy sample was taken. Histopathology showed epidermal acanthosis, papillomatosis, intense parakeratosis, pseudoepitheliomatous hyperplasia, dysplasia and moderately differentiated squamous cell carcinoma with areas of acantholysis. Immunohistochemistry (Ki67, EMA, cytokeratin 34βE12 and p63) was performed and all types of immunostaining were moderately to intense positive. Above-knee leg amputation and specific oncologic treatment were proposed as possible curative solutions but the patient refused. Ten months after diagnosis and discharge form the Department of Dermatology, the patient died. Patients with chronic venous leg ulcers and clinically suspicious lesions should be evaluated for malignant transformation of the venous lesion. When diagnosed, malignancy complicating a chronic venous leg ulcer requires a resolute treatment as it may be fatal.

  16. Neuropathic diabetic foot ulcers – evidence-to-practice

    PubMed Central

    Ndip, Agbor; Ebah, Leonard; Mbako, Aloysius

    2012-01-01

    Foot ulcers and their attendant complications are disquietingly high in people with diabetes, a majority of whom have underlying neuropathy. This review examines the evidence base underpinning the prevention and management of neuropathic diabetic foot ulcers in order to inform best clinical practice. Since it may be impractical to ask patients not to weight-bear at all, relief of pressure through the use of offloading casting devices remains the mainstay for management of neuropathic ulcers, whilst provision of appropriate footwear is essential in ulcer prevention. Simple non-surgical debridement and application of hydrogels are both effective in preparing the wound bed for healthy granulation and therefore enhancing healing. Initial empirical antibiotic therapy for infected ulcers should cover the most common bacterial flora. There is limited evidence supporting the use of adjunctive therapies such as hyperbaric oxygen and cytokines or growth factors. In selected cases, recombinant human platelet-derived growth factor has been shown to enhance healing; however, its widespread use cannot be advised due to the availability of more cost-effective approaches. While patient education may be beneficial, the evidence base remains thin and conflicting. In conclusion, best management of foot ulcers is achieved by what is taken out of the foot (pressure, callus, infection, and slough) rather than what is put on the foot (adjuvant treatment). PMID:22371655

  17. Neuropathic diabetic foot ulcers - evidence-to-practice.

    PubMed

    Ndip, Agbor; Ebah, Leonard; Mbako, Aloysius

    2012-01-01

    Foot ulcers and their attendant complications are disquietingly high in people with diabetes, a majority of whom have underlying neuropathy. This review examines the evidence base underpinning the prevention and management of neuropathic diabetic foot ulcers in order to inform best clinical practice. Since it may be impractical to ask patients not to weight-bear at all, relief of pressure through the use of offloading casting devices remains the mainstay for management of neuropathic ulcers, whilst provision of appropriate footwear is essential in ulcer prevention. Simple non-surgical debridement and application of hydrogels are both effective in preparing the wound bed for healthy granulation and therefore enhancing healing. Initial empirical antibiotic therapy for infected ulcers should cover the most common bacterial flora. There is limited evidence supporting the use of adjunctive therapies such as hyperbaric oxygen and cytokines or growth factors. In selected cases, recombinant human platelet-derived growth factor has been shown to enhance healing; however, its widespread use cannot be advised due to the availability of more cost-effective approaches. While patient education may be beneficial, the evidence base remains thin and conflicting. In conclusion, best management of foot ulcers is achieved by what is taken out of the foot (pressure, callus, infection, and slough) rather than what is put on the foot (adjuvant treatment).

  18. Consequences of Helicobacter pylori cure in ulcer patients.

    PubMed

    Labenz, J

    2000-02-01

    In the complex pathogenesis of genuine ulcer disease Helicobacter pylori (H. pylori) is an essential, although not on its own sufficient, causal factor. Eradication of the infection heals the active ulcer and, in the long term, leads to a drastic reduction in ulcer recurrence and attendant complications. Some patients remain symptomatic even without ulcer recurrence, and in these, pre-existing, exacerbated or induced gastro-oesophageal reflux disease is probably of some significance. Possible causes of ulcer relapse are reinfection, the use of ulcerogenic drugs and persistent gastric hypersecretion. In adults, and probably also in children from the age of six years, H. pylori reinfection is rare, provided that a sensitive and specific test for H. pylori is carried out at the earliest 4 weeks after concluding anti-bacterial treatment. The most common cause of the reappearance of H. pylori is recrudescence - true reinfection hardly ever occurs. The healing of H. pylori-associated ulcer disease improves the patient's quality of life and possibly also life expectancy. Computer-aided calculations, together with a randomized controlled study, have shown not only that individual patients benefit, but that also the health system profits financially. The hypothetical negative effects of H. pylori eradication treatment are still being controversially discussed.

  19. Diagnostic and Treatment Approaches for Refractory Peptic Ulcers

    PubMed Central

    2015-01-01

    Refractory peptic ulcers are defined as ulcers that do not heal completely after 8 to 12 weeks of standard anti-secretory drug treatment. The most common causes of refractory ulcers are persistent Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Simultaneous use of two or more H. pylori diagnostic methods are recommended for increased sensitivity. Serologic tests may be useful for patients currently taking proton pump inhibitors (PPIs) or for suspected false negative results, as they are not affected by PPI use. NSAID use should be discontinued when possible. Platelet cyclooxygenase activity tests can confirm surreptitious use of NSAIDs or aspirin. Cigarette smoking can delay ulcer healing. Therefore, patients who smoke should be encouraged to quit. Zollinger-Ellison syndrome (ZES) is a rare but important cause of refractory gastroduodenal ulcers. Fasting plasma gastrin levels should be checked if ZES is suspected. If an ulcer is refractory despite a full course of standard PPI treatment, the dose should be doubled and administration of another type of PPI considered. PMID:26240800

  20. Effects of topical application of honey on cutaneous wound healing in rabbits.

    PubMed

    Oryan, A; Zaker, S R

    1998-04-01

    Although it has been known for many centuries that honey can accelerate wound healing, there have only been isolated reports of its use in the healing of burns, ulcers, infected wounds and open wounds. None of these reports developed a model to assess the changes in morphological and biochemical properties due to topical application of honey on cutaneous wounds. In the present investigation, efficacy of honey in the healing of cutaneous wounds of rabbits was studied on the basis of histopathological and biochemical changes. For this reason 40 healthy White New Zealand rabbits were randomly assigned to four equal groups. Using aseptic surgical technique, a 3 cm incision was made on the skin of the left thigh of each rabbit and the wounds of five rabbits in each group were twice daily treated with topical application of 5 ml pure unheated honey. The other half remained as untreated controls. Rabbits in groups A, B, C and D were biopsied on days 2, 7, 14 and 21 postoperatively respectively, and biopsies from the lesions of all groups were collected for histopathological studies and from groups C and D for biomechanical evaluations as well. Treated lesions showed less oedema, fewer polymorphonuclear and mononuclear cell infiltration, less necrosis, better wound contraction, improved epithelialization and lower glycosaminoglycan and proteoglycan concentration on days 2 and 7 postoperatively and better tissue organization and consequently an improved tissue ultimate strength and yield strength on days 14 and 21 postoperation. These findings suggest that honey applied topically on cutaneous wounds accelerates the healing processes and appears to have an important property that makes it ideal as a dressing for cutaneous wounds. PMID:9673575

  1. Systemic treatment with strontium ranelate accelerates the filling of a bone defect and improves the material level properties of the healing bone.

    PubMed

    Zacchetti, Giovanna; Dayer, Romain; Rizzoli, René; Ammann, Patrick

    2014-01-01

    Rapid bone defect filling with normal bone is a challenge in orthopaedics and dentistry. Strontium ranelate (SrRan) has been shown to in vitro decrease bone resorption and increase bone formation, and represents a potential agent with the capacity to accelerate bone defect filling. In this study, bone tibial defects of 2.5 mm in diameter were created in 6-month-old female rats orally fed SrRan (625 mg/kg/d; 5/7 days) or vehicle for 4, 8, or 12 weeks (10 rats per group per time point) from the time of surgery. Tibias were removed. Micro-architecture was determined by micro-computed tomography (µCT) and material level properties by nanoindentation analysis. µCT analysis showed that SrRan administration significantly improved microarchitecture of trabecular bone growing into the defect after 8 and 12 weeks of treatment compared to vehicle. SrRan treatment also accelerated the growth of cortical bone over the defect, but with different kinetics compared to trabecular bone, as the effects were already significant after 4 weeks. Nanoindentation analysis demonstrated that SrRan treatment significantly increased material level properties of both trabecular bone and cortical bone filling the defect compared to vehicle. SrRan accelerates the filling of bone defect by improving cortical and trabecular bone microarchitecture both quantitatively and qualitatively. PMID:25243150

  2. Adenosine receptor agonists for promotion of dermal wound healing

    PubMed Central

    Valls, María D.; Cronstein, Bruce N.; Montesinos, M. Carmen

    2009-01-01

    Wound healing is a dynamic and complex process that involves a well coordinated, highly regulated series of events including inflammation, tissue formation, revascularization and tissue remodeling. However, this orderly sequence is impaired in certain pathophysiological conditions such as diabetes mellitus, venous insufficiency, chronic glucocorticoid use, aging and malnutrition. Together with proper wound care, promotion of the healing process is the primary objective in the management of chronic poorly healing wounds. Recent studies have demonstrated that A2A adenosine receptor agonists promote wound healing in normal and diabetic animals and one such agonist, Sonedenoson, is currently being evaluated as a prospective new therapy of diabetic foot ulcers. We will review the mechanisms by which adenosine receptor activation affects the function of the cells and tissues that participate in wound healing, emphasizing the potential beneficial impact of adenosine receptor agonists in diabetic impaired healing. PMID:19041853

  3. Progress in corneal wound healing.

    PubMed

    Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

    2015-11-01

    Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β (TGF-β) system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal

  4. Pioneering technique using Acellular Dermal Matrix in the rescue of a radiation ulcer

    PubMed Central

    NASEEM, S.; PATEL, A.D.; DEVALIA, H.

    2016-01-01

    Background Radiotherapy as an adjuvant to mastectomy is integral to the treatment of breast cancer, but can result in skin ulceration. Skin ulceration following radiotherapy is traditionally managed by removing the implant and allowing the skin to heal by secondary intention. Case report A 42-year-old woman underwent radiotherapy following a breast reconstruction. She developed a 2 x 3cm radiation ulcer. The ulcer was managed by removing the implant and performing capsulectomy. A Beckers 50 expander was placed and reinforced with acellular dermal matrix inferolaterally. At follow-up the patient had a good cosmetic outcome. Conclusion Post-radiation skin ulcers present a challenge to treat with no current standardised management. The use of acellular dermal matrix may present a new technique to promote healing in these testing cases. PMID:27142826

  5. Mathematical model for wound healing following autologous keratinocyte transplantation.

    PubMed

    Renner, Regina; Teuwen, Isabell; Gebhardt, Carl; Simon, Jan C

    2008-06-01

    In times of increasing economical pressure on the health care systems, it is important to optimise the outpatient treatment of chronic wounds. Another aim of wound healing research is to discover agents to accelerate healing. Wound healing trajectories or healing velocities can provide information to demonstrate the endpoints for wound healing. A great problem in clinical trials is to specify these parameters. Therefore, we developed a mathematical model for more transparency. In this initial project, we observed 19 wounds to construct the wound healing trajectories after transplantation of autologous keratinocytes, and the results are so encouraging that investigation in this area will continue. The developed mathematical model describes the clinical observed healing process. It was possible to find parameters to distinguish between old and young patients, retrospectively or prospectively calculate the healing rates and to determine exactly the endpoint of healing. Therefore, our model might be very useful in practices or for studies.

  6. Chronic leg ulcer: does a patient always get a correct diagnosis and adequate treatment?

    PubMed

    Mooij, Michael C; Huisman, Laurens C

    2016-03-01

    Patients with chronic leg ulcers have severely impaired quality of life and account for a high percentage of annual healthcare costs. To establish the cause of a chronic leg ulcer, referral to a center with a multidisciplinary team of professionals is often necessary. Treating the underlying cause diminishes healing time and reduces costs. In venous leg ulcers adequate compression therapy is still a problem. It can be improved by training the professionals with pressure measuring devices. A perfect fitting of elastic stockings is important to prevent venous leg ulcer recurrence. In most cases, custom-made stockings are the best choice for this purpose. PMID:26916772

  7. Retrograde mechanochemical ablation of the small saphenous vein for the treatment of a venous ulcer.

    PubMed

    Moore, Hayley M; Lane, Tristan R A; Franklin, Ian J; Davies, Alun H

    2014-10-01

    We present the first case of retrograde ablation of the small saphenous vein to treat active venous ulceration. A 73-year-old gentleman with complicated varicose veins of the left leg and a non-healing venous ulcer despite previous successful endovenous treatment to his left great saphenous vein underwent mechanochemical ablation of his small saphenous vein with the ClariVein® system, under local anaesthetic, using a retrograde cannulation technique. Post-operatively the patient had improved symptomatically and the ulcer size had reduced. This report highlights that patients with small saphenous vein incompetence and active ulceration can be treated successfully with retrograde mechanochemical ablation.

  8. Acceleration of cutaneous healing by electrical stimulation: degenerate electrical waveform down-regulates inflammation, up-regulates angiogenesis and advances remodeling in temporal punch biopsies in a human volunteer study.

    PubMed

    Sebastian, Anil; Syed, Farhatullah; Perry, Donna; Balamurugan, Vinayagapriya; Colthurst, James; Chaudhry, Iskander H; Bayat, Ardeshir

    2011-11-01

    We previously demonstrated the beneficial effect of a novel electrical stimulation (ES) waveform, degenerate wave (DW) on skin fibroblasts, and now hypothesize that DW can enhance cutaneous wound healing in vivo. Therefore, a punch biopsy was taken from the upper arm of 20 volunteers on day 0 and repeated on day 14 (NSD14). A contralateral upper arm biopsy was taken on day 0 and treated with DW for 14 days prior to a repeat biopsy on day 14 (ESD14). A near-completed inflammatory stage of wound healing in ESD14, compared to NSD14 was demonstrated by up-regulation of interleukin-10 and vasoactive intestinal peptide using quantitative real time polymerase chain reaction and down-regulation of CD3 by immunohistochemistry (IHC) (p < 0.05). In addition to up-regulation (p < 0.05) of mRNA transcripts for re-epithelialization and angiogenesis, IHC showed significant overexpression (p < 0.05) of CD31 (15.5%), vascular endothelial growth factor (66%), and Melan A (8.6 cells/0.95 mm²) in ESD14 compared to NSD14 (9.5%, 38% and 4.3 cells/0.95 mm², respectively). Furthermore, granulation tissue formation (by hematoxylin and eosin staining), and myofibroblastic proliferation demonstrated by alpha-smooth muscle actin (62.7%) plus CD3+ T lymphocytes (8.1%) showed significant up-regulation (p < 0.05) in NSD14. In the remodeling stage, mRNA transcripts for fibronectin, collagen IV (by IHC, 14.1%) and mature collagen synthesis (by Herovici staining, 71.44%) were significantly up-regulated (p < 0.05) in ESD14. Apoptotic (TUNEL assay) and proliferative cells (Ki67) were significantly up-regulated (p < 0.05) in NSD14 (5.34 and 11.9 cells/0.95 mm²) while the proliferation index of ESD14 was similar to normal skin. In summary, cutaneous wounds receiving DW electrical stimulation display accelerated healing seen by reduced inflammation, enhanced angiogenesis and advanced remodeling phase.

  9. Ileocolonic ulcer treated by endoscopic application of collagen-polyvinylpyrrolidone

    PubMed Central

    de Hoyos Garza, Andrés; Aguilar, Edgar A Esparza; Checa Richards, Griselda

    2007-01-01

    Ulceration is a complication that may occur after an ileocolonic anastomosis. Most of the etiologies remain speculative. The case of a 33-year-old woman with eosinophilic colitis is reported, in whom a colectomy with an ileocolonic anastomosis was performed. After four months, the patient presented with a stenosis in the ileocolonic anastomosis, necessitating surgical restoration. Four weeks later, the patient presented with rectal bleeding, and a colonoscopy showed an ulcer in the anastomosis. Collagen-polyvinylpyrrolidone was applied into and on the surface of the ulcer, and five days later the procedure was repeated. Follow-up endoscopies at seven days and three months showed complete healing of the ulcer and the patient remained without bleeding throughout a further four weeks of follow-up tests. It was concluded that this biological product could be an excellent treatment for these lesions. PMID:17703251

  10. Drug cutaneous side effect: focus on skin ulceration.

    PubMed

    D'Epiro, S; Salvi, M; Luzi, A; Mattozzi, C; Luci, C; Macaluso, L; Marzocca, F; Salvo, V; Cantisani, C; Paolino, G; Calvieri, S; Richetta, A G

    2014-01-01

    Skin ulcers are defined as tissue loss interesting the deeper layers of the dermis and hypodermis, with low tendency to spontaneous healing. They cause disability related to pain, risk of infection and amputation, chronic management, requiring working absence with notably economic burden. The major cause is often related to underlying vascular disease, infections, tumors, autoimmunity, trauma, even if literature occasionally reported several cases of drug inducing skin ulceration. Most of drugs involved are chemotherapy agents and more recently molecular target therapies. Evidences supporting these drugs as the major cause of skin ulcers include delay of onset after therapy initiation, improvement after withdrawal of the drug, recurrence after its reintroduction and, sometimes, simultaneous occurrence of other skin lesions that have previously been reported to be associated wi