Effects of curcumin supplementation on abdominal surgical wound healing.

PURPOSE: To evaluate the effects of curcumin supplementation on abdominal surgical wound healing in rats using clinical, histological, and hematological parameters. METHODS: Forty Wistar rats were randomly divided into two groups: the curcumin group, and the control group. The curcumin group received, in addition to water and standard feed, curcumin via gavage at the dose of 200 mg/kg for seven days preceding and seven days following surgery. The control group received only water and standard feed. Both groups underwent median laparotomy and left colotomy. On the eighth postoperative day, the groups were euthanized, and the left colon was resected for histological analysis. RESULTS: In the preoperative evaluation, there was a significant decrease in the mean C-reactive protein levels in the curcumin group (0.06) compared to the control group (0.112) (p = 0.0001). In the postoperative wound healing assessment, a significant decrease was observed in inflammatory infiltrate (p = 0.0006) and blood vessel count (p = 0.0002) in the curcumin group compared to the control group. CONCLUSIONS: Curcumin supplementation was able to significantly reduce inflammatory parameters in both pre-and post-operative phases of abdominal surgical wounds in rats.

Cilostazol protects against changes caused by streptozotocin-induced diabetic retinopathy / Cilostazol protege contra as alterações causadas pela retinopatia diabética induzida por estreptozotocina

ABSTRACT Purpose: This study investigates the protective effect of cilostazol on the development and evolution of diabetic retinopathy in rats. Methods: Sixty male rats were divided into four groups: untreated nondiabetic rats, untreated diabetic rats, cilostazol-treated nondiabetic rats, and cilostazol-treated diabetic rats. The thickness of the internal limiting membrane to the outer limiting membrane, inner plexiform layer, inner nuclear layer, and outer nuclear layer were measured. The number of cell nuclei per 50-μm length in retinal sections was counted to quantify the degree of retinal cell loss. Results: The number of nuclei in the ganglion cell layer was significantly higher in untreated nondiabetic rats (p<0.05). The mean number of nuclei in the cilostazol-treated nondiabetic rats was significantly higher than that in the cilostazol-treated diabetic rats (p<0.05). The cilostazol-treated nondiabetic rats had a significantly higher mean nuclei count in the inner nuclear layer and inner plexiform layer as compared with the other groups (p<0.05). The total mean retinal thickness of the cilostazol-treated nondiabetic rats was significantly higher than that of cilostazol-treated diabetic rats and untreated diabetic rats (p<0.05). Conclusion: By decreasing the loss of ganglion cells and reducing the sensorineural atrophy in the internal retinal layers, cilostazol had a protective effect against changes caused by diabetic retinopathy in diabetic rats.

RESUMO Objetivo: O objetivo deste estudo foi investigar o efeito protetor do cilostazol no desenvolvimento e na evolução da retinopatia diabética em ratos. Métodos: Sessenta ratos machos foram divididos em 4 grupos: ratos não-diabéticos não-tratados, ratos diabéticos não-tratados, ratos não-diabéticos tratados com cilostazol e ratos diabéticos tratados com cilostazol. A espessura da membrana limitante interna à membrana limitante externa, a camada plexiforme interna, a camada nuclear interna e a camada nuclear externa foram medidas. Para quantificar o grau de perda de células da retina, foi contado o número de núcleos de células por 50 μm de comprimento em secções retinianas. Resultados: O número de núcleos no GCL foi significativamente maior em Ratos não-diabéticos não-tratados com cilostazol (p<0,05). O número médio de núcleos em Ratos não-diabéticos tratados com cilostazol foi significativamente maior do que em Ratos diabéticos tratados com cilostazol (p<0,05). A contagem média de núcleos em camada nuclear interna e camada plexiforme interna de ratos não-diabéticos tratados com cilostazol foi significativamente maior do que nos outros grupos (p<0,05). A espessura retiniana média total de Ratos não-diabéticos tratados com cilostazol foi significativamente maior do que em Ratos diabéticos tratados com cilostazol e Ratos diabéticos não-tratados (p<0,05). Conclusão: Os resultados demonstraram que o cilostazol teve um efeito protetor contra as alterações causadas pela retinopatia diabética em ratos diabéticos, diminuindo a perda de células ganglionares e reduzindo a atrofia neurossensorial nas camadas retinianas internas.

Study of the Antioxidant, Antimicrobial, and Wound Healing Properties of Raw Hydrolyzed Extract from Nile Tilapia Skin (Oreochromis niloticus).

Oreochromis niloticus (Nile tilapia) skin is a by-product of Brazilian fish farming, rich in collagen. The present study aims to evaluate the wound healing, antioxidant, and antimicrobial potential of the raw hydrolyzed extract of Nile tilapia skin, as well as the identification of the main compounds. The in vitro activity was performed using antioxidant, antimicrobial and scratch wound healing assays. An in vivo experiment was performed to evaluate the wound healing potential. On days 1, 7, 14 and 21, the lesions were photographed to assess wound retraction and on the 7th , 14th and 21st  days the skins were removed for histological evaluation and the blood of the animals was collected for glutamic oxaloacetic transaminase and glutamic pyruvic transaminase determination. The chemical study was carried out through liquid chromatography-tandem mass spectrometry and de novo sequencing of peptides. The in vitro assays showed a reduction of the gap area in 24 h, dose-dependent antimicrobial activity for both bacteria, and antioxidant activity. The chemical analysis highlighted the presence of active biopeptides. The histological evaluation showed that the raw hydrolyzed extract of Nile tilapia skin has a healing potential, and does not present toxicological effects; therefore, is promising for the treatment of wounds.

Preclinical Trial of Ocotea puberula (Rich.) Nees ("Canela-Guaicá") in Wound Healing: Validation of a Traditional Medicine Practice Used by Indigenous Groups in Southern Brazil.

Background: "Canela-guaicá," "guaicá," or "canela-sebo" [Ocotea puberula (Rich.) Nees] is a native species that is traditionally used by Kaingang indigenous groups for wound healing in southern Brazil. The aim of this study was to extract the mucilage from O. puberula barks, perform its phytochemical and physicochemical characterization, and investigate its healing potential. Methods: A murine wound model was used as a preclinical trial for authentication of the traditional knowledge from Kaingang indigenous communities. Results: Alkaloids and polysaccharides were identified by usual qualitative reactions and Fourier-transform infrared spectroscopy. This natural product showed thermal stability and pseudoplastic properties that were considered suitable for the intended use. A higher initial exacerbation of inflammatory response after 7 days, an improved angiogenesis after 14 days, and an increased wound shrinkage after 21 days were statistically significant for the "canela-guaicá" bark extract in the preclinical trial when compared to the silver calcium alginate dressing (positive control). Conclusion: The healing potential of the "canela-guaicá" bark extract, traditionally used by the Kaingang indigenous community from southern Brazil, was preclinically validated. This study paves the way for designing novel wound dressings containing this natural product in order to treat acute and chronic wounds.

Cilostazol protects against changes caused by streptozotocin-induced diabetic retinopathy.

PURPOSE: This study investigates the protective effect of cilostazol on the development and evolution of diabetic retinopathy in rats. METHODS: Sixty male rats were divided into four groups: untreated nondiabetic rats, untreated diabetic rats, cilostazol-treated nondiabetic rats, and cilostazol-treated diabetic rats. The thickness of the internal limiting membrane to the outer limiting membrane, inner plexiform layer, inner nuclear layer, and outer nuclear layer were measured. The number of cell nuclei per 50-µm length in retinal sections was counted to quantify the degree of retinal cell loss. RESULTS: The number of nuclei in the ganglion cell layer was significantly higher in untreated nondiabetic rats (p<0.05). The mean number of nuclei in the cilostazol-treated nondiabetic rats was significantly higher than that in the cilostazol-treated diabetic rats (p<0.05). The cilostazol-treated nondiabetic rats had a significantly higher mean nuclei count in the inner nuclear layer and inner plexiform layer as compared with the other groups (p<0.05). The total mean retinal thickness of the cilostazol-treated nondiabetic rats was significantly higher than that of cilostazol-treated diabetic rats and untreated diabetic rats (p<0.05). CONCLUSION: By decreasing the loss of ganglion cells and reducing the sensorineural atrophy in the internal retinal layers, cilostazol had a protective effect against changes caused by diabetic retinopathy in diabetic rats.

THE USE OF SURGICAL ADHESIVE AND SUTURE FIXING MESHES TO THE ABDOMINAL WALL: AN EXPERIMENTAL STUDY IN RATS.

AIM: Proper fixation of the surgical mesh determines the success of a herniorrhaphy. Understanding the inflammatory response and the mechanical properties of the mesh helps to define whether a fixation method is superior. This study aimed to evaluate the healing of defects in the abdominal wall of rats, comparing the repair of macroporous polypropylene meshes fixed with surgical glue and polypropylene thread. METHODS: In 20 Wistar rats, a defect was produced in the abdominal wall, with the integrity of the parietal peritoneum. For correction, the meshes were fixed with surgical glue (2-octyl cyanoacrylate) (subgroup C1), or polypropylene suture (subgroup C2). The two subgroups of 10 animals were euthanized on the 90th postoperative day, and the fragments of the abdominal wall were submitted to macroscopic, histological, and tensiometric analysis. RESULTS: Macroscopic analysis did not show any abnormalities. Tensiometry on the 90th postoperative day in subgroup C1 showed mean rupture tension of 28.47N and in subgroup C2 32.06N (p=0.773). The inflammatory process score revealed that both groups are in the subacute phase (p=0.380). CONCLUSION: The fixation of a polypropylene macroporous mesh to repair an abdominal wall defect can be performed with surgical glue (2-octyl cyanoacrylate) or polypropylene suture, both methods being equally effective.

The use of surgical adhesive and suture fixing meshes to the abdominal wall: an experimental study in rats / O uso de cola cirúrgica e sutura na fixação de tela em parede abdominal: estudo experimental em ratos

ABSTRACT - BACKGROUND: Proper fixation of the surgical mesh determines the success of a herniorrhaphy. Understanding the inflammatory response and the mechanical properties of the mesh helps to define whether a fixation method is superior. AIM: This study aimed to evaluate the healing of defects in the abdominal wall of rats, comparing the repair of macroporous polypropylene meshes fixed with surgical glue and polypropylene thread. METHODS: In 20 Wistar rats, a defect was produced in the abdominal wall, with the integrity of the parietal peritoneum. For correction, the meshes were fixed with surgical glue (2-octyl cyanoacrylate) (subgroup C1), or polypropylene suture (subgroup C2). The two subgroups of 10 animals were euthanized on the 90th postoperative day, and the fragments of the abdominal wall were submitted to macroscopic, histological, and tensiometric analysis. RESULTS: Macroscopic analysis did not show any abnormalities. Tensiometry on the 90th postoperative day in subgroup C1 showed mean rupture tension of 28.47N and in subgroup C2 32.06N (p=0.773). The inflammatory process score revealed that both groups are in the subacute phase (p=0.380). CONCLUSION: The fixation of a polypropylene macroporous mesh to repair an abdominal wall defect can be performed with surgical glue (2-octyl cyanoacrylate) or polypropylene suture, both methods being equally effective.

RESUMO - RACIONAL: A adequada fixação da tela cirúrgica determina o sucesso de uma herniorrafia. Entender a resposta inflamatória e as propriedades mecânicas da tela contribui para definir se há superioridade de um método de fixação. OBJETIVO: Avaliar a cicatrização de defeitos em parede abdominal de ratos, comparando-se o reparo das telas de polipropileno macroporosas fixadas com cola cirúrgica e fio de polipropileno. MÉTODOS: Foi produzido defeito na parede abdominal de 20 ratos Wistar com integridade do peritônio parietal. Na correção, as telas foram fixadas com cola cirúrgica 2-octil cianoacrilato (C1) ou sutura (C2). Os dois subgrupos de 10 animais foram eutanasiados no 90º dia de pós-operatório e os fragmentos da parede abdominal foram submetidos a análise macroscópica, histológica e tensiométrica. RESULTADOS: A análise macroscópica não mostrou qualquer anormalidade. A tensiometria no 90º dia de pós-operatório no subgrupo C1 demonstrou tensão média de ruptura de 28,47N e no subgrupo C2 de 32,06N (p=0,773). O escore de processo inflamatório revelou que ambos os grupos se encontram na fase subaguda (p=0,380). CONCLUSÃO: A fixação de tela macroporosa de polipropileno para reparo de defeito em parede abdominal pode ser realizada com cola cirúrgica (2-octil cianoacrilato) ou sutura de polipropileno, sendo ambos os métodos igualmente eficazes.

Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis.

BACKGROUND: Tacrolimus (TAC) is a drug of natural origin used in conventional topical dosage forms to control atopic dermatitis. However, direct application of the drug often causes adverse side effects in some patients. Hence, drug nanoencapsulation could be used as an improved novel therapy to mitigate the adverse effects and enhance bioavailability of the drug. METHODS: Physicochemical properties, in vitro drug release experiments, and in vivo anti-inflammatory activity studies were performed. RESULTS: TAC-loaded nanocapsules were successfully prepared by the interfacial deposition of preformed polymer using poly(ε-caprolactone) (PCL). The nanoparticulate systems presented a spherical shape with a smooth and regular surface, adequate diameter (226 to 250 nm), polydispersity index below 0.3, and suitable electrical stability (-38 to -42 mV). X-ray diffraction confirmed that the encapsulation method provided mainly the drug molecular dispersion in the nanocapsule oily core. Fourier-transform infrared spectra suggested that nanoencapsulation did not result in chemical bonds between drug and polymer. In vitro drug dissolution experiments showed a controlled release with a slight initial burst. The release kinetics showed zero-order kinetics. As per the Korsmeyer-Peppas model, anomalous transport features were observed. TAC-loaded PCL nanocapsules exhibited excellent anti-inflammatory activity when compared to the free drug. CONCLUSIONS: TAC-loaded PCL nanocapsules can be suitably used as a novel nano-based dosage form to control atopic dermatitis.

Avaliação da absorção de proteínas em ratas submetidas à colocação de mini-implantes de silicone nanotexturizados e revestidos pela espuma de poliuretano / Evaluation of protein adsorption in rats submitted to nanotextured and polyurethane foam-coated silicone mini-implants

RESUMO Introdução: O controle da absorção de proteínas é necessário para a definição das propriedades dos biomateriais e de seus usos específicos. O plasma sanguíneo contém diversas proteínas diferentes, dentre elas o fibrinogênio, que apresenta importante papel na adesão celular e nos resultados de biocompatibilidade em implantes. Os objetivos deste estudo foram avaliar laboratorialmente as ratas submetidas à colocação de mini-implantes de silicone nanotexturizados e revestidos por espuma de poliuretano a partir da aferição do fibrinogênio sérico e mensuração da proteína plasmática. Métodos: Foram utilizadas 60 ratas albinas, divididas em dois grupos de 30 animais para cada tipo de mini-implante de silicone (nanotexturizado e espuma de poliuretano) e subdivididas em 3 subgrupos, conforme o tempo de eutanásia dos animais (30, 60 e 90 dias). Os mini-implantes foram inseridos no dorso dos animais abaixo do Panniculus carnosus. No momento das eutanásias, amostras de sangue foram obtidas por punção cardíaca. Utilizou-se a técnica de precipitação térmica para determinação das proteínas plasmáticas total e sérica, e o valor do fibrinogênio foi obtido mediante a diferença entre estas duas últimas. Resultados: Quando comparados os grupos entre si, observou-se que o grupo nanotexturizado apresentou uma maior quantidade de fibrinogênio e da proteína plasmática no subgrupo de 90 dias, com significância estatística (p=0,004). Ao comparar os subgrupos entre si, em ambos os grupos, evidenciou-se uma diferença significativa (p<0,001). Conclusão: Os mini-implantes nanotexturizados mostraram uma menor absorção de proteínas em relação aos implantes revestidos pela espuma de poliuretano, no subgrupo de 90 dias.

ABSTRACT Introduction: The control of protein absorption is necessary to define biomaterials' properties and their specific uses. Blood plasma contains several different proteins, including fibrinogen, which plays an important role in cell adhesion and biocompatibility results in implants. This study's objectives were to evaluate in the laboratory rats subjected to the placement of nano-textured silicone mini-implants and polyurethane foam-coated mini-implants based on the measurement of serum fibrinogen and plasma proteins. Methods: Sixty albino rats were used, divided into two groups of 30 animals for each type of silicone mini-implant (nanotextured and polyurethane foam) and subdivided into three subgroups, according to the animals' euthanasia time (30, 60 and 90 days). The mini-implants were inserted in the animals' backs below the Panniculus carnosus. At the time of euthanasia, blood samples were obtained by cardiac puncture. The thermal precipitation technique was used to determine total and serum plasma proteins, and the difference between the latter two obtained the fibrinogen value. Results: When the groups were compared, it was observed that the nanotextured group presented a higher amount of fibrinogen and plasma protein in the 90-day subgroup, with statistical significance (p=0.004). When comparing the subgroups among themselves, a significant difference was evidenced (p<0.001). Conclusion: The nanotextured mini-implants showed a lower protein absorption concerning polyurethane foam-coated implants in the 90-day subgroup.

Avaliação de biomarcadores sanguíneos em ratas submetidas à colocação de implantes de silicone nanotexturizados e revestidos pela espuma de poliuretano / Evaluation of blood biomarkers in rats submitted to nanotextured and polyurethane foam-coated silicone implants

RESUMO Introdução: Nas últimas décadas houve uma grande evolução na superfície de revestimento dos implantes mamários, o que resultou na diminuição das complicações. No pós-operatório a inflamação é uma constante e pode ser avaliada pelo hemograma, pois é um exame rápido, barato e com alta disponibilidade. O presente estudo tem como objetivo avaliar os biomarcadores sanguíneos em ratas submetidas à colocação de mini-implantes de silicone nanotexturizados e revestidos por espuma de poliuretano. Métodos: Foram utilizadas 60 ratas Wistar divididas em dois grupos para utilização de mini-implantes nanotexturizados e revestidos com espuma de poliuretano, subdivididos em subgrupos de acordo com a eutanásia dos animais nos 30, 60 e 90 dias. No momento da eutanásia, as amostras de sangue foram obtidas por punção cardíaca e foi analisado o hemograma. Resultados: A hemoglobina, o hematócrito, a hemoglobina corpuscular média, os leucócitos, os neutrófilos, os linfócitos e as plaquetas tiveram os resultados muito semelhantes em todos os subgrupos avaliados (30, 60 e 90 dias). Entretanto, quando os diferentes subgrupos foram comparados entre si dentro de cada grupo, obteve-se resultados estatisticamente significantes na hemoglobina corpuscular média (nanotexturizado p=0,032 e poliuretano p=0,007) e nos leucócitos (nanotexturizado p=0,038 e poliuretano p=0,034). Sobre as alterações dos biomarcadores sanguíneos no pós-operatório encontrou-se anemia hipocrômica, contagem de leucócitos normais, neutrofilia, linfopenia e trombocitopenia. Conclusão: Após a colocação de mini-implantes de silicone, as ratas de ambos os grupos evoluíram com anemia hipocrômica, contagem de leucócitos normais às custas de neutrofilia e linfopenia, e trombocitopenia.

ABSTRACT Introduction: In recent decades, there has been a great evolution in breast implants' lining surface, which has resulted in decreased complications. In the postoperative period, the inflammation is constant and can be evaluated by the blood count, as it is a fast, inexpensive, and highly available examination. The present study evaluates blood biomarkers in rats submitted to the placement of nanotextured silicone implants and implants coated with polyurethane foam. Methods: 60 Wistar rats were used divided into two groups for nanotextured mini-implants and others mini-implants coated with polyurethane foam, subdivided into subgroups according to the animals' euthanasia in the 30, 60, and 90 days. At the time of euthanasia, blood samples were obtained by cardiac puncture and the blood count was analyzed. Results: Hemoglobin, hematocrit, mean corpuscular hemoglobin, leukocytes, neutrophils, lymphocytes, and platelets had very similar results in all subgroups evaluated (30, 60, and 90 days). However, when the different subgroups were compared within each group, statistically significant results were obtained in the mean corpuscular hemoglobin (nanotextured p=0.032 and polyurethane p=0.007) and leukocytes (nanotextured p=0.038 and polyurethane p=0.034). Changes in postoperative blood biomarkers were hypochromic anemia, normal leukocyte count, neutrophilia, lymphopenia, and thrombocytopenia. Conclusion: After the placement of mini-silicone implants, the rats of both groups evolved with hypochromic anemia, normal leukocyte count at the expense of neutrophilia and lymphopenia, and thrombocytopenia.

Ursolic acid-loaded lipid-core nanocapsules reduce damage caused by estrogen deficiency in wound healing.

The skin aging process in women is accelerated due to decreases in serum estrogen levels triggered by the menopause process. Hence, poly(L-lactic acid) lipid-core nanocapsules containing ursolic acid (NPLA-UA) were developed using the interfacial deposition of the preformed polymer methodology as a strategy to reduce damages to the healing process caused by hormonal deficiency in ovariectomized rats. The colloidal suspensions of nanocapsules presented adequate size and morphology (254 and 375 nm), negative zeta potential (-31 and -37 mV), high encapsulation efficiency (99.89 %), and amorphous character. The analyses performed in an in vivo healing trial showed that the treatment with NPLA-UA resulted in faster wound retraction with less inflammatory response. In addition, the angiogenic process was stimulated increased synthesis of dermal collagen occurred. Ursolic acid-loaded, lipid-core nanocapsules are suitable for treating skin changes triggered by decreased estrogen in menopause.

Evaluation of wound healing effect of alginate film containing Aloe vera gel and cross-linked with zinc chloride.

PURPOSE: To develop a new wound dressing composed of alginate and Aloe vera gel and cross-linked with zinc ions. METHODS: The aloe-alginate film was characterized using scanning electron microscopy (SEM), swelling profile, mechanical properties, polysaccharide content and X-ray diffraction (XRD). Thirty Wistar rats were divided in two groups a) treated with aloe-alginate film and b) control (treated with sterile gauze). Wound contraction measurements and hystological analysis were performed on 7th, 14th and 21st days after wound surgery. RESULTS: The aloe-alginate film presented adequated mechanical resistance and malleability for application as wound dressing. There was no statistical difference in wound contraction between two groups. Histological assay demonstrated that aloe-alginate film presented anti-inflammatory activity, stimulated angiogenesis on proliferative phase and a more significant increased in collagen type I fibers and decreased type III fibers which promoted a mature scar formation when compared to control. CONCLUSIONS: The aloe-alginate film showed adequate physicochemical characteristics for wound dressing applications. The in vivo assay demonstrated that aloe-alginate film enhanced the healing process of incisional skin wounds.

Evaluation of wound healing effect of alginate film containing Aloe vera gel and cross-linked with zinc chloride

Abstract Purpose To develop a new wound dressing composed of alginate and Aloe vera gel and cross-linked with zinc ions. Methods The aloe-alginate film was characterized using scanning electron microscopy (SEM), swelling profile, mechanical properties, polysaccharide content and X-ray diffraction (XRD). Thirty Wistar rats were divided in two groups a) treated with aloe-alginate film and b) control (treated with sterile gauze). Wound contraction measurements and hystological analysis were performed on 7th, 14th and 21st days after wound surgery. Results The aloe-alginate film presented adequated mechanical resistance and malleability for application as wound dressing. There was no statistical difference in wound contraction between two groups. Histological assay demonstrated that aloe-alginate film presented anti-inflammatory activity, stimulated angiogenesis on proliferative phase and a more significant increased in collagen type I fibers and decreased type III fibers which promoted a mature scar formation when compared to control. Conclusions The aloe-alginate film showed adequate physicochemical characteristics for wound dressing applications. The in vivo assay demonstrated that aloe-alginate film enhanced the healing process of incisional skin wounds.