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1.
J Gene Med ; 26(7): e3720, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39041639

RESUMO

BACKGROUND: A novel adeno-associated virus 2 (AAV2)-carried multi-characteristic opsin (MCO) (MCO-010) is undergoing several clinical trials as a novel therapeutic modality for the treatment of degenerative retinal diseases including retinitis pigmentosa and Stargardt disease. The present study aimed to determine the ocular and systemic safety of MCO-010 and the AAV2 vehicle in adult Beagle dogs following intravitreal (IVT) injection. METHODS: The current safety/toxicology studies spanning 13 weeks described here utilized well-documented techniques to assess the effects of IVT injection of MCO-010 up to 2.2 × 1011 genome copies (gc) per eye, or the AAV2 capsid (vehicle control) on gross behavioral and immunogenic changes, alterations in body weights, blood biochemistry, hematology, blood coagulation, gross necropsy lesions, organ weight changes and histopathology in the dogs (n = 4 per group; two males and two females per group). Immunohistochemical and functional electroretinogram studies were also conducted to determine MCO expression in the retina and determine any retinal toxicity associated with MCO-010. RESULTS: There were no significant deleterious effects of the MCO-010 (or the AAV2 at the tested doses) on any of the examined parameters, including the absence of any severe ocular or systemic adverse events. However, as expected, inflammation after IVT delivery of AAV2 and MCO-010 was observed in the conjunctivae of all groups of animals, although this self-resolved within 1 week post-injection. Quantitative immunohistochemical analyses of MCO-010-associated mCherry revealed successful delivery of the gene therapy within the inner retina. CONCLUSIONS: In summary, MCO-010 demonstrated a favorable safety profile when administered to the eyes of adult Beagle dogs of both sexes at dose levels up to 2.2 × 1011 gc per eye, with no adverse effects observed. This dose was identified as the No Observed Adverse Effect Level (i.e. NOAEL) and guided selection of safe doses for human clinical trials.


Assuntos
Dependovirus , Vetores Genéticos , Injeções Intravítreas , Opsinas , Retina , Animais , Cães , Dependovirus/genética , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Feminino , Masculino , Retina/metabolismo , Opsinas/genética , Opsinas/metabolismo , Terapia Genética/métodos , Eletrorretinografia
2.
Acta Oncol ; 62(10): 1194-1200, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37589124

RESUMO

BACKGROUND: Knowledge-based planning (KBP) is a method for automated radiotherapy treatment planning where appropriate optimization objectives for new patients are predicted based on a library of training plans. KBP can save time and improve organ at-risk sparing and inter-patient consistency compared to manual planning, but its performance depends on the quality of the training plans. We used another system for automated planning, which generates multi-criteria optimized (MCO) plans based on a wish list, to create training plans for the KBP model, to allow seamless integration of knowledge from a new system into clinical routine. Model performance was compared for KBP models trained with manually created and automatic MCO treatment plans. MATERIAL AND METHODS: Two RapidPlan models with the same 30 locally advanced non-small cell lung cancer patients included were created, one containing manually created clinical plans (RP_CLIN) and one containing fully automatic multi-criteria optimized plans (RP_MCO). For 15 validation patients, model performance was compared in terms of dose-volume parameters and normal tissue complication probabilities, and an oncologist performed a blind comparison of the clinical (CLIN), RP_CLIN, and RP_MCO plans. RESULTS: The heart and esophagus doses were lower for RP_MCO compared to RP_CLIN, resulting in an average reduction in the risk of 2-year mortality by 0.9 percentage points and the risk of acute esophageal toxicity by 1.6 percentage points with RP_MCO. The oncologist preferred the RP_MCO plan for 8 patients and the CLIN plan for 7 patients, while the RP_CLIN plan was not preferred for any patients. CONCLUSION: RP_MCO improved OAR sparing compared to RP_CLIN and was selected for implementation in the clinic. Training a KBP model with clinical plans may lead to suboptimal output plans, and making an extra effort to optimize the library plans in the KBP model creation phase can improve the plan quality for many future patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radioterapia de Intensidade Modulada , Humanos , Neoplasias Pulmonares/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Órgãos em Risco
3.
J Appl Clin Med Phys ; 24(9): e14013, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37144958

RESUMO

PURPOSE: A new development on the RayStation treatment planning system (TPS) allows a plan to be planned by imposing a constraint on the leaf sequencing: all leaves move in the same direction before moving again in the opposite direction to create a succession of sliding windows (SWs). The study aims to investigate this new leaf sequencing, coupled with standard optimization (SO) and multi-criteria optimization (MCO) and to compare it with the standard sequencing (STD). METHODS: Sixty plans were replanned for 10 head and neck cancer patients (two dose levels simultaneously SIB, 56 and 70 Gy in 35 fractions). All plans were compared, and a Wilcoxon signed-rank test was performed. Pre-processing QA and metrics of multileaf collimator (MLC) complexity were studied. RESULTS: All methodologies met the dose requirements for the planning target volumes (PTVs) and organs at risk (OARs). SO demonstrates significantly best results for homogeneity index (HI), conformity index (CI), and target coverage (TC). SO-SW gives best results for PTVs (D98% and D2% ) but the differences between techniques are less than 1%. Only the D2%,PTV-56 Gy is higher with both MCO methods. MCO-STD offer the best sparing OARs (parotids, spinal cord, larynx, oral cavity). The gamma passing rates (GPRs) with 3%/3 mm criteria between the measured and calculated dose distributions are higher than 95%, slightly lowest with SW. The number of monitor units (MUs) and MLC metrics are higher in SW show a higher modulation. CONCLUSIONS: All plans are feasible for the treatment. A clear advantage of SO-SW is that the treatment plan is more straightforward to planning by the user due to the more advanced modulation. MCO stands out for its ease of use and will allow a less experienced user to offer a better plan than in SO. In addition, MCO-STD will reduce the dose to the OARs while maintaining good TC.


Assuntos
Neoplasias de Cabeça e Pescoço , Planejamento da Radioterapia Assistida por Computador , Humanos , Neoplasias de Cabeça e Pescoço/radioterapia , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos
4.
Nanotechnology ; 33(45)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35914509

RESUMO

High-efficiency bi-functional electrocatalysts with long-term stability are critical to the development of many kinds of fuel cells, because that the performance of battery is limited by the slow kinetics of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). In this work, porous MCo2O4(M = Zn, Cu, Fe, Mn) were prepared by hydrothermal method with NH4F and urea as surfactants. FeCo2O4with porous structure has more oxygen defects and the larger specific surface area than other MCo2O4(M = Zn, Cu, Mn), and it not onlysupplies more active sites but also avails the transmission of electrolyte and O2in the process of ORR and OER in 0.1 M KOH aqueous solution. Porous FeCo2O4electrode material produces less intermediate H2O2, and its ORR is mainly controlled by a 4e-reaction path. Compared with commercial Pt/C, the prepared FeCo2O4has comparable ORR activity and excellent OER activity. At the same time, the stability of FeCo2O4to ORR is significantly higher than that of commercial Pt/C. The porous FeCo2O4was prepared by facile synthesis procedure could be a potential promising bi-functional catalyst due to its high electrocatalytic activities and long-term stability for both the ORR and OER.

5.
Environ Res ; 204(Pt D): 112383, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34813864

RESUMO

Cobalt oxide (Co3O4) is a low-cost material exhibiting excellent physicochemical and photocatalytic properties indicating its potential use for next-generation eco-friendly energy storage and photocatalytic degradation applications. In this study, Co3O4 nanoarcs were synthesized using SBA-15 as a template by microwave-assisted method to form an S15/m-Co3O4 product. Characterization was done by low and wide-angle X-Ray diffraction, and Fourier transformed infra-red spectroscopic studies confirming the presence of S15/m-Co3O4. Scanning Electron Microscope images proved the agglomerated nanotube and nanoarcs like the structure of SBA-15 and S15/m- Co3O4, respectively. Electrochemical studies included cyclic voltammetry, charge/discharge, retention capacity, and electron impedance spectroscopy studies in a 3-electrode system. S15/m-Co3O4 nanoarcs, as the electrode material, was revealed to have a specific capacity of 87.5 C/g in 1 M KOH solution. Upon running 1000 cycles, the material had excellent capacity retention of 87%. The S15/m-Co3O4 product also underwent photocatalytic degradation studies. The Rhodamine R6G dye degradation by S15/m-Co3O4 under UV irradiation exhibited a high degradation percentage of 97.7%, following the first-order kinetics. S15/m-Co3O4 has proven to be biocompatible and can be used to enhance supercapacitors which are an ideal alternative to conventional batteries for energy storage applications. Thus, the data produced proves S15/m-Co3O4 nanoarcs is an excellent electrode material for pseudocapacitive application and a catalyst for photocatalytic degradation of dye molecules.


Assuntos
Óxidos , Catálise , Cobalto , Eletrodos , Óxidos/química , Dióxido de Silício
6.
Mikrochim Acta ; 189(5): 205, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488133

RESUMO

Novel cube-like transition metal oxide embedded on graphitic carbon nitride (MCO@GCN) formed a hybrid composite via hydrothermal assisted sonochemical synthesis. The synthesized composite was examined with various physical characterizations such as morphological SEM, EDX, XRD, and FT-IR spectroscopy. The electrocatalytic activity of MCO@GCN composite was further investigated when used  to modify a glassy carbon electrode (GCE). The electrochemical sensor was investigated using modified MCO@GCN/GCE towards environmental pollutant 2,4,6-trichlorophenol (2,4,6-TCP) detection with at a potential of (+ 0.654 V vs Ag/AgCl) in pH-7. The structural features have favored a high charge transfer ratio with excellent conductivity which showed a low detection limit (LOD) of 0.0068 µM and sensitivity of 23.57 µA·µM-1·cm-2 comprising a wide linear working range of 0.01-1720 µM by using differential pulse voltammetry. Besides, the MCO@GCN/GCE displayed excellent selectivity , repeatability, reproducibility, storage, and operational stability. Notably, the proposed MCO@GCN/GCE was validated with different environmental samples (tap, river, and industrial water) with RSD 0.62-2.86% and 96.51-99.66% (n = 3) recovery.


Assuntos
Carbono , Manganês , Carbono/química , Cobalto , Eletrodos , Grafite , Limite de Detecção , Compostos de Nitrogênio , Óxidos/química , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier
7.
Nutr Health ; 28(4): 741-750, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35522261

RESUMO

Background: The COVID-19 pandemic has negatively impacted the eating behaviours of people especially fruits and vegetable intake. No study has addressed the fruits and vegetables intake during the COVID-19 in Malaysia. Aim: to assess the daily intake of fruits and vegetables among Malaysian adults during the COVID-19 outbreak, perceived changes in intake, as well as factors associated with the changes in intake. Methods: A cross-sectional study was conducted through online platforms and a total of 506 participants were recruited. Semi food-frequency questionnaires were used to assess participants' fruit and vegetable intake. Socio-demographics information, knowledge, attitude and practices (KAP) of fruits and vegetables were collected. All statistical analyses were performed using SPSS. Results: The majority of participants (99.8%) did not achieve the recommended five servings per day, in which they consumed an average of 0.84 servings of fruits and vegetables per day. 46.4% of participants reported no changes in intake compared to before the outbreak. Fruits and vegetables intake was associated with physical activity level, knowledge, and beliefs of foods that may prevent/cure COVID-19. Binary logistic regression identified two significant risk factors of daily fruits and vegetables intake namely, being a non-Chinese (AOR = 1.905, 95% CI = 1.114-3.257) and having good practices scores (AOR = 2.543, 95% CI = 1.611-4.015). Conclusion: The study found a low daily intake of fruits and vegetables. The findings suggested that nutritional interventions are necessary to improve awareness on consuming more fruits and vegetables to improve overall health.


Assuntos
COVID-19 , Verduras , Adulto , Humanos , Frutas , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Pandemias , Comportamento Alimentar , Inquéritos e Questionários , Dieta
8.
Environ Monit Assess ; 195(1): 205, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36527450

RESUMO

Mining activities in the Chini Lake catchment area have been extensive for several years, contributing to acid mine drainage (AMD) events with high concentrations of iron (Fe) and other heavy metals impacting the surface water. However, during the restriction period due to the COVID-19 outbreak, anthropogenic activities have been suspended, which clearly shows a good opportunity for a better environment. Therefore, we aimed to analyze the variation of AMD-associated water pollution in three main zones of the Chini Lake catchment area using Sentinel-2 data for the periods pre-movement control order (MCO), during MCO, and post-MCO from 2019 to 2021. These three zones were chosen due to their proximity to mining areas: zone 1 in the northeastern part, zone 2 in the southeastern part, and zone 3 in the southern part of the Chini Lake area. The acid mine water index (AMWI) was a specific index used to estimate acid mine water. The AMWI values from Sentinel-2 images exhibited that the mean AMWI values in all zones during the MCO period decreased by 14% compared with the pre-MCO period. The spatiotemporal analysis found that the highest polluted zones were recorded in zone 1, followed by zone 3 and zone 2. As compared with during the MCO period, the maximum percentage of increment during post-MCO in all zones was up to 25%. The loosened restriction policy has resulted in more AMD flowing into surface water and increased pollution in Chini Lake. As a whole, our outputs revealed that Sentinel-2 data had a major potential for assessing the AMD-associated pollution of water.


Assuntos
COVID-19 , Poluentes Químicos da Água , Humanos , Monitoramento Ambiental/métodos , Malásia , Poluição da Água/análise , Ácidos/análise , Água/análise , Poluentes Químicos da Água/análise
9.
J Cell Mol Med ; 25(18): 8676-8686, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34418301

RESUMO

Gene therapy of retinal diseases using recombinant adeno-associated virus (rAAV) vector-based delivery has shown clinical success, and clinical trials based on rAAV-based optogenetic therapies are currently in progress. Recently, we have developed multi-characteristic opsin (MCO), which has been shown to effectively re-photosensitize photoreceptor-degenerated retina in mice leading to vision restoration at ambient light environment. Here, we report the biodistribution of the rAAV2 carried MCO (vMCO-I) in live samples and post-mortem organs following intraocular delivery in wild-type dogs. Immunohistochemistry showed that the intravitreal injection of vMCO-I resulted in gene transduction in the inner nuclear layer (INL) but did not induce detectable inflammatory or immune reaction in the dog retina. Vector DNA analysis of live body wastes and body fluids such as saliva and nasal secretions using quantitative polymerase chain reaction (qPCR) showed no correlative increase of vector copy in nasal secretions or saliva, minimal increase of vector copy in urine in the low-dose group 13 weeks after injection and in the faeces of the high-dose group at 3-13 weeks after injection suggesting clearance of the virus vector via urine and faeces. Further analysis of vector DNA extracted from faeces using PCR showed no transgene after 3 weeks post-injection. Intravitreal injection of vMCO-I resulted in few sporadic off-target presences of the vector in the mesenteric lymph node, liver, spleen and testis. This study showed that intravitreal rAAV2-based delivery of MCO-I for retinal gene therapy is safe.


Assuntos
Dependovirus/fisiologia , Terapia Genética/métodos , Doenças Retinianas/terapia , Animais , Cães , Feminino , Vetores Genéticos , Masculino
10.
Molecules ; 26(21)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34771038

RESUMO

The traceless Staudinger ligation with its two variants is a powerful biorthogonal conjugation method not only for the connection of biomolecules, but also for the introduction of fluorescence- or radiolabels under mild reaction conditions. Herein, the strategic evaluation of the traceless Staudinger ligation for radiolabeling 99mTc using the fac-[Tc(CO)3]+ core is presented. A convenient and high-yielding three-step synthetic procedure of dipicolylamine-based phosphanols as ligands for the mild radiolabeling was developed. The labeling was accomplished using a tricarbonyl kit and a 99mTc-pertechnetate generator eluate showing 87% radiochemical conversion. The respective rhenium-based, non-radioactive reference compounds were synthesized using (Et4N)2[Re(CO)3Br3] as precursor. All products were analyzed by NMR, MS, and elemental analysis. Additional XRD analyses were performed.

11.
Molecules ; 25(8)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331469

RESUMO

Pd-catalysed Stille and Suzuki cross-couplings were used to prepare 9-(3-indenyl)-, 6, and 9-(2-indenyl)-anthracene, 7; addition of benzyne led to the 9-Indenyl-triptycenes, 8 and 9. In 6, [4 + 2] addition also occurred to the indenyl substituent. Reaction of 6 through 9 with Cr(CO)6 or Re2(CO)10 gave their M(CO)3 derivatives, where the Cr or Re was complexed to a six- or five-membered ring, respectively. In the 9-(2-indenyl)triptycene complexes, slowed rotation of the paddlewheel on the NMR time-scale was apparent in the η5-Re(CO)3 case and, when the η6-Cr(CO)3 was deprotonated, the resulting haptotropic shift of the metal tripod onto the five-membered ring also blocked paddlewheel rotation, thus functioning as an organometallic molecular brake. Suzuki coupling of ferrocenylboronic acid to mono- or dibromoanthracene yielded the ferrocenyl anthracenes en route to the corresponding triptycenes in which stepwise hindered rotations of the ferrocenyl groups behaved like molecular dials. CuCl2-mediated coupling of methyl- and phenyl-indenes yielded their rac and meso 2,2'-biindenyls; surprisingly, however, the apparently sterically crowded rac 2,2'-Bis(9-triptycyl)biindenyl functioned as a freely rotating set of molecular gears. The predicted high rotation barrier in 9-phenylanthracene was experimentally validated via the Pd-catalysed syntheses of di(3-fluorophenyl)anthracene and 9-(1-naphthyl)-10-phenylanthracene.


Assuntos
Antracenos/química , Acoplamento Oxidativo , Paládio/química , Antracenos/síntese química , Técnicas de Química Sintética , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/química
12.
Arch Orthop Trauma Surg ; 139(8): 1141-1147, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31209615

RESUMO

INTRODUCTION: Correct femoral rotational alignment in total knee arthroplasty (TKA) is important for femoropatellar knee kinematics as well as for the overall clinical success. The goal of the present study was to evaluate how accurately standard instruments of various manufacturers with specific rotational settings in posterior referencing restore the posterior femoral condylar anatomy and allow a rotational alignment which matches a particular anatomic rotational landmark on CT. METHODS: The anatomical transepicondylar axis (aTEA) and the posterior condylar line (PCL) were identified and the angle formed by these two axes was measured on 100 consecutive CT scans of knees. A virtual posterior condylar resection was performed relative to the aTEA for femoral sizers of various manufacturers in different external rotations ranging from 3° to 7°. The resections of medial and lateral posterior condyle were calculated as well as the condylar twist angle (CTA) between PCL and aTEA. RESULTS: The posterior condylar resection varied between 9 mm and 14 mm on the medial side and between 4 mm and 10.5 mm on the lateral side. The mean CTA was 5.5° of internal rotation (SD ± 1.9°). External femoral rotation resulted in increased resection of the medial posterior condyle and decreased resection of the lateral posterior condyle. CONCLUSION: Femoral sizers using a posterior referencing technique increase, with rising external rotation, medial posterior condylar resection to an extent that may exceed the implant thickness in the majority of systems. Surgeons should be aware that current standard instruments do not restore the anatomy of the posterior medial and lateral condyle and do not align the femoral component parallel to the aTEA, which may result in internal rotation of a symmetric femoral component.


Assuntos
Artroplastia do Joelho/instrumentação , Fêmur/anatomia & histologia , Articulação do Joelho/diagnóstico por imagem , Ajuste de Prótese/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos , Artroplastia do Joelho/métodos , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Rotação , Tomografia Computadorizada por Raios X
13.
J Appl Clin Med Phys ; 19(2): 184-190, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29411526

RESUMO

This study compared the dosimetric performance of (a) volumetric modulated arc therapy (VMAT) with standard optimization (STD) and (b) multi-criteria optimization (MCO) to (c) intensity modulated radiation therapy (IMRT) with MCO for hippocampal avoidance whole brain radiation therapy (HA-WBRT) in RayStation treatment planning system (TPS). Ten HA-WBRT patients previously treated with MCO-IMRT or MCO-VMAT on an Elekta Infinity accelerator with Agility multileaf collimators (5-mm leaves) were re-planned for the other two modalities. All patients received 30 Gy in 15 fractions to the planning target volume (PTV), namely, PTV30 expanded with a 2-mm margin from the whole brain excluding hippocampus with margin. The patients all had metastatic lesions (up to 12) of variable sizes and proximity to the hippocampus, treated with an additional 7.5 Gy from a simultaneous integrated boost (SIB) to PTV37.5. The IMRT plans used eight to eleven non-coplanar fields, whereas the VMAT plans used two coplanar full arcs and a vertex half arc. The averaged target coverage, dose to organs-at-risk (OARs) and monitor unit provided by the three modalities were compared, and a Wilcoxon signed-rank test was performed. MCO-VMAT provided statistically significant reduction of D100 of hippocampus compared to STD-VMAT, and Dmax of cochleas compared to MCO-IMRT. With statistical significance, MCO-VMAT improved V30 of PTV30 by 14.2% and 4.8%, respectively, compared to MCO-IMRT and STD-VMAT. It also raised D95 of PTV37.5 by 0.4 Gy compared to both MCO-IMRT and STD-VMAT. Improved plan quality parameters such as a decrease in overall plan Dmax and total monitor units (MU) were also observed for MCO-VMAT. MCO-VMAT is found to be the optimal modality for HA-WBRT in terms of PTV coverage, OAR sparing and delivery efficiency, compared to MCO-IMRT or STD-VMAT.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana , Hipocampo/efeitos da radiação , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Prognóstico , Dosagem Radioterapêutica
14.
Mikrochim Acta ; 185(7): 358, 2018 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-29974265

RESUMO

This review (with (318) refs) describes progress made in the design and synthesis of morphologically different metal oxide nanoparticles made from iron, manganese, titanium, copper, zinc, zirconium, cobalt, nickel, tungsten, silver, and vanadium. It also covers respective composites and their function and application in the field of electrochemical and photoelectrochemical sensing of chemical and biochemical species. The proper incorporation of chemical functionalities into these nanomaterials warrants effective detection of target molecules including DNA hybridization and sensing of DNA or the formation of antigen/antibody complexes. Significant data are summarized in tables. The review concludes with a discussion or current challenge and future perspectives. Graphical abstract ᅟ.


Assuntos
Técnicas Biossensoriais/métodos , Eletroquímica/métodos , Metais/química , Óxidos/química , Eletrodos , Nanopartículas/química
15.
Int J Mol Sci ; 19(1)2018 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-29337899

RESUMO

Saccharomyces cerevisiae Fet3p is a multicopper oxidase that contains three cupredoxin-like domains and four copper ions located in three distinct metal sites (T1 in domain 3; T2 and the binuclear T3 at the interface between domains 1 and 3). To probe the role of the copper sites in Fet3p thermodynamic stability, we performed urea-induced unfolding experiments with holo-, apo- and three partially-metallated (T1, T2 and T1/T2 sites depleted of copper) forms of Fet3p. Using a combination of spectroscopic probes (circular dichroism, fluorescence intensity and maximum, 8-anilinonaphthalene-1-sulfonic acid (ANS) emission, oxidase activity and blue color), we reveal that all forms of Fet3p unfold in a four-state reaction with two partially-folded intermediates. Using phase diagrams, it emerged that Fet3p with all copper sites filled had a significantly higher stability as compared to the combined contributions of the individual copper sites. Hence, there is long-range inter-domain communication between distal copper sites that contribute to overall Fet3p stability.


Assuntos
Ceruloplasmina/metabolismo , Cobre/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Apoproteínas/metabolismo , Estabilidade Enzimática , Proteínas Mutantes/metabolismo , Desnaturação Proteica/efeitos dos fármacos , Dobramento de Proteína/efeitos dos fármacos , Espectrometria de Fluorescência , Ureia/farmacologia
16.
Polim Med ; 48(1): 57-63, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30740940

RESUMO

Dialysis membranes are the basic element of a hemodialyzer. Synthetic and natural materials characterized by various fiber arrangements are used in their production. The most up-to-date ones are made of synthetic polymers such as polyamide, phosphatidylserine (PS), polyacrylonitrile-based fiber (PAN), polyarylethersulfone, polyethersulfone, or polymethylmethacrylate. Dialysis membranes are characterized by the ability to remove uremic molecules, which can be divided into small water-soluble compounds, protein-bound compounds and larger "middle molecules". Newer membranes such as medium cut off membranes (MCO) allow the removal of a wider spectrum of uremic molecules, which reduces the risk of late complications of dialysis. Dialysis membranes are used in therapy methods such as low flux, high flux or HDx therapy. An important aim in dialysis membrane development is to increase their biocompatibility. Insufficient biocompatibility can result in complement activation or platelet activation, which can lead to an increased risk of cardiovascular complications. The aim of the study is to discuss the latest reports on dialysis membranes.


Assuntos
Membranas Artificiais , Diálise Renal , Materiais Biocompatíveis , Nylons , Polímeros
17.
J Nanosci Nanotechnol ; 17(1): 661-65, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29630329

RESUMO

The ultralong Cu@M (M = Co or Ni) nanowires (NWs) with core­shell structure were fabricated by a simple method by using the prepared Cu NWs as template. The crystal phases of Cu@M (M = Co or Ni) NWs were confirmed by X-ray diffraction (XRD). The morphology and microstructure of NWs were characterized by scanning electro microscopy (SEM) and transmission electro microscopy (TEM). Different diameters of Cu@M (M = Co or Ni) NWs varying from 120 to 550 nm with length about 10 µm were obtained via controlling the amounts of cobalt (nickel) nitrates in the reduction process. The magnetic properties of samples were measured using vibrating sample magnetometer (VSM). Results revealed that Cu NWs has a characteristic of paramagnetism after coating Co or Ni. The coercivity (H(c)) values of Cu@ Ni and Cu@Co NWs were 114.6 and 102.5 Oe, respectively. Possible formation mechanism for Cu@M (M = Co or Ni) NWs was preliminarily proposed.

18.
Eur Biophys J ; 45(2): 139-48, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26493065

RESUMO

In this study, we report the synthesis and characterization studies of amine-functionalized MFe2O4 (Co, Ni, Mn) nanoparticles. The synthesis process was accomplished by refluxing metal chloride precursors in ethylene glycol in the presence of sodium acetate and ethanolamine. The average crystallite sizes of the synthesized particles are found to be in the range of 8-10 nm. The synthesized particles are characterized using X-ray diffraction, Brunauer-Emmett-Teller technique, FTIR, dynamic light scattering, Raman and UV-visible spectroscopy for crystal structure, average size, surface area, pore diameter and hydrodynamic diameter, phase and functional group determination. The surface morphology and elemental composition were studied by scanning electron microscope and X-ray fluorescence respectively. Magnetic behavior up to fields of 3 T at room temperature measured in Quantum Design Physical Property Measurement System (QD PPMS) magnetometer showed the superparamagnetic behavior of these particles. Modulation of angiogenesis by the nanoparticles was studied in a chick embryo chorioallantoic membrane model by analysis of blood vessel development and effect on hemoglobin level using imaging and colorimetric methods. An enhancement in the angiogenesis compared to the saline control was observed for all the ferrite nanoparticles with a relatively optimal activity in case of CoFe2O4 nanoparticles.


Assuntos
Indutores da Angiogênese/química , Membrana Corioalantoide/irrigação sanguínea , Compostos Ferrosos/química , Nanopartículas de Magnetita/química , Neovascularização Fisiológica , Indutores da Angiogênese/farmacologia , Animais , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Cobalto/química , Manganês/química , Níquel/química
19.
Dig Endosc ; 28(4): 456-464, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26632261

RESUMO

AIMS: To compare the usefulness of the self-expanding metallic stent (SEMS) with that of the transanal drainage tube (TDT) and emergency surgery after failure of decompression (ESFD) in patients with malignant colonic obstruction (MCO), and to evaluate post-decompression histopathologic changes. METHODS: From January 2010 to June 2015, 39 patients with MCO received SEMS, TDT, and ESFD. We evaluated the outcomes including success rates of placement, clinical outcomes after decompression, and histopathologic findings of the resected specimens. RESULTS: Technical success rates were 100% for SEMS and 78.9% for TDT. Clinical success rates were 100% for SEMS and 80.0% for TDT. Postoperative ileus was significantly less frequent after SEMS than after TDT (p = 0.014). Histopathologic edema grade was significantly lower for SEMS than for TDT and ESFD (p < 0.0001). There was no significant difference between edema grade and duration of decompression in the TDT group (p = 0.629), while all patients with SEMS were classified in a low edema grade (grade 0-2). The rate of stoma creation was significantly higher in patients with a high edema grade (grade 3) than in those with a low edema grade (grade 0-2) (p = 0.003). There was no microscopic perforation in any group. CONCLUSION: Significantly greater resolution of histopathologic edema was achieved after placement of SEMS than after placement of TDT. These findings provide an indication of favorable clinical outcomes of SEMS in comparison with TDT and ESFD. This article is protected by copyright. All rights reserved.

20.
Int J Mol Sci ; 16(8): 19433-46, 2015 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-26287186

RESUMO

Thioredoxin is a multifunctional antioxidant enzyme that belongs to the reductase family. In this study, we cloned and characterized thioredoxin 1 cDNA from the Korean rose bitterling Rhodeus uyekii (RuTrx). The full-length RuTrx cDNA consists of 674 bp with a 324 nt open reading frame (ORF) encoding a 107 aa protein. The deduced RuTrx amino acid sequence indicated a characteristic redox active site, (31)WCGPC(35). Pairwise alignment revealed RuTrx amino acid identity (55.1%-83.2%) with orthologs from various species of mammalia, amphibia, fish and bird. Phylogenetic analysis was conducted to determine the evolutionary position of RuTrx. Expression analysis showed that RuTrx transcripts were present in all of the tissues examined, and was high in the hepatopancreas of R. uyekii. During early development, the expression of RuTrx transcripts was increased. Recombinant RuTrx protein (rRuTrx) was tested for its capacity to serve as an antioxidant enzyme using a metal-catalyzed oxidation (MCO) system. The ability of rRuTrx to protect against supercoiled DNA cleavage due to oxidative nicking increased in a dose-dependent manner. In Raw264.7 cells, Dihydroethidium (DHE) staining for ROS production indicated the antioxidant activity of rRuTrx. Together, these findings suggest that RuTrx may play a role in maintaining the redox state balance in Korean rose bitterling R. uyekii.


Assuntos
Cyprinidae/genética , Proteínas de Peixes/química , Proteínas de Peixes/genética , Tiorredoxinas/química , Tiorredoxinas/genética , Sequência de Aminoácidos , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Sequência de Bases , Cyprinidae/crescimento & desenvolvimento , Cyprinidae/metabolismo , Clivagem do DNA , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Dados de Sequência Molecular , Filogenia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Tiorredoxinas/metabolismo
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