Regulatory role and related mechanism of skin gamma-delta T cell subsets in wound re-epithelialization / 中华烧伤杂志

Re-epithelialization is one of the core links that determines the healing process of skin wounds. The proliferation and differentiation of epidermal stem cells to form new epidermal tissue is the histological basis of re-epithelialization, and the smooth progress of the cell differentiation process of epidermal stem cells-precursor cells-terminal cells is the cytological basis for the continuous formation of new epidermal tissue. The proliferation of stem cells and their differentiation into precursor cells are the determinants of the proliferative potential of newly formed epidermal tissue, while the expansion and differentiation of precursor cells into terminal cells are key factors determining the rate of new epidermal tissue formation. The tissue microenvironment plays a key regulatory role in the process of wound re-epithelialization, and cell growth factor and inflammatory mediators are the two main components of tissue microenvironment, which play regulatory role in different aspects of proliferation and differentiation of epidermal stem cells, jointly promoting the smooth progress of wound re-epithelialization As an important part of skin immune system, the subsets of gamma-delta (γδ) T cells play crucial role in dynamically shaping early wound microenvironment via secreting different cell growth factors and inflammatory factors. From the prospective of immune microenvironment of wound, this paper discusses the role of skin γδ T cells in maintaining the balance of stem cell proliferation and differentiation and regulating wound re-epithelialization, providing a new direction for the prevention and treatment of refractory wound.

Evaluation of the alcoholic extract of Dipteryx alata Vogel almonds and bark in skin wound healing in C57BL6 mice / [Avaliação do extrato alcoólico da casca e da semente da Dipteryx alata Vogel na cicatrização da pele de camundongos C57BL/6]

The aim of this study was to evaluate the topical application of alcoholic extracts of Dipteryx alata Vogel almonds and bark in skin wound healing in mice. Fifty-four C57BL/6 mice were equally distributed into three groups: Control, Almond, and Bark. A 9 mm skin fragment was resected from the dorsal region of the animals' thorax. The wounds were submitted to topical application of base cream (vehicle), 10% hydroalcoholic almond extract, or bark extract twice a day. Macroscopic, histological, and immunohistochemical evaluations were conducted on the 7th, 14th, and 21st postoperative days. No significant difference was observed regarding skin wound area among groups, with the parameter presenting only a temporal effect on healing (p>0.05). The almond and control groups exhibited more intense collagenization than the bark group (p<0.05). Dipteryx alata Vogel showed to be inert in the wound healing process in mice.(AU)

O objetivo deste estudo foi avaliar a aplicação tópica do extrato alcoólico da semente e da casca da Dipteryx alata Vogel na cicatrização de feridas cutâneas, em camundongos. Um total de 54 camundongos C57BL/6 foram utilizados neste estudo, distribuídos em três grupos de 18 animais (controle, semente e casca). Em todos os animais, um fragmento de pele foi ressecado da região dorsal do tórax utilizando-se instrumento de punção de 9mm de diâmetro, após o qual foi realizada aplicação tópica de creme base (veículo), extrato hidroalcoólico 10% de semente ou casca, duas vezes ao dia. As avaliações macroscópica, histológica e imuno-histoquímica foram realizadas no sétimo, 14º e 21º dias de pós-operatório. Não foi observada diferença significativa quanto à área da ferida cutânea entre os grupos, apenas um efeito temporal na cicatrização (P>0,05), indicando estágio possivelmente mais avançado desse processo. Porém, na avaliação histológica, os grupos semente e controle apresentaram colagenização mais intensa que o grupo casca (P<0,05). Dipteryx alata Vogel mostrou-se inerte no processo de cicatrização de feridas em camundongos.(AU)

Tratamento de ferida cirúrgica cutânea em ratos com óleo-resina de copaíba (copaíba reticulata) / Treatment of surgical wounds in rats with copaiba oil-resin (copaiba reticulata)

Foi avaliada a atividade cicatrizante do óleo-resina de copaíba "in natura" em feridas cirúrgicas cutâneas induzidas em ratos. Setenta e dois ratos foram distribuídos em três grupos: Grupo Controle Negativo (GCN), Grupo Controle Positivo (GCP) e Grupo Óleo-resina de Copaíba (GOC). A avaliação da hiperemia por escore na macroscopia mostrou que a chance de um animal apresentar um grau de hiperemia baixo quando tratado com o óleo-resina de copaíba é 1,46 vezes maior que um animal tratado com ácidos graxos essenciais e 2,14 vezes maiores que a chance de um animal tratado com óleo mineral. Com relação ao infiltrado inflamatório na microscopia a probabilidade de ser menor ocorre no GOC em comparação com os GCN e GCP. Em relação ao tempo de reepitelização, a chance de um animal apresentar uma reepitelização mais lenta tratado com ácidos graxos essenciais é de 1,2 vezes a chance de um animal tratado com óleo-resina de copaíba. A análise histológica mostrou que o tecido cicatricial após o tratamento com óleo-resina de copaíba apresentou maior contração da ferida e consequentemente redução do tamanho da ferida visto pela aproximação de anexos da pele no corte histológico. Concluiu-se que o tratamento com óleo-resina de copaíba proporciona maior contração da ferida e aproximação dos anexos da pele.

The healing activity of "in natura" oil-resin of copaíba resin was evaluated in cutaneous surgical wounds induced in rats. Seventy-two rats were divided into three groups: Negative Control Group (GCN), Positive Control Group (GCP) and Copaíba Oil-Resin Group (GOC). Evaluation of hyperemia by macroscopic score showed that the chance of an animal presenting a low degree of hyperemia when treated with copaiba oil-resin is 1.46 times higher than an animal treated with essential fatty acids and 2.14 times greater than the chance of an animal treated with mineral oil. With regard to inflammatory infiltrate under microscopy the probability of being smaller occurs in GOC compared to GCN and GCP. Regarding the time of re-epithelialization, the chance of an animal having a slower reepithelization treated with essential fatty acids is 1.2 times the chance of an animal treated with copaiba oil-resin. Histological analysis showed that cicatricial tissue after treatment with copaiba oil-resin presented greater contraction of the wound due to the approximation of skin attachments. It was concluded that the treatment with copaiba oil-resin provides greater contraction of the wound and approximation of the skin attachments.

Molecular mechanisms in the process of re-epithelization in wound healing and the action of honey in keratinocytes / Mecanismos moleculares en el proceso de re-epitelización en cicatrización de heridas y la acción de la miel en queratinocitos

SUMMARY: The treatment of chronic wounds has become a public health issue in recent years mainly due to comorbidities associated with an older population and bacterial resistance. Honey has emerged as an alternative treatment for chronic wounds but lack of knowledge of its mechanism of actionin the treated tissue and low quality of evidence in clinical triads has distanced the medical community from honey as a possible treatment. One of the main processes that is altered in chronic wounds is re-epithelialization mediated by keratinocytes, where proliferation and migration processes are altered. Markers of proliferation, migration and activation of keratinocytes, such as adhesion molecules, growth factors, membrane receptors, signal translating proteins, transcription factors, microRNAs, among others are deregulated in this process. In general, honeys from different floral origins have a positive effect on markers of proliferation and migration in keratinocytes. In conclusion there are still few studies that focus on the molecular action of honey in keratinocytes and fail to report details on the honey used not allowing to achieve the same results.

RESUMEN: El tratamiento de heridas crónicas (HC) se ha vuelto un tema de salud pública en los últimos años, principalmente debido a comorbilidades asociadas a una población de mayor edad y a la resistencia bacteriana. La miel ha surgido como un tratamiento alternativo para HC pero la falta de conocimiento de su mecanismo de acción en el tejido tratado y de la baja calidad de la evidencia en triadas clínicas, ha distanciado a la comunidad médica de la miel como posible tratamiento. Uno de los principales procesos que se ve alterado en las HC es la re-epitelización mediada por queratinocitos, donde se ven alterados los procesos de proliferación y migración. Marcadores de proliferación, migración y activación de queratinocitos, como moléculas de adhesión, factores de crecimiento, receptores de membrana, proteínas traductores de señales, factores de transcripción, microARNs, entre otras, se ven desreguladas en éste proceso. De manera general las mieles de diferentes orígenes florales tienen un efecto positivo en marcadores de proliferación y migración en queratinocitos. En conclusión aún existen pocos estudios que se enfoquen en la acción molecular de la miel en queratinocitos y los pocos que existen fallan en la entrega de información en relación a la miel utilizada que pueda hacer reproducibles los resultados.

Cicatrização de feridas cutâneas: uso da membrana de látex natural isolada e associada à fibrina rica em plaquetas em ratos Wistar / Healing of skin wounds: use of natural latex membrane isolated and associated with platelet-rich fibrin in Wistar rats

Devido à alta incidência de feridas e lesões de pele, a busca científica tem se focado no desenvolvimento de coberturas e substitutos epidérmicos alternativos às técnicas de enxertia que possuam a mesma função de evitar a exposição de feridas às variações externas. O látex natural derivado da Hevea brasiliensis estimula o processo de cicatrização, assim como a fibrina rica em plaquetas (PRF). A associação desses dois compostos tem como finalidade oferecer um suporte estrutural e estímulo à migração epitelial, associado à proteção e menor desidratação do leito cicatricial. No presente estudo, investigamos a resposta de reparo cicatricial em feridas agudas de espessura total em ratos Wistar, submetidos a três diferentes tratamentos: membrana de látex associada à PRF (ML+PRF), apenas a membrana de látex (ML) e controle com solução de cloreto de sódio a 0,9% estéril em. A avaliação macroscópica foi realizada por mensuração, posteriormente a amostra tecidual foi coletada e submetida à coloração com Hematoxilina & Eosina e Picrosirius Red para análise histológica. Para análise estatística, as variáveis quantitativas foram determinadas por ANOVA (pós-teste de Tukey) e as variáveis semiquantitativas determinadas pelo teste de Friedman (pósteste de Dunn), sendo considerados significantes quando p<0,05. Como resultados houve diminuição significativa no diâmetro da ferida e melhor reepitelização em relação aos controles , assim como houve estímulo à deposição de colágeno tipo I, que gera resistência tecidual. Não foram observadas complicações quanto ao uso dessa associação, portanto auxilia no reparo da pele em tratamento de feridas agudas de espessura total em ratos Wistar hígidos(AU)

Due to the high incidence of wounds and skin lesions, scientific research has focused on the development of alternative epidermal coverings and substitutes to grafting techniques that have the same function of preventing the exposure of wounds to external variations. The natural latex derived from Hevea brasiliensis stimulates the healing process, as well as platelet-rich fibrin (PRF). The association of these two compounds aims to provide structural support and stimulate epithelial migration, associated with protection and less dehydration of the healing bed. In the present study, we investigated the healing repair response in acute full-thickness wounds in Wistar rats, submitted to three different treatments: latex membrane associated with PRF (ML + PRF), only the latex membrane (ML), and control with a solution of 0.9% sodium chloride sterile. The macroscopic and microscopic evaluations were performed by measurement, followed by tissue sample collection and staining with Hematoxylin & Eosin and Picrosirius Red for histological analysis. For statistical analysis, quantitative variables were determined by ANOVA (Tukey's post-test) and semi-quantitative variables were determined by Friedman's test (Dunn's post-test), being considered significant when p<0.05. As a result, there was a significant decrease in the wound diameter and better re-epithelialization concerning the controls, as well as the deposition of type I collagen, which generates tissue resistance. No complications were observed regarding the use of this association. Therefore, it assists in skin repair in the treatment of acute full-thickness wounds in healthy Wistar rats(AU)

Efeito da estimulação elétrica no processo de reparação de tecido mole no palato: estudo em camundongos / Effect of electrical stimulation on soft tissue repair process at the palate: a study in mice

A estimulação elétrica (EE) tem sido usada no tratamento de lesões crônicas apresentando resultados favoráveis no fechamento da lesão cutânea entre outras aplicações clínicas. No entanto, a literatura carece de estudos avaliando se os efeitos da EE no fechamento da lesão oral. Diante disso, torna-se relevante investigar os efeitos da EE durante o processo de reparo da lesão oral em camundongos (Swiss). Métodos: Noventa animais foram divididos em grupos: Controle (C; n=45) que receberam a aplicação da EE com o aparelho desligado e Teste (EE; n=45) que receberam a EE (100 µA; 9 kHz; 660 mVpp; 1x/dia por 3 dias). Uma lesão de espessura total foi realizada com punch de biópsia de 1,5 mm de diâmetro. Os animais foram eutanasiados no 1o, 3o e 5o dia após a confecção da lesão. As amostras foram fixadas em paraformaldeído 4%, descalcificadas em ácido fórmico 20% e emblocadas em parafina. Os parâmetros avaliados foram: fechamento clínico da lesão; distância de reparação epitelial (DRE) e conjuntiva (DRC), concentração de citocinas IL-1ß, IL-6, IL-8, IL-10, TNF-α e VEGF; porcentagem de fibras colágenas e quantificação das proteínas de sinalização Smad2. Resultados: A área de fechamento clínico foi reduzida no grupo EE no 5º dia de avaliação (p=0,01). As DRE e DRC do grupo EE apresentaram menor distância em todos os tempos avaliados (p<0,05) com reduzida concentração de IL-6, TNF-α, IL-10 e VEGF (p<0,05). Não houve diferença na porcentagem de fibras colágenas e na phospho-Smad2. Conclusão: A EE teve efeito positivo nos parâmetros clínicos e histológicos com modulação da resposta inflamatória no início do processo de reparo da lesão(AU)

Background: Since Electrical Stimulation (ES) has used for chronic wounds treatment and other clinical applications showing favorable results in wound closure, it was hypothesized whether it could bring good results in oral wound closure. The aim was to investigate the ES effects during the oral wound healing process in mice (Swiss). Methods: Ninety animals were divided in groups: Control (C; n=45) which received a fictitious ES application, i.e. the ES applicance was shutted off and ES (ES; n=45) which received ES (100 µA; 9 kHz; 660 mVpp) once time a day for 3 days consecutively. A full thickness wound was done using a 1.5 mm diameter biopsy punch in the hard palate. The animals were euthanized on 1st, 3rd and 5th day post-wounding. The samples were fixed, decalcified and embedded in paraffin. The parameters evaluated were: clinical wound closure; distance of epithelial and connective wound edges (EWD and CWD); cytokines (IL-1ß, IL-6, IL-8, IL-10), TNF-α and VEGF by multiplex, percentage of collagen fibers and Smad proteins. Results: Clinical wound closure area was reduced on day 5 in ES group (p = 0.01). Both EWD and CWD distance were shorter in all times (p < 0.05) with a reduction of inflammatory cytokines production (p < 0.05). There were no difference in collagen percentage and phospho-Smad2. Conclusion: ES had a positive effect on clinical and histomorphometric wound closure outcomes showing a modulation of inflammatory response in the beginning of wound healing(AU)

Patterns in the amount of discharge at split-thickness skin graft donor sites

BACKGROUND: Split-thickness skin grafts (STSGs) are commonly used in the reconstruction of skin defects induced by trauma or burns. Although STSGs are used to successfully treat various wound types, donor site wounds can be challenging, and complications often develop. Therefore, optimal donor site dressings are required. In this study, we introduce an evidence base for patterns in how the discharge amount decreases over time, with the goal of providing insights into the selection of dressing materials. METHODS: Twenty patients with burns who received STSGs harvested from the thigh between January 2016 to April 2017 were prospectively reviewed. A donor site dressing with foam was changed daily. The weight of the foam dressing was measured before and after placement on the donor site. The wound area was calculated using Visi-Trak. The mean weight of the discharge amount per unit area (g/10 cm2) was calculated. RESULTS: The mean weight of the discharge amount per unit area (g/10 cm2) decreased from 3.84 to 2.02 (P < 0.05) and 1.09 (P < 0.05) on postoperative days 5 and 10, respectively. It further decreased to 0.61 by postoperative day 14. CONCLUSIONS: To prevent infections induced by donor site leakage, the use of highly-absorptive foam materials until 5 days after the operation is beneficial. Moreover, hydrocolloid or highly-absorptive foam materials can be used to promote re-epithelialization of the donor site after 5 days postoperatively. For re-epithelialization and wound protection, it is effective to use hydrocolloid materials starting on postoperative day 10.

Pain Relief Efficacy of Ibuprofen Releasing Foam Dressing (Biatain Ibu®) on Outpatient Patient with Partial Thickness Burn Wound

PURPOSE: Pain management in burn treatment is important in improving wound healing and quality of life. Ibuprofen is a proven pain relieving agent in patients with partial thickness burn by intraveous injection. The purpose of this study is to evaluate the efficacy of Biatain Ibu® (polyurethane foam containing ibuprofen) in pain control for outpatients with partial thickness burns. METHODS: A prospective randomized clinical trial was performed in outpatients with partial thickness burn from August 1, 2017 to July 31, 2018. Acute pain, chronic pain, complications, days for re-epithelialization and patient's satisfaction were compared between Biatain Ibu® and Biatain® groups. RESULTS: A total of 20 patients (Biatain Ibu®, n=10; Biatain®, n=10) were assessed in the trial. On Burn days 3, 5, 7, 11, 13, and 15, the acute pain levels were significantly lower in the Biatain Ibu® group than in the Biatain® group. Complications, chronic pain levels and days for re-epithelialization were not significantly different between the two groups. Patient's satisfaction was not statistically significant but was higher in the Biatain Ibu® group. CONCLUSION: Biatain Ibu® is effective in relieving pain in outpatients with partial thickness burn without decreasing patient satisfaction, wound healing ability or developing any complications.

O plasma rico em fatores de crescimento no tratamento de pacientes com úlceras venosas / Plasma rich in growth factors in the treatment of patients with venous ulcers

Objetivo geral: Analisar as propriedades do plasma rico em fatores de crescimento (PRGF) autólogo, para tratar pacientes com úlceras venosas. Método: Trata-se de um estudo quase- experimental realizado em um Hospital Universitário, cuja coleta de dados ocorreu no período de maio de 2016 a dezembro de 2017. Amostra composta por 18 pacientes com úlcera venosa, que atenderam aos critérios de inclusão. Os participantes compareceram por 12 semanas consecutivas, ao ambulatório para consulta de enfermagem e troca do curativo, com aplicação do PRGF a cada 15 dias. O preparo do PRGF utilizou a técnica de uma centrifugação e o gluconato de cálcio como ativador plaquetário. Realização da contagem de plaquetas e identificação dos fatores de crescimento no PRGF usado no tratamento. Resultados: Amostra homogênea quanto às variáveis socioeconômicas e clínicas, com predomínio de idosos, sexo masculino, ensino fundamental incompleto e renda entre um e dois salários mínimos. Obtenção de um PRGF com contagem baixa de plaquetas, mediana de 122 x 103 mm3 plaquetas, mas com principais fatores de crescimento plaquetários envolvidos na cicatrização (PDGF-AB, PDGF-BB, TGF-ß, VEGF, EGF e FGF2). Houve alta variabilidade na contagem de plaquetas e na concentração de fatores de crescimento, com correlação forte e significativa entre a quantidade de plaquetas e os fatores de crescimento PDGF-AB e PDGF-BB. As médias de cada fator de crescimento foram 1,52 ng/ml para o PDGF-AB, 1,38 ng/ml para o PDGF-BB, 1,40 ng/ml para o TGF-ß, 0,99 ng/ml para VEGF, 1,57 ng/ml para o EGF e 1.04 ng/ml para o FGF2. O tamanho inicial médio das úlceras neste estudo foi de 29,6 ± 23,9 /cm2 e o percentual médio de redução da área após 12 semanas de tratamento foi de 46,2%. O tamanho das úlceras após tratamento era significativamente menor do que o tamanho inicial das úlceras (p-valor do teste de Wilcoxon igual a 0,001). Entretanto, a redução da área das úlceras, no período das 12 semanas, não apresentou correlação com as concentrações dos fatores de crescimento no PRGF. A percentagem de tecido de epitalização apresentou crescimento em todo período do estudo com aumento significativo ao final de 12 tratamento (média = 58,1%) e o tecido desvitalizado apresentou decrescimento durante todo o período do estudo com redução significativa ao final de 12 semanas (média = 11%). Ao final de 12 semanas observou-se uma melhora significativa do tipo de exsudato nas úlceras e uma diminuição significativa da quantidade de exsudato nas úlceras. Conclusão: Neste estudo, foi confirmada a hipótese nula em que a concentração dos fatores de crescimento presentes no PRGF não apresentou relação estatisticamente significativa com a redução da área das úlceras venosas.

Objective: To analyze the properties of autologous plasma rich in growth factors (PRGF), to treat patients with venous ulcers. Method: It is a quasi-experimental clinical study performed in a University Hospital, the data collection occurred from May 2016 to December 2017. Sample of 18 patients with venous ulcer, who met the inclusion criteria. The participants attended weekly for 12 weeks to the outpatient clinic for nursing consultation and dressing change, with application of the plasma rich in growth factors (PRGF) for each 15 days. The PRGF preparation used the single- centrifugation technique and calcium gluconate as a platelet activator. Realization of platelet count and identification of growth factors in PRGF used in treatment. Platelet counting and identification of growth factors in the PRGF used in the treatment. Results: Homogeneous sample regarding socioeconomic and clinical variables, with predominance of the elderly, male gender, incomplete primary education and income between 1 and 2 minimum wages. A PRGF with a low platelet count, median of 122 x 103 mm3 platelets, but with the main platelet growth factors involved in the healing (PDGF-AB, PDGF-BB, TGF-ß, VEGF, EGF and FGF2). There was a high variability in platelet counts and in the concentration of growth factors, with a strong and significant correlation between the amount of platelets and the growth factors PDGF-AB and PDGF-BB. The means of each growth factor were 1.52 ng / ml for PDGF-AB, 1.38 ng / ml for PDGF-BB, 1.40 ng / ml for TGF-ß, 0.99 ng / ml for VEGF, 1.57 ng / ml for EGF and 1.04 ng / ml for FGF2. The initial mean size of the ulcers in this study was 29.6 ± 23.9 / cm2 and the percentage mean reduction in area after 12 weeks of treatment was 46.2%. The ulcer size after treatment was significantly smaller than the initial ulcer size (Wilcoxon p-value = 0.001). However, the area of ulcer reduction over the 12-week period did not correlate with growth factor concentrations in PRGF. The percentage of epitalization tissue increased throughout the study period with a significant increase at the end of 12 treatments (mean = 58.1%) and devitalized tissue decreased throughout the study period with a significant reduction at the end of 12 weeks (mean = 11%). At the end of 12 weeks there was a significant improvement in the type of exudate in the ulcers and a significant decrease in the amount of exudate in the ulcers. Conclusion: In this study, the null hypothesis was confirmed that the concentration of growth factors present in PRGF did not present statistically significant relationship with the reduction of venous ulcers area.

Objetivo general: Analizar las propiedades del plasma rico en factor de crecimiento autólogo (PRGF) para tratar pacientes con úlcera venosa. Método: Estudio cuasi experimental realizado en un hospital universitario. Datos recolectados entre mayo de 2016 y diciembre de 2017. Muestra compuesta por 18 pacientes con úlcera venosa que cumplieron los criterios de inclusión. Los participantes asistieron semanalmente, durante 12 semanas, a la clínica ambulatoria para consulta de enfermería y cambio de apósito, con aplicación de plasma rico en factor de crecimiento (PRGF) en frecuencia bisemanal. La preparación de PRGF utilizó la técnica de centrifugación; se empleó gluconato de calcio como activador plaquetario. Se efectuó recuento de plaquetas e identificación de los factores de crecimiento en el PRGF utilizado en el tratamiento. Resultados: Muestra homogénea en sus variables socioeconómicas y clínicas, con predominio de ancianos, varones, estudios primarios incompletos, con ingresos de entre 1 y 2 salarios mínimos. Se obtuvo un PRGF con bajo recuento de plaquetas, con mediana de 122 x 103 mm3 de plaquetas, aunque con importantes factores de crecimiento plaquetario involucrados en la curación (PDGF-AB, PDGF-BB, TGF-ß, VEGF, EGF y FGF2). Existió marcada variabilidad en el recuento plaquetario y en la concentración del factor de crecimiento, con marcada y significativa correlación entre la cantidad de plaquetas y factores de crecimiento PDGF-AB y PDGF-BB. Los promedios de cada factor de crecimiento fueron 1.52 ng / ml para PDGF-AB, 1.38 ng / ml para PDGF-BB, 1.40 ng / ml para TGF-ß, 0.99 ng / ml para VEGF, 1,57 ng / ml para EGF y 1,04 ng / ml para FGF2. El tamaño inicial promedio de las úlceras observadas en este estudio fue de 29,6 ± 23,9 / cm2, y la reducción porcentual media en el área luego de 12 semanas de tratamiento fue del 46,2%. El tamaño de las úlceras luego del tratamiento resultó ser significativamente inferior a su tamaño inicial (p-valor del test de Wilcoxon igual a 0,001). Sin embargo, la reducción del área de las úlceras, durante el período de 12 semanas, no se correlacionó con las concentraciones de los factores de crecimiento en el PRGF. El porcentaje de tejido epitelial aumentó durante todo el período del estudio, con un aumento significativo final en 12 tratamientos (media = 58,1%). El tejido desvitalizado disminuyó a lo largo del estudio, con reducción significativa luego de 12 semanas (promedio = 11%). Finalizadas las 12 semanas, hubo mejora significativa en el tipo de exudado de las úlceras y disminución significativa de la cantidad de exudado de las úlceras. Conclusión: En este estudio, se confirmó la hipótesis nula en que la concentración de los factores de crecimiento presentes en el PRGF no presentaba una relación estadísticamente significativa con la reducción del área de las úlceras venosas.

Effect of the bioprotectant agent trehalose on corneal epithelial healing after corneal cross-linking for keratoconus / Efeito do agente bioprotetor trealose na cicatrização epitelial da córnea após reticulação corneana para ceratocone

ABSTRACT Purpose: This study aimed to compare the effectiveness of eye drops containing a combination of sodium hyaluronate and trehalose and sodium hyaluronate for the treatment of corneal cross-linking and epithelial healing. Methods: This study included 46 eyes of 23 keratoconus patients who underwent corneal cross-linking on both eyes. Unpreserved trehalose 30 mg/mL and sodium hyaluronate 1.5 mg/mL (Thealoz Duo®; Thea, France) were applied six times a day on one eye of each patient and unpreserved sodium hyaluronate 0.15% (Eye Still®; Teka, Inc., Istanbul) was applied on the other eye. Patients were examined daily until complete re-epithelialization. Postoperative examinations to assess the measured size of epithelial defect were performed using slit-lamp biomicroscopy. Results: The study included 23 patients (13 females and 10 males) with a mean age of 20.9 ± 10.3 years. Corneal epithelial healing time after cross-linking was 2.3 ± 1.2 days for the trehalose and sodium hyaluronate group and 3.8 ± 2.9 days for the sodium hyaluronate group (p=0.03). Conclusion: The application of eye drops containing the combination of trehalose and sodium hyaluronate resulted in faster corneal re-epithelialization following corneal cross-linking than that of eye drops containing sodium hyaluronate alone.

RESUMO Objetivo: Este estudo teve como objetivo comparar a eficácia de colírios contendo uma combinação de hialurônico de sódio e hialuronato de sódio e trealose para o tratamento da cicatrização epitelial em pacientes com cross-linking corneano. Métodos: Este estudo inclui 46 olhos de 23 pacientes com ceratocone, que foram operados com cross-linking corneano em ambos os olhos. Trealose não preservada 30 mg/mL e hialuronato de sódio 1,5 mg/mL (Thealoz Duo®; Thea, França) foram aplicados seis vezes por dia em um olho de cada paciente e hialuronato de sódio não conservado, 0,15% (Eye Still®; Teka, Inc., Istambul) foi aplicada no outro olho. Os pacientes foram examinados diariamente até a completa reepitelização. Exames pós-operatórios para avaliar o tamanho medido do defeito epitelial foram realizados usando biomicroscopia com lâmpada de fenda. Resultados: O estudo incluiu 23 pacientes (13 mulheres e 10 homens) com idade média de 20,9 ± 10,3. O tempo de cicatrização epitelial da córnea após o cross-linking foi de 2,3 ± 1,2 dias para o grupo trealose e hialuronato de sódio e 3,8 ± 2,9 dias para o grupo hialurônico de sódio (p=0,03). Conclusão: A aplicação de gotas para os olhos contendo combinação de trealose e hialuronato de sódio resultou em uma re-epitelização da córnea mais rápida após o cross-linking corneano do que a de gotas contendo hialurônico de sódio apenas.

Comparación de dos técnicas de curación en pacientes quemados pediátricos / Comparison of two healing techniques in pediatric burned patients

Introducción: Existen varias curaciones para quemaduras. La sulfadiazina de plata se ha usado por años pero las membranas microporosas son cada vez más preferidas. Objetivos: Comparar la eficiencia de las membrana microporosa (Telfa Clear®) versus sulfadiazina de plata (Platsul®) en menores de 15 años hospitalizados por quemadura. Pacientes y Métodos: Estudio de cohorte retrospectivo de 87 pacientes, dividido en 2 grupos comparables en extensión y profundidad de la quemadura, edad y sexo. Durante enero a diciembre 2007 se curaron 52 pacientes con Platsul® y desde enero a octubre 2008 se curaron 35 con Telfa Clear®. Se evalúa tiempos y extensión de reepitelización, porcentaje de injertos, costos, días de hospitalización, número de curaciones, complicaciones, almacenamiento-estabilidad y costos. Estadística no paramétrica para el análisis univariado y regresión logística multivariado en Stata 11.2. Resultados: Los pacientes curados con Platsul® se injertaron más tardíamente y presentan más curaciones. Platsul® es peor evaluado por su almacenamiento-estabilidad y mayores costos. No hay diferencia en la incidencia de infección. Conclusiones: Ambas Técnicas son eficientes en permitir reepitelización, pero Platsul® puede demorar el injerto. La Telfa Clear® es mejor evaluado por el equipo de salud en cuanto a almacenamiento y estabilidad. El menor costo de Telfa Clear® es una ventaja.

Introduction: There are several dressings for burns. Silver sulfadiazine has been used for years but microporous membranes are increasingly preferred. Objectives: To compare the efficiency of microporous membrane (Telfa Clear®) versus silver sulfadiazine (Platsul®) in children younger than 15 years old hospitalized for burns. Patients and Methodology: Retrospective cohort study of 87 patients, divided into 2 comparable groups in extent and depth of the burn, age and sex. During January to December 2007, in 52 patients Platsul® were use and in 35 patients Telfa Clear® were use from January to October 2008. The time and extent of re-epithelialization, percentage of grafts, costs, length of stay, number of dressing change, complications, storage-stability and costs are evaluated. Non-parametric statistics were used for univariate analysis and logistic regression for multivariate analysis en Stata 11.2. Results: Platsul® was associate to a later graft and had a greater number of dressing changes. Platsul® is worst rated for its storage-stability and higher costs. No difference in infection rate was observed. Conclusions: Both techniques are efficient in allowing re-epithelialization, but burns treated with Platsul® were grafted later than when Telfa Clear® was used. Telfa Clear® is best evaluated by the health team in terms of storage and stability. The cost of Telfa Clear® is presented as an advantage.

Effect of powdered shells treatment of the snail Megalobulimus lopesi on wounds of diabetic rats

Abstract Purpose: To analyzed the healing effect of the powdered shell of the Megalobulimus lopesi snail on wounds of diabetic rats, since in non-diabetic rats the powdered shell presented healing potential. Methods: Seventy-two Wistar rats (Rattus norvegicus albinus) were divided into three groups: Control group (GC.diab), no therapeutic intervention on the wound; Vehicle's Control group, topical via, in diabetic rats (GCvt.diab): Powder Shell Group (PC) applied topically (GPCvt.diab): Experimental group was administered topically shortly after wound dressing and once a day during the experimental period (3, 7, 14 and 21 days) the composition containing the powdered shell of the snail. The following variables related to the healing potential were analyzed: macroscopic one, where the capacity of reduction of the wound area was evaluated; histological analysis in HE, angiogenic activity, morphometric analysis (re-epithelization), leukocyte inflammatory infiltrate; leukocyte count and also differentiation in peripheral blood. Results: The topical application in wounds of diabetic rats presented healing activity, accelerating wound closure, stimulating angiogenesis and being pro-inflammatory in the early and anti-inflammatory stages in the final times of the healing process. Conclusion: The topical administration of the powdered shell on wounds of diabetic patients becomes a therapeutic option of low cost, with ease in the administration and access as well.

Immune mechanisms in the different phases of acute tubular necrosis

Acute kidney injury is a clinical syndrome that can be caused by numerous diseases including acute tubular necrosis (ATN). ATN evolves in several phases, all of which are accompanied by different immune mechanisms as an integral component of the disease process. In the early injury phase, regulated necrosis, damage-associated molecular patterns, danger sensing, and neutrophil-driven sterile inflammation enhance each other and contribute to the crescendo of necroinflammation and tissue injury. In the late injury phase, renal dysfunction becomes clinically apparent, and M1 macrophage-driven sterile inflammation contributes to ongoing necroinflammation and renal dysfunction. In the recovery phase, M2-macrophages and anti-inflammatory mediators counteract the inflammatory process, and compensatory remnant nephron and cell hypertrophy promote an early functional recovery of renal function, while some tubules are still badly injured and necrotic material is removed by phagocytes. The resolution of inflammation is required to promote the intrinsic regenerative capacity of tubules to replace at least some of the necrotic cells. Several immune mechanisms support this wound-healing-like re-epithelialization process. Similar to wound healing, this response is associated with mesenchymal healing, with a profound immune cell contribution in terms of collagen production and secretion of profibrotic mediators. These and numerous other factors determine whether, in the chronic phase, persistent loss of nephrons and hyperfunction of remnant nephrons will result in stable renal function or progress to decline of renal function such as progressive chronic kidney disease.

Early Wound Healing Score: a system to evaluate the early healing of periodontal soft tissue wounds

PURPOSE: Numerous indices have been proposed to analyse wound healing in oral soft tissues, but each has specific shortcomings. A new method of analysis, the Early Wound Healing Score (EHS), was evaluated in the present study. The aim was to assess more accurately early healing by primary intention of surgical incisions in periodontal soft tissues. METHODS: Twenty-one patients were treated with different surgical procedures comprising 1 or 2 vertical releasing incisions as part of a surgical access flap. Twenty-four hours after surgery, early wound healing at the vertical releasing incisions was assessed using the EHS. This score assessed clinical signs of re-epithelialization (CSR), clinical signs of haemostasis (CSH), and clinical signs of inflammation (CSI). Since complete wound epithelialization was the main outcome, the CSR score was weighted to be 60% of the total final score. Accordingly, a score of 0, 3, or 6 points was possible for the assessment of CSR, whereas scores of 0, 1, or 2 points were possible for CSH and CSI. Higher values indicated better healing. Accordingly, the score for ideal early wound healing was 10. RESULTS: Thirty vertical releasing incisions were assessed in 21 patients. At 24 hours after incision, 16 vertical releasing incisions (53.33%) received the maximum score of CSR, while 6 cases (20%) received an EHS of 10. None of the cases received 0 points. CONCLUSION: The EHS system may be a useful tool for assessing early wound healing in periodontal soft tissue by primary intention after surgery.

Adipose Stem Cells with Conditioned Media for Treatment of Acne Vulgaris Scar

This study was to investigate the effect of subcutaneous injection of the adipose stem cells (ASCs) with conditioned media (CM) in the treatment of acne vulgaris scar. We used Adult male New Zealand white rabbit ears as an animal model and induced acne formation by Kignman method. Adipose tissue was isolated and harvested from the scapula of rabbits, and ASCs were cultured and expanded until passage 1. There have four groups in our experiment, include phosphate buffered saline (PBS), ASCs with PBS (ASC + PBS), CM, and ASCs with CM (ASC + CM) group. This solution of 0.6 ml injected to subcutaneous in each group. ASC + PBS and ASC + CM groups were containing ASCs of 5.0 × 106 cells/ml. We analyzed the treatment of 4 groups to scar tissue after 2 and 4 weeks by hematoxylin and eosin stain, immunohistochemistry, and RNA expression level of tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and matrix metalloproteinase-2 (MMP-2). Also, the expression of keratin 16 (K16) was detected by western blot analysis. H&E stain showed that infiltration of inflammation cells was significantly reduced at 2 and 4 weeks, as well as re-epithelialization was improved in the ASC + CM group. The ASC + CM gourp was reduced both expression levels of TNF-α, IL-1α, and MMP-2 and K16 protein level. In conclusion, the ASCs with CM has a significant curative effect on acne vulgaris scar, more to the point, the CM has a key role on treatment. It could be applied to a therapeutic approach to regenerate to treat acne vulgaris scar.

Application of a paste-type acellular dermal matrix for coverage of chronic ulcerative wounds

BACKGROUND: Chronic wounds occur due to failure of the normal healing process, associated with a lack of deposition of cellular components and a suitable microenvironment such as the extracellular matrix (ECM). Acellular dermal matrix (ADM) is viewed as an ECM substitute, and a paste-type ADM has recently been introduced. We hypothesized that CGPaste, an injectable paste-type ADM, could serve as a scaffold and promote wound healing. METHODS: We retrospectively studied seven patients in whom CGPaste was applied between 2017 and 2018, who had pressure ulcers, necrotizing fasciitis, diabetic foot ulcers, traumatic defects, and osteomyelitis. The goal of applying CGPaste was to achieve complete wound healing with re-epithelialization or growth of granulation tissue, depending upon the wound bed status. CGPaste was injected based on the wound size along with the application of a dressing. RESULTS: Four of the seven patients showed granulation tissue on their wound bed, while the other three patients had a bony wound bed. The mean wound area was 453.57 mm2 and the depth was 10.71 mm. Wound healing occurred in five of the seven patients (71.43%). The mean duration of complete healing was 2.4 weeks. Two patients showed failure due to paste absorption (29.57%); these patients had wound beds comprising bone with relatively large and deep wounds (40×30 and 30×20 mm2 in area and 15 and 10 mm in depth). CONCLUSIONS: CGPaste is an effective option for coverage of small and deep chronic wounds for which a flap operation or skin grafting is unfeasible.

Topical Administration of the Recombinant Human Epidermal Growth Factor (EGF) Containing Ointment on the Tendon Exposed Skin Defect in Foot Digit: A Case Report

Contact burn is usually caused by prolonged contact to hot material and results in deep dermal injury. As a result, skin and soft tissue defects occur, and coverage of defect is required. When defect is located in the foot phalanxes, reconstruction becomes more challenging owing to anatomical features. If the patient has medical histories such as diabetes mellitus, peripheral arterial obstructive disease, or chronic kidney disease, peripheral circulation may be worsened, and reconstruction becomes more difficult. We present the case of a patient with contact burn wound on his foot phalanxes and dorsum, where extensor digitorum tendons were exposed. Initial trial of skin graft was failed and they were completely epithelialized through secondary-intention healing with the administration of ointment containing recombinant human epidermal growth factor.

The Clinical Usefulness of Thermo-Sensitive Hydrogel-Type Allogeneic Keratinocytes for Treatment of Deep Second-Degree Burn

PURPOSE: Aim of this study was to assess the safety and effectiveness of Keraheal-Allo® (Biosolution Co., Ltd., Korea) in patients with deep second-degree burn as a part of post marketing surveillance. METHODS: Seventy-five patients with deep second-degree burn were enrolled from April 2017 to October 2017. Keraheal-Allo, a thermos-sensitive hydrogel-type allogeneic keratinocytes, was applied to 90 deep second-degree burn sites of 75 patients. After application of Keraheal-Allo, the efficacy was assessed as the period of 100% re-epithelialization that was evaluated every time dressing was changed. RESULTS: The mean re-epithelialization period in the treated sites with KeraHeal-allo was 13.67±5.11 days. There was no severe adverse event. CONCLUSION: In conclusion, this thermo-sensitive hydrogel-type allogeneic keratinocytes have the clinical usefulness in terms of the safety, efficacy and ease of use.

Evaluation of a polyurethane foam dressing impregnated with 3% povidone-iodine (Betafoam) in a rat wound model

PURPOSE: The purpose of this study was to evaluate the efficacy of Betafoam in terms of wound healing and safety. METHODS: Fifty-four male adult Sprague-Dawley rats (weight, 200–250 g) were used in the study. Full-thickness skin defects were created on the back of each rats. The rats were assigned to 6 groups according to the type of wound dressing used (n = 9 for each group): Betafoam, Allevyn-Ag, Mepilex-Ag, Medifoam silver, Polymem-Ag, and gauze. The wound size, histological findings, and amount of DNA on the changed dressings for each group were analyzed and compared. RESULTS: All groups showed an effective decrease in wound size. However, the differences between Betafoam and the other dressings were statistically significant on day 14 (P < 0.05). The number of newly generated blood vessels in the Betafoam group was significantly higher than in the gauze, Allevyn-Ag, and Medifoam silver groups (P < 0.001). In the Betafoam group, the proportion of collagen deposition was highest and showed a significantly superior arrangement of collagen fibers compared with the gauze, Allevyn-Ag, Mepilex-Ag, and Medifoam silver groups. The total content of the remaining DNA counts of the exchanged dressings were significantly lower in the Betafoam group than the others. CONCLUSION: Betafoam is effective in wound healing and provides the best performance amongst the various types of dressing materials in terms of re-epithelialization, angiogenesis, collagen deposition, and tissue invasion.

Effect of Topical Erythropoietin (EPO) on palatal wound healing subsequent to Free Gingival Grafting (FGG)

Abstract 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.