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1.
BMC Complement Altern Med ; 19(1): 115, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159783

RESUMO

BACKGROUND: Skin burn wound is a notable medical burden worldwide. Rapid and effective treatment of burnt skin is vital to fasten wound closure and healing properly. Amniotic graft and Aloe vera are widely used as wound managing biomaterials. Sophisticated processing, high cost, availability, and the requirement of medics for transplantation limit the application of amnion grafts. We aim to prepare a novel gel from amnion combined with the Aloe vera extract for burn wound healing which overcome the limitations of graft. METHODS: Two percent human amniotic membrane (AM), Aloe vera (AV) and AM+AV gels were prepared. In vitro cytotoxicity, biocompatibility, cell attachment, proliferation, wound healing scratch assays were performed in presence of the distinct gels. After skin irritation study, second-degree burns were induced on dorsal region of Wistar rats; and gels were applied to observe the healing potential in vivo. Besides, macroscopical measurement of wound contraction and re-epithelialization; gel treated skin was histologically investigated by Hematoxylin and eosin (H&E) staining. Finally, quantitative assessment of angiogenesis, inflammation, and epithelialization was done. RESULTS: The gels were tested to be non-cytotoxic to nauplii and compatible with human blood and skin cells. Media containing 500 µg/mL AM+AV gel were observed to promote HaCaT and HFF1 cells attachment and proliferation. In vitro scratch assay demonstrated that AM+AV significantly accelerated wound closure through migration of HaCaT cells. No erythema and edema were observed in skin irritation experiments confirming the applicability of the gels. AV and AM+AV groups showed significantly accelerated wound closure through re-epithelialization and wound contraction with P < 0.01. Macroscopically, AM and AM+AV treated wound recovery rates were 87 and 90% respectively with P < 0.05. Histology analysis revealed significant epitheliazation and angiogenesis in AM+AV treated rats compared to control (P < 0.05). AM+AV treated wounds had thicker regenerated epidermis, increased number of blood vessels, and greater number of proliferating keratinocytes within the epidermis. CONCLUSION: We demonstrated that a gel consisting of a combination of amnion and Aloe vera extract has high efficacy as a burn wound healing product. Amniotic membrane combined with the carrier Aloe vera in gel format is easy to produce and to apply.


Assuntos
Âmnio , Queimaduras/tratamento farmacológico , Preparações de Plantas/uso terapêutico , Animais , Artemia , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Fitoterapia , Preparações de Plantas/farmacologia , Ratos Wistar , Reepitelização/efeitos dos fármacos
2.
Int J Nanomedicine ; 14: 3345-3360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190796

RESUMO

Background: Designing a wound dressing that effectively prevents multi-drug-resistant bacterial infection and promotes angiogenesis and re-epithelialization is of great significance for wound management. Methods and results: In this study, a biocompatible composite membrane comprising biomimetic polydopamine-modified eggshell membrane nano/microfibres coated with KR-12 antimicrobial peptide and hyaluronic acid (HA) was developed in an eco-friendly manner. The physicochemical properties of the composite membrane were thoroughly characterized, and the results showed that the surface hydrophilicity and water absorption ability of the composite membrane were improved after the successive conjugation of the HA and the KR-12 peptide. Furthermore, the in vitrobiological results revealed that the composite membrane had excellent antibacterial activity against Gram-positive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, and it could prevent MRSA biofilm formation on its surface. Additionally, it promoted the proliferation of keratinocytes and human umbilical vein endothelial cells and increased the secretion of VEGF. Finally, an in vivo animal study indicated that the composite membrane could promote wound healing via accelerating angiogenesis and re-epithelialization, which were demonstrated by the enhanced expression of angiogenetic markers (CD31 and VEGF) and keratinocyte proliferation marker (PCNA), respectively. Conclusion: These results indicated that the composite membrane is a potential candidate of wound dressings.


Assuntos
Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Casca de Ovo/química , Ácido Hialurônico/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Peptídeos/farmacologia , Reepitelização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Galinhas , Escherichia coli/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Peptídeos/química , Porosidade , Staphylococcus aureus/efeitos dos fármacos
3.
Int J Mol Sci ; 20(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987108

RESUMO

The aim of this study is to assess if an adhesive biopolymer, sodium hyaluronate (NaHA), has synergistic effects with s-PRGF (a serum derived from plasma rich in growth factors and a blood derivative that has already shown efficacy in corneal epithelial wound healing), to reduce time of healing or posology. In vitro proliferation and migration studies, both in human corneal epithelial (HCE) cells and in rabbit primary corneal epithelial (RPCE) cultures, were carried out. In addition, we performed studies of corneal wound healing in vivo in rabbits treated with s-PRGF, NaHA, or the combination of both. We performed immunohistochemistry techniques (CK3, CK15, Ki67, ß4 integrin, ZO-1, α-SMA) in rabbit corneas 7 and 30 days after a surgically induced epithelial defect. In vitro results show that the combination of NaHA and s-PRGF offers the worst proliferation rates in both HCE and RPCE cells. Addition of NaHA to s-PRGF diminishes the re-epithelializing capability of s-PRGF. In vivo, all treatments, given twice a day, showed equivalent efficacy in corneal epithelial healing. We conclude that the combined use of s-PRGF and HaNA as an adhesive biopolymer does not improve the efficacy of s-PRGF alone in the wound healing of corneal epithelial defects.


Assuntos
Epitélio Anterior/patologia , Ácido Hialurônico/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Soro/química , Animais , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Epitélio Anterior/efeitos dos fármacos , Fibrose , Humanos , Integrina beta4/metabolismo , Antígeno Ki-67/metabolismo , Coelhos , Reepitelização/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismo
4.
Kaohsiung J Med Sci ; 35(1): 24-32, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30844141

RESUMO

Several studies have reported the beneficial effects of Lawsonia inermis on wound healing, but the mechanism of action is still unknown. This study aimed to investigate the effectiveness of a new ointment formulation of hydroethanolic extract leaves of L. inermis on wound healing by gene expression of glucose transporter-1 (Glut-1) and insulin-like growth factor I (Igf-1) in Wistar rats. The animals were topically treated with different doses of L. inermis. An experimentally induced circular excisional wound model of 314 mm2 surface area was surgically created. The percentage of wound contraction and histopathological changes was assessed at different time points following wound induction. The expression of Glut-1 and Igf-1 was evaluated by reverse-transcription PCR. Topical administration of L. inermis, dose dependently, shortened inflammatory phase, accelerated cellular proliferation, and enhanced wound contraction ratio. It also improved revascularization, collagen deposition, and re-epithelialization rate and promoted intracytoplasmic carbohydrate storage (P < 0.05). Moreover, the mRNA levels of Igf-1 and Glut-1 were significantly higher in the L. inermis-treated groups than the control group (P < 0.05). Topical administration of L. inermis promoted the healing process by reducing tissue inflammation and increasing glucose uptake, which was mediated by up-regulating the expression of Igf-1 and Glut-1.


Assuntos
Etanol/química , Glucose/metabolismo , Inflamação/patologia , Lawsonia (Planta)/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Água/química , Cicatrização/efeitos dos fármacos , Administração Tópica , Fosfatase Alcalina/metabolismo , Antioxidantes/metabolismo , Carboidratos/análise , Epiderme/efeitos dos fármacos , Epiderme/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Flavonoides/análise , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Fenóis/análise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reepitelização/efeitos dos fármacos
5.
Wound Repair Regen ; 27(3): 257-267, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30675745

RESUMO

Although partial thickness burns are the most frequently reported burn injuries, there is no consensus on the optimal treatment. The objective of this study was to compare the clinical effectiveness and scar quality of Flaminal® Forte to silver sulfadiazine (Flamazine®) in the treatment of partial thickness burns. In this two-arm open label multicenter randomized controlled trial, adult patients with acute partial thickness burns and an affected total body surface area of less than 30% were randomized between Flaminal® Forte and Flamazine® and followed for 12 months. Dressing changes in the Flamazine® group were performed daily, and in the Flaminal® group during the first 3 days post burn and thereafter every other day until complete wound healing or surgery. Forty-one patients were randomly allocated to Flaminal® Forte and 48 patients to Flamazine®. The primary outcome was time to wound healing, which did not differ between the groups: median 18 days with Flaminal® Forte (range 8-49 days) versus 16 days with Flamazine® (range 7-48 days; p = 0.24). Regarding the secondary outcomes during hospital admission, there were no statistically significant differences between the groups concerning need for surgery, pain scores, pruritus, or pain-related and anticipatory anxiety. More patients in the Flaminal® group developed wound colonization (78% versus 32%, p < 0.001), but the treatment groups did not differ regarding the incidence of local infections and use of systemic antibiotics. In terms of scar quality, no statistically significant differences between both treatment groups were found regarding subjective scar assessment (Patient and Observer Scar Assessment Scale (POSAS)), scar melanin and pigmentation (DermaSpectrometer®), and scar elasticity and maximal extension (Cutometer®) during 12 month postburn. In conclusion, time to wound healing did not differ, but the use of Flaminal® Forte seemed favorable because less dressing changes are needed which lowers the burden of wound care.


Assuntos
Alginatos/uso terapêutico , Anti-Infecciosos Locais/uso terapêutico , Queimaduras/tratamento farmacológico , Cicatriz/patologia , Glucose Oxidase/uso terapêutico , Lactoperoxidase/uso terapêutico , Polietilenoglicóis/uso terapêutico , Sulfadiazina de Prata/uso terapêutico , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/patologia , Adulto , Idoso , Alginatos/farmacologia , Anti-Infecciosos Locais/farmacologia , Queimaduras/patologia , Cicatriz/prevenção & controle , Combinação de Medicamentos , Feminino , Glucose Oxidase/farmacologia , Humanos , Lactoperoxidase/farmacologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/farmacologia , Reepitelização/efeitos dos fármacos , Sulfadiazina de Prata/farmacologia , Resultado do Tratamento , Cicatrização/fisiologia , Infecção dos Ferimentos/tratamento farmacológico
6.
Biomater Sci ; 7(3): 995-1010, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30603758

RESUMO

The objective of this study was to develop a novel delivery system for recombinant human epidermal growth factor (rhEGF) for chronic wound treatment. Such a delivery system should be of good cargo stability and system mechanical properties in order to guarantee a satisfactory wound-healing effect. rhEGF-containing lyotropic liquid crystalline precursors (rhEGF-LLCPs) with in situ gelation capability were considered as a promising candidate to achieve this aim. Various properties of the optimal formulations (rhEGF-LLCP1 and rhEGF-LLCP2) were characterized, including apparent viscosity, gelation time, in vitro release and phase behavior. The stability of rhEGF and system mechanical properties (i.e. mechanical rigidity and bioadhesive force) were verified. Interestingly, rhEGF-LLCP2 with a larger internal water channel diameter exhibited faster release rate in vitro and then better bioactivity in Balb/c 3T3 and HaCaT cell models. Moreover, rhEGF-LLCP2 showed distinct promotion effects on wound closure, inflammatory recovery and re-epithelization process in Sprague-Dawley rat models. In conclusion, rhEGF-LLCP emerged as a prospective candidate to preserve the stability and enhance the wound-healing effect of rhEGF, which might serve as a new delivery system for chronic wound therapies.


Assuntos
Fator de Crescimento Epidérmico/metabolismo , Cristais Líquidos/química , Cicatrização , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Fator de Crescimento Epidérmico/genética , Géis/química , Humanos , Masculino , Camundongos , Estabilidade Proteica , Ratos , Ratos Sprague-Dawley , Reepitelização/efeitos dos fármacos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Reologia , Pele/efeitos dos fármacos , Pele/patologia , Viscosidade , Cicatrização/efeitos dos fármacos
7.
Eur J Pharm Biopharm ; 135: 61-71, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30552972

RESUMO

Thrombomodulin (TM) is a type-I transmembrane glycoprotein expressed on the surfaces of endothelial cells and epidermal keratinocytes. It is known to regulate blood coagulation, inflammation, and cell-cell adhesion. A recombinant TM, which contains an epidermal growth factor-like domain and serine/threonine-riches domain, has been demonstrated to stimulate cell proliferation and migration of keratinocytes and wound healing. In this study, we developed the biodegradable hydrogels and evaluated the efficacy of sustained release of rhTM from the hydrogel for the treatment of diabetic wounds. The hydrogels were composed of gelatin with or without hyaluronic acid, and fabricated by chemical cross-linking followed by lyophilization. Gelatin-based hydrogels had porous structure, good swelling property, and were biodegradable with characteristics of slow rhTM release in a short term. The once every-3-day rhTM-loaded hydrogel (with hyaluronic acid) markedly promoted wound healing and were superior to rhTM solution, once daily rhTM hydrogel (without hyaluronic acid), hydrogel controls, and once every-3-day rhEGF hydrogel treatment groups. The rhTM hydrogels enhanced granulation tissue formation, re-epithelialization, collagen deposition, and angiogenesis in wound repair. The once every-3-day rhTM hydrogel was stable and drug release was maintained up to 11-month of storage at 4 °C. The developed rhTM hydrogels could meet the needs for clinical practice, and may have future medical applications for wound care in diabetic patients.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Gelatina/química , Ácido Hialurônico/química , Trombomodulina/administração & dosagem , Cicatrização/efeitos dos fármacos , Animais , Colágeno/metabolismo , Preparações de Ação Retardada , Diabetes Mellitus Experimental/complicações , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Hidrogéis , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/efeitos dos fármacos , Reepitelização/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Trombomodulina/química
8.
Braz Oral Res ; 32: e55, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29898030

RESUMO

Free gingival grafting, the most predictable technique to increase the keratinized gingiva, leaves an open wound on the palate and the resulting discomfort during the healing phase is a significant concern. This study was intended to evaluate the effect of topical erythropoietin on healing of the donor site. Twelve patients lacking an attached gingiva at two sites in the mandible were included. In the test group, 1 mL of gel containing erythropoietin at a concentration of 4,000 IU mL-1 was applied to the donor site, whereas the control group was treated with 2 mL of the gel alone. On the second day after surgery, the same procedure was repeated. H2O2 was used to evaluate the amount of epithelialization. Clinical healing was compared using photographs and direct examination. The EPO group showed significantly better keratinization only on day 21. Comparison of clinical healing based on direct examination revealed significantly better healing in the test group on day 28. Furthermore, inflammation in the test group was lower than in the control group on the same day. Topical application of EPO improves palatal wound healing during the third and fourth weeks after free gingival graft procedures.


Assuntos
Eritropoetina/administração & dosagem , Retalhos de Tecido Biológico , Gengiva/transplante , Palato/efeitos dos fármacos , Palato/cirurgia , Reepitelização/efeitos dos fármacos , Administração Bucal , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reepitelização/fisiologia , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento
9.
Khirurgiia (Mosk) ; (6): 91-100, 2018.
Artigo em Russo | MEDLINE | ID: mdl-29953106

RESUMO

AIM: To evaluate the efficacy and safety of collagen biomaterial application during the 4-week follow-up of patients with diabetic foot syndrome. MATERIAL AND METHODS: 75 patients with diabetic foot (Wagner II (69.3%) and III (30.7%)) aged 30-80 years were included in the multicenter study, among them were 50.7% with the wound unhealed for 1.5-6 months and 49.3% over 6-48 months. Patients were randomized into 2 groups: 1) standard therapy (n=37), 2) the additional use of the collagen material Collost (n=38). Observation period was at least 4 weeks for each patient. The size of ulcers, results of general and biochemical blood tests, oximetry, microbiological testing, ultrasound of lower extremities vessels as well as a detailed medical history, social and functional status, level of cardiovascular comorbidity and ongoing therapy were estimated. RESULTS: Additional use of a collagen biomaterial has led to a significant reduction ulcers of all sizes from 13.5 to 2.1 cm2 (in the comparison group - from 12.5 to 7 cm2). The best dynamics have been registered in Wagner II (4.4-fold average wound area regress in Collost group, from 8.8 to 2.0 cm2; average wound area regress by 1.8 times, from 10 to 5.6 cm2 in the comparison group) than in Wagner III group (in the main group from 55 to 21.3 cm2; in the control group from 36 to 32.4 cm2) and in ulcers existing less than 6 months. Treatment with biological material Collost within standard therapy after 4 weeks led to increase of complete epithelialization by 2.6% (21.1% as compared to 14.7%), while decreasing the frequency of ineffective treatment by 4.1 (7.9% in primary and 32.4% in the comparison group). CONCLUSION: We have proved the efficacy and safety of collagen biomaterial topical application in a diabetic foot syndrome treatment.


Assuntos
Curativos Biológicos , Colágeno/administração & dosagem , Pé Diabético/terapia , Cicatrização/efeitos dos fármacos , Idoso , Materiais Biocompatíveis/administração & dosagem , Pé Diabético/diagnóstico , Pé Diabético/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reepitelização/efeitos dos fármacos , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Molecules ; 23(4)2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29614757

RESUMO

ß-glucans are derived from a variety of sources including yeast, grain and fungus and belong to the class of drugs known as biological response modifiers. They possess a broad spectrum of biological activities that enhance immunity in humans. One promising area for ß-glucans' application is dermatology, including wound care. Topical applications of ß-glucans are increasing, especially due to their pluripotent properties. Macrophages, keratinocytes and fibroblasts are considered the main target cells of ß-glucans during wound healing. ß-glucans enhance wound repair by increasing the infiltration of macrophages, which stimulates tissue granulation, collagen deposition and reepithelialization. ß-glucan wound dressings represent a suitable wound healing agent, with great stability and resistance to wound proteases. This review summarizes the current knowledge and progress made on characterizing ß-glucans' wound healing properties in vitro and in vivo and their safety and efficacy in managing non-healing wounds or other chronic dermatological conditions and diseases.


Assuntos
beta-Glucanas/farmacologia , Animais , Colágeno/metabolismo , Humanos , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Reepitelização/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
11.
Vet J ; 233: 63-65, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29486881

RESUMO

Spontaneous chronic corneal epithelial defects (SCCEDs) are characteristic ulcers in dogs that are refractory to healing. The aim of the study was to evaluate the use of a topical regenerative agent to promote healing of SCCEDs. Nineteen dogs (20 eyes) were randomized to receive either regenerative agent (10 eyes) or placebo (10 eyes) every 48h following corneal debridement, which was repeated 1 week later if the SCCED had not yet healed. The mean±standard deviation time to re-epithelialization was 17.3±12.8 days for the group treated with a topical regenerative agent and 19.3±11.7 days for the group treated with a placebo; the cumulative healing rates were not statistically different (P>0.650). A positive association was found between the initial size of the ulcer and the time to re-epithelialization (r=0.555, P=0.011). Although well tolerated by dogs, there was no therapeutic advantage in using a topical regenerative agent for re-epithelialization of SCCEDs.


Assuntos
Doenças da Córnea/veterinária , Doenças do Cão/tratamento farmacológico , Glicosaminoglicanos/administração & dosagem , Reepitelização/efeitos dos fármacos , Animais , Doenças da Córnea/tratamento farmacológico , Doenças da Córnea/cirurgia , Desbridamento/veterinária , Doenças do Cão/cirurgia , Cães , Método Duplo-Cego , Epitélio/cirurgia , Feminino , Masculino , Soluções Oftálmicas , Placebos
12.
J Mater Sci Mater Med ; 29(3): 31, 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29536274

RESUMO

Topical application of honey for tissue regeneration, has recently regained attention in clinical practice with controlled studies affirming its efficacy and indicating its role in regeneration over repair. Parallely, to overcome difficulties of applying raw honey, several product development studies like nanofibrous matrices have been reported. However, one approach concentrated on achieving highest possible honey loading in the nanofiber membranes while other studies have found that only specific honey dilutions result in differential cellular responses on wound healing and re-epithelization. From these results, it can be suggested that high honey loading provides optimum external microenvironment, low-loaded membranes could provide a more conducive internal microenvironment for tissue regeneration. With this hypothesis, this paper sought to evaluate ability of low-honey loaded nanofibers to modulate the anti-oxidant, anti-biofilm and anti-inflammatory properties which are important to be maintained in wound micro-environment. A loading-dependent reduction of biofilm formation and anti-oxidant activity was noted in different concentration ranges investigated. After scratch assay, a certain honey loading (0.5%) afforded the maximum re-epithelization. Since there is lack of methods to determine anti-inflammatory properties of nanofiber membranes during epithelial healing process, we performed anti-inflammatory assessment of nano-fibers by evaluating the expressions of pro-inflammatory markers-Cycloxygenase-2 (COX-2) and Interleukin-6 (IL-6) and to confirm the optimized concentration. Considering the role of COX-2 and IL-6, the novel methodology used in this study can also be developed as an assay for anti-inflammatory matrices for wound healing.


Assuntos
Antibacterianos , Anti-Inflamatórios , Antioxidantes , Regeneração Tecidual Guiada/métodos , Mel , Nanofibras , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Microambiente Celular/efeitos dos fármacos , Cercopithecus aethiops , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Galvanoplastia , Escherichia coli , Teste de Materiais , Testes de Sensibilidade Microbiana , Nanofibras/química , Reepitelização/efeitos dos fármacos , Células Vero , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia
13.
PLoS Negl Trop Dis ; 12(3): e0006357, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29554101

RESUMO

BACKGROUND: Healing times following treatment with antibiotics, and factors that influence healing, have not been reported in Australian patients with Mycobacterium ulcerans. METHODOLOGY/PRINCIPAL FINDINGS: Healing times were determined for all M. ulcerans cases treated by a single physician with antibiotics at Barwon Health, Victoria, from 1/1/13-31/12/16. Lesions were categorised by induration size: category A ≤ 400mm2, Category B 401-1600mm2 and Category C ≥1601mm2. A logistic regression analysis was performed to determine risk factors for prolonged wound healing (>150 days from antibiotic commencement). 163 patients were included; 92 (56.4%) were male and median age was 58 years (IQR 39-73 years). Baseline lesion size [available in 145 (89.0%) patients] was categorised as A in 46 (31.7%), B in 67 (46.2%) and C in 32 (22.1%) patients. Fifty (30.7%) patients had surgery. In those treated with antibiotics alone, 83.0% experienced a reduction in induration size after 2 weeks, then 70.9% experienced an increase in induration size from the lowest point, and 71.7% experienced an increase in ulceration size. A linear relationship existed between the time induration resolved and wound healing began. Median time to heal was 91 days (IQR 70-148 days) for category A lesions; significantly shorter than for category B lesions (128 days, IQR 91-181 days, p = 0.05) and category C lesions (169 days, IQR 159-214 days, p<0.001). Fifty-seven (35.0%) patients experienced a paradoxical reaction. Of those treated with antibiotics alone, lesions experiencing a paradoxical reaction had longer healing times [median time to heal 177 days (IQR 154-224 days) compared to 107 days (IQR 79-153 days), p<0.001]. On multivariable logistic regression, lesion size at baseline (p<0.001) and paradoxical reactions (p<0.001) were independently associated with prolonged healing times. For category A and B lesions, healing time was significantly shorter with antibiotics plus excision and direct closure compared with antibiotics alone [Category A lesions median 55 days (IQR 21-63 days) compared with 91 days (IQR 70-148 days), p<0.001; Category B lesions median 74 days (IQR 21-121 days) compared to 128 days (IQR 97-181 days), p<0.001]. CONCLUSIONS: In Australian patients treated with antibiotics M. ulcerans lesions usually initially improve, then clinically deteriorate with increased induration and ulceration, before healing after the inflammation associated with lesions resolves. The time to complete healing of lesions is generally long, and is further prolonged in those with larger initial lesion size or who develop paradoxical reactions. For small lesions (<4cm2), excisional surgery may reduce healing times.


Assuntos
Antibacterianos/uso terapêutico , Úlcera de Buruli/tratamento farmacológico , Mycobacterium ulcerans/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Austrália , Úlcera de Buruli/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reepitelização/efeitos dos fármacos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Plast Reconstr Surg ; 141(3): 669-678, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29481398

RESUMO

BACKGROUND: Acute wound healing is a dynamic process that results in the formation of scar tissue. The mechanisms of this process are not well understood; numerous signaling pathways are thought to play a major role. Here, the authors have identified ß-catenin-dependent Wnt signaling as an early acute-phase reactant in acute wound healing and scar formation. METHODS: The authors created 6-mm full-thickness excisional cutaneous wounds on adult ß-catenin-dependent Wnt signal (BAT-gal) reporter mice. The expression of canonical Wnt after wounding was analyzed using X-gal staining and quantitative real-time polymerase chain reaction. Next, recombinant mouse Wnt3a (rmWnt3a) was injected subcutaneously to the wound edge, daily. The mice were killed at stratified time points, up to 15 days after injury. Histologic analysis, quantitative real-time polymerase chain reaction, and Western blot were performed. RESULTS: Numerous individual Wnt ligands increased in expression after wounding, including Wnt3a, Wnt4, Wnt10a, and Wnt11. A specific pattern of Wnt activity was observed, localized to the hair follicle and epidermis. Mice injected with rmWnt3a exhibited faster wound closure, increased scar size, and greater expression of fibroblast growth factor receptor-2 and type I collagen. CONCLUSIONS: The authors' data suggest that ß-catenin-dependent Wnt signaling expression increases shortly after cutaneous wounding, and exogenous rmWnt3a accelerates reepithelialization, wound matrix maturation, and scar formation. Future experiments will focus on the intersection of Wnt signaling and other known profibrotic cytokines.


Assuntos
Via de Sinalização Wnt/fisiologia , Cicatrização/fisiologia , beta Catenina/metabolismo , Animais , Proliferação de Células/fisiologia , Células Cultivadas , Cicatriz/fisiopatologia , Fibroblastos/metabolismo , Hipóxia/fisiopatologia , Injeções Subcutâneas , Camundongos Endogâmicos , Reepitelização/efeitos dos fármacos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Proteínas Recombinantes , Pele/lesões , Fator de Crescimento Transformador beta/metabolismo , Proteínas Wnt/metabolismo , Proteína Wnt3A/administração & dosagem , Proteína Wnt3A/farmacologia
15.
BMC Complement Altern Med ; 18(1): 32, 2018 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-29378560

RESUMO

BACKGROUND: Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro-/anti-inflammatory factors on transforming growth factor-ß(TGF-ß) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. METHODS: SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. RESULTS: Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula accelerated re-epithelialization of diabetic wound healing. CONCLUSION: The present study found that diabetic delayed wound healing time is closely related to the high expression level of activin/follistatin, which leads to excessive inflammation in the process of re-epithelization. SJHY Formula accelerates re-epithelialization and healing time of diabetic wounds through decreasing the high expression of activin/follistatin.


Assuntos
Ativinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Folistatina/metabolismo , Reepitelização/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/complicações , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Úlcera/tratamento farmacológico
16.
Lasers Med Sci ; 33(5): 1003-1008, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29349512

RESUMO

Photobiomodulation is a widely used tool in regenerative medicine thanks to its ability to modulate a plethora of physiological responses. Wound re-epithelialization is strictly regulated by locally produced chemical mediators, such as nitric oxide (NO), a highly reactive free radical generated by the nitric oxide synthase (NOS) enzymatic family. In this study, it has been hypothesized that a 980-nm low-level laser stimulation could increase NO production in human keratinocytes and that such event might be directly related to the re-epithelialization process. Human keratinocytes were irradiated with increasing energy outputs (10-75 J) in the absence or presence of L-NAME, a NOS inhibitor. Laser stimulation induced an increase in NO production, resulting in an energy-dependent increase in both keratinocytes proliferation and re-epithelialization ability. The direct link between increased NO production and the observed physiological responses was confirmed by their inhibition in L-NAME pre-treated samples. Since NO production increase is a quick event, it is conceivable that it is due to an increase in existing NOS activity rather than to a de novo protein synthesis. For this reason, it could be hypothesized that photobiomodulation-derived NO positive effects on keratinocytes behavior might rely on a near infrared mediated increase in NOS conformational stability and cofactors as well as substrate binding ability, finally resulting in an increased enzymatic activity.


Assuntos
Terapia com Luz de Baixa Intensidade , Óxido Nítrico/biossíntese , Reepitelização/efeitos da radiação , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Inibidores Enzimáticos/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Reepitelização/efeitos dos fármacos , Espectroscopia de Luz Próxima ao Infravermelho
17.
Inflammation ; 41(2): 474-484, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29196961

RESUMO

The α7 nicotinic acetylcholine receptor (α7-nAChR) is associated with inflammation, re-epithelialization, and angiogenesis in wound healing process. A recent study demonstrated that PNU-282987, a selective agonist of α7-nAChR, accelerates the repair of diabetic excisional wounds. Whether α7-nAChR activation promotes non-diabetic wounds healing is unknown. The aim of this study was to evaluate the effects of α7-nAChR activation on non-diabetic wound healing. The effects were evaluated in two wound models. In the first model, the wound was covered with a semi-permeable transparent dressing. In the second model, the wound was left uncovered. In both models, the mice were randomly assigned to two treatment groups: saline or PNU282987 (25 mice in each group). In covered wounds, we found that α7-nAChR activation inhibited re-epithelialization, angiogenesis, and epithelial cells proliferation, promoted neo-epithelial detachment, and suppressed neutrophil infiltration and the expression of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). However, in uncovered wounds, we observed that α7-nAChR activation promoted re-epithelialization and angiogenesis, inhibited neutrophil infiltration and the expression of high mobility group box (HMGB)-1, epidermal growth factor (EGF), and VEGF. In conclusion, this data demonstrated that α7-nAChR activation inhibited wound healing in covered wounds but played an opposite role in uncovered wounds. The opposite effect might be primarily due to inhibition of inflammation.


Assuntos
Benzamidas/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Receptor Nicotínico de Acetilcolina alfa7/uso terapêutico , Animais , Bandagens/efeitos adversos , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Reepitelização/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7/agonistas
18.
Biochim Biophys Acta Mol Basis Dis ; 1864(1): 178-188, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28993190

RESUMO

Studies have indicated that the definitive engraftment and transdifferentiation potential of stem cells do not seem crucial for its property of tissue repair. Our previous study showed that transplantation of adipose-derived mesenchymal stem cells (ADMSCs) enhanced the healing of sutured gastric perforation. This study aimed to investigate the paracrine role of ADMSCs in the experimental gastric mucosal injury. Normoxia-conditioned medium (Nor CM) and hypoxia (HPO) CM were obtained after culturing ADMSCs in 20% O2 and 5% O2 for 48h. Cell migration, proliferation, viability, and angiogenesis in vitro were significantly enhanced upon incubation with CM, especially the HPO CM. Experiments in vivo using a rodent model of gastric ulcer demonstrated that HPO CM treatment significantly accelerated wound healing by suppressing inflammation and promoting neovascularization and re-epithelization. Meanwhile, the infusion of HPO CM activated the COX2-PGE2 axis both in vitro and in vivo. And the upregulation of COX2 was further dependent on the activation of ErK1/2-MAPK pathway. In addition, vascular endothelial growth factor, tissue inhibitors of metalloproteinases-1, and chemokine (C-C motif) ligand 20 (CCL-20) were analyzed as being highly abundant factors secreted by ADMSCs under hypoxic condition. Notably, the blockade of CCL-20 abrogated the HPO CM-induced COX2 signaling in the primary gastric mucosal epithelial cells, while incubation with recombinant CCL-20 increased the expression of COX2. In conclusion, the secretome from hypoxia-conditioned ADMSCs facilitates the repair of gastric mucosal injury through the enhancement of angiogenesis and re-epithelization, as well as the activation of COX2-PGE2 axis with a paracrine activity involving CCL-20 factor.


Assuntos
Meios de Cultivo Condicionados/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Células-Tronco Mesenquimais/metabolismo , Proteoma/metabolismo , Gastropatias/terapia , Cicatrização/efeitos dos fármacos , Animais , Hipóxia Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Mucosa Gástrica/lesões , Mucosa Gástrica/fisiopatologia , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Cultura Primária de Células , Proteoma/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reepitelização/efeitos dos fármacos , Gastropatias/patologia
19.
Molecules ; 22(12)2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-29189737

RESUMO

Dry eye syndrome is a common disease which can damage the corneal epithelium. It is treated with eye drops to stimulate tear production and hydrate the corneal surface. The most prescribed artificial tear remedies contain hyaluronic acid (HA), which enhances epithelial wound healing, improving tissue health. To the best of our knowledge, only a few recent studies have investigated cross-linked HA (HA-CL) in eye drops for human applications. This work consists in an in vitro evaluation of the re-epithelialization ability of two different preparations containing a recently synthetized HA cross-linked with urea: 0.02% (w/v) HA-CL (solution 1, S1), and 0.4% (w/v) HA-CL (solution 2, S2). The study was conducted on both 2D human corneal cells (HCEpiC) and 3D reconstructed tissues of human corneal epithelium (HCE). Viability by 3(4,5-dimethylthiazol-2)2,5-diphenyltetrazolium bromide (MTT) test, pro-inflammatory cytokine release (interleukin-8, IL-8) by ELISA, and morphology by hematoxylin and eosin (HE) staining were evaluated. In addition, to understand the molecular basis of the re-epithelialization properties, cyclin D1 levels were assessed by western blot. The results showed no cellular toxicity, a slight decrease in IL-8 release, and restoration of epithelium integrity when the wounded 3D model was treated with S1 and S2. In parallel, cyclin D1 levels increased in cells treated with both S1 and S2.


Assuntos
Ácido Hialurônico/análise , Lubrificantes Oftálmicos/química , Lubrificantes Oftálmicos/farmacologia , Análise de Variância , Biomarcadores , Linhagem Celular , Sobrevivência Celular , Ciclina D1/metabolismo , Estabilidade de Medicamentos , Síndromes do Olho Seco , Epitélio Anterior/efeitos dos fármacos , Humanos , Ácido Hialurônico/química , Concentração de Íons de Hidrogênio , Lubrificantes Oftálmicos/análise , Lubrificantes Oftálmicos/síntese química , Reepitelização/efeitos dos fármacos , Viscosidade , Cicatrização/efeitos dos fármacos
20.
Medicine (Baltimore) ; 96(41): e8224, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29019891

RESUMO

INTRODUCTION: Fingertip amputation injuries are common in all ages. Conservatively treated fingertips can regenerate skin and soft tissues to form a functionally and cosmetically excellent new fingertip. Little is known about this ability that, in humans, is confined to the fingertips. Even less is known about the role of the bacteria that regularly colonize these wounds without negative impact on regeneration and healing.As an alternative to surgery, self-adhesive film dressings are commonly used to establish a wet chamber around the injury. These dressings leak malodorous wound fluid eventually until the wound is dry. Having that into consideration, we have therefore developed a silicone finger cap that forms a mechanically protected, wet chamber around the injury for optimal regeneration conditions. It contains a puncturable reservoir for excess wound fluid, which can be thus routinely analyzed for diagnostic and research purposes.This study protocol explains the first randomized controlled trial (RCT) on the semiocclusive treatment of fingertip amputations in both children and adults comparing traditional film dressings with the novel silicone finger cap. Being the first RCT using 2 medical devices not yet certified for this indication, it will gather valuable information for the understanding of fingertip regeneration and the design of future definitive studies. METHODS AND ANALYSIS: By employing an innovative pseudo-cross-over-design with a dichotomous primary endpoint based on patients preference, this pilot study will gain statistically significant data with a very limited sample size. Our RCT will investigate acceptance, safety, effectiveness, and efficacy of this novel medical device while gathering information on the clinical course and outcome of conservatively treated fingertip injuries. A total of 22 patients older than 2 years will be randomly assigned to start the conservative treatment with either the traditional film-dressing or the novel finger cap. The treatment will be changed to the other alternative for another 2 weeks before the patient or the guardian is confronted with the decision of which method they would prefer for the rest of the treatment (if required). ETHICS AND DISSEMINATION: Ethical approval (EK 148042015) of the study protocol has been obtained from Institutional Review Board at the TU Dresden. The trial is registered at the European Database on Medical Devices (EUDAMED-No.: CIV-15-03-013246) and at ClinicalTrials.gov (NCT03089060).


Assuntos
Tratamento Conservador/métodos , Traumatismos dos Dedos/terapia , Equipamentos de Proteção , Lesões dos Tecidos Moles/terapia , Adulto , Amputação Traumática/complicações , Pesquisa Comparativa da Efetividade , Desenho de Equipamento , Feminino , Traumatismos dos Dedos/etiologia , Humanos , Masculino , Curativos Oclusivos , Projetos Piloto , Reepitelização/efeitos dos fármacos , Projetos de Pesquisa , Silicones/uso terapêutico , Lesões dos Tecidos Moles/etiologia , Técnicas de Fechamento de Ferimentos
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