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Coenzyme Q10 (CoQ10) is crucial for human beings, especially in the fields of biology and medicine. The aim of this experiment was to investigate the conditions for increasing CoQ10 production. At present, microbial fermentation is the main production method of CoQ10, and the production process of microbial CoQ10 metabolism control fermentation is very critical. Metabolic flux is one of the most important determinants of cell physiology in metabolic engineering. Metabolic flux analysis (MFA) is used to estimate the intracellular flux in metabolic networks. In this experiment, Rhodobacter sphaeroides was used as the research object to analyze the effects of aqueous ammonia (NH3·H2O) and calcium carbonate (CaCO3) on the metabolic flux of CoQ10. When CaCO3 was used to adjust the pH, the yield of CoQ10 was 274.43 mg·L-1 (8.71 mg·g-1 DCW), which was higher than that of NH3·H2O adjustment. The results indicated that when CaCO3 was used to adjust pH, more glucose-6-phosphate (G6P) entered the pentose phosphate (HMP) pathway and produced more NADPH, which enhanced the synthesis of CoQ10. At the chorismic acid node, more metabolic fluxes were involved in the synthesis of p-hydroxybenzoic acid (pHBA; the synthetic precursor of CoQ10), enhancing the anabolic flow of CoQ10. In addition, Ca2+ produced by the reaction of CaCO3 with organic acids promotes the synthesis of CoQ10. In summary, the use of CaCO3 adjustment is more favorable for the synthesis of CoQ10 by R. sphaeroides than NH3·H2O adjustment. The migration of metabolic flux caused by the perturbation of culture conditions was analyzed to compare the changes in the distribution of intracellular metabolic fluxes for the synthesis of CoQ10. Thus, the main nodes of the metabolic network were identified as G6P and chorismic acid. This provides a theoretical basis for the modification of genes related to the CoQ10 synthesis pathway.
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Rhodobacter sphaeroides , Ubiquinona , Humanos , Análise do Fluxo Metabólico , Rhodobacter sphaeroides/genética , Ácido Corísmico/metabolismo , Concentração de Íons de HidrogênioRESUMO
INTRODUCTION: The objective of this study is to explore the impacts of Omaha System-based continuing care on medication compliance, quality of life (QOL), and prognosis of coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI). METHODS: A total of 100 CHD patients who were hospitalized and received PCI were selected and divided into the control group and the observation group, 50 patients per group, according to a random number table method. The control group was given routine care, while the observation group was applied Omaha System-based continuing care on the basis of the control group. RESULTS: Follow-up demonstrated that the Morisky-Green score of the observation group was significantly higher than that of the control group (P<0.001), indicating that the medication compliance of the observation group was significantly better than that of the control group (P<0.001). The short form-36 (SF-36) scores were notably higher after nursing compared with on admission; SF-36 scores of the observation group were significantly increased than those of the control group (P<0.001). The incidence of major adverse cardiac event (MACE) in the observation group was significantly lower than in the control group (P<0.001). The nursing satisfaction of the observation group was considerably higher than that of the control group (P<0.01). CONCLUSION: Omaha System-based continuing care could improve the medication compliance and QOL, reduce the incidence of MACE, and benefit the prognosis of CHD patients after PCI.
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Doença das Coronárias , Intervenção Coronária Percutânea , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/cirurgia , Humanos , Adesão à Medicação , Intervenção Coronária Percutânea/métodos , Prognóstico , Qualidade de VidaRESUMO
ABSTRACT Introduction: The objective of this study is to explore the impacts of Omaha System-based continuing care on medication compliance, quality of life (QOL), and prognosis of coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI). Methods: A total of 100 CHD patients who were hospitalized and received PCI were selected and divided into the control group and the observation group, 50 patients per group, according to a random number table method. The control group was given routine care, while the observation group was applied Omaha System-based continuing care on the basis of the control group. Results: Follow-up demonstrated that the Morisky-Green score of the observation group was significantly higher than that of the control group (P<0.001), indicating that the medication compliance of the observation group was significantly better than that of the control group (P<0.001). The short form-36 (SF-36) scores were notably higher after nursing compared with on admission; SF-36 scores of the observation group were significantly increased than those of the control group (P<0.001). The incidence of major adverse cardiac event (MACE) in the observation group was significantly lower than in the control group (P<0.001). The nursing satisfaction of the observation group was considerably higher than that of the control group (P<0.01). Conclusion: Omaha System-based continuing care could improve the medication compliance and QOL, reduce the incidence of MACE, and benefit the prognosis of CHD patients after PCI.
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A series of hyperbranched, thermo-responsive and mussel-inspired polypeptides were synthesized and used for surgical adhesion, hemostasis and interventional embolization. These polypeptides showed excellent tissue-adhesive properties according to adhesive strength tests on porcine skin and bone in vitro, where the maximum lap-shear adhesion strength on porcine skin was 114.5 kPa and the maximum tensile adhesion strength on bone was 786 kPa. In vivo animal experiments indicated that these polypeptides exhibit superior hemostatic properties and healing effects in skin incisions and osteotomy gap; the skin incision healing and osteotomy gap remodeling were completed in all rats after 14 and 60 days, respectively. In vivo evaluation of the embolization ability of these polypeptides was performed on rabbit kidney models, resulting in successful occlusion of renal arteries, which led to gross ischemic changes in the embolized kidneys up to 16 days. A trial embolization procedure on H22 tumor-bearing rat models also confirmed the gelability of these polypeptides in tumor arteries, which might cause damage to embolized tumors. Therefore, these polypeptides are expected to be good candidates as surgical tissue adhesives, antibleeding materials, and effective embolic materials.
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Inspired by marine mussel adhesive proteins, polymers with catechol side groups have been extensively explored in industrial and academic research. Here, Pluronic L-31 alcoholate ions were used as the initiator to prepare a series of polypeptide-Pluronic-polypeptide triblock copolymers via ring-opening polymerization of l-DOPA-N-carboxyanhydride (DOPA-NCA), l-arginine-NCA (Arg-NCA), l-cysteine-NCA (Cys-NCA), and ε-N-acryloyl lysine-NCA (Ac-Lys-NCA). These copolymers demonstrated good biodegradability, biocompatibility, and thermoresponsive properties. Adhesion tests using porcine skin and bone as adherends demonstrated lap-shear adhesion strengths up to 106 kPa and tensile adhesion strengths up to 675 kPa. The antibleeding activity and tissue adhesive ability were evaluated using a rat model. These polypeptide-Pluronic copolymer glues showed superior hemostatic properties and superior effects in wound healing and osteotomy gaps. Complete healing of skin incisions and remodeling of osteotomy gaps were observed in all rats after 14 and 60 days, respectively. These copolymers have potential uses as tissue adhesives, antibleeding, and tissue engineering materials.
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Peptídeos/química , Adesivos , Animais , Materiais Biocompatíveis , Hemostasia , Poloxâmero , Ratos , Suínos , Adesivos TeciduaisRESUMO
BACKGROUND AND PURPOSE: The 45° oblique (Pöschl) plane allows reliable depiction of the vestibular aqueduct, with virtually its entire length often visible on 1 CT image. We measured its midpoint width in this plane, aiming to determine normal measurement values based on this plane. MATERIALS AND METHODS: We retrospectively evaluated temporal bone CT studies of 96 pediatric patients without sensorineural hearing loss. Midvestibular aqueduct widths were measured in the 45° oblique plane by 2 independent readers by visual assessment (subjective technique). The vestibular aqueducts in 4 human cadaver specimens were also measured in this plane. In addition, there was a specimen that had undergone CT scanning before sectioning, and measurements made on that CT scan and on the histologic section were compared. Measurements from the 96 patients' CT images were then repeated by using findings derived from the radiologic-histologic comparison (objective technique). RESULTS: All vestibular aqueducts were clearly identifiable on 45° oblique-plane CT images. The mean for subjective measurement was 0.526 ± 0.08 mm (range, 0.337-0.947 mm). The 97.5th percentile value was 0.702 mm. The mean for objective measurement was 0.537 ± 0.077 mm (range, 0.331-0.922 mm). The 97.5th percentile value was 0.717 mm. CONCLUSIONS: Measurements of the vestibular aqueduct can be performed reliably and accurately in the 45° oblique plane. The mean midpoint width was 0.5 mm, with a range of 0.3-0.9 mm. These may be considered normal measurement values for the vestibular aqueduct midpoint width when measured in the 45° oblique plane.
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Aqueduto Vestibular/anatomia & histologia , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Aqueduto Vestibular/diagnóstico por imagemRESUMO
We reported here for the first time on the use of cotton thread combined with novel gold nanoparticle trimer reporter probe for low-cost, sensitive and rapid detection of a lung cancer related biomarker, human ferritin. A model system comprising ferritin as an analyte and a pair of monoclonal antibodies was used to demonstrate the proof-of-concept on the dry-reagent natural cotton thread immunoassay device. Results indicated that the using of novel gold nanoparticle trimer reporter probe greatly improved the sensitivity comparing with traditional gold nanoparticle reporter probe on the cotton thread immunoassay device. The assay avoids multiple incubation and washing steps performed in most conventional protein analyses. Although qualitative tests are realized by observing the color change of the test zone, quantitative data are obtained by recording the optical responses of the test zone with a commercial scanner and corresponding analysis software. Under optimal conditions, the cotton thread immunoassay device was capable of measuring 10 ng/mL human ferritin under room temperature which is sensitive enough for clinical diagnosis. Moreover, the sample solution employed in the assays is just 8 µL, which is much less than traditional lateral flow strip based biosensors.
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Ferritinas/análise , Ouro/química , Imunoensaio/métodos , Nanopartículas Metálicas/química , Sondas Moleculares/química , Técnicas Biossensoriais , Fibra de Algodão , Ferritinas/sangue , Humanos , Imunoensaio/instrumentação , TemperaturaRESUMO
We used cotton thread as substrate to develop a novel room temperature DNA detection device for low-cost, sensitive and rapid detection of a human genetic disease, hereditary tyrosinemia type I related DNA sequences. A novel adenosine based molecular beacon (ABMB) probe modified on gold nanoparticle was used as reporter probe. In the presence of coralyne, a small molecule which can react with adenosines, the ABMB would form a hairpin structure just like traditional molecular beacon used extensively. In the presence of target DNA sequences, the hairpin structure of ABMB modified on gold nanoparticles will be opened and the biotin group modified at one end of the DNA probes will be released and react with the streptavidin immobilized on the test zone of the cotton thread. The response of the thread based DNA test device is linear over the range of 2.5-100 nM complementary DNA. The ability of our developed device for discriminating the single base mismatched DNA related to a human genetic disease, hereditary tyrosinemia type I, was improved comparing with previous report. It is worth mentioning that the whole assay procedure for DNA test is performed under room temperature which simplified the assay procedures greatly.
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Adenosina/análise , Fibra de Algodão , Sondas Moleculares , Ácidos Nucleicos/análise , Temperatura , Humanos , Hibridização de Ácido NucleicoRESUMO
We report here for the first time by using dry-reagent cotton thread-based point-of-care diagnosis devices for low-cost, sensitive and rapid detection of a lung cancer related biomarker, squamous cell carcinoma antigen (SCCA) and a human genetic disease, hereditary tyrosinemia type I related DNA sequences. A model system comprising SCCA as an analyte and a pair of monoclonal antibodies is used to demonstrate the proof-of-concept on the dry-reagent cotton thread based immunoassay device. An enhancement protocol was employed by using two kinds of gold nanoparticle labels for SCCA test which greatly improved the sensitivity of the device. The assay avoids the multiple incubation and washing steps performed in most conventional protein analyses, which is similar with the lateral flow strip technology. Under optimal conditions, the thread based immunoassay device was capable of measuring 1ng/mL SCCA in 20min which meet the requirement for clinical diagnosis. DNA detection was successfully realized by using a novel adenosine based molecular beacon probe as reporter probes in the cotton thread based device, the linear range is 75-3000fmol which is suitable for quantitative test.
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Antígenos de Neoplasias/sangue , Ouro/química , Imunoensaio/instrumentação , Nanopartículas Metálicas/química , Ácidos Nucleicos/análise , Sistemas Automatizados de Assistência Junto ao Leito , Serpinas/sangue , Animais , Antígenos de Neoplasias/análise , Técnicas Biossensoriais/instrumentação , Fibra de Algodão , Desenho de Equipamento , Humanos , Camundongos , Fitas Reagentes/análise , Serpinas/análiseRESUMO
BACKGROUND AND PURPOSE: Intracranial collaterals influence the prognosis of patients treated with intravenous tissue plasminogen activator in acute anterior circulation ischemic stroke. We compared the methods of scoring collaterals on pre-tPA brain CT angiography for predicting functional outcomes in acute anterior circulation ischemic stroke. MATERIALS AND METHODS: Two hundred consecutive patients with acute anterior circulation ischemic stroke treated with IV-tPA during 2010-2012 were included. Two independent neuroradiologists evaluated intracranial collaterals by using the Miteff system, Maas system, the modified Tan scale, and the Alberta Stroke Program Early CT Score 20-point methodology. Good and extremely poor outcomes at 3 months were defined by modified Rankin Scale scores of 0-1 and 5-6 points, respectively. RESULTS: Factors associated with good outcome on univariable analysis were younger age, female sex, hypertension, diabetes mellitus, atrial fibrillation, small infarct core (ASPECTS ≥8), vessel recanalization, lower pre-tPA NIHSS scores, and good collaterals according to Tan methodology, ASPECTS methodology, and Miteff methodology. On multivariable logistic regression, only lower NIHSS scores (OR, 1.186 per point; 95% CI, 1.079-1.302; P = .001), recanalization (OR, 5.599; 95% CI, 1.560-20.010; P = .008), and good collaterals by the Miteff method (OR, 3.341; 95% CI, 1.203-5.099; P = .014) were independent predictors of good outcome. Poor collaterals by the Miteff system (OR, 2.592; 95% CI, 1.113-6.038; P = .027), Maas system (OR, 2.580; 95% CI, 1.075-6.187; P = .034), and ASPECTS method ≤5 points (OR, 2.685; 95% CI, 1.156-6.237; P = .022) were independent predictors of extremely poor outcomes. CONCLUSIONS: Only the Miteff scoring system for intracranial collaterals is reliable for predicting favorable outcome in thrombolyzed acute anterior circulation ischemic stroke. However, poor outcomes can be predicted by most of the existing methods of scoring intracranial collaterals.
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Encéfalo/irrigação sanguínea , Angiografia Cerebral/métodos , Circulação Colateral/fisiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Alberta , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: Idiopathic intracranial hypertension or pseudotumour cerebri is primarily a disorder of young obese women characterised by symptoms and signs associated with raised intracranial pressure in the absence of a space-occupying lesion or other identifiable cause. SUMMARY: The overall incidence of idiopathic intracranial hypertension is approximately two per 100,000, but is considerably higher among obese individuals and, given the global obesity epidemic, is likely to rise further. The pathophysiology of this condition is poorly understood, but most theories focus on the presence of intracranial venous hypertension and/or increased cerebrospinal fluid outflow resistance and how this relates to obesity. A lack of randomised clinical trials has resulted in unsatisfactory treatment guidelines and although weight loss is important, especially when used in conjunction with drugs that reduce cerebrospinal fluid production, resistant cases remain difficult to manage and patients invariably undergo neurosurgical shunting procedures. The use of transverse cerebral sinus stenting remains contentious and long-term benefits are yet to be determined. CONCLUSION: An understanding of the clinical features, diagnostic work-up and therapeutic options available for patients with idiopathic intracranial hypertension is important both for neurologists and ophthalmologists as visual loss maybe permanent if untreated.
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Pseudotumor Cerebral/diagnóstico , Pseudotumor Cerebral/epidemiologia , Feminino , Humanos , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/terapia , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/epidemiologia , Doenças do Nervo Óptico/terapia , Pseudotumor Cerebral/terapia , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND: Cerebral cavernous malformation (CCM) is a hemorrhagic stroke disease affecting up to 0.5% of North Americans that has no approved nonsurgical treatment. A subset of patients have a hereditary form of the disease due primarily to loss-of-function mutations in KRIT1, CCM2, or PDCD10. We sought to identify known drugs that could be repurposed to treat CCM. METHODS AND RESULTS: We developed an unbiased screening platform based on both cellular and animal models of loss of function of CCM2. Our discovery strategy consisted of 4 steps: an automated immunofluorescence and machine-learning-based primary screen of structural phenotypes in human endothelial cells deficient in CCM2, a secondary screen of functional changes in endothelial stability in these same cells, a rapid in vivo tertiary screen of dermal microvascular leak in mice lacking endothelial Ccm2, and finally a quaternary screen of CCM lesion burden in these same mice. We screened 2100 known drugs and bioactive compounds and identified 2 candidates, cholecalciferol (vitamin D3) and tempol (a scavenger of superoxide), for further study. Each drug decreased lesion burden in a mouse model of CCM vascular disease by ≈50%. CONCLUSIONS: By identifying known drugs as potential therapeutics for CCM, we have decreased the time, cost, and risk of bringing treatments to patients. Each drug also prompts additional exploration of biomarkers of CCM disease. We further suggest that the structure-function screening platform presented here may be adapted and scaled to facilitate drug discovery for diverse loss-of-function genetic vascular disease.
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Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Modelos Animais de Doenças , Reposicionamento de Medicamentos/métodos , Hemangioma Cavernoso do Sistema Nervoso Central/tratamento farmacológico , Animais , Células Cultivadas , Neoplasias do Sistema Nervoso Central/patologia , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/uso terapêutico , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Humanos , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Resultado do TratamentoRESUMO
Intracranial pial arteriovenous fistulas (AVF) are rare vascular malformation especially in the first 2 years of life. The pathology in this age group is associated with greater morbidity and mortality. We report a rare case of 36-day-old male infant with a pial AVF associated with an arterial aneurysm, who presented with intraventricular hemorrhage and hydrocephalus. In addition, an online review of the literatures on pediatric pial AVF was performed using PubMed on published case reports and articles from 1980 to April 2013.
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Fístula Arteriovenosa/patologia , Malformações Arteriovenosas Intracranianas/patologia , Pia-Máter/patologia , Fístula Arteriovenosa/cirurgia , Angiografia Cerebral , Hemorragia Cerebral/etiologia , Humanos , Hidrocefalia/etiologia , Recém-Nascido , Malformações Arteriovenosas Intracranianas/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pia-Máter/cirurgiaRESUMO
In the manuscript, a quantitative lateral flow nucleic acid biosensor (Lateral flow nucleic acid biosensor, LFNB) based on blue dye doped latex beads was proposed and its feasibility for detecting deoxyribonucleic acid (DNA) in plasma was investigated. A 60-mer DNA sequence (T1) was selected as model to demonstrate the protocol. Blue dyes doped latex bead bearing DNA probe would be captured on the corresponding test line in the presence of target DNA, to form an evident blue band. Although qualitative tests are realized by observing the color change of the test zone, quantitative data are obtained by recording the optical responses of the test zone with a portable "Strip Reader" instrument conveniently. The strip has been applied for the detection of synthesized DNA sample in human plasma sample with a detection limit of 3.75 fmol. Interference was not evident even the target DNA was spiked with 50 µL plasma which indicated the well shielding of the latex bead reporters and quantified chromatographic separations of unwanted materials of the strip comparing with traditional gold nanoparticle based LFNB platforms.
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Técnicas Biossensoriais , DNA/sangue , Corantes , Sondas de DNA , Humanos , Indicadores e Reagentes , MicroesferasRESUMO
The arteriovenous fistula (AVF) is the preferred form of vascular access for maintenance hemodialysis, but it often fails to mature to become clinically usable, likely due to aberrant hemodynamic forces. A robust pipeline for serial assessment of hemodynamic parameters and subsequent lumen cross-sectional area changes has been developed and applied to a data set from contrast-free MRI of a dialysis patient's AVF collected over a period of months after AVF creation surgery. Black-blood MRI yielded images of AVF lumen geometry, while cine phase-contrast MRI provided volumetric flow rates at the in-flow and out-flow locations. Lumen geometry and flow rates were used as inputs for computational fluid dynamics (CFD) modeling to provide serial wall shear stress (WSS), WSS gradient, and oscillatory shear index (OSI) profiles. The serial AVF lumen geometries were co-registered at 1mm intervals using respective lumen centerlines, with the anastomosis as an anatomical landmark. Lumen enlargement was limited at the vein region near the anastomosis and a downstream vein valve, potentially attributed to the physical inhibition of wall expansion at those sites. This work is the first serial and detail study of lumen and hemodynamic changes in human AVF using MRI and CFD. This novel protocol will be used for a multicenter prospective study to identify critical hemodynamic factors that contribute to AVF maturation failure.
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Fístula Arteriovenosa/fisiopatologia , Hemodinâmica/fisiologia , Humanos , Hidrodinâmica , Imageamento por Ressonância Magnética , Diálise RenalRESUMO
PURPOSE: The goal is to identify thermal exposures capable of reducing or eliminating cell survival on expanded polytetrafluoroethylene (ePTFE), in an effort to develop a mild hyperthermia treatment of neointimal hyperplasia in ePTFE vascular grafts. MATERIALS AND METHODS: Viable and dead bovine aortic endothelial cells were quantified following different thermal exposure conditions: cells on collagen-coated ePTFE sheets or tissue culture polystyrene dishes were heated at 42° and 45°C to determine their thermal sensitivity on different surfaces, and cells cultured on collagen-coated ePTFE sheets were heated at 43-50°C for various durations, followed by incubation at 37°C for 0 and 20 h, respectively. Significant cell death was set to be 50%. Two types of cell death, apoptosis and necrosis, were distinguished by cell morphology and membrane integrity assessments. RESULTS: The attachment and survival of cells on ePTFE sheets were more sensitive to inhibition by mild heating than those on tissue culture dishes. Exposure to 45°C for 90 min and 50°C for 30 min caused significant necrotic cell death on ePTFE (65% and 75%, respectively). A 37°C/20-h incubation following 30-min exposures at 47° and 50°C increased total cell death (necrosis + apoptosis) from 20% to 50% and 75% to 100%, respectively. CONCLUSION: Cells grown on ePTFE were more susceptible to mild hyperthermia-induced death, compared to those on tissue culture dishes. Significant cell death on ePTFE mainly via apoptosis can be achieved by optimising temperature and duration of exposure.
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Morte Celular , Endotélio Vascular , Temperatura Alta , Hiperplasia/prevenção & controle , Enxerto Vascular/métodos , Animais , Prótese Vascular , Bovinos , Células Cultivadas , Materiais Revestidos Biocompatíveis , Células Endoteliais , Endotélio Vascular/citologia , Hiperplasia/patologia , Politetrafluoretileno , Túnica Íntima/patologiaRESUMO
BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) vascular grafts frequently develop occlusive neointimal hyperplasia as a result of myofibroblast over-growth, leading to graft failure. ePTFE exhibits higher ultrasound attenuation than native soft tissues. We modelled the selective absorption of ultrasound by ePTFE, and explored the feasibility of preventing hyperplasia in ePTFE grafts by ultrasound heating. Specifically, we simulated the temperature profiles of implanted grafts and nearby soft tissues and blood under ultrasound exposure. The goal was to determine whether ultrasound exposure of an ePTFE graft can generate temperatures sufficient to prevent cell growth on the graft without damaging nearby soft tissues and blood. METHODS: Ultrasound beams from two transducers (1.5 and 3.2 MHz) were simulated in two graft/tissue models, with and without an intra-graft cellular layer mimicking hyperplasia, using the finite-difference time-domain (FDTD) method. The resulting power deposition patterns were used as a heat source for the Pennes bioheat equation in a COMSOL(®) Multiphysics heat transfer model. 50°C is known to cause cell death and therefore the transducer powers were adjusted to produce a 13°C temperature rise from 37°C in the ePTFE. RESULTS: Simulations showed that both the frequency of the transducers and the presence of hyperplasia significantly affect the power deposition patterns and subsequent temperature profiles on the grafts and nearby tissues. While neither transducer significantly raised the temperature of the blood, the 1.5-MHz transducer was less focused and heated larger volumes of the graft and nearby soft tissues than the 3.2-MHz transducer. The presence of hyperplasia had little effect on the blood's temperature, but further increased the temperature of the graft and nearby soft tissues in response to either transducer. Skin cooling and blood flow play a significant role in preventing overheating of the native tissues. CONCLUSIONS: Modelling shows that ultrasound can selectively heat ePTFE grafts and produce temperatures that cause cell death on the graft. The temperature increase in blood is negligible and that in the adjacent soft tissues may be minimized by skin cooling and using appropriate transducers. Therefore, ultrasound heating may have the potential to reduce neointimal hyperplasia and failure of ePTFE vascular grafts.
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Hipertermia Induzida , Modelos Biológicos , Ultrassom , Enxerto Vascular/efeitos adversos , Simulação por Computador , Humanos , Hiperplasia , Temperatura , Fatores de Tempo , TransdutoresRESUMO
Elastin is an essential component of arteries which provides structural integrity and instructs smooth muscle cells to adopt a quiescent state. Despite interaction of endothelial cells with elastin in the internal elastic lamina, the potential for exploiting this interaction therapeutically has not been explored in detail. In this study, we show that tropoelastin (a precursor of elastin) stimulates endothelial cell migration and adhesion more than smooth muscle cells. The biological activity of tropoelastin on endothelial cells is contained in the VGVAPG domain and in the carboxy-terminal 17-amino acids. We show that the effects of the carboxy-terminal 17 amino acids, but not those of VGVAPG, are mediated by integrin α(V)ß(3). We demonstrate that tropoelastin covalently linked to stainless steel disks promotes adhesion of endothelial progenitor cells and endothelial cells to the metal surfaces. The adherent cells on the tropoelastin-coated metal surfaces form monolayers that can withstand and respond to arterial shear stress. Because of the unique effects of tropoelastin on endothelial and smooth muscle cells, coating intravascular devices with tropoelastin may stimulate their endothelialization, inhibit smooth muscle hyperplasia, and improve device performance.
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Movimento Celular/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Tropoelastina/administração & dosagem , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , HumanosRESUMO
The invention of wireless capsule endoscopy has opened new ways of diagnosing and treating diseases in the gastrointestinal tract. Current wireless capsules can perform simple operations such as imaging and data collection (like temperature, pressure, and pH) in the gastrointestinal tract. Researchers are now focusing on adding more sophisticated functions such as drug delivery, surgical clips/tags deployment, and tissue samples collection. The finite on-board power on these capsules is one of the factors that limits the functionalities of these wireless capsules. Thus multiple application-specific capsules would be needed to complete an endoscopic operation. This would give rise to a multi-capsule environment. Having a modular "plug-and-play" capsule design would facilitate doctors in configuring multiple application-specific capsules, e.g. tagging capsule, for use in the gastrointestinal tract. This multi-capsule environment also has the advantage of reducing power consumption through asymmetric multi-hop communication.
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Cápsulas Endoscópicas , Trato Gastrointestinal/fisiologia , Humanos , Instrumentos CirúrgicosRESUMO
Nanoparticles are important catalysts for many chemical transformations. However, owing to their structural dispersions, heterogeneous distribution of surface sites and surface restructuring dynamics, nanoparticles are intrinsically heterogeneous and challenging to characterize in ensemble measurements. Using a single-nanoparticle single-turnover approach, we study the redox catalysis of individual colloidal Au nanoparticles in solution, using single-molecule detection of fluorogenic reactions. We find that for product generation, all Au nanoparticles follow a Langmuir-Hinshelwood mechanism but with heterogeneous reactivity; and for product dissociation, three nanoparticle subpopulations are present that show heterogeneous reactivity between multiple dissociation pathways with distinct kinetics. Correlation analyses of single-turnover waiting times further reveal activity fluctuations of individual Au nanoparticles, attributable to both catalysis-induced and spontaneous dynamic surface restructuring that occurs at different timescales at the surface catalytic and product docking sites. The results exemplify the power of the single-molecule approach in revealing the interplay of catalysis, heterogeneous reactivity and surface structural dynamics in nanocatalysis.