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1.
Proc Natl Acad Sci U S A ; 111(37): 13313-8, 2014 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-25157174

RESUMO

Biofilm-protected microbial infections in skin are a serious health risk that remains to be adequately addressed. The lack of progress in developing effective treatment strategies is largely due to the transport barriers posed by the stratum corneum of the skin and the biofilm. In this work, we report on the use of Ionic Liquids (ILs) for biofilm disruption and enhanced antibiotic delivery across skin layers. We outline the syntheses of ILs, analysis of relevant physicochemical properties, and subsequent neutralization effects on two biofilm-forming pathogens: Pseudomonas aeruginosa and Salmonella enterica. Further, the ILs were also examined for cytotoxicity, skin irritation, delivery of antibiotics through the skin, and treatment of biofilms in a wound model. Of the materials examined, choline-geranate emerged as a multipurpose IL with excellent antimicrobial activity, minimal toxicity to epithelial cells as well as skin, and effective permeation enhancement for drug delivery. Specifically, choline-geranate was comparable with, or more effective than, bleach treatment against established biofilms of S. enterica and P. aeruginosa, respectively. In addition, choline-geranate increased delivery of cefadroxil, an antibiotic, by >16-fold into the deep tissue layers of the skin without inducing skin irritation. The in vivo efficacy of choline-geranate was validated using a biofilm-infected wound model (>95% bacterial death after 2-h treatment). This work establishes the use of ILs for simultaneous enhancement of topical drug delivery and antibiotic activity.


Assuntos
Sistemas de Liberação de Medicamentos , Líquidos Iônicos/farmacologia , Pseudomonas aeruginosa/fisiologia , Salmonella enterica/fisiologia , Administração Cutânea , Biofilmes/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Humanos , Irritantes/toxicidade , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Reprodutibilidade dos Testes , Salmonella enterica/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele Artificial/microbiologia , Espectroscopia de Infravermelho com Transformada de Fourier
2.
Anal Chem ; 84(4): 1831-9, 2012 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-22239072

RESUMO

Flow cytometry can simultaneously measure and analyze multiple properties of single cells or particles with high sensitivity and precision. Yet, conventional flow cytometers have fundamental limitations with regards to analyzing particles larger than about 70 µm, analyzing at flow rates greater than a few hundred microliters per minute, and providing analysis rates greater than 50,000 per second. To overcome these limits, we have developed multinode acoustic focusing flow cells that can position particles (as small as a red blood cell and as large as 107 µm in diameter) into as many as 37 parallel flow streams. We demonstrate the potential of such flow cells for the development of high throughput, parallel flow cytometers by precision focusing of flow cytometry alignment microspheres, red blood cells, and the analysis of a CD4+ cellular immunophenotyping assay. This approach will have significant impact toward the creation of high throughput flow cytometers for rare cell detection applications (e.g., circulating tumor cells), applications requiring large particle analysis, and high volume flow cytometry.


Assuntos
Acústica , Eritrócitos , Citometria de Fluxo/instrumentação , Citometria de Fluxo/métodos , Microesferas , Linfócitos T CD4-Positivos/imunologia , Contagem de Eritrócitos , Humanos , Imunofenotipagem , Técnicas Analíticas Microfluídicas
3.
Semin Cardiothorac Vasc Anesth ; 24(4): 293-303, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32706293

RESUMO

Coronavirus disease 2019 (COVID-19) has a clinical course predominated by acute respiratory failure due to viral pneumonia with possible acute respiratory distress syndrome. However, nearly one third of infected patients, especially those with preexisting cardiovascular (CV) disease, are reported to present with some combination of acute cardiac injury, myocarditis, heart failure, cardiogenic shock, or significant dysrhythmias. In addition, COVID-19 infections are also associated with high rates of thromboembolic and disseminated intravascular coagulation complications. Severe myocarditis and heart failure have both been reported as the initial presenting conditions in COVID-19 infection. This review highlights the important considerations related to the CV manifestations of COVID-19 infections, describes the mechanisms and clinical presentation of CV injury, and provides practical management and therapy suggestions. This narrative review is based primarily on the multiple case series and cohorts from the largest initial COVID-19 outbreak centers (ie, Wuhan, China, and Italy); hence, nearly all presented data and findings are retrospective in nature with the attendant limitations of such reports.


Assuntos
Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Assistência Perioperatória/métodos , Pneumonia Viral/complicações , Betacoronavirus , COVID-19 , Doenças Cardiovasculares/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Humanos , Pandemias , Pneumonia Viral/fisiopatologia , SARS-CoV-2
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