Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice / Las Moléculas Pequeñas Aceleran la Curación de Heridas en la Piel: Eficacia de Shikonin y Mecanismo de Acción en Ratones

SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.

El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.

Propriedades Químicas e Farmacológicas do Gênero Copaifera no Tratamento de Lesões/feridas: Revisão Integrativa / Chemical and Pharmacological Properties of the Genus Copaifera in the Treatment of Injuries/wounds: Integrative Review / Propiedades Químicas y Farmacológicas del Género Copaifera en el Tratamiento de Lesiones/heridas: Revisión Integradora

Objetivo:Identificar propriedades químicas e farmacológicas do gênero Copaifera no tratamento de lesões e feridas. Método: Revisão integrativa da literatura realizada nas bases de dados LILACS, MEDLINE, PubMed, Taylor & Francis e Scopus, em janeiro de 2022, por meio da estratégia de busca: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" e "Pharmacology" AND "Copaifera" AND "Wounds and Injuries". Foram incluídos artigos originais, de texto completo, identificados de acordo nível de evidência, redigidos em português, inglês ou espanhol. Resultados: Na busca primária foram encontrados 261 artigos. Após a seleção sistematizada, 12 estudos foram selecionados para análise qualitativa. Espécies do gênero Copaifera apresentam propriedades farmacológicas favoráveis ao tratamento de feridas: controle da dor inflamatória, diminuição da reação inflamatória, reepitelização e reparo tecidual, angiogênese, retração da ferida e remodelagem de cicatrizes. Dentre as propriedades químicas associadas ao tratamento de lesões, destacam-se presença de compostos bioativos: diterpenos, 3-hidroxi-copálico, sesquiterpenos, éster kolavic-15-metílico. Entre os diterpenos testados, o caurenoico e os ácidos copálicos mostraram atividades hemolíticas significativas. Apenas o ácido copálico e o ácido hardwíckiico inibiram a produção de óxido nítrico em macrófagos ativados por lipopolissacarídeos. Conclusão: As plantas do gênero Copaifera apresentam propriedades químicas e farmacológicas favoráveis ao tratamento de lesões e feridas

Objective:To identify chemical and pharmacological properties of Copaifera in the treatment of injuries and wounds. Method: Integrative literature review conducted in the LILACS, MEDLINE, PubMed, Taylor & Francis and Scopus databases in January 2022, using the search strategy: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" and "Pharmacology" AND "Copaifera" AND "Wounds and Injuries." Original articles, full text, identified according to level of evidence, written in Portuguese, English or Spanish, were included. Results: In the primary search 261 articles were found. After systematized selection, 12 studies were selected for qualitative analysis. Species of the genus Copaifera have pharmacological properties favorable for wound treatment: control of inflammatory pain, reduction of inflammatory reaction, tissue reepithelialization and repair, angiogenesis, wound retraction and scar remodeling. Among the chemical properties associated with the treatment of injuries, the presence of bioactive compounds stand out: diterpenes, 3-hydroxy-copalic, sesquiterpenes, kolavic-15-methyl ester. Among the tested diterpenes, kaurenoic and copalic acids showed significant hemolytic activities. Only copalic acid and hardwickiic acid inhibited nitric oxide production in lipopolysaccharide-activated macrophages. Conclusion: Plants of the genus Copaifera have chemical and pharmacological properties favorable for the treatment of injuries and wounds.

Objetivo:Identificar las propiedades químicas y farmacológicas del género Copaifera en el tratamiento de lesiones y heridas. Método: Revisión integradora de la literatura realizada en las bases de datos LILACS, MEDLINE, PubMed, Taylor & Francis y Scopus, en enero de 2022, mediante la estrategia de búsqueda: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" e "Pharmacology" AND "Copaifera" AND "Wounds and Injuries". Se incluyeron artículos originales, a texto completo, identificados según el nivel de evidencia, escritos en portugués, inglés o español. Resultados: En la búsqueda primaria se encontraron 261 artículos. Tras una selección sistematizada, se seleccionaron 12 estudios para el análisis cualitativo. Las especies del género Copaifera presentan propiedades farmacológicas favorables para el tratamiento de las enfermedades: control del dolor inflamatorio, disminución de la reacción inflamatoria, reepitelización y reparación tecidual, angiogénesis, retracción de la piel y remodelación de las cicatrices. Entre las propiedades químicas asociadas al tratamiento de las lesiones, destaca la presencia de compuestos bioactivos: diterpenos, 3-hidroxicopálico, sesquiterpenos, éster kolavico-15-metilo. Entre los diterpenos probados, los ácidos kaurenoico y copálico mostraron actividades hemolíticas significativas. Sólo el ácido copálico y el ácido hardwickiico inhibieron la producción de óxido nítrico en macrófagos activados por lipopolisacáridos. Conclusión: Las plantas del género Copaifera presentan propiedades químicas y farmacológicas favorables para el tratamiento de lesiones y heridas.

Investigation of the histopathological level of Ki-67, caspase-3 expressions of the effects of hesperidin on wound healing in the rat esophagus

Purpose: The effects of hesperidin application on the wound caused by esophageal burns were investigated in this study. Methods: Wistar albino rats were divided into three groups: Control group: only 1 mL of 0.09% NaCl was administered i.p. for 28 days; Burn group: An alkaline esophageal burn model was created with 0.2 mL of 25% NaOH orally by gavage­1 mL of 0.09% NaCl was administered i.p. for 28 days; Burn+Hesperidin group: 1 mL of 50 mL/kg of hesperidin was given i.p. for 28 days to rats after burn injury. Blood samples were collected for biochemical analysis. Esophagus samples were processed for histochemical staining and immunohistochemistry. Results: Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were significantly increased in Burn group. Glutathione (GSH) content and histological scores of epithelialization, collagen formation, neovascularization was decreased. After hesperidin treatment, these values were significantly improved in the Burn+Hesperidin group. In the Burn group, epithelial cells and muscular layers were degenerated. Hesperidin treatment restored these pathologies in Burn+Hesperidin group. Ki-67 and caspase-3 expressions were mainly negative in control group; however, the expression was increased in the Burn group. In the Burn+Hesperidin group, Ki-67 and caspase-3 immune activities were reduced. Conclusion: Hesperidin dosage and application methods can be developed as an alternative treatment for burn healing and treatment.

Development and clinical application of hydrogel formulations containing papain and urea for wound healing

Abstract Hydrogels are used for wound treatment, as they may contain one or more active components and protect the wound bed. Papain is one of the active substances that have been used with this purpose, alongside urea. In this paper, carboxypolymethylene hydrogels containing papain (2% and 10% concentrations) and urea (5% concentration) were produced. Physical-chemical stability was performed at 0, 7, 15 and 30 days at 2-8ºC, 25ºC and 40ºC, as well as the rheological aspects and proteolytic activity of papain by gel electrophoresis. Clinical efficacy of the formulations in patients with lower limb ulcers was also evaluated in a prospective, single-center, randomized, double-blind and comparative clinical trial. The results showed 7-day stability for the formulations under 25ºC, in addition to approximately 100% and 15% of protein activity for 10% and 2% papain hydrogel, respectively. The rheological profile was non-Newtonian for the 10% papain hydrogel tested. There were no significant differences regarding the mean time for healing of the lesions, although 10% papain presented a better approach to be used in all types of tissue present in the wound bed.

Hancornia speciosa serum latex fraction: a non-allergenic biomaterial / Fração soro do látex de Hancornia speciosa: um biomaterial não alergênico

Plant-derived products can assist in the healing process of dermal wounds. It has been demonstrated that Hancornia speciosa latex present angiogenic, osteogenic, anti-inflammatory, and antioxidant activities. Then, it could contribute to the wound healing process. However, natural products in contact with skin may cause dermatitis. The objective of this work was to evaluate the allergic and irritant potential of H. speciosa serum fraction latex using in vitro assays. The obtained results showed that the H. speciosa serum fraction latex has a slightly irritant potential and is not cytotoxic neither allergenic for human cells. Moreover, we identified a remarkable low amount of proteins in this material in comparison to Hevea brasiliensis latex. This result could explain the non-allergenic potential of H. speciosa serum fraction latex because proteins present in latex are the main responsible for allergy. This biomaterial could be used as a non-allergenic source for development of new medicines.

Produtos derivados de plantas podem auxiliar no processo de cicatrização de feridas cutâneas. Foi demonstrado que o látex de Hancornia speciosa apresenta atividades angiogênicas, osteogênicas, antiinflamatórias e antioxidantes. Então, este biomaterial pode contribuir para o processo de cicatrização de feridas. No entanto, produtos naturais em contato com a pele podem causar dermatites. O objetivo deste trabalho foi avaliar o potencial alérgico e irritante do látex da fração soro de H. speciosa por meio de ensaios in vitro. Os resultados obtidos mostraram que o látex da fração do soro de H. speciosa possui um potencial pouco irritante e não é citotóxico nem alergênico para células humanas. Além disso, foi identificado uma notável baixa quantidade de proteínas neste material em comparação ao látex de Hevea brasiliensis. Esse resultado poderia explicar o potencial não alergênico do látex da fração soro de H. speciosa, pois as proteínas presentes no látex são as principais responsáveis pela alergia. Este biomaterial pode ser utilizado como fonte não alergênica para desenvolvimento de novos medicamentos.

Does systemic anticancer gemcitabine compromise oral soft tissue wound healing? / ¿La gemcitabina anticancerígena sistémica compromete la cicatrización de heridas en tejidos blandos orales?

Background: Numerous types of cancer are of substantial medical and social concern, posing a major challenge to modern medicine. Chemotherapeutic drugs include the use of nucleosides, which are composed of nucleic acid and sugar. Objective: This study aims to assess the impact of systemic chemotherapeutic drugs at a therapeutic dose on the wound healing process of the oral mucosa. Material and Methods: 30 healthy rats were randomly divided into two main groups based on the study material, 15 rats in each group. Group A (control) was given a single dose of normal saline (1ml/kg, intraperitoneal), and Group B (study) a single injection of gemcitabine (50 mg /Kg, intraperitoneal). After anesthesia, a full-thickness soft tissue incision (0.5 cm length) on the right side of the buccal mucosa was made in the animals of both groups. Each group was subdivided according to the time of sacrifice into 3, 7, 14 days after surgery, at the end of the experimental periods, specimens were collected for histopathological study, and samples of blood were obtained from retro-orbital venous plexus and collected in microfuge tubes and levels of antioxidant enzymes were measured by ELISA. The data were analyzed statistically at a 0.05 level of significance. Results: Gemcitabine delayed the onset of wound cascade (inflammation and re-epithelization) which lead to worsening healing of the oral tissue; it also resulted in a decrease of the antioxidant activity of glutathione peroxidase and catalase, as well as activated caspase 3, which induces cell apoptosis. Conclusion: Gemcitabine showed negative feedback on oral tissue wound healing through delayed wound healing cascade and by inducing apoptosis.

Antecedentes: numerosos tipos de cáncer son motivo de gran preocupación médica y social, lo que representa un gran desafío para la medicina moderna. Los fármacos quimioterapéuticos incluyen el uso de nucleósidos, que están compuestos de ácido nucleico y azúcar. Objetivo: Este estudio tiene como objetivo evaluar el impacto de los fármacos quimioterapéuticos sistémicos a una dosis terapéutica en el proceso de cicatrización de heridas de la mucosa oral. Material y Métodos: 30 ratas sanas se dividieron aleatoriamente en dos grupos principales según el material de estudio, 15 ratas en cada grupo. Al grupo A (control) se le administró una dosis única de solución salina normal (1 ml/kg, intraperitoneal) y al grupo B (estudio) una inyección única de gemcitabina (50 mg/kg, intraperitoneal). Después de la anestesia, se realizó una incisión de tejido blando de espesor total (0,5 cm de longitud) en el lado derecho de la mucosa bucal en los animales de ambos grupos. Cada grupo se subdividió de acuerdo al tiempo de sacrificio en 3, 7, 14 días después de la cirugía, al final de los períodos experimentales se colectaron especímenes para estudio histopatológico, se obtuvieron muestras de sangre del plexo venoso retroorbitario y se recolectaron en tubos de microcentrífuga y los niveles de enzimas antioxidantes se midieron por ELISA. Los datos se analizaron estadísticamente a un nivel de significación de 0,05. Resultados: La gemcitabina retrasó el inicio de la cascada de heridas (inflamación y reepitelización) que condujo a un empeoramiento de la cicatrización del tejido oral; también resultó en una disminución de la actividad antioxidante de la glutatión peroxidasa y la catalasa, así como de la caspasa 3 activada, que induce la apoptosis celular. Conclusión: La gemcitabina mostró retroalimentación negativa sobre la cicatrización de heridas del tejido oral a través de una cascada de cicatrización retardada y mediante la inducción de apoptosis.

Ozonioterapia como opção ao tratamento de lesões cutâneas em humanos: revisão integrativa da literatura / Ozone therapy as an option for the treatment of skin lesions in humans: an integrative literature review / La ozonoterapia como opción para el tratamiento de lesiones cutáneas en humanos: revisión bibliográfica integradora

Este trabalho teve como objetivo realizar uma revisão integrativa sobre a Ozonioterapia como prática complementar no tratamento de lesões em seres humanos. Efetuou-se busca sistematizada nos portais: Biblioteca virtual em saúde (BVS), Biblioteca virtual em saúde de medicinas tradicionais complementares e integrativas (BVS MTCI) e Business source complete (EBSCO) nas seguintes bases de dados: Literatura latino-americana e do caribe em ciências da saúde (LILACS), Base de dados de Enfermagem (BDENF) e Medical literature analysis and retrievel system Online (MEDLINE), com cruzamento dos descritores: ozônio; ferimentos; lesões; cicatrização de feridas. Após os critérios de inclusão serem aplicados, observou-se que dez artigos atingiram todos os critérios previamente definidos. Os estudos apontam que a Ozonioterapia apresenta resultados positivos como opção na terapêutica complementar de lesões. Porém, é um recurso terapêutico com baixa adesão. Faz se necessário maior empenho cientifico sobre a temática. PALAVRAS-CHAVE: Ozônio; Ferimentos; Lesões; Cicatrização de feridas.

Currently, there are several treatments as well as ozone therapy that aim to improve wounds. This work aimed to carry out an integrative review on Ozone Therapy as a complementary practice in the treatment of injuries in humans. A systematic search was conducted on the portals: Virtual Health Library (VHL), Virtual Health Library of Complementary and Integrative Traditional Medicines (VHL MTCI) and Business Source Complete (EBSCO) in the following databases: Latin American and Caribbean Literature in Health Science (LILACS) , Nursing Database (BDENF) and Online Medical Literature Review and Retrieval System (MEDLINE), by crossing descriptors: Ozone, Wounds and Injuries, Healing injuries. After the inclusion criteria were applied, it was observed that ten articles reached all the criteria previously defined. The studies indicate that Ozone therapy presents positive results as a complementary therapy option on wounds. However, it is a therapeutical resource with low adherence. It is necessary a greater scientific commitment on the theme.

Este trabajo tuvo como objetivo realizar una revisión integradora sobre la ozonoterapia como práctica complementaria en el tratamiento de lesiones en humanos. Se realizó una búsqueda sistemática en los siguientes portales: Biblioteca Virtual de Salud (BVS), Biblioteca Virtual de Salud de Medicinas Tradicionales, Complementarias e Integrativas (BVS MTCI) y Business Source Complete (EBSCO) en las siguientes bases de datos: Latin American and Caribbean Health Sciences Literature (LILACS), Nursing Database (BDENF) y Medical Literature Analysis and Retrieval System Online (MEDLINE), utilizando las palabras clave: ozono; heridas; lesiones; curación de heridas. Una vez aplicados los criterios de inclusión, se observó que diez artículos cumplían todos los criterios previamente definidos. Los estudios demostraron que la ozonoterapia tiene resultados positivos como opción terapéutica complementaria para las lesiones. Sin embargo, es un recurso terapéutico con un bajo cumplimiento. Es necesario un mayor esfuerzo científico sobre el tema.

Walnut ointment promotes full-thickness burning wound healing: role of linoleic acid

Purpose: To investigate the active ingredients of walnut ointment (WO) and its mechanism in repairing wounds. Methods: The ingredients of WO were detected by gas chromatography­mass spectrometry. The effect of linoleic acid (LA) was tested by in vitro Alamar Blue (AB) reagent. Image J software, histological and immunohistochemical analysis were used to confirm the healing effect of LA in the porcine skin model. The animals were euthanized after the experiment by injection of pentobarbital sodium. Results: LA, 24% in WO, promotes keratinocytes and fibroblasts proliferation, which were 50.09% and 15.07% respectively higher than control (p < 0.05). The healing rate of the LA group (96.02% ± 2%, 98.58% ± 0.78%) was higher than the saline group (82.11% ± 3.37%, 88.72% ± 1.73%) at week 3 and week 4 (p < 0.05). The epidermal thickness of the LA was 0.16 ± 0.04 mm greater and the expression of the P63 and CK10 proteins was stronger in the LA group than the control (p < 0.05). Conclusions: LA, which is the main components in WO can promote full-thickness burning wounds (FBWs) by stimulating cell proliferation and differentiation.

Preparation and in vitro evaluation of Vancomycin loaded Montmorillonite-Sodium Alginate topical gel for wound infection

Abstract Despite decades of research, wound healing remains a significant public health problem. This study aimed to develop and evaluate a topical sodium alginate gel containing vancomycin (Van) loaded MMT NPs for wound healing applications. Van was loaded in MMT at different conditions (pHs of 6, 7 and temperatures of 40, 50 °C) (Van/MMT NPs). The optimum formulation (with the smallest particle size and a high value of zeta potential; 270.8 ± 77.35 nm and -35.96 ± 2.73, respectively) showed a high drug-loading capacity (entrapment efficacy of 96%) and a sustained release pattern of Van (95%) over 480 min. The optimum Van/MMT NPs were embedded into the sodium alginate (SA) gel (Van/MMT NPs/SA gel). The Van/ MMT NPs/SA gel showed a sustained and slow release pattern of Van (95%) over 50 h. FTIR tests revealed the electrostatic interaction between MMT and Van. The broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) of Van, Van/ MMT NPs, and Van/MMT NPs/SA gel against Staphylococcus aureus. The results showed the promising antibacterial activity of Van/MMT NPs/SA gel, thus, this gel can be a promising formulation for the management of infected wounds

Aloe vera and wound healing: a brief review

Abstract Aloe vera possesses a great therapeutic importance in traditional medicine. It has attracted the attention of modern medical fields due to its wide pharmacological applications. The bioactive substances in Aloe vera proved to have antioxidant, anti-inflammatory, antibacterial, and antiviral properties. Taken into our consideration the long history of clinical applications of Aloe vera in traditional medicine, especially for promoting the healing of cutaneous wounds with rare adverse effects, it provides a cheap alternative to many expensive synthetic drugs. Recent techniques in tissue engineering created novel scaffolds based on Aloe gel extracts for wound healing applications. Nonetheless, further guided researche is required to foster the development of Aloe vera based scaffolds for the benefit of worldwide populations. Here, I systemically summarize the main events following wounding and the mechanism of action of Aloe vera in promoting the healing process. I hope to provide a solid piece of information that might be helpful for designing new research studies into this topic.

Curcumin nanoliposomes mitigate wound tissue inflammatory response caused by tooth extraction

Abstract Curcumin is a plant-derived compound with polypharmacological properties that are hampered by its poor solubility, fast degradation, etc. Wound closure complications that follow tooth extraction are numerous, and relatively frequently additional treatment is needed to prevent unwanted process chronification. The present study aims to compare the effects of free and the nanoliposome-encapsulated curcumin on tooth extraction wound closure. The experiments were performed on Wistar rats where both forms of curcumin were applied topically on a tooth extraction wound for seven days. Changes in tissue oxidative stress (malondialdehyde and oxidized proteins concentrations, and catalase activity) and inflammation (nitric oxide levels and myeloperoxidase activity) related parameters were studied three and seven days following the tooth extraction. Also, the extent of pathohistological changes and osteopontin immunohistochemical expression were studied. The obtained results indicate that both forms of curcumin prevent an increase in oxidative stress and inflammation-related parameters in the studied samples at 3-and 7-day time points. Additionally, we found that curcumin diminished tissue inflammatory response and osteopontin expression, while at the same time it caused faster granulation tissue maturation. The encapsulation of curcumin in nanoliposomes proved to be better in improving the extraction wound healing process than the free curcumin, giving this formulation a potential in the pharmaceutical industry.

Effects of the healing activity of rosemary-of-Chapada (Lippia gracilis Schauer) on cutaneous lesions in rats

Purpose: To evaluate the effects of rosemary leaf essential oil-based ointments on the healing of rat skin lesions. Methods: Sixty adult male rats, with dorsal excisional skin wounds made surgically under anesthesia, were divided into three groups (n = 20): Sham group (untreated wounds); control group (CG, wounds treated with vehicle); and essential oil (EO) treated group (wounds treated with essential oil-based ointments), administered topically once daily. Skin wounds were evaluated at 4, 7, 14, and 21 days after EO or vehicle treatments. Lesions were analyzed macroscopically for the contraction degree. Formalin-fixed paraffin-embedded sections of skin wounds were used for histopathological evaluation. Results: Macroscopic evaluation showed wounds edges with thin crust without firmness and yellowish color, along with an improvement in wound contraction in EO group when compared to the other groups. A reduced inflammatory reaction, along with newly formed small diameter capillaries and more organized and elongated collagen fibers, were more frequently observed in EO group than in the other groups. Moreover, blood vessel number and collagen fibers density were significantly higher in EO group. Conclusions: Skin lesion treatment with rosemary leaf essential oil-based ointments accelerates the initial stages of healing, reduces inflammation, and increases angiogenesis, collagen fibers density, and wound contraction in rats.

Pouteria ramiflora leaf extract on emulgel in wound healing activity in diabetic rats / Ação do extrato de folhas de Pouteria ramiflora em emulgel na atividade de cicatrização de feridas em ratos diabéticos

The genus Pouteria has been studied because it presents various activities, among which is its anti-inflammatory potential. The effects of Pouteria ramiflora Carbopol gel on the healing of skin wounds in diabetic rats were evaluated by microscopic imaging. Streptozotocin was administered intraperitoneally in animals that had fasted for 12 hours, a situation confirmed by the glycemic index (> 240 mg dL-¹). An excision on the back of the animals was performed and three groups were formed: Control (Gel), Ethanolic extract (Ext) and Gel + extract 2% (Ext+gel); the histopathological evaluation occurred on the 7th, 14th, 21st and 30th days after the post-operative period. The results of the phytochemical prospecting of P. ramiflora extract demonstrated the major presence of phenolic compounds and flavonoids; the assessment of the inflammatory infiltrate on the 7th day was higher on group Ext and Ext+gel when compared to group Control; on the 14th day control and Ext (p<0.05). The quantification of fibroblasts was higher on the 7th day among the three treatments, control and Ext (p<0.05), on the 21st day. Angiogenesis showeda higher number of vessels in Ext+gel group (p<0.05) on the 7th day; in Control, Ext and Ext+gel (p<0.05) on the 14th day; and Control and Ext (p<0.05)on the 21st day. The histopathological results showed that the formulation Ext+gel was efficient in tissue reparation and decrease in inflammatory cells on the diabetic's animals.

O gênero Pouteria apresenta várias aplicações terapêuticas e, dentre elas, grande potencial antiflamatório. Os efeitos do gel de Pouteria ramiflora sobre a cicatrização de feridas na pele de ratos diabéticos foram avaliados pela histomorfometria. A estreptozotocina foi administrada por via intraperitoneal em animais após jejum de 12 horas, a confirmação de indução da diabetes foi confirmada pelo índice glicêmico (> 240 mg dL-1). Foi realizada uma incisão no dorso do animal e foram criados 3 grupos de tratamento: controle (gel carbopol), extrato etanólico (Ext) e Gel + extrato etanólico à 2% (Ext+gel); a avaliação histopatológica foi realizada no 7º, 14º, 21º e 30º dias após o período pós operatório. Os resultados da prospecção fitoquímica dos extratos de P. ramiflora demonstraram majoritariamente a presença de compostos fenólicos e flavonóides; o infiltrado inflamatório avaliado no 7º dia foi maior para animais do grupo controle em relação aos grupos Ext (p<0.05) e Ext+gel 2% (p<0.05); no 14º dia o controle e Exp (p<0.05) apresentaram aumento significativo dos infiltrados inflamatórios. A presença de fibroblastos foi elevada no 7º dia em todos os tratamentos. O processo da angiogênese mostrou um maior número de vasos sanguíneos entre os grupos Ext e Ext+gel (p<0.05) no 7º dia; no 14º dia o grupo controle, Ext (p<0.05), Control e Ext+gel (p<0.05) apresentaram aumento de vascularização, e no 21º dia apenas os grupos controle e Ext (p<0.05). Os resultados histopatológicos mostraram que a formulação gel carbopol + extrato etanólico a 2% foi eficiente na reparação de tecidos e na diminuição de células inflamatórias nos animais diabéticos.

Research advances on application of botulinum toxin type A in scar prevention and treatment / 中华烧伤杂志

The wound healing time, tension of wound edge, proliferation of fibroblast, and extracellular matrix deposition are the important factors of scar formation, and botulinum toxin type A can regulate the above. Prevention and treatment of scar with botulinum toxin type A is one of the hot topics of clinical research in recent years. This paper briefly reviews researches by scholars at home and abroad on the mechanism, clinical application, complications, and adverse effects of botulinum toxin type A in scar prevention and treatment.

Rehabilitation therapy with insulin-like growth factor after acute skeletal muscle injury / Terapia de reabilitação com fator de crescimento semelhante à insulina após lesão muscular esquelética aguda / Terapia de rehabilitación con factor de crecimiento semejante a la insulina después de una lesión aguda del músculo esquelético

ABSTRACT Introduction Skeletal muscle injuries account for 10% to 50% of treadmill sports injuries. Insulin-like growth factor (IGF) is a family of polypeptides with both insulin-like anabolic and growth-promoting effects. Sports play a vital role in the recovery of skeletal muscle injuries. Objective The paper analyzes the ability of insulin-like growth factor 1 (IGF-1) to repair skeletal muscle injury caused by treadmill exercise. Method We injected drugs under the wound after exercise-induced injury in rats. The control group was injected with saline, and the experimental group was injected with an insulin-like growth factor. We conduct histological and electron microscopic structural analysis of rats, Results: After an injury, the experimental group formed a basal lamina protective film earlier than the control group, activated myoblasts, formed myofilaments, formed myotubes, and fused into muscle fibers earlier than the control group. The healing quality was also better. The experimental group was endogenous. The mRNA content of sex IGF-1 and IGF-2 both increased earlier than the control group. Conclusion Local injection of exogenous insulin-like growth factor-1 can stimulate the proliferation of myoblasts and accelerate the post-traumatic repair process of skeletal muscle caused by treadmill sports. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução As lesões do músculo esquelético representam de 10% a 50% das lesões em esteira esportiva. O fator de crescimento semelhante à insulina (IGF) é uma família de polipeptídeos com efeitos anabólicos e de promoção do crescimento semelhantes à insulina. Os esportes desempenham um papel vital na recuperação de lesões musculares esqueléticas. Objetivo o artigo analisa a capacidade do fator de crescimento semelhante à insulina 1 (IGF-1) em reparar lesões musculares esqueléticas causadas por exercícios em esteira. Método Injetamos drogas sob a ferida após lesão induzida por exercício em ratos. O grupo controle foi injetado com solução salina e o grupo experimental foi injetado com um fator de crescimento semelhante à insulina. Realizamos análises histológicas e microscópicas eletrônicas estruturais de ratos. Resultados Após a lesão, o grupo experimental formou um filme protetor da lâmina basal mais cedo do que o grupo controle, mioblastos ativados, miofilamentos formados, miotubos formados e fundidos em fibras musculares mais cedo do que o grupo controle. A qualidade da cura também foi melhor. O grupo experimental era endógeno. O conteúdo do sexo IGF-1 e IGF-2 mRNA aumentou mais cedo do que no grupo de controle. Conclusão A injeção local de fator de crescimento semelhante à insulina 1 exógeno pode estimular a proliferação de mioblastos e acelerar o processo de reparo muscular esquelético pós-traumático causado por esportes em esteira. Nível de evidência II; Estudos terapêuticos: investigação dos resultados do tratamento.

RESUMEN Introducción Las lesiones del músculo esquelético representan del 10% al 50% de las lesiones deportivas en cinta. El factor de crecimiento semejante a la insulina (IGF) es una familia de polipéptidos con efectos anabólicos y estimulantes del crecimiento semejantes a la insulina. Los deportes juegan un papel vital en la recuperación de las lesiones del músculo esquelético. Objetivo El artículo analiza la capacidad del factor de crecimiento semejante a la insulina 1 (IGF-1) para reparar la lesión del músculo esquelético causada por el ejercicio en cinta. Método inyectamos drogas debajo de la herida después de una lesión inducida por el ejercicio en ratas. Al grupo de control se le inyectó solución salina y al grupo experimental se le inyectó un factor de crecimiento semejante a la insulina. Realizamos análisis estructurales histológicos y microscópicos electrónicos de ratas, Resultados: Después de una lesión, el grupo experimental formó una película protectora de la lámina basal antes que el grupo de control, activó mioblastos, formó miofilamentos, formó miotubos y se fusionó en fibras musculares antes que el grupo de control. La calidad de curación también fue mejor. El grupo experimental fue endógeno. El contenido de ARNm de IGF-1 e IGF-2 de sexo aumentaron antes que en el grupo de control. Conclusión La inyección local de factor de crecimiento semejante a la insulina 1 exógeno puede estimular la proliferación de mioblastos y acelerar el proceso de reparación postraumático del músculo esquelético causado por los deportes en cinta. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

The action of subconjunctival cyclophosphamide in rabbits / Ação da ciclofosfamida subconjuntival em coelhos

ABSTRACT Objective: To observe clinically, in rabbits, the side effects of topical injection of subconjunctival cyclophosphamide, studying its role as an antifibrotic drug. Methods: Prospective study in 20 albino rabbits of New Zealand race. All rabbits were treated with cyclophosphamide, 10mg/ml in a volume of 0.3 ml, in the left eye through subconjunctival injection. They were evaluated for 1, 7, 30, and 60 days after the procedure. All the animals were examined for the detection of ocular reactions such as necrosis, hyperemia, chemosis, secretion, opacity, and iritis. Other side effects as changes in the behavior, in the feed, and the water consumption were also evaluated. Results: It was observed that from the 20 rabbits studied, three rabbits (15%) showed side effects only at the 24 hours analysis. One rabbit (5%) presented hyperemia, one rabbit (5%) had hyperemia associated with iritis, and one rabbit (5%) presented hyperemia associated with secretion. These reactions were not observed at 1, 7, 30, and 60 days. Conclusion: Cyclophosphamide subconjunctival injection induces minor side effects on the conjunctiva of rabbits such as hyperemia, associated with iritis and secretion.

RESUMO Objetivo: Observar clinicamente os efeitos colaterais de injeção subconjuntival de ciclofosfamida, pensando em sua ação como um agente antifibrótico. Métodos: Estudo prospectivo realizado com 20 coelhos albinos da raça Nova Zelândia. Todos os coelhos foram submetidos a 0,3 ml de injeção subconjuntival de ciclofosfamida 10mg/ml no olho esquerdo e foram avaliados de acordo com os efeitos locais no primeiro dia após a injeção, 7, 30 e 60 dias. Foram examinados para detecção de reações oculares como necrose, hiperemia, quemose, secreção, opacidade corneana, irite além de alterações comportamentais e variação no consumo de água e alimentação. Resultados: Dos 20 coelhos estudados, apenas 3 apresentaram reações oculares e somente na leitura de 24 horas. Um coelho (5%) apresentou hiperemia, 1 coelho (5%) apresentou hiperemia associada a presença de irite e 1 coelho (5%) apresentou hiperemia associada a presença de secreção. As reações não foram mais observadas durante os exames de 7, 30 e 60 dias. Conclusão: A ciclofosfamida subconjuntival causou poucos efeitos colaterais na conjuntiva dos coelhos. Os únicos efeitos encontrados foram hiperemia, irite e secreção.

Healing effects of natural latex serum 1% from Hevea brasiliensis in an experimental skin abrasion wound model

Abstract Background Dermabrasion is related with mechanical and surgical traumas on the skin; usually topical antiseptics and/or saline have been used for healing. Natural products for wound healing can also be used for abrasions, such as latex from Hevea brasiliensis. Objective This study aimed to evaluate the in vitro viability and migratory/proliferative effects of latex serum from H. brasiliensis and to compare with a commercially available standard antiseptic solution and saline in experimental dermabrasion on rats. Methods For in vitro evaluation, MTT and scratch assays were used. In vivo testing was performed in 72 rats submitted to dermabrasion, treated with saline, antiseptic, or latex serum. This study evaluated re-epithelialization, neutrophilic infiltration, and the quantification of crust and epidermis. Results Latex showed viability at 1% and 0.1% concentrations and migratory/proliferative activity at 0.01% concentrations. The re-epithelialization was highest in latex group on 7th day. The latex group displayed lower thickness of crusts and greater extent of epidermal layers. The latex and antiseptic groups showed increases of myeloperoxidase levels on the 2nd day and showed important reductions from the 7th day. Study limitations Acute superficial wound model in rats and non-use of gel-cream (medium) without latex. Conclusion In conclusion, non-toxic latex stimulated migration/proliferation of keratinocytes in vitro and significantly accelerated wound healing in animal excoriation models compared to chlorhexidine or saline.

Efeito do extrato de Bidens pilosa L, Mel e pomadas homeopática e alopática na cicatrização de feridas cutâneas de ratos Wistar / [Effect of Bidens pilosa L, Honey extract and homeopathic and allopathic ointments on the healing of skin wounds of Wistar rats]

Cicatrização de ferida é um processo dinâmico, que tem por objetivo restaurar a continuidade do tecido lesionado. No entanto, em alguns casos, é necessário favorecer condições adequadas para viabilizar o processo fisiológico. Neste estudo foram utilizados ratos Wistar, divididos aleatoriamente entre cinco grupos, com 12 animais cada, sendo eles: grupo P (Bidens pilosa L.), grupo mel, grupo Co1 (pomada comercial alopática), grupo Co2 (pomada comercial homeopática) e grupo CT (controle). As lesões foram geradas por incisão com punch de 8mm, sendo tratadas diariamente de forma tópica. Foram eutanasiados quatro animais por grupo, no terceiro, sétimo e 14º dias do experimento, e o material coletado foi armazenado em formalina 10% e encaminhado para processamento histológico. Posteriormente, realizou-se a contagem de leucócitos mononucleares, fibroblastos e neovasos e avaliou-se a arquitetura de fibras colágenas. Os resultados da contagem foram analisados pela ANOVA, seguida pelo teste de Tukey (P<0,05). O modelo experimental proposto neste estudo demonstrou que todos os tratamentos apresentaram potencial cicatrizante, com exceção do mel. A aplicação tópica do creme do extrato de Bidens pilosa L. a 10% apresentou melhor perfil anti-inflamatório; a pomada alopática apresentou boa aderência à superfície da lesão e a pomada homeopática, grande potencial angiogênico, com menor tempo de cicatrização.(AU)

Wound healing is a dynamic process that aims to restore the continuity of injured tissue. However, in some cases it is necessary to favor adequate conditions to enable the physiological process. Wistar rats were randomly divided into 5 groups with 12 animals each, namely: group P (Bidens pilosa L.), group honey, group Co1 (commercial allopathic ointment), group Co2 (commercial homeopathic ointment) and group CT (control). The lesions were generated by an 8mm punch incision and were treated topically daily. Four animals per group were euthanized on the 3rd, 7th and 14th day of the experiment and the collected material was stored in 10% formalin and sent for histological processing, after which mononuclear, fibroblasts and neovascular leukocytes were counted and collagen fiber architecture was evaluated. Counting results were analyzed by ANOVA, followed by Tukey test (p <0.05). The experimental model proposed in this study showed that all treatments had healing potential, except honey. The topical application of 10% Bidens pilosa L. extract cream showed the best anti-inflammatory profile; Allopathic ointment showed good adhesion to the surface of the lesion and homeopathic ointment showed great angiogenic potential with shorter healing time.(AU)

Wound healing effect of Pistacia lentiscus L. seed oil: confirmation of its uses in Mediterranean traditional medicine / Efecto curativo de heridas del aceite de semilla de Pistacia lentiscus L: confirmación de sus usos en medicina tradicional mediterránea

In order to evaluate the potential of this formulation (P. lentiscus L. oil-based ointment) to heal wounds, experimental wounds were done on guinea pigs and efficiency was comparatively assessed against a reference ointment, Cicaderma®. Wound contraction was performed on days 5, 10 and 15. Tissue sections were also evaluated histopathological on days 7, 14 and 21. Results showed that for all days (5, 10 and 15), the highest wound contraction values were attained for the P. lentiscus oil-based ointment treated group with wound contraction values of 19.38, 55.8 and 77.11%, respectively, as compared to the reference drug Cicaderma® where contractions were 7.97%, 49.53% and 71.44%, respectively. Vehicle and negative control groups however showed no statistically significant wound healing activity on the excision wound model. These experimental studies revealed that the P. lentiscus oil-based ointment displays remarkable wound healing activity, in accordance with its use in traditional medicine.

Con el fin de evaluar el potencial de esta formulación (ungüento a base de aceite de P. lentiscus L.) para curar heridas, se realizaron heridas experimentales en cobayos y se evaluó comparativamente su eficacia respecto de un ungüento de referencia, Cicaderma®. La contracción de la herida se realizó los días 5, 10 y 15. Las secciones de tejido también se evaluaron histopatológicamente los días 7, 14 y 21. Los resultados mostraron que para todos los días (5, 10 y 15), se obtuvieron los valores más altos de contracción de la herida para el grupo tratado con ungüento a base de aceite de P. lentiscus con valores de contracción de la herida de 19.38, 55.8 y 77.11%, respectivamente, en comparación con el medicamento de referencia Cicaderma® en donde las contracciones fueron 7.97%, 49.53% y 71.44%, respectivamente. Sin embargo, los grupos de control de vehículo y negativo no mostraron actividad de curación de heridas estadísticamente significativa en el modelo de herida por escisión. Estos estudios experimentales revelaron que la pomada a base de aceite de P. lentiscus muestra una notable actividad de curación de heridas, de acuerdo con su uso en la medicina tradicional.

Reparación de lesiones musculares por incisión quirúrgica coadyuvada con una formulación basada en miel nativa (Ulmoplus®): estudio experimental en modelo animal de conejo (Pryctolagus cuniculus) / Repair of muscle injuries by coadjugated surgical incision with a native honey formulation (Ulmoplus®): experimental study on rabbit animal model (Oryctolagus cuniculus)

Para promover la reparación y regeneración muscular, se han desarrollado diferentes estrategias, sin embargo, aún no existe un tratamiento único aceptado. Investigaciones relacionan los efectos terapéuticos de la miel en el proceso de cicatrización de heridas de diversas etiologías. Considerando lo anterior, el propósito de este estudio fue evaluar los efectos de una formulación basada en miel nativa (Ulmoplus®) en la reparación de lesiones musculares por incisión quirúrgica. A cinco conejos (Oryctolagus cuniculus) se les realizó una incisión de 20 mm de largo y 3 mm de ancho en la región anterior de cada pierna, atravesando la epidermis, dermis y el músculo tibial anterior, hasta alcanzar el periostio de la tibia. La pierna izquierda de cada animal fue clasificada como grupo sutura (S) y la derecha como grupo sutura más Ulmoplus® (S+U). Posteriormente, al grupo S+U se le aplicó Ulmoplus® en toda la extensión de la herida. Luego, en ambos grupos, la incisión fue suturada con cuatro puntos intradérmicos (vicryl 2/0). Un animal fue considerado como control para obtener imágenes histológicas del músculo tibial anterior sin injuria. A los 10 días post incisión, fueron tomadas las biopsias del músculo y posteriormente fueron procesadas para su observación en microscopio de luz. El estudio se llevó a cabo considerando las recomendaciones de la Guía para el Cuidado y Uso de Animales de Laboratorio. A los 10 días post incisión, las injurias, en ambos grupos de animales, se encontraban cerradas y sin signos de infección. El músculo tibial anterior de los especímenes del grupo S se encontraba en la fase de reparación, con procesos concomitantes de fagocitosis del tejido necrotizado, regeneración de miofibras y formación de tejido conectivo cicatrizal. El músculo tibial anterior de los animales del grupo S+U se encontraba en la fase de remodelación, ya que la arquitectura muscular se evidenciaba restablecida. Ulmoplus®, como coadyuvante en el proceso de cierre de heridas quirúrgicas de músculo esquelético utilizando sutura convencional, es una buena alternativa, ya que acelera el proceso de reparación muscular, y reduce el tejido conectivo cicatrizal.

To promote muscle repair and regeneration, different strategies have been developed, however, there is still no single accepted treatment. Research relates the therapeutic effects of honey in the wound healing process of various etiologies. The aim of this study was to evaluate the effects of native honey formulation (Ulmoplus®) in the repair of muscle injuries by surgical incision. In five rabbits (Oryctolagus cuniculus) were made an incision 20 mm long and 3 mm wide in the anterior region of each leg, crossing the epidermis, dermis and anterior tibial muscle, until reaching the tibia periosteum. The left leg of each animal was classified as a suture group (S) and the right leg as a suture group plus Ulmoplus® (S + U). Subsequently, Ulmoplus® was applied to the entire S + U group throughout the entire length of the wound. Then, in both groups, the incision was sutured with four intradermal points (vicryl 2/0). An animal was considered as a control to obtain histological images of the anterior tibial muscle without injury. At 10 days post incision, muscle biopsies were taken and subsequently processed for observation under light microscopy. The study was carried out considering the recommendations of the Guide for the Care and Use of Laboratory Animals. At 10 days post incision, the injuries, in both groups of animals, were closed and without signs of infection. The anterior tibial muscle of the S group specimens was in the repair phase, with concomitant processes of phagocytosis of the necrotized tissue, myofiber regeneration and formation of scar connective tissue. The anterior tibial muscle of the animals of the S + U group was in the remodeling phase, since the muscular architecture was evidenced restored. Ulmoplus®, as an adjunct in the process of closing surgical wounds of skeletal muscle using conventional suture, is a good alternative, since it accelerates the muscle repair process and reduces scar connective tissue.