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1.
Adv Wound Care (New Rochelle) ; 9(8): 462-471, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32857020

RESUMO

Objective: In recent years, reticulated open-cell foam-based closed-incision negative pressure therapy (ROCF-ciNPT) has shown effectiveness in management of various postoperative incisions. These dressings consist of a skin interface layer that absorbs fluid from the skin surface and reduces the potential for microbial colonization within the dressing by means of ionic silver. This study examines the ability of silver to reduce the bioburden within the dressing as well as the localized effect due to potential silver mobility. Approach: Ability of silver to reduce bioburden within the ROCF-ciNPT dressing was assessed using Staphylococcus aureus, Pseudomonas aeruginosa, and Candida spp. Furthermore, silver mobility was assessed using an in vitro skin model to study the zone of inhibition along with released silver quantification. Using a porcine model, diffusion of silver into blood and tissue was studied using emission spectrometry and histology. Results: Microbial growth in the ROCF-ciNPT dressing was significantly reduced (∼2.7-4.9 log reduction) compared to a silver-free negative control. No zone of inhibition was observed for microbial colonies for up to 7 days with minimal localized silver release (<5.5 ppm release). In vivo studies demonstrated no measurable concentration (<0.2 µg/g) of silver in the blood, urine, feces, kidney, and liver tissue biopsy. Innovation: This study provides an important insight into silver concentration and mobility within the ROCF-ciNPT dressing, given emerging concerns associated with potential silver cytotoxicity. Conclusion: These results indicate the concentration of silver (0.019% silver by weight) in the ROCF-ciNPT dressings has been adequate to reduce bioburden within the skin interface layer, while severely limiting the amount of silver leaching out.


Assuntos
Candida/efeitos dos fármacos , Candidíase/terapia , Tratamento de Ferimentos com Pressão Negativa/métodos , Infecções por Pseudomonas/terapia , Prata/farmacocinética , Infecções Estafilocócicas/terapia , Staphylococcus aureus/efeitos dos fármacos , Infecção da Ferida Cirúrgica/terapia , Ferida Cirúrgica/terapia , Animais , Bandagens , Candidíase/sangue , Candidíase/microbiologia , Candidíase/urina , Modelos Animais de Doenças , Masculino , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/urina , Pseudomonas aeruginosa/efeitos dos fármacos , Prata/sangue , Prata/urina , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/urina , Ferida Cirúrgica/sangue , Ferida Cirúrgica/urina , Infecção da Ferida Cirúrgica/sangue , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/urina , Suínos , Resultado do Tratamento , Cicatrização
2.
Theranostics ; 10(17): 7710-7729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685015

RESUMO

Osteosarcoma is a common malignant bone cancer easily to metastasize. Much safer and more efficient strategies are still needed to suppress osteosarcoma growth and lung metastasis. We recently presented a pure physical method to fabricate Ångstrom-scale silver particles (AgÅPs) and determined the anti-tumor efficacy of fructose-coated AgÅPs (F-AgÅPs) against lung and pancreatic cancer. Our study utilized an optimized method to obtain smaller F-AgÅPs and aimed to assess whether F-AgÅPs can be used as an efficient and safe agent for osteosarcoma therapy. We also investigated whether the induction of apoptosis by altering glucose metabolic phenotype contributes to the F-AgÅPs-induced anti-osteosarcoma effects. Methods: A modified method was developed to prepare smaller F-AgÅPs. The anti-tumor, anti-metastatic and pro-survival efficacy of F-AgÅPs and their toxicities on healthy tissues were compared with that of cisplatin (a first-line chemotherapeutic drug for osteosarcoma therapy) in subcutaneous or orthotopic osteosarcoma-bearing nude mice. The pharmacokinetics, biodistribution and excretion of F-AgÅPs were evaluated by testing the levels of silver in serum, tissues, urine and feces of mice. A series of assays in vitro were conducted to assess whether the induction of apoptosis mediates the killing effects of F-AgÅPs on osteosarcoma cells and whether the alteration of glucose metabolic phenotype contributes to F-AgÅPs-induced apoptosis. Results: The newly obtained F-AgÅPs (9.38 ± 4.11 nm) had good stability in different biological media or aqueous solutions and were more effective than cisplatin in inhibiting tumor growth, improving survival, attenuating osteolysis and preventing lung metastasis in osteosarcoma-bearing nude mice after intravenous injection, but were well tolerated in normal tissues. One week after injection, about 68% of F-AgÅPs were excreted through feces. F-AgÅPs induced reactive oxygen species (ROS)-dependent apoptosis of osteosarcoma cells but not normal cells, owing to their ability to selectively shift glucose metabolism of osteosarcoma cells from glycolysis to mitochondrial oxidation by inhibiting pyruvate dehydrogenase kinase (PDK). Conclusion: Our study suggests the promising prospect of F-AgÅPs as a powerful selective anticancer agent for osteosarcoma therapy.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas Metálicas/administração & dosagem , Osteossarcoma/tratamento farmacológico , Prata/administração & dosagem , Adolescente , Animais , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Feminino , Frutose/química , Humanos , Lactente , Recém-Nascido , Injeções Intravenosas , Neoplasias Pulmonares/secundário , Masculino , Nanopartículas Metálicas/química , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Osteossarcoma/secundário , Oxirredução/efeitos dos fármacos , Cultura Primária de Células , Piruvato Desidrogenase Quinase de Transferência de Acetil/antagonistas & inibidores , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Eliminação Renal , Transdução de Sinais/efeitos dos fármacos , Prata/farmacocinética , Prata/urina , Distribuição Tecidual , Efeito Warburg em Oncologia/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
3.
Neurol Res ; 31(3): 234-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19040800

RESUMO

OBJECTIVE: Infection is a major complication and risk factor of cerebrospinal fluid (CSF) shunting procedures. Recently, antibiotic-impregnated shunt systems have been developed in an attempt to prevent or reduce the CSF infection. The aim of this study was to determine the efficacy of silver-impregnated polyurethane ventricular catheter for shunting of CSF in patients with infected hydrocephalus. METHODS: Seven patients who had hydrocephalus with high protein level and positive CSF culture underwent implantation of ventriculoperitoneal shunt with silver-impregnated polyurethane ventricular catheter. All of them experienced shunt failure previously due to infection. The Silverline ventricular catheter, which was connected to the Miethke gravity-assisted valve system and peritoneal catheter, was used in all patients. The mean follow-up period after operation was 14 months. Cerebrospinal fluid samples from the reservoir of the shunts were obtained at the end of the third month after operation in all patients. RESULTS: The CSF protein level of the patients was reduced significantly, and the CSF culture became negative after shunt placement with silver-impregnated polyurethane ventricular catheters. The mean CSF silver (Ag) level was 0.51 ng/ml [parts per billion (ppb)], and blood Ag level was 3.65 ng/ml (ppb) at the first month after operation. No shunt obstruction or infection was observed in the follow-up period. CONCLUSION: Silver-impregnated polyurethane ventricular catheters appear to be safe and well tolerated in patients who sustained infected hydrocephalus. Preliminary results suggest a complete improvement of infection. Longer follow-up and large number of patients are needed to more accurately assess the efficacy of these catheters.


Assuntos
Infecções Relacionadas a Cateter/complicações , Infecções Relacionadas a Cateter/prevenção & controle , Hidrocefalia/complicações , Hidrocefalia/cirurgia , Prata/administração & dosagem , Derivação Ventriculoperitoneal/efeitos adversos , Derivação Ventriculoperitoneal/métodos , Adolescente , Adulto , Cateteres de Demora , Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Glucose/líquido cefalorraquidiano , Humanos , Hidrocefalia/líquido cefalorraquidiano , Lactente , Masculino , Pessoa de Meia-Idade , Reoperação , Prata/sangue , Prata/líquido cefalorraquidiano , Prata/urina
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