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1.
Proc Natl Acad Sci U S A ; 112(34): 10669-72, 2015 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-26240350

RESUMO

Paleoanthropologists and vertebrate paleontologists have for decades debated the etiology of tooth wear and its implications for understanding the diets of human ancestors and other extinct mammals. The debate has recently taken a twist, calling into question the efficacy of dental microwear to reveal diet. Some argue that endogenous abrasives in plants (opal phytoliths) are too soft to abrade enamel, and that tooth wear is caused principally by exogenous quartz grit on food. If so, variation in microwear among fossil species may relate more to habitat than diet. This has important implications for paleobiologists because microwear is a common proxy for diets of fossil species. Here we reexamine the notion that particles softer than enamel (e.g., silica phytoliths) do not wear teeth. We scored human enamel using a microfabrication instrument fitted with soft particles (aluminum and brass spheres) and an atomic force microscope (AFM) fitted with silica particles under fixed normal loads, sliding speeds, and spans. Resulting damage was measured by AFM, and morphology and composition of debris were determined by scanning electron microscopy with energy-dispersive X-ray spectroscopy. Enamel chips removed from the surface demonstrate that softer particles produce wear under conditions mimicking chewing. Previous models posited that such particles rub enamel and create ridges alongside indentations without tissue removal. We propose that although these models hold for deformable metal surfaces, enamel works differently. Hydroxyapatite crystallites are "glued" together by proteins, and tissue removal requires only that contact pressure be sufficient to break the bonds holding enamel together.


Assuntos
Proteínas do Esmalte Dentário/fisiologia , Dieta , Alimentos/efeitos adversos , Dente Molar/ultraestrutura , Paleodontologia/métodos , Abrasão Dentária/patologia , Alumínio , Cobre , Esmalte Dentário/fisiologia , Esmalte Dentário/ultraestrutura , Fricção , Dureza , Humanos , Técnicas In Vitro , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Microesferas , Modelos Biológicos , Nanosferas/efeitos adversos , Tamanho da Partícula , Ligação Proteica , Dióxido de Silício , Espectrometria por Raios X , Propriedades de Superfície , Abrasão Dentária/etiologia , Zinco
2.
Environ Pollut ; 346: 123546, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38369092

RESUMO

The widespread presence of microplastics (MPs) contamination in drinking water has raised concerns regarding water safety and public health. In this study, a micro-Raman spectrometer was used to trace the occurrence of MP transport from a water source to a drinking water treatment plant (DWTP)1 with an advanced treatment process and DWTP2 with a conventional treatment process and the contributions of different processes to the risk reduction of MPs were explored. Six types of MPs were detected: polyethylene terephthalate, polyethylene, polypropylene, polystyrene, polyamide, and polyvinyl chloride. 2-5 µm (35.8-41.2%) and polyethylene terephthalate (27.1-29.9%) were the most frequently detected MP sizes and types of water source samples, respectively. The abundance of MPs in treated water decreased by 72.7-83.0% compared to raw water. Ozonation and granular activated carbon (52.7%), and sand filtration (47.5%) were the most effective processes for removing MPs from DWTP1 and DWTP2, respectively. Both DWTPs showed significant removal effects on polyethylene terephthalate, with 80.0-88.1% removal rates. The concentrations of polystyrene increase by 30.0-53.4% after chlorination. The dominant components in the treated water of DWTP1 and DWTP2 were polypropylene (24.7%) and polyethylene 27.7%, respectively, and MPs of 2-5 µm had the highest proportion (55.3-64.3%). Pollution load index and potential ecological risk index of raw water treated by DWTPs were reduced by 48.0-58.7% and 94.5-94.7%, respectively. The estimated daily intake of MPs in treated water for infants was 45.5-75.0 items/kg/d, respectively, approximately twice that of adults. This study contributes to the knowledge gap regarding MP pollution in drinking water systems.


Assuntos
Água Potável , Poluentes Químicos da Água , Humanos , Microplásticos , Plásticos , Polipropilenos , Poliestirenos , Polietilenotereftalatos , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Polietileno , China
3.
Chemosphere ; 346: 140534, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37926166

RESUMO

Electrochemical activation of persulfate (EA-PS) is gradually attracting attention as an emerging method for wastewater treatment. In this study, a novelty flow-through EA-PS system was first attempted for pollutants degradation using boron and cobalt co-doping carbon felt (B, Co-CF) as the cathode. SEM images, XPS and XRD spectra of B, Co-CF were investigated. The optimal doping ration between B and Co was 1:2. Increasing current density, PS concentration and flow rate, decreasing initial pH accelerated the removal of AO7. The mechanism involved in EA-PS were the comprehensive effect of DET, •OH and SO4•-. B, Co-CF cathode for flow-through system was stable with five cycles efficient AO7 decay performance. EA-PS in flow-through system was an efficient method with low cost and efficient pollutants degradation. This work provides a feasible strategy for synergistically enhancing PS activation and promoting the degradation of organic pollutants.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Carbono , Fibra de Carbono , Oxirredução , Poluentes Químicos da Água/análise
4.
Eye Contact Lens ; 39(6): 376-80, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24172065

RESUMO

OBJECTIVE: Contact lens safety is an important topic in clinical studies. Corneal infections usually occur because of the use of bacteria-carrying contact lenses. The current study investigated the impact of plasma surface modification on bacterial adherence to rigid contact lenses made of fluorosilicone acrylate materials. METHODS: Boston XO and XO2 contact lenses were modified using plasma technology (XO-P and XO2-P groups). Untreated lenses were used as controls. Plasma-treated and control lenses were incubated in solutions containing Staphylococcus aureus or Pseudomonas aeruginosa. MTT colorimetry, colony-forming unit counting method, and scanning electron microscopy were used to measure bacterial adhesion. RESULTS: MTT colorimetry measurements showed that the optical density (OD) values of XO-P and XO2-P were significantly lower than those of XO and XO2, respectively, after incubation with S. aureus (P < 0.01). The OD value of XO-P was also much lower than that of XO after incubation with P. aeruginosa (P < 0.01). Colony-forming unit counting revealed that a significantly lower number of bacterial colonies attached to the XO-P versus XO lenses and to the XO2-P versus XO2 lenses incubated with S. aureus (P < 0.01). Fewer bacterial colonies attached to the XO-P versus XO lenses incubated with P. aeruginosa (P < 0.01). Further, scanning electron microscopy suggested different bacterial adhesion morphology on plasma-treated versus control lenses. CONCLUSION: Plasma surface modification can significantly decrease bacterial adhesion to fluorosilicone acrylate contact lenses. This study provides important evidence of a unique benefit of plasma technology in contact lens surface modification.


Assuntos
Aderência Bacteriana , Lentes de Contato/microbiologia , Polímeros , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/fisiologia , Contagem de Colônia Microbiana , Microscopia Eletrônica de Varredura , Propriedades de Superfície
5.
Discov Med ; 35(178): 777-786, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37811615

RESUMO

BACKGROUND: Doxorubicin (Dox) is a clinical first-line broad-spectrum anticancer agent. A dose-dependent cardiotoxic and myelosuppressive response limits the clinical use of Dox. Recent research indicates that Dox-induced cardiotoxicity is associated with senescent cell accumulation and that antiaging therapy can alleviate aging-related disorders. Cepharanthine (Cep) is commonly used to treat various acute and chronic illnesses, including leukopenia, snakebites, dry mouth, and hair loss. Whether Cep alleviates Dox-induced senescence is unknown. METHODS: The expression of genes and proteins associated with aging was examined using NIH3T3 cell lines. The experiments were divided into a control group, a Dox group, and a Cep group on different days. NIH3T3 senescent cells were detected by senescence-ß-galactosidase (SA-ß-Gal) staining, and Western blotting was used to detect the protein levels of p16, p53, AMP-activated protein kinase (AMPK), mammalian target of the rapamycin (mTOR), p62, and Light Chain 3 (LC3). Fluorescence was used to detect the expression of monomeric red fluorescence protein-green fluorescence protein-Light Chain 3 (mRFP-GFP-LC3) and LC3 puncta in NIH3T3 cells. Real-time quantitative reverse transcription polymerase chain reaction (RT‒qPCR) was used to test the expression of senescence-associated secretory phenotypes (SASP: Interleukin 6 (IL-6), Interleukin 1 beta (IL-1ß), and Interleukin 8 (IL-8)). Cell Counting Kit-8 (CCK-8) was used to assess NIH3T3 cell viability. RESULTS: Here, we reported that Cep reversed the Dox-induced increase in the proportion of SA-ß-Gal-positive cells and the high expression of aging-related proteins (p53, p < 0.05; p16, p < 0.05) and aging-related genes (IL-6, p < 0.05; IL-1ß, p < 0.05; IL-8, p < 0.05) on the 3rd day. Mechanistically, Cep reduced the increase in the levels of phospho-mTOR (p < 0.05) on Days 1 and 3 and p62 protein (p < 0.05) caused by Dox on Day 1 and reversed the decline in LC3II/LC3I levels (p < 0.05) caused by Dox on Day 3, which is associated with the regulation of senescence. Additionally, the viability of NIH3T3 cells was significantly increased in the concentration range of 0.5-5 µM Cep (p < 0.05). CONCLUSIONS: We first found that Cep could suppress SA-ß-Gal activity (p < 0.05) and the development of SASP. Additionally, in Cep-treated cells, Cep could restore autophagy dysfunction and suppress the mTOR signaling pathway. This research provides a new view on the mechanics of aging and autophagy and aids in developing novel antiaging drugs.


Assuntos
Interleucina-8 , Proteína Supressora de Tumor p53 , Camundongos , Animais , Humanos , Interleucina-8/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Interleucina-6/metabolismo , Células NIH 3T3 , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Senescência Celular , Doxorrubicina/toxicidade , Autofagia , Mamíferos/metabolismo
6.
Huan Jing Ke Xue ; 44(7): 3997-4005, 2023 Jul 08.
Artigo em Zh | MEDLINE | ID: mdl-37438298

RESUMO

Microplastics (MPs), as a new type of pollutant, are widely detected in sewage treatment plants. Currently, research on MPs in traditional sewage treatment systems has mainly been focused on the pollution level and distribution characteristics, with a lack of studying the impact of MPs on the sludge granulation. In order to explore the effect of MPs on the granulation process, a microplastic exposure test was conducted by adding polyethylene terephthalate microplastics (PET-MPs), which are widespread in the environment. The operating performance of the system, extracellular polymeric substance (EPS) composition, and flora enrichment were analyzed on the sludge granulation. The results showed that the exposure of PET-MPs significantly accelerated the sludge granulation process, whereas the increase in EPS content dominated by PN enhanced the sludge surface hydrophobicity; the granulation rate and EPS secretion were proportional to the exposed particle size. Microplastics and EPS secretions synergistically promoted the formation of granular sludge. However, continuous microplastic exposure led to deterioration of the system decontamination performance and inhibited the degradation process of pollutants, with the most negative effect of nitrite nitrogen accumulation under 250 µm PET-MPs exposure, as high as (5.08±0.24) mg·L-1. The high-throughput sequencing revealed that the microbial community diversity fell in the experimental group. The dominant bacteria at the phylum level were Proteobacteria and Bacteroidota on the sludge granulation. Rhodocyclaceae, Sphingomonadaceae, Flavobacteriaceae, and Rhodanobacteraceae promoted flocculation by increasing EPS secretion. The decrease in Comamonadaceae and Chitinophagaceae weakened the ammonia and nitrite oxidation capacity of the system, whereas the decrease in Rhodobacteraceae, Hyphomonadaceae, and Xanthomonadaceae inhibited the removal of nitrate nitrogen.


Assuntos
Poluentes Ambientais , Matriz Extracelular de Substâncias Poliméricas , Microplásticos , Plásticos , Esgotos , Bacteroidetes , Nitrogênio
7.
Nat Commun ; 12(1): 6600, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34815411

RESUMO

Living cells have the capability to synthesize molecular components and precisely assemble them from the nanoscale to build macroscopic living functional architectures under ambient conditions. The emerging field of living materials has leveraged microbial engineering to produce materials for various applications but building 3D structures in arbitrary patterns and shapes has been a major challenge. Here we set out to develop a bioink, termed as "microbial ink" that is produced entirely from genetically engineered microbial cells, programmed to perform a bottom-up, hierarchical self-assembly of protein monomers into nanofibers, and further into nanofiber networks that comprise extrudable hydrogels. We further demonstrate the 3D printing of functional living materials by embedding programmed Escherichia coli (E. coli) cells and nanofibers into microbial ink, which can sequester toxic moieties, release biologics, and regulate its own cell growth through the chemical induction of rationally designed genetic circuits. In this work, we present the advanced capabilities of nanobiotechnology and living materials technology to 3D-print functional living architectures.


Assuntos
Tinta , Nanofibras/química , Impressão Tridimensional , Engenharia de Proteínas , Bactérias/genética , Bactérias/metabolismo , Materiais Biocompatíveis/química , Bioimpressão/métodos , Escherichia coli/genética , Escherichia coli/metabolismo , Engenharia Genética , Hidrogéis/química , Reologia , Engenharia Tecidual
8.
J Colloid Interface Sci ; 551: 1-9, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31071490

RESUMO

Ultrasound-responsive chemistry was exploited in manufacture of drug delivery nanoparticulates for pursuit of on-demand ultrasound-stimulated drug release function. In principle, the ultrasound-labile oxyl-alkylhydroxylamine (-oa-) linkage was tailored between the segments of amphiphiles. Consequently, the hydrophobic chemotherapeutic doxorubicin could be readily assembled with the hydrophobic segments of amphiphiles into interior compartments, whereas the hydrophilic segments represented as the external surroundings. Upon ultrasonication, the proposed phase-segregated self-assemblies were determined to be subjected to evident structural rearrangement as a consequence of -oa- cleavage. Simultaneously, the release rate of doxorubicin payloads appeared to accelerate due to the ultrasound-induced structural destabilization, consequently eliciting potent cytotoxic efficacy at the affected cells. Another noteworthy characteristic of the proposed self-assemblies was poly (lactobionamidoethyl methacrylate) (pLAMA) as the hydrophilic components of the amphiphiles, characterized to possess galactosylated residues. In view of the specific affinity of galactosylated residues (and lactosylated residues) to asialoglycoprotein receptors (overexpressed on the surface of intractable hepatocellular carcinoma), the proposed self-assemblies were determined to impart preferential affinities to hepatocellular carcinoma. Together with the strategic ultrasound-stimulated drug release property, our proposed drug delivery system demonstrated appreciably pharmaceutical efficacy on hepatocellular carcinoma.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Portadores de Fármacos/química , Hidroxilaminas/química , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Ácidos Polimetacrílicos/química , Ondas Ultrassônicas , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Galactose/química , Células Hep G2 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cinética , Polimerização
9.
J Am Heart Assoc ; 7(3)2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29378731

RESUMO

BACKGROUND: Ischemic stroke is a complex disease with multiple etiologies and clinical manifestations. Paired immunoglobulin-like receptor B (PirB), which is originally thought to function exclusively in the immune system, is now also known to be expressed by neurons. A growing number of studies indicate that PirB can inhibit neurite outgrowth and restrict neuronal plasticity. The aim of the study is to investigate whether PirB can be an attractive theranostic target for ischemic stroke. METHODS AND RESULTS: First, we investigated the spatial-temporal expression of PirB in multiple ischemic stroke models, including transient middle cerebral artery occlusion, photothrombotic cerebral cortex ischemia, and the neuronal oxygen glucose deprivation model. Then, anti-PirB immunoliposome nanoprobe was developed by thin-film hydration method and investigated its specific targeting in vitro and in vivo. Finally, soluble PirB ectodomain (sPirB) protein delivered by polyethylene glycol-modified nanoliposome was used as a therapeutic reagent for ischemic stroke by blocking PirB binding to its endogenous ligands. These results showed that PirB was significantly upregulated after cerebral ischemic injury in ischemic stroke models. Anti-PirB immunoliposome nanoprobe was successfully developed and specifically bound to PirB in vitro. There was accumulation of anti-PirB immunoliposome nanoprobe in the ischemic hemisphere in vivo. Soluble PirB ectodomains remarkably improved ischemic stroke model recovery by liposomal delivery system. CONCLUSIONS: These data indicated that PirB was a significant element in the pathological process of cerebral ischemia. Therefore, PirB may act as a novel theranostic target for ischemic stroke.


Assuntos
Encéfalo/diagnóstico por imagem , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/terapia , Imagem Molecular/métodos , Nanopartículas , Fragmentos de Peptídeos/administração & dosagem , Receptores Imunológicos/administração & dosagem , Receptores Imunológicos/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Nanomedicina Teranóstica/métodos , Animais , Apoptose , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Células Cultivadas , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Ligantes , Lipossomos , Imageamento por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurônios/patologia , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Receptores Imunológicos/genética , Recuperação de Função Fisiológica , Fatores de Tempo , Regulação para Cima
10.
J R Soc Interface ; 14(135)2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29070592

RESUMO

The nanoscale responses of teeth to chewing loads are poorly understood. This has contributed to debate concerning the aetiology of enamel wear and resistance to fracture. Here we develop a new model for reactions of individual hydroxyapatite nanofibres to varying loads and directions of force. Hydroxyapatite nanofibres, or crystallites, composed of chains of bonded nanospheres, are the fundamental building blocks of enamel. This study indicates that these nanofibres respond to contact pressure in three distinct ways depending on force magnitude and direction: (i) plucking (nanosphere loss when the strength of the bonding protein 'glue' is exceeded), (ii) plastic deformation (compression to gradually bend nanofibres and squeeze the protein layer), and (iii) fragmentation (nanofibres fracture when the strength of H-bonds that bind smaller nanoparticles into nanospheres is exceeded). Critical contact pressure to initiate plucking is the lowest, followed by plastic deformation, and then fragmentation. Further, lower contact pressures are required for a response with shear forces applied perpendicular to the long axes of crystallites than with crushing forces parallel to them alone. These nanoscale responses are explained as a function of the interfacial nanochemical bonding between and within individual crystallites. In other words, nanochemistry plays a critical role in the responses of enamel to varying chewing loads.


Assuntos
Esmalte Dentário/fisiologia , Mastigação/fisiologia , Dente Molar/fisiologia , Fenômenos Biomecânicos , Força de Mordida , Humanos
11.
Mater Sci Eng C Mater Biol Appl ; 70(Pt 1): 418-429, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27770912

RESUMO

The greatest crux in the combination of chemotherapy and gene therapy is the construction of a feasible and biocompatible carrier for loading the therapeutic drug and gene simultaneously. Here, a new amphiphilic bifunctional pullulan derivative (named as PDP) synthesized by grafting lipophilic desoxycholic acid and low-molecular weight (1kDa) branched polyethylenimine onto the backbone of pullulan was evaluated as a nano-carrier for the co-delivery of drug and gene for potential cancer therapy. PDP exhibited good blood compatibility and low cytotoxicity in the hemolysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. By self-assembly process, the amphiphilic PDP polymer formed cationic core-shell nanomicelles in aqueous solution with an average diameter of 160.8nm and a zeta potential of approximate 28mV. The PDP micelles had relative higher drug encapsulation efficiency (84.05%) and loading capacity (7.64%) for doxorubicin (DOX), an effective anti-tumor drug, demonstrating sustained drug release profile and good DNA-binding ability. The flow cytometry and confocal laser scanning microscopy showed that PDP/DOX micelles could be successfully internalized by MCF-7 cells, and presenting higher cytotoxicity against MCF-7 cells than that of free DOX. Furthermore, PDP micelles could efficiently transport tumor suppressor gene p53 into MCF-7 cells, and the expressed exogenous p53 protein induced MCF-7 cells to die. More excitedly, in comparison with single DOX or p53 delivery, the co-delivery of DOX and gene p53 using PDP micelles displayed higher cytotoxicity, induced higher apoptosis rate of tumor cells and blocked more effectively the migration of cancer cells in vitro. In tumor-bearing mice, co-delivery of DOX and p53 also exhibited enhanced antitumor efficacy as compared with single delivery of DOX or p53 alone. In summary, these results demonstrated that it is highly promising to use cationic PDP micelles for effectively co-delivering functional gene and chemotherapeutic agent, and thus improving antitumor efficacy and systemic toxicity.


Assuntos
Materiais Biocompatíveis/química , Ácido Desoxicólico/química , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Glucanos/química , Neoplasias/tratamento farmacológico , Polietilenoimina/química , Proteína Supressora de Tumor p53/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cátions , Morte Celular/efeitos dos fármacos , DNA/metabolismo , Ácido Desoxicólico/síntese química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Glucanos/síntese química , Células Hep G2 , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Nanopartículas/química , Plasmídeos/metabolismo , Polietilenoimina/síntese química , Espectroscopia de Prótons por Ressonância Magnética , Ovinos , Transfecção , Proteína Supressora de Tumor p53/metabolismo
12.
Circ Cardiovasc Interv ; 10(7)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28701488

RESUMO

BACKGROUND: Mechanical strength of bioresorbable scaffolds (BRS) is highly dependent on strut dimensions and polymer features. To date, the successful development of thin-walled BRS has been challenging. We compared the biomechanical behavior and vascular healing profile of a novel thin-walled (115 µm) sirolimus-eluting ultrahigh molecular weight amorphous poly-l-lactic acid-based BRS (APTITUDE, Amaranth Medical [AMA]) to Absorb (bioresorbable vascular scaffold [BVS]) using different experimental models. METHODS AND RESULTS: In vitro biomechanical testing showed no fractures in the AMA-BRS when overexpanded 1.3 mm above nominal dilatation values (≈48%) and lower number of fractures on accelerated cycle testing over time (at 21 K cycles=20.0 [19.5-20.5] in BVS versus 4.0 [3.0-4.3] in AMA-BRS). In the healing response study, 35 AMA-BRS and 23 BVS were implanted in 58 coronary arteries of 23 swine and followed-up to 180 days. Scaffold strut healing was evaluated in vivo using weekly optical coherence tomography analysis. At 14 days, the AMA-BRS demonstrated a higher percentage of embedded struts (71.0% [47.6, 89.1] compared with BVS 40.3% [20.5, 63.2]; P=0.01). At 21 days, uncovered struts were still present in the BVS group (3.8% [2.1, 10.2]). Histopathology revealed lower area stenosis (AMA-BRS, 21.0±6.1% versus BVS 31.0±4.5%; P=0.002) in the AMA-BRS at 28 days. Neointimal thickness and inflammatory scores were comparable between both devices at 180 days. CONCLUSIONS: A new generation thinned wall BRS displayed a more favorable biomechanical behavior and strut healing profile compared with BVS in normal porcine coronary arteries. This novel BRS concept has the potential to improve the clinical outcomes of current generation BRS.


Assuntos
Implantes Absorvíveis , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Vasos Coronários/patologia , Intervenção Coronária Percutânea/instrumentação , Poliésteres/química , Sirolimo/administração & dosagem , Cicatrização , Animais , Biópsia , Angiografia Coronária , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Teste de Materiais , Modelos Animais , Peso Molecular , Intervenção Coronária Percutânea/efeitos adversos , Desenho de Prótese , Falha de Prótese , Sus scrofa , Fatores de Tempo , Tomografia de Coerência Óptica
13.
Thromb Haemost ; 115(3): 533-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26489782

RESUMO

Zinc released from activated platelets binds fibrin(ogen) and attenuates fibrinolysis. Although zinc also affects clot formation, the mechanism and consequences are poorly understood. To address these gaps, the effect of zinc on clot formation and structure was examined in the absence or presence of factor (F) XIII. Zinc accelerated a) plasma clotting by 1.4-fold, b) fibrinogen clotting by 3.5- and 2.3-fold in the absence or presence of FXIII, respectively, c) fragment X clotting by 1.3-fold, and d) polymerisation of fibrin monomers generated with thrombin or batroxobin by 2.5- and 1.8-fold, respectively. Whereas absorbance increased up to 3.3-fold when fibrinogen was clotted in the presence of zinc, absorbance of fragment X clots was unaffected by zinc, consistent with reports that zinc binds to the αC-domain of fibrin(ogen). Scanning electron microscopic analysis revealed a two-fold increase in fibre diameter in the presence of zinc and in permeability studies, zinc increased clot porosity by 30-fold with or without FXIII. Whereas FXIII increased clot stiffness from 128 ± 19 Pa to 415 ± 27 Pa in rheological analyses, zinc reduced clot stiffness by 10- and 8.5-fold in the absence and presence of FXIII, respectively. Clots formed in the presence of zinc were more stable and resisted rupture with or without FXIII. Therefore, zinc accelerates clotting and reduces fibrin clot stiffness in a FXIII-independent manner, suggesting that zinc may work in concert with FXIII to modulate clot strength and stability.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fibrina/química , Zinco/química , Batroxobina/química , Sítios de Ligação , Coagulantes/química , Relação Dose-Resposta a Droga , Fator XIII/química , Produtos de Degradação da Fibrina e do Fibrinogênio/química , Fibrinogênio/química , Fibrinólise , Humanos , Microscopia Eletrônica de Varredura , Polímeros/química , Domínios Proteicos , Reologia , Trombina/química , Fatores de Tempo
14.
Eur J Med Chem ; 40(8): 798-804, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16122582

RESUMO

PEG-amide vancomycin derivatives (V(3) position) have been synthesized and found to behave as prodrugs in vivo, demonstrating anti-microbial activity in mice when challenged with Staphylococcus aureus. The corresponding PEG-carbamate derivatives do not manifest this in vivo activity, although both classes of compounds have similar in vitro rat plasma stability. Thus, it appears that extra vascular cleavage of the amide bond can occur if the condition of extended circulation of the conjugate is met, resulting in the release of vancomycin.


Assuntos
Amidas/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Polietilenoglicóis/química , Vancomicina/análogos & derivados , Vancomicina/farmacologia , Amidas/química , Animais , Antibacterianos/metabolismo , Biotransformação , Carbamatos/química , Camundongos , Testes de Sensibilidade Microbiana , Polietilenoglicóis/metabolismo , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Ratos , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/química
15.
J Med Chem ; 46(23): 5021-30, 2003 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-14584952

RESUMO

The facile reaction of vancomycin with various PEG linkers, at the V(3) position, has been selectively accomplished by using an excess of base in DMF. Using rPEG as a blocking group for V(3) provides crystalline derivatives that can be further PEGylated to give pure V(3)-X(1) latentiated species (transport forms). V(3) tetrameric species were also prepared in order to increase the loading of drug on PEG. All PEG-vancomycin transport forms show significant antibacterial activity that is on the same order of native vancomycin. Significant increases in the AUC were observed for all PEG-vancomycin conjugates thus making them potential single dose therapies.


Assuntos
Antibacterianos/farmacocinética , Sistemas de Liberação de Medicamentos , Polietilenoglicóis/química , Vancomicina/farmacocinética , Animais , Antibacterianos/síntese química , Antibacterianos/farmacologia , Transporte Biológico , Cristalização , Dimerização , Portadores de Fármacos , Injeções Intravenosas , Camundongos , Ratos , Relação Estrutura-Atividade , Vancomicina/química , Vancomicina/farmacologia
16.
Oncol Res ; 14(9): 455-68, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15490977

RESUMO

6-Mercaptopurine (6-MP) is an orally administered, water-insoluble purine analog that is effective against acute lymphatic leukemia. Oral absorption of 6-MP, however, is quite erratic, with only 16-50% of the administered dose reaching the blood. In this report, water-soluble parenterally administered poly(ethylene glycol) (PEG) prodrugs of 6-MP were synthesized using several chemical approaches that enabled the protection of the thiol group through a modification of the benzyl elimination (BE) system. In our earlier work on antimetabolites, it was found that branching of the PEG allowed greater loading of the active drug. This approach was also utilized within this work to give multiloaded systems. The resulting conjugates were stable in pH 7.4 PBS buffer as well as in rat plasma for extended periods. However, these conjugates did act as prodrugs in vivo and a number of PEG-6-MP constructs had significant (P < 0.05) activity in murine leukemia, as well as certain solid tumors, compared with unconjugated 6-MP in a solubilizing vehicle. The fact that some PEG-6-MP conjugates were stable during in vitro plasma dissociation assays, but demonstrated in vivo anticancer activity, suggests extravascular cleavage of the linking group. This work demonstrates that PEG conjugation is an effective means of solubilizing 6-MP for parenteral administration.


Assuntos
Compostos de Benzil/administração & dosagem , Mercaptopurina/administração & dosagem , Polietilenoglicóis/administração & dosagem , Pró-Fármacos/administração & dosagem , Compostos de Sulfidrila/administração & dosagem , Animais , Compostos de Benzil/farmacocinética , Linhagem Celular Tumoral , Feminino , Infusões Intravenosas , Mercaptopurina/farmacocinética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Polietilenoglicóis/farmacocinética , Pró-Fármacos/farmacocinética , Ratos , Ratos Sprague-Dawley , Compostos de Sulfidrila/farmacocinética
17.
Nat Commun ; 5: 4496, 2014 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-25092496

RESUMO

The ability to measure subtle changes in arterial pressure using devices mounted on the skin can be valuable for monitoring vital signs in emergency care, detecting the early onset of cardiovascular disease and continuously assessing health status. Conventional technologies are well suited for use in traditional clinical settings, but cannot be easily adapted for sustained use during daily activities. Here we introduce a conformal device that avoids these limitations. Ultrathin inorganic piezoelectric and semiconductor materials on elastomer substrates enable amplified, low hysteresis measurements of pressure on the skin, with high levels of sensitivity (~0.005 Pa) and fast response times (~0.1 ms). Experimental and theoretical studies reveal enhanced piezoelectric responses in lead zirconate titanate that follow from integration on soft supports as well as engineering behaviours of the associated devices. Calibrated measurements of pressure variations of blood flow in near-surface arteries demonstrate capabilities for measuring radial artery augmentation index and pulse pressure velocity.


Assuntos
Chumbo/química , Monitorização Fisiológica/instrumentação , Pele/patologia , Titânio/química , Zircônio/química , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Calibragem , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Elastômeros , Eletroquímica/métodos , Eletrodos , Desenho de Equipamento , Humanos , Teste de Materiais , Monitorização Ambulatorial/instrumentação , Monitorização Ambulatorial/métodos , Monitorização Fisiológica/métodos , Nanotecnologia/tendências , Semicondutores , Razão Sinal-Ruído , Silício/química
18.
Int J Ophthalmol ; 7(3): 574-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24967210

RESUMO

We report a case of syndromic gingival fibromatosis with notable ocular lesions, bilateral congenital cataracts, esotropia, and high myopia of a 21-year-old male patient from China. The patient was diagnosed with gingival fibromatosis based on his massive gingival overgrowth and histological findings that were consistent with gingival fibromatosis through a gingival biopsy. Lens opacity features were presented and phacoemulsificaion with intraocular lens(IOL) implantation was performed to manage the cataracts in both eyes. Transmission electronic microscopy was used to investigate the ultrastructure of the removed lens tissue. We also review the literature on gingival fibromatosis and briefly summarize the ocular manifestations of this rare disease.

19.
Adv Healthc Mater ; 3(10): 1597-607, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24668927

RESUMO

Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here, an electronic sensor platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing is reported. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of "epidermal" electronics system in a realistic clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management.


Assuntos
Eletrônica Médica/instrumentação , Monitorização Fisiológica/instrumentação , Cicatrização/fisiologia , Idoso , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Silicones , Temperatura Cutânea/fisiologia , Fita Cirúrgica , Termografia/instrumentação
20.
Appl Biochem Biotechnol ; 163(2): 223-34, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20652442

RESUMO

Three biosurfactant-producing indigenous microorganisms (XDS1, XDS2, XDS3) were isolated from a petroleum reservoir in the Daqing Oilfield (China) after polymer flooding. Their metabolic, biochemical, and oil-degradation characteristics, as well as their oil displacement in the core were studied. These indigenous microorganisms were identified as short rod bacillus bacteria with white color, round shape, a protruding structure, and a rough surface. Strains have peritrichous flagella, are able to produce endospores, are sporangia, and are clearly swollen and terminal. Bacterial cultures show that the oil-spreading values of the fermentation fluid containing all three strains are more than 4.5 cm (diameter) with an approximate 25 mN/m surface tension. The hydrocarbon degradation rates of each of the three strains exceeded 50%, with the highest achieving 84%. Several oil recovery agents were produced following degradation. At the same time, the heavy components of crude oil were degraded into light components, and their flow characteristics were also improved. The surface tension and viscosity of the crude oil decreased after being treated by the three strains of microorganisms. The core-flooding tests showed that the incremental oil recoveries were 4.89-6.96%. Thus, XDS123 treatment may represent a viable method for microbial-enhanced oil recovery.


Assuntos
Bacillus/metabolismo , Petróleo/microbiologia , Tensoativos/isolamento & purificação , Bacillus/classificação , Bacillus/isolamento & purificação , Biotecnologia , China , Fermentação , Flagelos/fisiologia , Hidrocarbonetos/metabolismo , Polímeros/química , Esporângios/fisiologia , Tensão Superficial , Tensoativos/química , Tensoativos/metabolismo , Viscosidade
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