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1.
Surg Innov ; 26(3): 312-320, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30895890

RESUMEN

BACKGROUND: During minimally invasive surgery, efficient and nontoxic hemostats are important for difficult to access bleeding areas. Polylactic acid is an ecofriendly hemostatic agent and we aimed to evaluate the efficacy of a polylactic acid nonwoven fabric (PLAF) developed by Toray Industries, Inc, on liver hemostasis in a preclinical study. MATERIALS AND METHODS: PLAF consists of both 1-µm diameter fibers and 100-µm diameter beaded fibers. Four rats were used, and 2 trough-shaped resections of the liver parenchyma were performed (n = 8 lobes). Immediately after the resection, PLAF (PLAF group: n = 4 lobes) or rayon gauze (Rayon group: n = 4 lobes) were applied on the resected plane and compressed manually. We compared the mean time to hemostasis and blood loss per lobe, as well as histological findings between the groups. RESULTS: The PLAF group had a significantly shorter bleeding time ( P = .006), and showed lower blood loss compared with the Rayon group ( P = .076). Histopathological evaluation showed a large amount of beads on the liver surface in the PLAF group. Aggregated red blood cells evident by electron microscopy and von Willebrand factor immunofluorescence were seen surrounding the beads. The PLAF group showed significantly greater von Willebrand factor expression than the Rayon group ( P = .004). DISCUSSION: This new PLAF showed superior outcomes thanks to its unique characteristic of forming beaded nanofibers, and it has the potential to be an efficient hemostat in minimally invasive surgery in the human body.


Asunto(s)
Hemostasis Quirúrgica/métodos , Hemostáticos/farmacología , Hígado/cirugía , Poliésteres/farmacología , Textiles , Animales , Modelos Animales , Ratas , Ratas Sprague-Dawley
2.
Mol Ther ; 25(7): 1588-1595, 2017 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-28457664

RESUMEN

Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias Colorrectales/terapia , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/terapia , MicroARNs/genética , Nanoestructuras/administración & dosificación , Compuestos Organoplatinos/farmacología , Animales , Antineoplásicos/química , Colesterol/química , Colesterol/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Dihidroxifenilalanina/química , Dihidroxifenilalanina/metabolismo , Modelos Animales de Enfermedad , Portadores de Fármacos , Sinergismo Farmacológico , Femenino , Células HCT116 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Ratones , Ratones Desnudos , MicroARNs/administración & dosificación , MicroARNs/metabolismo , Nanoestructuras/química , Compuestos Organoplatinos/química , Oxaliplatino , Polietilenglicoles/química , Polietilenglicoles/metabolismo , Análisis de Supervivencia , Ensayos Antitumor por Modelo de Xenoinjerto
3.
BMJ Open ; 9(5): e028269, 2019 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-31142533

RESUMEN

INTRODUCTION: The prevalence of surgical site infection (SSI) remains higher in gastrointestinal surgery than in other surgeries. Although several guidelines have indicated the efficacy of chlorhexidine and povidone-iodine in reducing the SSI rate, the optimal recommendation has still not been established. Therefore, it is necessary to determine the more effective antiseptic for surgical site preparation. Olanexidine (1.5% olanedine, Otsuka Pharmaceutical Factory, Tokushima, Japan), which is a new antiseptic in Japan, has antimicrobial activity against a wide range of bacteria, including Gram-positive and Gram-negative bacteria. Our study will contribute to determining a new antiseptic for use in gastrointestinal and other surgeries. METHODS AND ANALYSIS: We propose a multicentre, randomised controlled clinical trial for comparing two treatments, that is, 1.5% olanexidine or 10% povidone-iodine, for surgical skin preparation to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. Patients aged ≥20 years at the time of consent will be included. The primary outcome measure is the 30-day postoperative SSI rate. For the primary analysis, which is aimed at comparing the treatment effects, the adjusted risk ratio and its 95% CI will be estimated using the Mantel-Haenszel method. ETHICS AND DISSEMINATION: The protocol was first approved by the Institutional Review Board of Keio University School of Medicine, followed by the institutional review board of each participating site. Participant recruitment began in June 2018. The final results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: UMIN 000031560; Pre-results.


Asunto(s)
Biguanidas/uso terapéutico , Procedimientos Quirúrgicos del Sistema Digestivo , Povidona Yodada/uso terapéutico , Proyectos de Investigación , Infección de la Herida Quirúrgica/prevención & control , Antiinfecciosos Locales , Humanos
4.
Int J Artif Organs ; 41(4): 190-200, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29528759

RESUMEN

BACKGROUND: High-mobility-group box chromosomal protein 1 has been identified as an important mediator of various kinds of acute and chronic inflammation. In this study, we aimed to develop a column that effectively adsorbs high-mobility-group box chromosomal protein 1 by altering the pore size of the fiber. MATERIALS AND METHODS: First, we produced three types of porous polymethylmethacrylate fiber by altering the concentration of polymethylmethacrylate dissolved in dimethylsulfoxide. We then selected a fiber based on the results of an in vitro incubation test of high-mobility-group box chromosomal protein 1 adsorption. Using the selected fiber, we constructed a new column and tested its high-mobility-group box chromosomal protein 1 adsorption capacity during 4-h extracorporeal hemoperfusion in a swine acute liver failure model. RESULTS: Electron microscope observation showed that the three types of fibers had different pore sizes on the surface and in cross section, which were dependent on the concentration of polymethylmethacrylate. In the in vitro incubation test, fiber with moderate-sized pores demonstrated the highest adsorption capacity. In the in vivo hemoperfusion study, the ratio of the high-mobility-group box chromosomal protein 1 concentration at the outlet versus the inlet of the column was significantly lower with the new column than with the control column during 4-h extracorporeal hemoperfusion. The normalized plasma level of high-mobility-group box chromosomal protein 1 at 12 h after the completion of hemoperfusion was significantly lower with the new column than with the control column. CONCLUSION: The newly developed polymethylmethacrylate column adsorbs high-mobility-group box chromosomal protein 1 during hemoperfusion in swine ALF model.


Asunto(s)
Proteína HMGB1/sangre , Hemoperfusión/métodos , Fallo Hepático Agudo/terapia , Adsorción , Animales , Modelos Animales de Enfermedad , Fallo Hepático Agudo/sangre , Polimetil Metacrilato , Porosidad , Porcinos
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