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1.
Behav Neurosci ; 138(2): 125-141, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38661671

RESUMEN

Selenium is an essential trace element that is delivered to the brain by the selenium transport protein selenoprotein P (SEPP1), primarily by binding to its receptor low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), at the blood-brain barrier. Selenium transport is required for several important brain functions, with transgenic deletion of either Sepp1 or Lrp8 resulting in severe neurological dysfunction and death in mice fed a selenium-deficient diet. Previous studies have reported that although feeding a standard chow diet can prevent these severe deficits, some motor coordination and cognitive dysfunction remain. Importantly, no single study has directly compared the motor and cognitive performance of the Sepp1 and Lrp8 knockout (KO) lines. Here, we report the results of a comprehensive parallel analysis of the motor and spatial learning and memory function of Sepp1 and Lrp8 knockout mice fed a standard mouse chow diet. Our results revealed that Sepp1 knockout mice raised on a selenium-replete diet displayed motor and cognitive function that was indistinguishable from their wild-type littermates. In contrast, we found that although Lrp8-knockout mice fed a selenium-replete diet had normal motor function, their spatial learning and memory showed subtle deficits. We also found that the deficit in baseline adult hippocampal neurogenesis exhibited by Lrp8-deficit mice could not be rescued by dietary selenium supplementation. Taken together, these findings further highlight the importance of selenium transport in maintaining healthy brain function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Proteínas Relacionadas con Receptor de LDL , Ratones Noqueados , Selenio , Aprendizaje Espacial , Animales , Ratones , Selenio/administración & dosificación , Selenio/deficiencia , Selenio/farmacología , Aprendizaje Espacial/fisiología , Aprendizaje Espacial/efectos de los fármacos , Proteínas Relacionadas con Receptor de LDL/genética , Proteínas Relacionadas con Receptor de LDL/metabolismo , Masculino , Selenoproteína P/genética , Selenoproteína P/metabolismo , Dieta , Memoria Espacial/fisiología , Memoria Espacial/efectos de los fármacos , Ratones Endogámicos C57BL , Hipocampo/metabolismo , Memoria/fisiología , Memoria/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Aprendizaje por Laberinto/efectos de los fármacos
3.
Sci Rep ; 13(1): 14089, 2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-37640771

RESUMEN

Left ventricular (LV) myocardial mass is important in the evaluation of cardiac remodeling and requires accurate assessment when performed on linear measurements in two-dimensional echocardiography (Echo). We aimed to compare the accuracy of the Devereaux formula (DEV) and the Teichholz formula (TEICH) in calculating LV myocardial mass in Echo using cardiac magnetic resonance (CMR) as the reference method. Based on preceding mathematical calculations, we identified primarily LV size rather than wall thickness as the main source of bias between DEV and TEICH in a retrospective derivation cohort (n = 1276). Although LV mass from DEV and TEICH were correlated with CMR, TEICH did not show a proportional bias as did DEV (- 2 g/m2 vs. + 22 g/m2). This could be validated in an independent prospective cohort (n = 226) with symptomatic non-ischemic heart failure. DEV systematically overestimated LV mass in all tiers of LV remodeling as compared to TEICH. In conclusion, the TEICH method accounts for the changes in LV geometry with increasing LV mass and thus better reflects the different pattern of LV remodeling than the DEV method. This has important clinical implications, as TEICH may be more appropriate for use in clinical practice, rather than DEV, currently recommended.


Asunto(s)
Insuficiencia Cardíaca , Corazón , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Imagen por Resonancia Magnética , Miocardio
4.
J Telemed Telecare ; : 1357633X231174484, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37287248

RESUMEN

INTRODUCTION: Telecare can be an effective way to deliver healthcare to patients' homes. Avatar or virtual agent-equipped technologies have the potential to increase user engagement and adherence to telecare. This study aimed to identify telecare interventions assisted by avatars/virtual agents, reflect the concepts of telecare and give an overview on its outcomes. METHODS: A scoping review guided by the PRISMA-ScR checklist was conducted. MEDLINE, CINAHL, PsycINFO and grey literature were searched through 12 July 2022. Studies were included if patients were remotely cared for by healthcare professionals and received telecare interventions assisted by avatars/virtual agents in their homes. Studies underwent quality appraisal, and were synthesized along the dimensions 'study characteristics', 'intervention' and 'outcomes'. RESULTS: Out of 535 records screened, 14 studies were included, reporting the effects of avatar/virtual agent-assisted telecare interventions, tailored to specific patient groups. Telecare interventions mainly focused on teletherapy and telemonitoring. Telecare services were rehabilitative, preventive, palliative, promotive and curative. Modes of communication were asynchronous, synchronous or a mix of both. Tasks of the implemented avatars/virtual agents comprised delivering health interventions, monitoring, assessment, guidance and strengthening agency. Telecare interventions led to improved clinical outcomes and higher adherence. Most studies reported sufficient system usability and high satisfaction among participants. CONCLUSIONS: Telecare interventions were overall target group related and integrated in a service model. This combined with the use of avatars and virtual agents leads to improved adherence to telecare in the home setting. Further studies could account for relatives' experiences with telecare.

5.
Diagnostics (Basel) ; 13(7)2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-37046515

RESUMEN

Left ventricular ejection fraction (LVEF) is a key parameter in evaluating left ventricular (LV) function using echocardiography (Echo), but its manual measurement by the modified biplane Simpson (MBS) method is time consuming and operator dependent. We investigated the feasibility of a server-based, commercially available and ready-to use-artificial intelligence (AI) application based on convolutional neural network methods that integrate fully automatic view selection and measurement of LVEF from an entire Echo exam into a single workflow. We prospectively enrolled 1083 consecutive patients who had been referred to Echo for diagnostic or therapeutic purposes. LVEF was measured independently using MBS and AI. Test-retest variability was assessed in 40 patients. The reliability, repeatability, and time efficiency of LVEF measurements were compared between the two methods. Overall, 889 Echos were analyzed by cardiologists with the MBS method and by the AI. Over the study period of 10 weeks, the feasibility of both automatic view classification and seamlessly measured LVEF rose to 81% without user involvement. LVEF, LV end-diastolic and end-systolic volumes correlated strongly between MBS and AI (R = 0.87, 0.89 and 0.93, p < 0.001 for all) with a mean bias of +4.5% EF, -12 mL and -11 mL, respectively, due to impaired image quality and the extent of LV function. Repeatability and reliability of LVEF measurement (n = 40, test-retest) by AI was excellent compared to MBS (coefficient of variation: 3.2% vs. 5.9%), although the median analysis time of the AI was longer than that of the operator-dependent MBS method (258 s vs. 171 s). This AI has succeeded in identifying apical LV views and measuring EF in one workflow with comparable results to the MBS method and shows excellent reproducibility. It offers realistic perspectives for fully automated AI-based measurement of LVEF in routine clinical settings.

6.
Environ Sci Pollut Res Int ; 30(5): 13688-13696, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36136197

RESUMEN

Microplastics (MPs) are nowadays abundant, persistent, and ubiquitous in the environment, representing a new threat for terrestrial, marine, and freshwater ecosystems. Although anuran populations and species are globally declining, the effect of MP exposure on this taxon has been poorly investigated. With the aim of assessing the effects of microplastic exposure on the defensive responses of Italian agile frog (Rana latastei) tadpoles, we exposed them to three different concentrations (1, 7, and 50 mg L-1) of a mixture of plastic polymers (HPDE, PVC, PS, and PES) for 2 weeks. Then, we measured the total distance covered by individual tadpoles before and after exposure to tadpole-fed dragonfly larvae (Aeshna cyanea) cues. As expected, predation risk sharply lowered the total distance travelled by tadpoles; however, MP concentration did not affect their defensive performances. We also collected data on tadpole development, activity, and mortality. In contrast with previous experiments, neither tadpole growth nor mortality varied with MP concentration. Our results indicate that the intensity of MP effects on growth and development may depend on tadpole size, with large tadpoles being less susceptible to the negative effects of MP exposure.


Asunto(s)
Microplásticos , Odonata , Animales , Larva , Plásticos/toxicidad , Ecosistema , Ranidae , Anuros , Conducta Predatoria
7.
BMJ Open ; 12(9): e062159, 2022 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-36123104

RESUMEN

INTRODUCTION: Chronic diseases in older adults are one of the major epidemiological challenges of current times and leading cause of disability, poor quality of life, high healthcare costs and death. Self-management of chronic diseases is essential to improve health behaviours and health outcomes. Technology-assisted interventions have shown to improve self-management of chronic diseases. Virtual avatars can be a key factor for the acceptance of these technologies. Addison Care is a home-based telecare solution equipped with a virtual avatar named Addison, connecting older persons with their caregivers via an easy-to-use technology. A central advantage is that Addison Care provides access to self-management support for an up-to-now highly under-represented population-older persons with chronic disease(s), which enables them to profit from e-health in everyday life. METHODS AND ANALYSIS: A pragmatic, non-randomised, one-arm pilot study applying an embedded mixed-methods approach will be conducted to examine user experience, usability and user engagement of the virtual avatar Addison. Participants will be at least 65 years and will be recruited between September 2022 and November 2022 from hospitals during the discharge process to home care. Standardised instruments, such as the User Experience Questionnaire, System Usability Scale, Instrumental Activities of Daily Living scale, Short-Form-8-Questionnaire, UCLA Loneliness Scale, Geriatric Depression Scale, Stendal Adherence with Medication Score and Self-Efficacy for Managing Chronic Diseases Scale, as well as survey-based assessments, semistructured interviews and think-aloud protocols, will be used. The study seeks to enrol 20 patients that meet the criteria. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethic committee of the German Society for Nursing Science (21-037). The results are intended to be published in peer-reviewed journals and disseminated through conference papers. TRIAL REGISTRATION NUMBER: DRKS00025992.


Asunto(s)
Automanejo , Telemedicina , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Humanos , Proyectos Piloto , Calidad de Vida , Automanejo/métodos , Tecnología
8.
Chemosphere ; 308(Pt 1): 136281, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36064015

RESUMEN

Microplastics (MPs) are recognised as an emerging environmental problem that needs to be carefully monitored. So far, MPs have been widely recorded in marine and freshwater ecosystems. Still, few studies have focused on MP occurrence in terrestrial ecosystems, although soils are suspected to be one of the main MP reservoirs. To test a non-invasive method for assessing MP contamination in terrestrial ecosystems, we analysed the pellets of a top terrestrial predator, the barn owl (Tyto alba). Sixty pellets were collected from three agricultural areas (20 pellets each) and analysed to assess both barn owl diet and MP content. Thirty-four MPs were confirmed by micro-Fourier Transform Infrared Spectroscopy (µ-FTIR) analysis in 33% of the pellets (min-max 1-5 MPs per pellet). Most of the detected items were microfibres (88.2%). Polyethylene terephthalate, polyacrylonitrile and polyamide were the most abundant polymers. One of the three sites was significantly less contaminated. In the two sites with the highest MP occurrences, barn owl diet was characterised by predation on synanthropic rodents, particularly brown rats (Rattus norvegicus), which may indicate habitat degradation and increased exposure to MPs. Analyses also suggest that Savi's pine vole (Microtus savii) is the prey least at risk of MP contamination, probably due to its strictly herbivorous diet. We argue that the analysis of barn owl pellets may represent a cost-effective method for monitoring MP contamination in terrestrial ecosystems.


Asunto(s)
Estrigiformes , Contaminantes Químicos del Agua , Animales , Arvicolinae , Ecosistema , Monitoreo del Ambiente , Microplásticos , Nylons , Plásticos , Tereftalatos Polietilenos , Ratas , Roedores , Suelo , Contaminantes Químicos del Agua/análisis
9.
Water Res ; 222: 118848, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-35901554

RESUMEN

Since nanoplastics are currently considered potentially hazardous to the environment and human health, reliability of studies on nanoplastic exposure becomes crucial. However, analytical challenges limit our understanding of their formation and detection, thus hampering their biological interactions assessment. Here we provide a combined approach to quantitatively and qualitatively detect the release of nanoplastics in water matrix and, in particular, to measure direct exposure of consumers by simulated use of drinking water plastic bottles. We measured that the polyethylene sealing of the bottles released particles with a size distribution ranging from few hundreds nanometers up to about one micron and estimated a mass release in the order of few tenths of nanograms per opening/closing cycle. We observe that mechanical stress alters the physical-chemical characteristics of the generated secondary nanoplastics and degrades the material properties compared to the original bulk source, thus complicating their spectroscopic chemical identification. Our findings demonstrate that understanding material degradation processes is therefore crucial for identifying and quantifying nanoplastics in real samples. Moreover, methods allowing quantitative studies on the release of nanoplastic as a source of exposure are considered essential for proper assessment of their potential health hazards and to promote improvements in consumer products plastic packaging design.


Asunto(s)
Agua Potable , Contaminantes Químicos del Agua , Humanos , Microplásticos , Plásticos , Reproducibilidad de los Resultados , Contaminantes Químicos del Agua/análisis
10.
Environ Pollut ; 303: 119137, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35318069

RESUMEN

Microplastics (MPs) have been reported to threaten a wide variety of terrestrial, marine, and freshwater organisms. However, knowledge about the effects of MPs on anuran amphibians, one of the most threatened taxa worldwide, is still limited. To assess the effects of MPs on the growth and survival of the Italian agile frog (Rana latastei) and green toad (Bufotes balearicus), we exposed tadpoles to three different concentrations (1, 7, and 50 mg L-1) of an environmental relevant mixture of microplastics (HPDE, PVC, PS and PES), recording data on their activity level, weight and mortality rates. While the effects of MPs on green toad tadpoles were negligible, Italian agile frog tadpoles were severely affected both in terms of growth and activity level, with high mortality rates even at the lowest MP density (1 mg L-1). Our results suggest that MP contamination of freshwater habitats may contribute to the ongoing decline of anuran amphibians.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Animales , Anuros , Bufonidae , Larva , Plásticos/toxicidad , Ranidae , Contaminantes Químicos del Agua/análisis
11.
Environ Int ; 163: 107200, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35349910

RESUMEN

Three-dimensional (3D) structured organoids are the most advanced in vitro models for studying human health effects, but their application to evaluate the biological effects associated with microplastic exposure was neglected until now. Fibers from synthetic clothes and fabrics are a major source of airborne microplastics, and their release from dryer machines is poorly understood. We quantified and characterized the microplastic fibers (MPFs) released in the exhaust filter of a household dryer and tested their effects on airway organoids (1, 10, and 50 µg mL-1) by optical microscopy, scanning electron microscopy (SEM), confocal microscopy and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). While the presence of MPFs did not inhibit organoid growth, we observed a significant reduction of SCGB1A1 gene expression related to club cell functionality and a polarized cell growth along the fibers. The MPFs did not cause relevant inflammation or oxidative stress but were coated with a cellular layer, resulting in the inclusion of fibers in the organoid. This effect could have long-term implications regarding lung epithelial cells undergoing repair. This exposure study using human airway organoids proved suitability of the model for studying the effects of airborne microplastic contamination on humans and could form the basis for further research regarding the toxicological assessment of emerging contaminants such as micro- or nanoplastics.


Asunto(s)
Microplásticos , Plásticos , Humanos , Organoides , Textiles
12.
Sci Total Environ ; 823: 153638, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35131241

RESUMEN

Microplastics (MPs) are emerging contaminants in freshwater systems that have already attracted much scientific interest, but little attention has been paid to a multi-matrix analysis of MP occurrences along the length of a river. The present research provides the first record of MP contamination of four abiotic and biotic matrices from a river ecosystem simultaneously analysed. MPs were isolated and identified by micro-Fourier Transform Infrared (µ-FTIR) spectroscopy from samples collected along the Ticino River in North Italy during spring 2019. Abiotic samples were surface water (n = 18, 33 MPs m-3) and sediment (n = 18, 11 MPs kg-1), while biological samples consisted of stomach and gut content of fish (n = 18, wels catfish, Silurus glanis, 0.032 MPs g-1) and macroinvertebrates (n = 90, caddisfly larvae, Hydropsychidae, 0.03 MPs mg-1). MPs were found in biota from all stations; 44% of fish and 61% of macroinvertebrate samples contained MPs. The calculated unit-consistent concentration ratios indicate that both S. glanis and Hydropsychidae larvae had a consistent higher amount of MPs than their respective medium (sediment and water), strongly suggesting an efficient uptake pathway into organisms. MP levels in surface water, sediment, fish and macroinvertebrates were not correlated and did not increase with the river's length. From our mass balance calculations, the Ticino River transports a consistent amount of MP (yearly load of 3.40 × 1011 ± 1.1 × 1011 MPs) to the Po River. This MP load was almost half than an estimated MP load from wastewater treatment plants (WWTPs). On that basis and supported by the finding that MP concentration in sediment was mostly opposed to that in surface water but was on average 750-fold higher compared to the water matrix, we surmise that the complex hydrological network of the Ticino River retains a consistent amount of MPs which might build up over time.


Asunto(s)
Bagres , Contaminantes Químicos del Agua , Animales , Ecosistema , Monitoreo del Ambiente/métodos , Insectos , Microplásticos , Plásticos/análisis , Ríos/química , Contaminantes Químicos del Agua/análisis
13.
Parkinsonism Relat Disord ; 88: 90-95, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34153885

RESUMEN

INTRODUCTION: We aimed to study the various cardiac manifestations of the two core neuroacanthocytosis (NA) syndromes, namely chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS). So far, cardiac involvement has been described as specific feature only for MLS. METHODS: We studied six patients with ChAc (mean age 44.5 years, five men, one woman) and six patients with MLS (mean age 57.1 years, all men). Cardiac evaluation included echocardiography and/or cardiac magnetic resonance imaging (cardiac MRI), 24-h ECG-recording and examination of cardiac biomarkers. RESULTS: Cardiac involvement of ChAc was found in four of six patients. Two patients showed mildly reduced left ventricular ejection fraction (LVEF), two other patients mild to moderate left ventricular (LV) dilatation. Neither an increase in ventricular ectopic beats nor ventricular tachycardia were evident in ChAc. Four of five MLS patients showed left ventricle dilatation and reduced left ventricular ejection fraction (LVEF). Two of these, in addition, had critical ventricular tachycardia. High sensitive troponin T was elevated in all patients, for whom data were available (n = 10). In contrast, elevation of high sensitive troponin I was found in one of six ChAc and one of two MLS patients. CONCLUSION: For the first time, we reveal cardiac involvement in a cohort of six ChAc patients, while the risk to develop heart failure seems lower than in MLS. Our study confirms the malignant nature of MLS in terms of ventricular arrhythmias and progression to advanced heart failure. Herein, we define disease-specific recommendations for cardiac assessment in both conditions.


Asunto(s)
Arritmias Cardíacas/etiología , Cardiomiopatías/etiología , Neuroacantocitosis/complicaciones , Adulto , Arritmias Cardíacas/sangre , Arritmias Cardíacas/diagnóstico por imagen , Arritmias Cardíacas/fisiopatología , Cardiomiopatías/sangre , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/fisiopatología , Ecocardiografía , Electrocardiografía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Troponina I/sangre , Troponina T/sangre
14.
Environ Sci Pollut Res Int ; 27(33): 41731-41739, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32696405

RESUMEN

Previous research has reported avian plastic ingestion in marine bird species. Yet, while research attention on plastic pollution is shifting from marine to freshwater ecosystems, very few information on plastic ingestion is available for freshwater birds. Here, we examined the presence of microplastic in regurgitated pellets of the common kingfisher (Alcedo atthis) collected along the Ticino River (North Italy). In total, 133 kingfisher's pellets were examined between March and October 2019 from 54 transects along the river. Plastic elements were detected and identified by visual inspection followed by µ-FTIR and SEM-EDS. Overall, we found 12 (micro)plastics from at least three different polymers in 7.5% of the pellets. This study provides the first report of plastic uptake of this bird species. It highlights the importance of spectroscopic techniques in plastic monitoring studies in order to avoid misidentification of items found. Documenting the presence of plastic ingestion by top carnivores such as fish-eating birds is necessary to understand the pervasiveness and impact of (micro)plastic pollution in food webs of freshwater ecosystems.


Asunto(s)
Ríos , Contaminantes Químicos del Agua , Animales , Aves , Ecosistema , Monitoreo del Ambiente , Italia , Microplásticos , Plásticos , Contaminantes Químicos del Agua/análisis
15.
Bioresour Technol ; 300: 122671, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31901776

RESUMEN

The aim of this work was to prove a process temperature of 45 °C as a practical alternative to commonly applied mesophilic (37 °C) and thermophilic (55 °C) anaerobic digestion (AD). Regarding methane production, no differences were found between the three temperature regimes. However, the maximum possible loading rate at 45 °C exceeded that at 37 °C and 55 °C. Pathogen inactivation at 45 °C was higher than at 37 °C and similarly efficient as at 55 °C. At each process temperature, a unique microbial community established. In addition, the archaeome at 55 °C was dominated by hydrogenotrophs, while at 37 °C and 45 °C it was dominated by acetotrophs. For the investigated substrate mixture, liquid cattle manure with wheat straw as co-substrate, 45 °C turned out to be preferable for AD. For other substrates, these findings still need to be confirmed.


Asunto(s)
Estiércol , Metano , Anaerobiosis , Animales , Reactores Biológicos , Bovinos , Temperatura , Triticum
16.
JACC Case Rep ; 2(8): 1103-1105, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34317425

RESUMEN

The presence of a left ventricular (LV) thrombus is considered an absolute contraindication to transcatheter aortic valve implantation (TAVI) because of the very high embolic risk. We report a case of TAVI under complete protection of the cerebral arteries in a patient with a large LV thrombus, severely impaired LV function, and no surgical options. (Level of Difficulty: Beginner.).

17.
Water Res ; 166: 115082, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31542550

RESUMEN

Plastic particle ingestion has become of concern as a possible threat to human health. Previous works have already explored the presence of microplastic (MP) in bottled drinking water as a source of MP intake. Here, we consider the release of MP particles from single-use PET mineral water bottles upon exposure to mechanical stress utilizing SEM plus EDS, which allows the implementation of morphological and elemental analysis of the plastic material surface and quantification of particle concentrations in sample water. The aim of this study was to better evaluate the sources of MP intake from plastic bottles, especially considering the effect of daily use on these bottles such as the abrasion of the plastic material. For that, we analysed MP release of PET bottlenecks and HDPE caps on their surfaces after a series of bottle openings/closings (1 x, 10 x, 100 x). Furthermore, we investigated, if the inner surface of the PET bottles released MPs, counted particle increase of the water and identified MPs in the PET bottled water after exposing the bottles to mechanical stress (squeezing treatment; none, 1 min, 10 min). The results showed a considerable increase of MP particle occurrence on the surface of PET and HDPE material (bottlenecks and caps) after opening and closing the bottles. After 100 times the effect was impressive, especially on caps. Moreover, great differences exist in cap abrasion between brands which uncovers a discrepancy in plastic behavior of brands. Interestingly, particle concentrations in the bottled mineral water did not significantly increase after exposure to mechanical stress (squeezing treatment). The morphological analysis of the inner wall surface of the bottles supported this observation, as no stress cracks could be detected after the treatment, implying that the bottles itself are not a consistent source of MP particles after this extent of mechanical stress. However, chances of MP ingestion by humans increase with frequent use of the same single-use plastic bottle, though only from the bottleneck-cap system.


Asunto(s)
Agua Potable , Aguas Minerales , Contaminantes Químicos del Agua , Humanos , Plásticos , Estrés Mecánico
18.
Eur J Pharm Biopharm ; 141: 37-50, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31103742

RESUMEN

Specific cell targeting and efficient intracellular delivery are major hurdles for the widespread therapeutic use of nucleic acid technologies, particularly siRNA mediated gene silencing. To enable receptor-mediated cell-specific targeting, we designed a synthesis scheme that can be generically used to engineer Designed Ankyrin Repeat Protein (DARPin)-siRNA bioconjugates. Different linkers, including labile disulfide-, and more stable thiol-maleimide- and triazole- (click chemistry) tethers were employed. Crosslinkers were first attached to a 3'-terminal aminohexyl chain on the siRNA sense strands. On the protein side thiols of a C-terminal cysteine were used as anchoring sites for disulfide- and thiol-maleimide conjugate formations, while strain-promoted azido-alkyne cycloadditions were carried out at a metabolically introduced N-terminal azidohomoalanine. After establishing efficient purification methods, highly pure products were obtained. Bioconjugates of EpCAM-targeted DARPins with siRNA directed at the luciferase gene were evaluated for cell-specific binding, uptake and gene silencing. As shown by flow cytometry and fluorescence microscopy, all constructs retained the highly specific and high-affinity antigen recognition properties of the native DARPin. As expected, internalization was observed only in EpCAM-positive cell lines, and predominantly endolysosomal localization was detected. Disulfide linked conjugates showed lower serum stability against cleavage at the linker and thus lower internalization into endosomes compared to thiol-maleimide- and triazole-linked conjugates, yet induced more pronounced gene silencing. This indicates that the siRNA payload needs to be liberated from the protein in the endosome. Our data confirm the promise of DARPin-siRNA bioconjugates for tumor targeting, but also identified endosomal retention and limited cytosolic escape of the siRNA as the rate-limiting step for more efficient gene silencing.


Asunto(s)
Endosomas/metabolismo , Silenciador del Gen/fisiología , Proteínas Musculares/metabolismo , Proteínas Nucleares/metabolismo , ARN Interferente Pequeño/metabolismo , Alanina/análogos & derivados , Alanina/metabolismo , Línea Celular Tumoral , Química Clic/métodos , Molécula de Adhesión Celular Epitelial/metabolismo , Células HeLa , Humanos , Células MCF-7 , Maleimidas/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Triazoles/metabolismo
19.
Clin Immunol ; 198: 62-70, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30389480

RESUMEN

The mechanism of the efficacy of Intravenous immunoglobulins (IVIG) in autoimmune and inflammatory diseases is not well understood. This study aimed at understanding mechanisms of IVIG-mediated suppression of effector cell activities of peripheral blood mononuclear cells (PBMC) in antibody-dependent cellular cytotoxicity (ADCC). We were particularly interested in CD56dim NK cells, the main ADCC effector cells in PBMC. Exposure of PBMC to IVIG for at least 48 h induced a caspase-3-dependent apoptotic cell death of CD56dim NK cells without affecting CD56bright NK cells. Induction of apoptosis in CD56dim NK cells and concomitant suppression of ADCC effector activities of PBMC was associated with the monomer fraction of IVIG. Moreover, it was independent of IgG sialyation, did not depend on engagement of FcγRIII and could not be mimicked by IVIG (Fab')2 or IVIG Fc preparations. The described effect could contribute to the reduction of peripheral NK cells observed during IVIG therapy in patients.


Asunto(s)
Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Apoptosis/efectos de los fármacos , Antígeno CD56/análisis , Inmunoglobulinas Intravenosas/farmacología , Células Asesinas Naturales/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Humanos , Células Asesinas Naturales/inmunología , Receptores de IgG/análisis
20.
Respir Res ; 19(1): 171, 2018 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-30200966

RESUMEN

BACKGROUND: There is a need for non-invasive parameters that are sensitive to the development of the bronchiolitis obliterans syndrome (BOS) in lung transplantation (LTx) patients. We studied whether the pulmonary diffusing capacity for inhaled nitric oxide is capable of detecting BOS stages. METHODS: Sixty-one LTx patients were included into this cross-sectional study (19/29/7/3/3 in BOS stages 0/0-p/1/2/3). For analysis stages 0/0-p versus 1/2/3 ("BOS binary-early"), and stages 0/0-p/1 versus 2/3 ("BOS binary-late") were summarized. Measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) were compared with spirometry and bodyplethysmography, and their relative importance was evaluated by discriminant analysis. RESULTS: Regarding the recognition of "BOS binary-early", among spirometric parameters forced expiratory volume in 1 s (FEV1) was best, among bodyplethysmographic parameters airway resistance, and among diffusing parameters DLNO. Regarding "BOS binary-late", DLNO was inferior to bodyplethysmographic parameters. CONCLUSION: Although the study comprised only measurements at a single time point and no follow-up, DLNO outperformed FEV1, the time course of which is used in detecting BOS. Together with its pathophysiological plausibility, this result suggests that the measurement of DLNO, possibly over time, could be an easily applicable tool for the monitoring of LTx patients and should be evaluated in larger studies.


Asunto(s)
Bronquiolitis Obliterante/diagnóstico , Monóxido de Carbono/fisiología , Trasplante de Pulmón/tendencias , Óxido Nítrico/fisiología , Capacidad de Difusión Pulmonar/fisiología , Adulto , Bronquiolitis Obliterante/etiología , Bronquiolitis Obliterante/metabolismo , Monóxido de Carbono/análisis , Estudios de Cohortes , Estudios Transversales , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Óxido Nítrico/análisis , Valor Predictivo de las Pruebas , Capacidad de Difusión Pulmonar/métodos
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