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1.
Medicine (Baltimore) ; 99(40): e22588, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019476

RESUMO

BACKGROUND: The objective of this meta-analysis was to summarize and identify the available evidence from studies to estimate the clinical value of traditional Chinese medicine (TCM) in the treatment of recurrent aphthous stomatitis (RAS) and provides clinicians with evidence on which to base their clinical decision making. METHODS: This review will include all studies comparing clinical efficacy of TCM in the treatment of RAS. The search strategy will be performed in 9 databases. We will not establish any limitations to language and publication status, published from inception to the August 2020. Two reviewers will screen, select studies, extract data, and assess quality independently. Outcome is clinical efficacy, pain relief, duration of wound healing, effect on wound healing, rate of recurrence, adverse events, and safety. The methodological quality including the risk of bias of the included studies will be evaluated. We will carry out statistical analysis using RevMan 5.3 software. RESULTS: This study will summarize current evidence to assess the efficacy and safety of TCM in the treatment of RAS. CONCLUSION: The findings of this study will provide helpful evidence for the clinician, and will promote further studies, as well as studying the value of TCM. REGISTRATION NUMBER: INPLASY202080126 (DOI number: 10.37766/inplasy2020.8.0126).


Assuntos
Medicina Tradicional Chinesa/métodos , Medição da Dor/estatística & dados numéricos , Estomatite Aftosa/terapia , China/epidemiologia , Tomada de Decisão Clínica , Feminino , Humanos , Incidência , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Estudos Observacionais como Assunto , Medição da Dor/efeitos dos fármacos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Segurança , Estomatite Aftosa/epidemiologia , Resultado do Tratamento , Cicatrização/efeitos dos fármacos
2.
PLoS One ; 15(9): e0237851, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877414

RESUMO

This study examined the antibacterial effect of protoporphyrin IX-ethylenediamine derivative (PPIX-ED)-mediated photodynamic antimicrobial chemotherapy (PPIX-ED-PACT) against Pseudomonas aeruginosa in vitro and in vivo. PPIX-ED potently inhibited the growth of Pseudomonas aeruginosa by inducing reactive oxygen species production via photoactivation. Atomic force microscopy revealed that PPIX-ED-PACT induced the leakage of bacterial content by degrading the bacterial membrane and wall. As revealed using acridine orange/ethidium bromide staining, PPIX-ED-PACT altered the permeability of the bacterial membrane. In addition, the antibacterial effect of PPIX-ED-PACT was demonstrated in an in vivo model of P. aeruginosa-infected wounds. PPIX-ED (100 µM) decreased the number of P. aeruginosa colony-forming units by 4.2 log10. Moreover, histological analysis illustrated that the wound healing rate was 98% on day 14 after treatment, which was 10% higher than that in the control group. According to the present findings, PPIX-ED-PACT can effectively inhibit the growth of P. aeruginosa in vitro and in vivo.


Assuntos
Antibacterianos/uso terapêutico , Fotoquimioterapia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/fisiologia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Animais , Antibacterianos/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/efeitos da radiação , Etilenodiaminas/química , Etilenodiaminas/farmacologia , Etilenodiaminas/uso terapêutico , Feminino , Luz , Camundongos , Camundongos Endogâmicos BALB C , Viabilidade Microbiana/efeitos dos fármacos , Modelos Biológicos , Células NIH 3T3 , Fotodegradação , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Protoporfirinas/química , Protoporfirinas/farmacologia , Protoporfirinas/uso terapêutico , Pseudomonas aeruginosa/efeitos da radiação , Cicatrização/efeitos dos fármacos
3.
Int J Nanomedicine ; 15: 5825-5838, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821104

RESUMO

Background and Purpose: The extracellular matrix (ECM) derived from bone marrow mesenchymal stem cells (BMSCs) has been used in regenerative medicine because of its good biological activity; however, its poor mechanical properties limit its application in bone regeneration. The purpose of this study is to construct a three dimensional-printed hydroxyapatite (3D-HA)/BMSC-ECM composite scaffold that not only has biological activity but also sufficient mechanical strength and reasonably distributed spatial structure. Methods: A BMSC-ECM was first extracted and formed into micron-sized particles, and then the ECM particles were modified onto the surface of 3D-HA scaffolds using an innovative linking method to generate composite 3D-HA/BMSC-ECM scaffolds. The 3D-HA scaffolds were used as the control group. The basic properties, biocompatibility and osteogenesis ability of both scaffolds were tested in vitro. Finally, a critical skull defect rat model was created and the osteogenesis effect of the scaffolds was evaluated in vivo. Results: The compressive modulus of the composite scaffolds reached 9.45±0.32 MPa, which was similar to that of the 3D-HA scaffolds (p>0.05). The pore size of the two scaffolds was 305±47 um and 315±34 um (p>0.05), respectively. A CCK-8 assay indicated that the scaffolds did not have cytotoxicity. The composite scaffolds had good cell adhesion ability, with a cell adhesion rate of up to 76.00±6.17% after culturing for 7 hours, while that of the 3D-HA scaffolds was 51.85±4.77% (p<0.01). In addition, the composite scaffold displayed higher alkaline phosphatase (ALP) activity, osteogenesis-related mRNA expression, and calcium nodule formation, thus confirming that the composite scaffolds had good osteogenic activity. The composite scaffolds exhibited good bone repair in vivo and were superior to the 3D-HA scaffolds. Conclusion: We conclude that BMSC-ECM is a good osteogenic material and that the composite scaffolds have good osteogenic ability, which provides a new method and concept for the repair of bone defects.


Assuntos
Durapatita/farmacologia , Matriz Extracelular/metabolismo , Células-Tronco Mesenquimais/citologia , Tecidos Suporte/química , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Adesão Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Hidrodinâmica , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/ultraestrutura , Osteogênese/efeitos dos fármacos , Osteogênese/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacos
4.
Bone Joint J ; 102-B(8): 1095-1106, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32731821

RESUMO

AIMS: Achilles tendon injuries are a frequent problem in orthopaedic surgery due to their limited healing capacity and the controversy surrounding surgical treatment. In recent years, tissue engineering research has focused on the development of biomaterials to improve this healing process. The aim of this study was to analyze the effect of tendon augmentation with a nanostructured fibrin-agarose hydrogel (NFAH) or genipin cross-linked nanostructured fibrin-agarose hydrogel (GP-NFAH), on the healing process of the Achilles tendon in rats. METHODS: NFAH, GP-NFAH, and MatriDerm (control) scaffolds were generated (five in each group). A biomechanical and cell-biomaterial-interaction characterization of these biomaterials was then performed: Live/Dead Cell Viability Assay, water-soluble tetrazolium salt-1 (WST-1) assay, and DNA-released after 48 hours. Additionally, a complete section of the left Achilles tendon was made in 24 Wistar rats. Animals were separated into four treatment groups (six in each group): direct repair (Control), tendon repair with MatriDerm, or NFAH, or GP-NFAH. Animals were euthanized for further histological analyses after four or eight weeks post-surgery. The Achilles tendons were harvested and a histopathological analysis was performed. RESULTS: Tensile test revealed that NFAH and GP-NFAH had significantly higher overall biomechanical properties compared with MatriDerm. Moreover, biological studies confirmed a high cell viability in all biomaterials, especially in NFAH. In addition, in vivo evaluation of repaired tendons using biomaterials (NFAH, GP-NFAH, and MatriDerm) resulted in better organization of the collagen fibres and cell alignment without clinical complications than direct repair, with a better histological score in GP-NFAH. CONCLUSION: In this animal model we demonstrated that NFAH and GP-NFAH had the potential to improve tendon healing following a surgical repair. However, future studies are needed to determine the clinical usefulness of these engineered strategies. Cite this article: Bone Joint J 2020;102-B(8):1095-1106.


Assuntos
Tendão do Calcâneo/cirurgia , Microambiente Celular/efeitos dos fármacos , Colágeno/uso terapêutico , Elastina/uso terapêutico , Regeneração/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia , Tendão do Calcâneo/lesões , Animais , Materiais Biocompatíveis/farmacologia , Modelos Animais de Doenças , Fibrina/farmacologia , Hidrogéis/farmacologia , Masculino , Nanoestruturas , Distribuição Aleatória , Ratos , Ratos Wistar , Tendões/fisiologia , Engenharia Tecidual/métodos , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia
5.
PLoS One ; 15(8): e0237705, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833973

RESUMO

Polychlorinated biphenyls (PCBs) are environmental pollutants and endocrine disruptors, harmfully affecting reproductive, endocrine, neurological and immunological systems. This broad influence has implications for processes such as wound healing, which is modulated by the immunological response of the body. Conversely, while PCBs can be linked to diminished wound healing, outside of PCB pollution systems, exercise has been shown to accelerate wound healing. However, the potential for moderate intensity exercise to modulate or offset the harmful effects of a toxin like PCB are yet unknown. A key aim of the present study was to examine how PCB exposure at different doses (0, 100, 500, 1000 ppm i.p.) altered wound healing in exercised versus non-exercised subgroups of mice. We examined PCB effects on immune function in more depth by analyzing the concentrations of cytokines, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) in these wounds inflicted by punch biopsy. Mice were euthanized at Day 3 or Day 5 after PCB injection (n = 3-6) and skin excised from the wound area was homogenized and analyzed for cytokine content. Results revealed that wound healing was not signficantly impacted by either PCB exposure or exercise, but there were patterns of delays in healing that depended on PCB dose. Changes in cytokines were also observed and depended on PCB dose and exercise experience. For example, IL-1ß concentrations in Day 5 mice without PCB administration were 33% less in exercised mice than mice not exercised. However, IL-1ß concentrations in Day 3 mice administered 100 ppm were 130% greater in exercised mice than not exercisedmice. Changes in the other measured cytokines varied with mainly depressions at lesser PCB doses and elevations at higher doses. Exercise had diverse effects on cytokine levels, but increased cytokine levels in the two greater doses. Explanations for these diverse effects include the use of young animals with more rapid wound healing rates less affected by toxin exposure, as well as PCB-mediated compensatory effects at specific doses which could actually enhance immune function. Future work should examine these interactions in more detail across a developmental time span. Understanding how manipulating the effects of exposure to environemntal contaminants using behavioral modification could be very useful in certain high risk populations or exposed individuals.


Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Condicionamento Físico Animal/fisiologia , Bifenilos Policlorados/toxicidade , Cicatrização/imunologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Pele/imunologia , Pele/lesões , Pele/metabolismo , Cicatrização/efeitos dos fármacos
6.
Life Sci ; 258: 118195, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781073

RESUMO

AIMS: The estrogen-ERα axis participates in osteoblast maturation. This study was designed to further evaluated the roles of the estrogen-ERα axis in bone healing and the possible mechanisms. MAIN METHODS: Female ICR mice were created a metaphyseal bone defect in the left femurs and administered with methylpiperidinopyrazole (MPP), an inhibitor of ERα. Bone healing was evaluated using micro-computed tomography. Colocalization of ERα with alkaline phosphatase (ALP) and ERα translocation to mitochondria were determined. Levels of ERα, ERß, PECAM-1, VEGF, and ß-actin were immunodetected. Expression of chromosomal Runx2, ALP, and osteocalcin mRNAs and mitochondrial cytochrome c oxidase (COX) I and COXII mRNAs were quantified. Angiogenesis was measured with immunohistochemistry. KEY FINDINGS: Following surgery, the bone mass was time-dependently augmented in the bone-defect area. Simultaneously, levels of ERα were specifically upregulated and positively correlated with bone healing. Administration of MPP to mice consistently decreased levels of ERα and bone healing. As to the mechanisms, osteogenesis was enhanced in bone healing, but MPP attenuated osteoblast maturation. In parallel, expressions of osteogenesis-related ALP, Runx2, and osteocalcin mRNAs were induced in the injured zone. Treatment with MPP led to significant inhibition of the alp, runx2, and osteocalcin gene expressions. Remarkably, administration of MPP lessened translocation of ERα to mitochondria and expressions of mitochondrial energy production-related coxI and coxII genes. Furthermore, exposure to MPP decreased levels of PECAM-1 and VEGF in the bone-defect area. SIGNIFICANCE: The present study showed the contributions of the estrogen-ERα axis to bone healing through stimulation of energy production, osteoblast maturation, and angiogenesis.


Assuntos
Regeneração Óssea , Diferenciação Celular , Metabolismo Energético , Receptor alfa de Estrogênio/metabolismo , Neovascularização Fisiológica , Osteoblastos/citologia , Transdução de Sinais , Fosfatase Alcalina/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Calo Ósseo/efeitos dos fármacos , Calo Ósseo/patologia , Diferenciação Celular/efeitos dos fármacos , Cromossomos de Mamíferos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Camundongos Endogâmicos ICR , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteogênese/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Regulação para Cima/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
7.
Int J Nanomedicine ; 15: 4969-4990, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764930

RESUMO

Background: Polyphenols possess antioxidant, anti-inflammatory and antimicrobial properties and have been used in the treatment of skin wounds and burns. We previously showed that tannic acid-modified AgNPs sized >26 nm promote wound healing, while tannic acid-modified AgNPs sized 13 nm can elicit strong local inflammatory response. In this study, we tested bimetallic Au@AgNPs sized 30 nm modified with selected flavonoid and non-flavonoid compounds for wound healing applications. Methods: Bimetallic Au@AgNPs were obtained by growing an Ag layer on AuNPs and further modified with selected polyphenols. After toxicity tests and in vitro scratch assay in HaCaT cells, modified lymph node assay as well as the mouse splint wound model were further used to access the wound healing potential of selected non-toxic modifications. Results: Tannic acid, gallic acid, polydatin, resveratrol, catechin, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate and procyanidin B2 used to modify Au@AgNPs exhibited good toxicological profiles in HaCaT cells. Au@AgNPs modified with 15 µM tannic acid, 200 µM resveratrol, 200 µM epicatechin gallate, 1000 µM gallic acid and 200 µM procyanidin B2 induced wound healing in vivo and did not lead to the local irritation or inflammation. Tannic acid-modified Au@AgNPs induced epithelial-to-mesenchymal transition (EMT) - like re-epithelialization, while other polyphenol modifications of Au@AgNPs acted through proliferation and wound closure. Conclusion: Bimetallic Au@AgNPs can be used as a basis for modification with selected polyphenols for topical uses. In addition, we have demonstrated that particular polyphenols used to modify bimetallic nanoparticles may show different effects upon different stages of wound healing.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Polifenóis/química , Polifenóis/farmacologia , Prata/química , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Biflavonoides/química , Catequina/análogos & derivados , Catequina/química , Camundongos , Proantocianidinas/química , Taninos/química
8.
Int J Nanomedicine ; 15: 5097-5111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764939

RESUMO

Introduction: In this in-vitro study, we designed a 3D printed composite of zinc oxide (ZnO) nanoparticles (NPs) with photocatalytic activities encapsulated within hydrogel (alginate) constructs, for antibacterial purposes applicable towards wound healing. We primarily sought to confirm the mechanical properties and cell compatibility of these ZnO NP infused scaffolds. Methods: The antibacterial property of the ZnO NPs was confirmed by hydroxyl radical generation using ultraviolet (U.V.) photocatalysis. Titanium dioxide (TiO2), a well-known antibacterial compound, was used as a positive control (1% w/v) for the ZnO NP-based alginate constructs and their antibacterial efficacies compared. Among the ZnO group, 3D printed gels containing 0.5% and 1% w/v of ZnO were analyzed and compared with manually casted samples via SEM, swelling evaluation, and rheological analysis. Envisioning an in-vivo application for the 3D printed ZnO NP-based alginates, we studied their antibacterial properties by bacterial broth testing, cytocompatibility via live/dead assay, and moisture retention capabilities utilizing a humidity sensor. Results: 3D printed constructs revealed significantly greater pore sizes and enhanced structural stability compared to manually casted samples. For all samples, the addition of ZnO or TiO2 resulted in significantly stiffer gels in comparison with the alginate control. Bacterial resistance testing on Staphylococcus epidermidis indicated the addition of ZnO NPs to the gels decreased bacterial growth when compared to the alginate only gels. Cell viability of STO-fibroblasts was not adversely affected by the addition of ZnO NPs to the alginate gels. Furthermore, the addition of increasing doses of ZnO NPs to the alginate demonstrated increased humidity retention in gels. Discussion: The customization of 3D printed alginates containing antibacterial ZnO NPs leads to an alternative that allows accessible mobility of molecular exchange required for improving chronic wound healing. This scaffold can provide a cost-effective and durable antibacterial treatment option.


Assuntos
Alginatos/química , Alginatos/farmacologia , Hidrogéis/química , Nanopartículas/química , Cicatrização/efeitos dos fármacos , Óxido de Zinco/química , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/citologia
9.
PLoS One ; 15(8): e0237746, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810144

RESUMO

In recent years, several studies suggested that the ability of hyperbaric oxygen therapy (HBOT) to promote healing in patients with diabetic ulcers and chronic wounds is due to the reduction of inflammatory cytokines and to a significant decrease in neutrophils recruitment to the damaged area. α4 and ß2 integrins are receptors mediating the neutrophil adhesion to the endothelium and the comprehension of the effects of hyperbaric oxygenation on their expression and functions in neutrophils could be of great importance for the design of novel therapeutic protocols focused on anti-inflammatory agents. In this study, the α4 and ß2 integrins' expression and functions have been evaluated in human primary neutrophils obtained from patients with chronic non-healing wounds and undergoing a prolonged HBOT (150 kPa per 90 minutes). The effect of a peptidomimetic α4ß1 integrin antagonist has been also analyzed under these conditions. A statistically significant decrease (68%) in ß2 integrin expression on neutrophils was observed during the treatment with HBO and maintained one month after the last treatment, while α4 integrin levels remained unchanged. However, cell adhesion function of both neutrophilic integrins α4ß1 and ß2 was significantly reduced 70 and 67%, respectively), but α4ß1 integrin was still sensitive to antagonist inhibition in the presence of fibronectin, suggesting that a combined therapy between HBOT and integrin antagonists could have greater antinflammatory efficacy.


Assuntos
Oxigenação Hiperbárica , Integrina alfa4beta1/antagonistas & inibidores , Neutrófilos/imunologia , Peptidomiméticos/uso terapêutico , Úlcera Cutânea/terapia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD18/análise , Antígenos CD18/metabolismo , Adesão Celular/imunologia , Doença Crônica/terapia , Terapia Combinada/métodos , Feminino , Seguimentos , Humanos , Integrina alfa4beta1/análise , Integrina alfa4beta1/metabolismo , Masculino , Pessoa de Meia-Idade , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Peptidomiméticos/farmacologia , Cultura Primária de Células , Úlcera Cutânea/sangue , Úlcera Cutânea/imunologia , Úlcera Cutânea/patologia , Resultado do Tratamento , Cicatrização/efeitos dos fármacos , Cicatrização/imunologia
10.
Acta Cir Bras ; 35(5): e202000507, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32638846

RESUMO

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.


Assuntos
Alginatos , Aloe , Cloretos , Preparações de Plantas , Cicatrização , Compostos de Zinco , Alginatos/farmacologia , Animais , Cloretos/química , Cloretos/farmacologia , Preparações de Plantas/farmacologia , Ratos , Ratos Wistar , Cicatrização/efeitos dos fármacos , Compostos de Zinco/química , Compostos de Zinco/farmacologia
11.
Ann Surg ; 272(2): 248-252, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675537

RESUMO

BACKGROUND: There is limited evidence for the use of postoperative antibiotics for simple appendicitis (SA) in children. Our aim was to conduct a prospective double-blinded randomized controlled trial to investigate this after a laparoscopic appendicectomy. METHODS: Following ethical approval, children (≤16 years) undergoing appendicectomy were recruited at a single institution. Patients were randomized intraoperatively to receive either 2 postoperative intravenous doses of placebo or antibiotics (Abx). All patients received a dose of Abx at induction of anesthesia. Primary outcome was the incidence of postoperative wound infection (WI), and secondary outcome was the incidence of intra-abdominal abscess formation. Data are reported as number of cases (%), median (range), relative risk, and analyzed using Mann Whitney U test, Chi-square test, as appropriate, a P-value ≤0.05 was considered significant. RESULTS: A total of 304 patients were randomized. Sixty-one were subsequently excluded due to protocol violations or recruitment errors; therefore, 243 were included in the final analysis. One hundred twenty-two patients received placebo and 121 Intravenous Abx. There was no difference between the sex (50F/72 M vs 47F/74 M, P = 0.8), median age (12.4 vs 12.2 years, P = 0.5), and postoperative length of stay in a hospital (27.2 vs 25.6 hours, P = 0.7). There was also no difference in the preoperative blood results. A total of 9 WIs occurred: 8/122 (6.6%) placebo versus 1/121 (0.8%) Abx, P = 0.01 [relative risk for WI 7.9 (95% confidence interval: 1.0-62.4)]. There were no intra-abdominal abscess in either groups. CONCLUSIONS: This prospective randomized double blinded randomized controlled trial has revealed a significant decrease in WI rates by giving 2 postoperative intravenous doses of Abx, suggesting postoperative Abx are of benefit in SA.


Assuntos
Antibacterianos/administração & dosagem , Apendicectomia/métodos , Apendicite/cirurgia , Laparoscopia/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Cicatrização/efeitos dos fármacos , Apendicectomia/efeitos adversos , Apendicite/diagnóstico , Austrália , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Injeções Intravenosas , Laparoscopia/efeitos adversos , Tempo de Internação , Masculino , Estudos Prospectivos , Medição de Risco , Estatísticas não Paramétricas , Resultado do Tratamento , Cicatrização/fisiologia
12.
Toxicol Lett ; 332: 155-163, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32645460

RESUMO

Chronic exposure to arsenic increases the risk of developing a variety of human cancers including lung carcinomas. However, the exact molecular mechanism underlying arsenic carcinogenicity remains largely unknown. Autophagy is a conserved catabolic process for maintaining cellular protein homeostasis whose defects might result in accumulation of dysfunctional organelles and damaged proteins thus promoting tumorigenesis. In the present study, we found that chronic exposure of human bronchial epithelial BEAS-2B cells to sub-lethal dose of sodium arsenite led to autophagy activation and induced an epithelial-to-mesenchymal transition (EMT) to enhance cell migratory and invasive capability. The malignant transformation was mediated via activation of MEK/ERK1/2 signaling. Importantly, inhibition of autophagy in these arsenic-exposed cells by pharmacological intervention or genetic deletion further promoted the EMT and increased the generation of inflammasomes. Both autophagy inhibitor and genetic deletion of autophagy core gene Beclin-1 produced similar effects. These results may suggest the important role of autophagy in sodium arsenite-induced lung tumorigenesis which may serve as a potential target in prevention and treatment of arsenic-imposed lung cancer.


Assuntos
Arsênico/toxicidade , Autofagia/fisiologia , Brônquios/patologia , Neoplasias Brônquicas/induzido quimicamente , Neoplasias Brônquicas/patologia , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína Beclina-1/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Inflamassomos/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
13.
PLoS One ; 15(7): e0236761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726347

RESUMO

The effect of dressings saturated with either a standardized suspension of probiotic bacteria or saline on healing of traumatic distal limb wounds in horses was evaluated for 24 days, and the systemic inflammatory effect was assessed. The wounds were divided in two groups based on the phase of healing: wounds with an incomplete (ICGB) or a complete granulation bed (CGB). The wound area was expressed as percentage of the wound area at day 0 and defined as relative wound area. The mean relative wound area decreased faster in probiotic than saline treated wounds. The difference was most obvious in CGB and increased rapidly from day 0 until day 12 up to 30%, and stabilized around 25% thereafter until the end of the observation period, but it was not statistically significant because of the large variation within the treatment groups. The mean wound area of CGB decreased to 28.4% (range: 6.3 to 49.3) with probiotic and to 51.9% (range: 29.3 to 81.7) with saline treatment at day 24. Additionally, the rate to 50% healing in CGB was 3.4 faster with probiotic compared to saline treatment, whereas in ICGB this was 1.9 faster. Topical probiotics did not increase serum amyloid A and white blood cell counts. Although the mentioned differences were not statistically significant, the clinical relevance of the effect of treatment with probiotics in CGB wounds is clear, supported by the differences in mean wound area in course of time and the time required to reach 50% healing (day 12 for probiotic vs more than day 24 for saline treated wounds). Thus the probiotic treated wounds reached 50% reduction in wound area in half of the time of the saline treated wounds. The topical use of probiotics can be considered as safe as it did not cause a systemic effect.


Assuntos
Extremidades/fisiologia , Cavalos/fisiologia , Probióticos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Bacteriologia , Feminino , Hematologia , Cavalos/sangue , Cavalos/microbiologia , Masculino
14.
Cell Prolif ; 53(8): e12866, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32643284

RESUMO

OBJECTIVES: High glucose (HG)-mediated bone marrow mesenchymal stem cell (BMSC) dysfunction plays a key role in impaired bone formation induced by type 1 diabetes mellitus (T1DM). Morroniside is an iridoid glycoside derived from the Chinese herb Cornus officinalis, and it has abundant biological activities associated with cell metabolism and tissue regeneration. However, the effects and underlying mechanisms of morroniside on HG-induced BMSC dysfunction remain poorly understood. MATERIALS AND METHODS: Alkaline phosphatase (ALP) staining, ALP activity and Alizarin Red staining were performed to assess the osteogenesis of BMSCs. Quantitative real-time PCR and Western blot (WB) were used to investigate the osteo-specific markers, receptor for advanced glycation end product (RAGE) signalling and glyoxalase-1 (Glo1). Additionally, a T1DM rat model was used to assess the protective effect of morroniside in vivo. RESULTS: Morroniside treatment reverses the HG-impaired osteogenic differentiation of BMSCs in vitro. Morroniside suppressed advanced glycation end product (AGEs) formation and RAGE expression by triggering Glo1. Moreover, the enhanced osteogenesis due to morroniside treatment was partially blocked by the Glo1 inhibitor, BBGCP2. Furthermore, in vivo, morroniside attenuated bone loss and improved bone microarchitecture accompanied by Glo1 upregulation and RAGE downregulation. CONCLUSIONS: These findings suggest that morroniside attenuates HG-mediated BMSC dysfunction partly through the inhibition of AGE-RAGE signalling and activation of Glo1 and may be a potential treatment for diabetic osteoporosis.


Assuntos
Glicosídeos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacos
15.
Cochrane Database Syst Rev ; 7: CD008058, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32725896

RESUMO

BACKGROUND: Burn injuries are an important health problem. They occur frequently in the head and neck region. The face is the area central to a person's identity that provides our most expressive means of communication. Topical interventions are currently the cornerstone of treatment of burns to the face. OBJECTIVES: To assess the effects of topical interventions on wound healing in people with facial burns of any depth. SEARCH METHODS: In December 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) that evaluated the effects of topical treatment for facial burns were eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, risk of bias assessment and GRADE assessment of the certainty of the evidence. MAIN RESULTS: In this first update, we included 12 RCTs, comprising 507 participants. Most trials included adults admitted to specialised burn centres after recent burn injuries. Topical agents included antimicrobial agents (silver sulphadiazine (SSD), Aquacel-Ag, cerium-sulphadiazine, gentamicin cream, mafenide acetate cream, bacitracin), non-antimicrobial agents (Moist Exposed Burn Ointment (MEBO), saline-soaked dressings, skin substitutes (including bioengineered skin substitute (TransCyte), allograft, and xenograft (porcine Xenoderm), and miscellaneous treatments (growth hormone therapy, recombinant human granulocyte-macrophage colony-stimulating factor hydrogel (rhGMCS)), enzymatic debridement, and cream with Helix Aspersa extract). Almost all the evidence included in this review was assessed as low or very low-certainty, often because of high risk of bias due to unclear randomisation procedures (i.e. sequence generation and allocation concealment); lack of blinding of participants, providers and sometimes outcome assessors; and imprecision resulting from few participants, low event rates or both, often in single studies. Topical antimicrobial agents versus topical non-antimicrobial agents There is moderate-certainty evidence that there is probably little or no difference between antimicrobial agents and non-antimicrobial agents (SSD and MEBO) in time to complete wound healing (hazard ratio (HR) 0.84 (95% confidence interval (CI) 0.78 to 1.85, 1 study, 39 participants). Topical antimicrobial agents may make little or no difference to the proportion of wounds completely healed compared with topical non-antimicrobial agents (comparison SSD and MEBO, risk ratio (RR) 0.94, 95% CI 0.68 to 1.29; 1 study, 39 participants; low-certainty evidence). We are uncertain whether there is a difference in wound infection (comparison topical antimicrobial agent (Aquacel-Ag) and MEBO; RR 0.38, 95% CI 0.12 to 1.21; 1 study, 40 participants; very low-certainty evidence). No trials reported change in wound surface area over time or partial wound healing. There is low-certainty evidence for the secondary outcomes scar quality and patient satisfaction. Two studies assessed pain but it was incompletely reported. Topical antimicrobial agents versus other topical antimicrobial agents It is uncertain whether topical antimicrobial agents make any difference in effects as the evidence is low to very low-certainty. For primary outcomes, there is low-certainty evidence for time to partial (i.e. greater than 90%) wound healing (comparison SSD versus cerium SSD: mean difference (MD) -7.10 days, 95% CI -16.43 to 2.23; 1 study, 142 participants). There is very low-certainty evidence regarding whether topical antimicrobial agents make a difference to wound infection (RR 0.73, 95% CI 0.46 to 1.17; 1 study, 15 participants). There is low to very low-certainty evidence for the proportion of facial burns requiring surgery, pain, scar quality, adverse effects and length of hospital stay. Skin substitutes versus topical antimicrobial agents There is low-certainty evidence that a skin substitute may slightly reduce time to partial (i.e. greater than 90%) wound healing, compared with a non-specified antibacterial agent (MD -6.00 days, 95% CI -8.69 to -3.31; 1 study, 34 participants). We are uncertain whether skin substitutes in general make any other difference in effects as the evidence is very low certainty. Outcomes included wound infection, pain, scar quality, adverse effects of treatment and length of hospital stay. Single studies showed contrasting low-certainty evidence. A bioengineered skin substitute may slightly reduce procedural pain (MD -4.00, 95% CI -5.05 to -2.95; 34 participants) and background pain (MD -2.00, 95% CI -3.05 to -0.95; 34 participants) compared with an unspecified antimicrobial agent. In contrast, a biological dressing (porcine Xenoderm) might slightly increase pain in superficial burns (MD 1.20, 95% CI 0.65 to 1.75; 15 participants (30 wounds)) as well as deep partial thickness burns (MD 3.00, 95% CI 2.34 to 3.66; 10 participants (20 wounds)), compared with antimicrobial agents (Physiotulle Ag (Coloplast)). Miscellaneous treatments versus miscellaneous treatments Single studies show low to very low-certainty effects of interventions. Low-certainty evidence shows that MEBO may slightly reduce time to complete wound healing compared with saline soaked dressing (MD -1.7 days, 95% CI -3.32 to -0.08; 40 participants). In addition, a cream containing Helix Aspersa may slightly increase the proportion of wounds completely healed at 14 days compared with MEBO (RR 4.77, 95% CI 1.87 to 12.15; 43 participants). We are uncertain whether any miscellaneous treatment in the included studies makes a difference in effects for the outcomes wound infection, scar quality, pain and patient satisfaction as the evidence is low to very low-certainty. AUTHORS' CONCLUSIONS: There is mainly low to very low-certainty evidence on the effects of any topical intervention on wound healing in people with facial burns. The number of RCTs in burn care is growing, but the body of evidence is still hampered due to an insufficient number of studies that follow appropriate evidence-based standards of conducting and reporting RCTs.


Assuntos
Anti-Infecciosos/uso terapêutico , Queimaduras/terapia , Traumatismos Faciais/terapia , Pele Artificial , Administração Tópica , Anti-Infecciosos/administração & dosagem , Viés , Carboximetilcelulose Sódica/administração & dosagem , Carboximetilcelulose Sódica/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Cicatrização/efeitos dos fármacos
16.
Life Sci ; 258: 118085, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32663578

RESUMO

BACKGROUND: An integral intestinal barrier is essential for intestinal homeostasis. Yet, as a side effect of cancer treatment, chemotherapeutic drugs have been reported to cause mucositis. In a recent study, we found that alginate oligosaccharides (AOS) prevent busulfan induced intestinal mucositis. However, it is not known if AOS improves small intestine epithelial cell integrity and migration, which are two essential processes for maintaining the mechanical barrier function of the small intestine. In the current investigation, we aimed to explore the effects of AOS on the integrity and migration of small intestine cells using swine intestinal epithelial IPEC-J2 cells. METHODS: Cell integrity was determined using the TEER assay. Cell migration capability was detected using a wound healing experiment. Small interfering RNA (siRNA) was used to inhibit mannose receptor (MR) expression. Western blotting and immunofluorescence staining were used to determine protein expression. RESULTS: Increasing levels of AOS improved cell integrity as measure by TEER. At the same time, AOS improved IPEC-J2 cell migration capacity as shown in the wound closure assay. It is interesting to note that AOS increased the expression of intestinal microvillus proteins and junction proteins to benefit cell integrity. MR siRNA blocked the action of AOS on cell integrity and cell migration and inhibited the expression of microvillus and cell junction proteins. CONCLUSION: We identified the underlying mechanisms by which AOS improved small intestinal mucositis. As a novel, natural food additive, AOS may be administered to prevent intestinal mucositis induced by chemotherapy or other issues.


Assuntos
Alginatos/farmacologia , Movimento Celular/efeitos dos fármacos , Intestino Delgado/citologia , Oligossacarídeos/farmacologia , Animais , Linhagem Celular , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/metabolismo , Proteínas dos Microfilamentos/metabolismo , Microvilosidades/efeitos dos fármacos , Microvilosidades/metabolismo , Miosinas/metabolismo , RNA Interferente Pequeno/metabolismo , Receptores de Superfície Celular/metabolismo , Suínos , Proteínas de Junções Íntimas/metabolismo , Cicatrização/efeitos dos fármacos
17.
PLoS One ; 15(7): e0232565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722676

RESUMO

In vitro scratch wound healing assay, a simple and low-cost technique that works along with other image analysis tools, is one of the most widely used 2D methods to determine the cellular migration and proliferation in processes such as regeneration and disease. There are open-source programs such as imageJ to analyze images of in vitro scratch wound healing assays, but these tools require manual tuning of various parameters, which is time-consuming and limits image throughput. For that reason, we developed an optimized plugin for imageJ to automatically recognize the wound healing size, correct the average wound width by considering its inclination, and quantify other important parameters such as: area, wound area fraction, average wound width, and width deviation of the wound images obtained from a scratch/ wound healing assay. Our plugin is easy to install and can be used with different operating systems. It can be adapted to analyze both individual images and stacks. Additionally, it allows the analysis of images obtained from bright field, phase contrast, and fluorescence microscopes. In conclusion, this new imageJ plugin is a robust tool to automatically standardize and facilitate quantification of different in vitro wound parameters with high accuracy compared with other tools and manual identification.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Software , Cicatrização , Linhagem Celular , Movimento Celular , Meios de Cultivo Condicionados/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Células-Tronco Mesenquimais/química , Reprodutibilidade dos Testes , Cicatrização/efeitos dos fármacos
18.
Gerokomos (Madr., Ed. impr.) ; 31(2): 119-124, jun. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193894

RESUMO

Las úlceras de la extremidad inferior siguen siendo en la actualidad un problema global. Las opciones analgésicas para el control del dolor se basan generalmente en medidas farmacológicas con acción local y/o sistémica. El sevoflurano es un anestésico general inhalatorio, asociado a sus efectos sobre el sistema nervioso central, y tradicionalmente no se emplea por otras vías que no sea inhalado. Sin embargo, hoy en día se le conoce una acción analgésica a nivel central y también periférico. Actualmente, su uso clínico ha llevado a algunos autores a considerar la posibilidad de nuevos efectos del sevoflurano a través de la vía tópica. OBJETIVO: Sintetizar las evidencias científicas disponibles sobre el uso del sevoflurano aplicado de forma tópica en úlceras de la extremidad inferior. METODOLOGÍA: Revisión sistematizada de la literatura científica, siguiendo la guía PRISMA. La búsqueda de estudios se realizó en las principales bases de datos bibliográficas, sin límite de fechas ni de idiomas. También se realizó una búsqueda incluyendo resúmenes de congresos. RESULTADOS: Se obtuvieron un total de 120 referencias. Finalmente, ocho de ellas correspondían a los estudios incluidos para la síntesis cualitativa. En la mayoría de los estudios se encontró una disminución del dolor de 8 a 2 puntos en las escalas empleadas. CONCLUSIONES: Los escasos estudios parecen sugerir un importante efecto analgésico aplicado de forma tópica, un probable efecto antibacteriano y un posible efecto promotor de la cicatrización. Sin embargo, son necesarios más estudios comparativos con un tamaño de muestra mayor, con mejor calidad en sus diseños


Leg ulcers are a global problem daily. The analgesic options for pain control are generally based on pharmacological measures with local and / or systemic action. Sevoflurane is a general inhalation anesthetic, associated with its effects on the central nervous system, its use not being traditional by other routes that are not inhaled. However, today it is known an analgesic action at the central level and at the peripheral level. Actually, the clinical use of this product has led some authors to consider the possibility of new effects of Sevoflurane topically. OBJECTIVE: To synthesize the available scientific evidences about the use of Sevoflurane topically on leg ulcers. METHODOLOGY: Systematized review of the scientific literature, following the PRISMA guide. The main bibliographic databases were searched without date or language limits. Also references lists and congress abstracts were searched. RESULTS: 120 references were identified. Finally, 8 of them were selected for qualitative synthesis. In most studies, was found a decrease in pain of 8 to 2 points in the scales used. CONCLUSIONS: The few studies suggest an analgesic effect applied topically, a probable antibacterial effect and a possible healing promoting effect. However, comparative studies of large sample are needed, with a better quality designs


Assuntos
Humanos , Sevoflurano/uso terapêutico , Extremidade Inferior/lesões , Úlcera do Pé/tratamento farmacológico , Administração Tópica , Prática Clínica Baseada em Evidências/métodos , Enfermagem Baseada em Evidências/métodos , Cicatrização/efeitos dos fármacos
19.
Int J Nanomedicine ; 15: 3887-3901, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581536

RESUMO

pH-sensitive hydrogels have been developed greatly over the past few years. This has been possible due to the synthesis of new hydrogel systems with increased sensitivity - a sensitivity of up to 10-5 pH units has already been established. Recently, pH-sensitive hydrogels have shown to be very useful in biomedical applications, such as targeted cancer treatment and treatment of skin lesions. Prolonged drug release has been made available through the use of such hydrogels. The synthesis of pH-sensitive hydrogels is also quick and cost-effective. This review presents a background on the properties of pH-sensitive hydrogels and discusses some of the hydrogels with different sensitivity ranges and their possible applications. A range of synthesis processes have also been briefly introduced along with the fabrication of different structures such as microcantilevers and contact lenses.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/química , Animais , Bandagens , Liberação Controlada de Fármacos , Indústria Alimentícia , Humanos , Hidrogéis/uso terapêutico , Concentração de Íons de Hidrogênio , Cicatrização/efeitos dos fármacos
20.
Plast Reconstr Surg ; 146(1): 83-89, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32590649

RESUMO

BACKGROUND: Hypertrophic scars and keloids, which are abnormalities of fibrosis, often occur in surgical wounds; however, their exact cause and preventive measures are unknown. The administration of dipeptidyl peptidase-4 inhibitors to humans is expected to suppress fibrosis in wounds and minimize hypertrophic scar and keloid formation. METHODS: This study aimed to verify the suppressive effect of dipeptidyl peptidase-4 inhibitors on the formation of hypertrophic scars or keloids using real world data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. It is a retrospective cohort study, and data were extracted from the National Database between April of 2013 and March of 2015. Patients who underwent median sternotomy were included in the study based on their claimed surgical codes. Subjects who were prescribed dipeptidyl peptidase-4 inhibitors constituted the treatment group; subjects who were not prescribed or administered dipeptidyl peptidase-4 inhibitors during that period constituted the nontreatment group. RESULTS: Subjects included 5430 patients throughout Japan (3509 men and 1921 women). Of the 446 subjects who were treated with dipeptidyl peptidase-4 inhibitors within 1 year before the procedure, fewer than 10 (<2 percent) developed either hypertrophic scars or keloids. Of the 4984 subjects who were not treated, 152 (3.05 percent) were at significantly lower risk for hypertrophic scars and keloids (p = 0.04). A logistic regression analysis was performed to adjust for confounding factors, with history of hypertrophic scar formation as the explained variable. CONCLUSION: This study revealed that dipeptidyl peptidase-4 inhibitors suppress the onset of hypertrophic scars or keloids after surgery in humans. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Cicatriz Hipertrófica/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Queloide/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Esternotomia , Adulto , Idoso , Feminino , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cicatrização/efeitos dos fármacos
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