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1.
Materials (Basel) ; 17(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38930317

RESUMO

This work examines the influence of the degradation behaviors of biotic and abiotic conditions on three types of biodegradable products: cups from PLA and from cellulose, and plates from sugarcane. The main objective of this study was to evaluate if biodegradable products can be degraded in composts that were stabilized by backyard composting. Furthermore, the impact of crucial abiotic parameters (temperature and pH) for the degradation behaviors process was investigated. The changes in the biopolymers were analyzed by FTIR spectroscopy. This work confirmed that abiotic and biotic conditions are important for an effective disintegration of the investigated biodegradable products. Under abiotic conditions, the degradation behaviors of PLA were observable under both tested temperature (38 and 59 °C) conditions, but only at the higher temperature was complete disintegration observed after 6 weeks of incubation in mature compost. Moreover, our research shows that some biodegradable products made from cellulose also need additional attention, especially with respect to incorporated additives, as composting could be altered and optimal conditions in composting may not be achieved. This study shows that the disintegration of biodegradable products is a comprehensive process and requires detailed evaluation during composting. The results also showed that biodegradable products can also be degraded post composting and that microplastic pollution from biodegradable polymers in soil may be removed by simple physical treatments.

2.
Waste Manag Res ; : 734242X241251417, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773885

RESUMO

Printed circuit boards (PCBs) are the most complex and valuable component of electronic devices, but only 34% of them are recycled in an environmentally sound manner. Improving the recycling rate and efficiency requires a fast, reliable and uncostly analytical method. Although the X-ray fluorescence (XRF) shows high potential, it is often unreliable. In this study, we propose a novel XRF methodology for the elemental analysis of PCBs, using the certified reference material (CRM) to decrease uncertainty and enhance accuracy. The results show significant improvement in robustness and accuracy of portable XRF(pXRF) analyses for elements Cu, Pb, Ni, As and Au, with a relative average inaccuracy of approximately 5% compared to referenced values. The methodology validation carried out by comparing pXRF and inductively coupled plasma mass spectroscopy analyses of personal computer motherboard samples shows no statistically significant difference for elements Cu, Cr and Ag. The study shows that the calibration of pXRF by CRMs enables the necessary analysis of PCBs in an efficient and reliable manner and could be also be applied to different types of PCBs and other electronic components, batteries or contaminated soil samples.

3.
J Hazard Mater ; 468: 133772, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38377904

RESUMO

Microplastics (MPs) present in terrestrial environments show potential leaching risk to deeper soil layers and aquifer systems, which threaten soil health and drinking water supply. However, little is known about the environmental fate of MPs in natural sediments. To examine the MPs transport mechanisms in natural sediments, column experiments were conducted using different natural sediments and MPs (10-150 µm) with conservative tracer. Particle breakthrough curves (BTCs) and retention profiles (RPs) were numerically interpreted in HYDRUS-1D using three different models to identify the most plausible deposition mechanism of MPs. Results show that the retention efficiency for a given particle size increased with decreasing grain size, and RPs exacerbated their hyper-exponential shape in finer sediments. Furthermore, the amounts of MPs present in the effluent increased to over 85 % as MPs size decreased to 10-20 µm in both gravel and coarse sand columns, while all larger MPs (125-150 µm) were retained in the coarse sand column. The modeling results suggested that the blocking mechanism becomes more important with increasing particle sizes. In particular, the attachment-detachment without blocking was the most suited parameterization to interpret the movement of small MPs, while a depth-dependent blocking approach was necessary to adequately describe the fate of larger particles.

4.
Environ Monit Assess ; 196(1): 5, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38044370

RESUMO

Microplastics (MP), small plastic particles under 5 mm, are pollutants known to carry heavy metals in ecosystems. Composts are a significant source of soil microplastics. This study examined MSW composts from Kochi and Kozhikode in India for microplastic concentrations and heavy metals' accumulation thereon. Microplastics were isolated using zinc chloride density separation, with Fenton's reagent used for organic matter oxidation. Resin types were identified using FTIR analysis that showed the presence of PE, PP, PS, nylon, PET, and allyl alcohol copolymer. In Kozhikode's compost, the average concentration of microplastics was 840 ± 30 items/kg, while Kochi had 1600 ± 111 items/kg, mainly polyethylene films. PE was the most prevalent resin, comprising 58.3% in Kozhikode and 73.37% in Kochi. Heavy metal analysis of MP showed significant concentrations of lead, cadmium, zinc, copper, and manganese adsorbed on the surface of microplastics. The concentrations of heavy metals in the MP before Fenton oxidation ranged from 1.02 to 2.02 times the corresponding concentrations in compost for Kozhikode and 1.23 to 2.85 times for Kochi. Source apportionment studies revealed that 64% of microplastics in Kozhikode and 77% in Kochi originated from single-use plastics. Ecological risk indices, PLI and PHI, showed that composts from both locations fall under hazard level V. The study revealed that compost from unsegregated MSW can act as a significant source of microplastics and heavy metals in the soil environment, with single-use plastics contributing major share of the issue.


Assuntos
Compostagem , Metais Pesados , Poluentes Químicos da Água , Microplásticos , Plásticos , Ecossistema , Monitoramento Ambiental , Metais Pesados/análise , Solo , Poluentes Químicos da Água/análise
5.
Heliyon ; 9(8): e18443, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37609390

RESUMO

Disease-modifying therapies to treat Alzheimer's disease (AD) are of fundamental interest for aging humans, societies, and health care systems. Predictable disease progression in transgenic AD models favors preclinical studies employing a preventive study design with an early pre-symptomatic treatment start, instead of assessing a truly curative approach with treatment starting after diagnosed disease onset. The aim of this study was to investigate the pharmacokinetic profile and efficacy of RD2 to enhance short-term memory and cognition in cognitively impaired aged Beagle dogs - a non-transgenic model of truly sporadic AD. RD2 has previously demonstrated pharmacodynamic efficacy in three different transgenic AD mouse models in three different laboratories. Here, we demonstrate that oral treatment with RD2 significantly reduced cognitive deficits in cognitively impaired aged Beagle dogs even beyond the treatment end, which suggests in combination with the treatment dependent CSF tau oligomer decrease a disease-modifying effect of RD2 treatment.

6.
Materials (Basel) ; 16(13)2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37444865

RESUMO

Despite the development of biorefinery processes, the possibility of coupling the "conventional" composting process with the production of biochemicals is not taken into account. However, net carbon monoxide (CO) production has been observed during bio-waste composting. So far, O2 concentration and temperature have been identified as the main variables influencing CO formation. This study aimed to investigate CO net production during bio-waste composting under controlled laboratory conditions by varying aeration rates and temperatures. A series of composting processes was carried out in conditions ranging from mesophilic to thermophilic (T = 35, 45, 55, and 65 °C) and an aeration rate of 2.7, 3.4, 4.8, and 7.8 L·h-1. Based on the findings of this study, suggestions for the improvement of CO production throughout the composting process have been developed for the first time. The highest concentrations of CO in each thermal variant was achieved with an O2 deficit (aeration rate 2.7 L·h-1); additionally, CO levels increased with temperature, reaching ~300 ppm at 65 °C. The production of CO in mesophilic and thermophilic conditions draws attention to biological CO formation by microorganisms capable of producing the CODH enzyme. Further research on CO production efficiency in these thermal ranges is necessary with the characterization of the microbial community and analysis of the ability of the identified bacteria to produce the CODH enzyme and convert CO from CO2.

7.
Waste Manag ; 162: 18-26, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36921437

RESUMO

The quantity and type of macro- and microplastics was investigated in rotting material during the composting process of two state-of-the-art composting plants in Austria. Microplastics >0.2 mm, were found already after the first turning event in both facilities. The generation of microplastics was more extensive in the plant that used shorter turning intervals during the first four weeks and generated approx. 21 particles per week and kg-1 DM. After 4 weeks of operation less microplastic particles were detected, which suggested that particles were fractionated to smaller sizes during processing. In addition, a total of nine composts from three different facilities that were operated in various settlement structures were compared. 7 to 232 macro- and microplastic particles per kg DM were found, whereas the highest plastic burden was observed in the composts made from biowaste that originated from the most densely populated area.


Assuntos
Compostagem , Microplásticos , Plásticos , Solo , Plantas
8.
Environ Pollut ; 317: 120461, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36272608

RESUMO

Investigations of the behavior and effects of engineered nanoparticles (ENPs) on human health and the environment need detailed knowledge of their fate and transport in environmental compartments. Such studies are highly challenging due to low environmental concentrations, varying size distribution of the particles and the interference with the natural background. A strategy to overcome these limits is to use mimics of ENPs with unique detectable properties that match the properties of the ENPs as nanotracers. A special class of ENPs that can be tracked are quantum dots (QDs). QDs are composed of different metals, metalloids, or more recently also carbon (e.g., graphene), that result in unique optical properties. This allows the tracking of such particles by fluorescence microscopic and photometric techniques. Many types of QDs consist of heavy elements, allowing to track and visualize these particles also by electron microscopy and to quantitate the particles indirectly based on these elements. QDs can also be surface modified in various ways which enable them to be used as a label or as traceable mimics for ENPs. This review reflects a broad range of methods to synthesize and modify QDs based on metals, metalloids, and graphene for studying the environmental fate of nanoparticles and discusses and compares analytical methods that can be used for tracking and quantifying QDs. In addition, we review applications of QDs as ENP mimics in environmental studies of surface waters, soils, microorganisms, and plants with respect to the applied analytical techniques.


Assuntos
Grafite , Nanopartículas , Pontos Quânticos , Humanos , Solo
9.
MethodsX ; 9: 101885, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36385913

RESUMO

Decolorization assays allow to assess the ability of white rot fungi to degrade persistent organic molecules such as textile dyes and can contribute to discover microorganisms that can be used for bioremediation. The decolorization can be overlayed by the absorption from metabolites that are produced by fungi during screening, which interfere with the results. To compensate for this interference a method was developed by using different controls to subtract interfering signals. The method was designed for simple screening in multiwell plates that can be operated with a plate reader. It was applied to four different textile dyes (Reactive Black 5, Reactive Blue 4, Reactive Green 19, and Reactive Orange 16) that were degraded by the white rot fungus Phanerochaete velutina. The four textile dyes showed different results with a different degree of interference. The controls allow to compensate for interfering signals and to calculate kinetic parameters for the decolorization reaction and the enzymatic degradation.•Determine the non-enzymatic degradation of the dyes in experiments without fungi.•Determine the absorbance of metabolites and subtract it from the decolorization data to obtain the degradation of the dye.•Determine kinetic parameters of the degradation to compare the efficiency of the enzymes towards dyes.

10.
Polymers (Basel) ; 14(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35956603

RESUMO

Plastics are a ubiquitous material with good mechanical, chemical and thermal properties, and are used in all industrial sectors. Large quantities, widespread use, and insufficient management of plastic wastes lead to low recycling rates. The key challenge in recycling plastic waste is achieving a higher degree of homogeneity between the different polymer material streams. Modern waste sorting plants use automated sensor-based sorting systems capable to sort out commodity plastics, while many engineering plastics, such as polyoxymethylene (POM), will end up in mixed waste streams and are therefore not recycled. A novel approach to increasing recycling rates is tracer-based sorting (TBS), which uses a traceable plastic additive or marker that enables or enhances polymer type identification based on the tracer's unique fingerprint (e.g., fluorescence). With future TBS applications in mind, we have summarized the literature and assessed TBS techniques and spectroscopic detection methods. Furthermore, a comprehensive list of potential tracer substances suitable for thermoplastics was derived from the literature. We also derived a set of criteria to select the most promising tracer candidates (3 out of 80) based on their material properties, toxicity profiles, and detectability that could be applied to enable the circularity of, for example, POM or other thermoplastics.

11.
Cell Rep Med ; 3(5): 100630, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35584626

RESUMO

The elimination of amyloid beta (Aß) oligomers is a promising strategy for therapeutic drug development of Alzheimer's disease (AD). AD mouse models that develop Aß pathology have been used to demonstrate in vivo efficacy of compounds that later failed in clinical development. Here, we analyze the concentration and size distribution of Aß oligomers in different transgenic mouse models of AD and in human brain samples by surface-based fluorescence intensity distribution analysis (sFIDA), a highly sensitive method for detecting and quantitating protein aggregates. We demonstrate dose- and time-dependent oligomer elimination by the compound RD2 in mouse and human AD brain homogenates as sources of native Aß oligomers. Such ex vivo target engagement analyses with mouse- and human-brain-derived oligomers have the potential to enhance the translational value from pre-clinical proof-of-concept studies to clinical trials.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Transgênicos
12.
Heliyon ; 8(12): e11878, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36590569

RESUMO

The remarkable optoelectronic capabilities of perovskite structures enable the achievement of astonishingly high-power conversion efficiencies on the laboratory scale. However, a critical bottleneck of perovskite solar cells is their sensitivity to the surrounding humid environment affecting drastically their long-term stability. Internal additive materials together with surface passivation, polymer-mixed perovskite, and quantum dots, have been investigated as possible strategies to enhance device stability even in unfavorable conditions. Quantum dots (QDs) in perovskite solar cells enable power conversion efficiencies to approach 20%, making such solar cells competitive to silicon-based ones. This mini-review summarized the role of such QDs in the perovskite layer, hole-transporting layer (HTL), and electron-transporting layer (ETL), demonstrating the continuous improvement of device efficiencies.

13.
Materials (Basel) ; 14(22)2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34832452

RESUMO

The quantity of biodegradable plastics is increasing steadily and taking a larger share in the residual waste stream. As the calorific value of biodegradable plastic is almost two-fold lower than that of conventional ones, its increasing quantity decreases the overall calorific value of municipal solid waste and refuse-derived fuel which is used as feedstock for cement and incineration plants. For that reason, in this work, the torrefaction of biodegradable waste, polylactic acid (PLA), and paper was performed for carbonized solid fuel (CSF) production. In this work, we determined the process yields, fuel properties, process kinetics, theoretical energy, and mass balance. We show that the calorific value of PLA cannot be improved by torrefaction, and that the process cannot be self-sufficient, while the calorific value of paper can be improved up to 10% by the same process. Moreover, the thermogravimetric analysis revealed that PLA decomposes in one stage at ~290-400 °C with a maximum peak at 367 °C, following a 0.42 reaction order with the activation energy of 160.05 kJ·(mol·K)-1.

14.
Environ Pollut ; 290: 118041, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34523513

RESUMO

The presence of manufactured nano-objects (MNOs) in various consumer or their (future large-scale) use as nanoagrochemical have increased with the rapid development of nanotechnology and therefore, concerns associated with its possible ecotoxicological effects are also arising. MNOs are releasing along the product life cycle, consequently accumulating in soils and other environmental matrices, and potentially leading to adverse effects on soil biota and their associated processes. Earthworms, of the group of Oligochaetes, are an ecologically significant group of organisms and play an important role in soil remediation, as well as acting as a potential vector for trophic transfer of MNOs through the food chain. This review presents a comprehensive and critical overview of toxic effects of MNOs on earthworms in soil system. We reviewed pathways of MNOs in agriculture soil environment with its expected production, release, and bioaccumulation. Furthermore, we thoroughly examined scientific literature from last ten years and critically evaluated the potential ecotoxicity of 16 different metal oxide or carbon-based MNO types. Various adverse effects on the different earthworm life stages have been reported, including reduction in growth rate, changes in biochemical and molecular markers, reproduction and survival rate. Importantly, this literature review reveals the scarcity of long-term toxicological data needed to actually characterize MNOs risks, as well as an understanding of mechanisms causing toxicity to earthworm species. This review sheds light on this knowledge gap as investigating bio-nano interplay in soil environment improves our major understanding for safer applications of MNOs in the agriculture environment.


Assuntos
Oligoquetos , Poluentes do Solo , Animais , Bioacumulação , Ecotoxicologia , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
15.
Ecotoxicol Environ Saf ; 215: 112093, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33721667

RESUMO

Organic aromatic compounds used for dyeing and coloring in the textile industry are persistent and hazardous pollutants that must be treated before they are discharged into rivers and surface waters. Therefore, we investigated the potential of the white rot fungus Phanerochaete velutina to decolorize commonly used reactive dyes. The fungus decolorized in average 55% of Reactive Orange 16 (RO-16) after 14 days at a maximum rate of 0.09 d-1 and a half-life of 8 days. Furthermore, we determined the inhibitory effects of co-present inorganic contaminants Nickel (Ni) and Cobalt (Co) salts on the decolorization potential and determined IC50 values of 5.55 mg l-1 for Co and a weaker inhibition by Ni starting from a concentration of 20 mg l-1. In the decolorization assay for Remazol Brilliant Blue R (RBBR) we observed the interference of a metabolite of P. velutina, which did not allow us to investigate the kinetics of the reaction. The formation of the metabolite, however, could be used to obtain IC50 values of 3.37 mg l-1 for Co and 7.58 mg l-1 for Ni. Our results show that living white rot fungi, such as P. velutina, can be used for remediation of dye polluted wastewater, alternatively to enzyme mixtures, even in the co-presence of heavy metals.


Assuntos
Biodegradação Ambiental , Corantes/metabolismo , Phanerochaete/metabolismo , Poluentes Químicos da Água/metabolismo , Antraquinonas , Compostos Azo , Cobalto , Metais Pesados , Níquel , Sais , Indústria Têxtil , Têxteis , Águas Residuárias , Poluentes Químicos da Água/análise
16.
Mol Oncol ; 15(2): 503-522, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33155399

RESUMO

Epithelial ovarian cancer involves the shedding of single tumor cells or spheroids from the primary tumor into ascites, followed by their survival, and transit to the sites of metastatic colonization within the peritoneal cavity. During their flotation, anchorage-dependent epithelial-type tumor cells gain anoikis resistance, implicating integrins, including αvß3. In this study, we explored anoikis escape, cisplatin resistance, and prosurvival signaling as a function of the αvß3 transmembrane conformational activation state in cells suspended in ascites. A high-affinity and constitutively signaling-competent αvß3 variant, which harbored unclasped transmembrane domains, was found to confer delayed anoikis onset, enhanced cisplatin resistance, and reduced cell proliferation in ascites or 3D-hydrogels, involving p27kip upregulation. Moreover, it promoted EGF-R expression and activation, prosurvival signaling, implicating FAK, src, and PKB/Akt. This led to the induction of the anti-apoptotic factors Bcl-2 and survivin suppressing caspase activation, compared to a signaling-incapable αvß3 variant displaying firmly associated transmembrane domains. Dissecting the mechanistic players for αvß3-dependent survival and peritoneal metastasis of ascitic ovarian cancer spheroids is of paramount importance to target their anchorage independence by reversing anoikis resistance and blocking αvß3-triggered prosurvival signaling.


Assuntos
Anoikis , Integrina alfaVbeta3/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Ovarianas/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Feminino , Humanos , Integrina alfaVbeta3/genética , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética
17.
Eur J Pharm Sci ; 156: 105581, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035662

RESUMO

Amyloid-ß (Aß) plays a central role in the development and progression of Alzheimer's disease (AD) with Aß oligomers representing the most toxic species. The all-d-enantiomeric peptide RD2, which recently successfully completed clinical phase I, specifically eliminates Aß oligomers in vitro as well as in vivo and improves cognitive deficits in various transgenic AD mouse models even after oral administration. To further enhance the oral absorption of RD2, folic acid has been conjugated to the d-peptide promoting an endocytosis-mediated uptake via a folate receptor located in the intestine. Two different conjugation strategies were selected to obtain prodrugs with folic acid being cleaved after intestinal absorption releasing unmodified RD2 in order to enable RD2's unaltered systemic efficacy. Both conjugates remained stable in simulated gastrointestinal fluids. But only one of them was suitable as prodrug as it was cleaved to RD2 in vitro in human blood plasma and liver microsomes and in vivo in mice after intravenous injection leading to a systemic release of RD2. Furthermore, the conjugate's permeability in vitro and after oral administration in mice was strongly enhanced compared to unconjugated RD2 demonstrating the prodrug's functionality. However, the conjugate seemed to have impaired the mice's wellbeing shortly after oral administration possibly resulting from strain-specific hypersensitivity to folic acid. Nevertheless, we assume that the prodrug is actually non-toxic, especially in lower concentrations as verified by a cell viability test. Furthermore, lower dosages can be applied with unaltered efficacy due to its enhanced oral absorption.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Doença de Alzheimer/tratamento farmacológico , Animais , Ácido Fólico , Camundongos , Camundongos Transgênicos , Estereoisomerismo
18.
J Hazard Mater ; 394: 122477, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32240897

RESUMO

Semiconductor quantum dots (QDs) are nanocrystals used in diverse optoelectronics. At the end of their useful life they are likely to end up in landfills, where they could be mobilzed by infiltrating rain water. In this work, spectroscopic and light scattering techniques were employed to investigate the environmental fate of QDs exposed to leachates from Austrian landfill sites containing municipal solid and bulky wastes. Brij-58-coated CdSe QDs, a model for surfactant stabilized hydrophobic nanoparticles, primarily sedimented before being degraded on a slower timescale in the course of 6 months. In contrast, N-acetyl-l-cystein-coated CdTe QDs, which represent electrostatically stabilized nanoparticles with a small covalently linked stabilizing molecule, mainly underwent a degradation mechanism that was accelerated by temperature. 71-95 % of this QD type was still dispersed in all leachates after 6 months at low temperature. Leachate temperature and composition, such as the DOC, as well as the used particle coating determined the mechanistic route of clearance of sedimentation versus degradation. Our study shows, that mechanistic investigations are necessary to determine the persistence of nanoparticles depending on their coatings in waste matrices which can be further used to assess hazardous risks of such nanowastes.

19.
ACS Sens ; 4(11): 3042-3050, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31674772

RESUMO

Amyloid-ß oligomers (AßO) have become representative biomarkers for early diagnosis of Alzheimer's disease. Here, we report on an aptasensor based on stem-loop probes for sensitive and specific detection of AßO by an amperometric transducer principle using alternating current voltammetry (ACV). Stem-loop probes with redox-active moieties are immobilized on a gold substrate as a receptor element. The signal transduction mechanism relies on redox ferrocene (Fc) reporting via charge transfer on a molecular recognition event involving a conformational change of the molecular beacon. The stem-loop structures were optimized by considering the aptamers' stem length, spacer, and different ferrocene terminals. In addition, the sensor assembly and signal recording including aptamer concentration and ACV frequency dependence are discussed. Using the optimized stem-loop probe (B-3' Fc), the aptasensor showed a decrease of the Fc peak current induced by AßO binding within the broad concentration range spanning 6 orders of magnitude. Furthermore, the detection limit of the sensor can be further decreased by optimizing the ACV frequency, however at the cost of a narrowed detection range. In this work, a label-free electrochemical aptasensor is demonstrated, which facilitates the quantification of the concentration of AßO with high selectivity and subpicomolar sensitivity, which may be conducive to improving the diagnosis and pharmacology studies of Alzheimer's disease.


Assuntos
Peptídeos beta-Amiloides/análise , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais , Técnicas Eletroquímicas , Corantes Fluorescentes/química , Tamanho da Partícula , Conformação Proteica , Propriedades de Superfície
20.
Mol Neurobiol ; 56(3): 2211-2223, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30003517

RESUMO

Oligomers of the amyloid-ß (Aß) protein are suspected to be responsible for the development and progression of Alzheimer's disease. Thus, the development of compounds that are able to eliminate already formed toxic Aß oligomers is very desirable. Here, we describe the in vivo efficacy of the compound RD2, which was developed to directly and specifically eliminate toxic Aß oligomers. In a truly therapeutic, rather than a preventive study, oral treatment with RD2 was able to reverse cognitive deficits and significantly reduce Aß pathology in old-aged transgenic Alzheimer's Disease mice with full-blown pathology and behavioral deficits. For the first time, we demonstrate the in vivo target engagement of RD2 by showing a significant reduction of Aß oligomers in the brains of RD2-treated mice compared to placebo-treated mice. The correlation of Aß elimination in vivo and the reversal of cognitive deficits in old-aged transgenic mice support the hypothesis that Aß oligomers are relevant not only for disease development and progression, but also offer a promising target for the causal treatment of Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Peptídeos/uso terapêutico , Aprendizagem Espacial/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Cognição/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Peptídeos/farmacologia , Aprendizagem Espacial/fisiologia
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