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1.
Environ Sci Technol ; 58(11): 4859-4871, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38441001

RESUMO

Plastics are complex chemical mixtures of polymers and various intentionally and nonintentionally added substances. Despite the well-established links between certain plastic chemicals (bisphenols and phthalates) and adverse health effects, the composition and toxicity of real-world mixtures of plastic chemicals are not well understood. To assess both, we analyzed the chemicals from 36 plastic food contact articles from five countries using nontarget high-resolution mass spectrometry and reporter-gene assays for four nuclear receptors that represent key components of the endocrine and metabolic system. We found that chemicals activating the pregnane X receptor (PXR), peroxisome proliferator receptor γ (PPARγ), estrogen receptor α (ERα), and inhibiting the androgen receptor (AR) are prevalent in plastic packaging. We detected up to 9936 chemical features in a single product and found that each product had a rather unique chemical fingerprint. To tackle this chemical complexity, we used stepwise partial least-squares regressions and prioritized and tentatively identified the chemical features associated with receptor activity. Our findings demonstrate that most plastic food packaging contains endocrine- and metabolism-disrupting chemicals. Since samples with fewer chemical features induce less toxicity, chemical simplification is key to producing safer plastic packaging.


Assuntos
Disruptores Endócrinos , Embalagem de Alimentos , Polímeros , Disruptores Endócrinos/química , Disruptores Endócrinos/farmacologia , Plásticos
2.
Environ Sci Technol ; 58(11): 4872-4883, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38440973

RESUMO

G protein-coupled receptors (GPCRs) are central mediators of cell signaling and physiological function. Despite their biological significance, GPCRs have not been widely studied in the field of toxicology. Herein, we investigated these receptors as novel targets of plastic chemicals using a high-throughput drug screening assay with 126 human non-olfactory GPCRs. In a first-pass screen, we tested the activity of triphenol phosphate, bisphenol A, and diethyl phthalate, as well as three real-world mixtures of chemicals extracted from plastic food packaging covering all major polymer types. We found 11 GPCR-chemical interactions, of which the chemical mixtures exhibited the most robust activity at adenosine receptor 1 (ADORA1) and melatonin receptor 1 (MTNR1A). We further confirm that polyvinyl chloride and polyurethane products contain ADORA1 or MTNRA1 agonists using a confirmatory secondary screen and pharmacological knockdown experiments. Finally, an analysis of the associated gene ontology terms suggests that ADORA1 and MTNR1A activation may be linked to downstream effects on circadian and metabolic processes. This work highlights that signaling disruption caused by plastic chemicals is broader than that previously believed and demonstrates the relevance of nongenomic pathways, which have, thus far, remained unexplored.


Assuntos
Receptores Acoplados a Proteínas G , Transdução de Sinais , Humanos , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Ensaios de Triagem em Larga Escala , Polímeros
3.
HNO ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861031

RESUMO

BACKGROUND: The size of the human cochlear, measured by the diameter of the basal turn, varies between 7 and 11 mm. For hearing rehabilitation with cochlear implants (CI), the size of the cochlear influences the individual frequency map and the choice of electrode length. OTOPLAN® (CAScination AG [Bern, Switzerland] in cooperation with MED-EL [Innsbruck, Austria]) is a software tool with CE marking for clinical applications in CI treatment which allows for precise pre-planning based on cochlear size. This literature review aims to analyze all published data on the application of OTOPLAN®. MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to identify relevant studies published in the PubMed search engine between January 2015 and February 2023 using the search terms "otoplan" [title/abstract] OR "anatomy-based fitting" [title/abstract] OR "otological software tool" [title/abstract] OR "computed tomography-based software AND cochlear" [title/abstract]. RESULTS: The systematic review of the literature identified 32 studies on clinical use of OTOPLAN® in CI treatment. Most studies were reported from Germany (7 out of 32), followed by Italy (5), Saudi Arabia (4), the USA (4), and Belgium (3); 2 studies each were from Austria and China, and 1 study from France, India, Norway, South Korea, and Switzerland. In the majority of studies (22), OTOPLAN® was used to assess cochlear size, followed by visualizing the electrode position using postoperative images (5), three-dimensional segmentation of temporal bone structures (4), planning the electrode insertion trajectory (3), creating a patient-specific frequency map (3), planning of a safe drilling path through the facial recess (3), and measuring of temporal bone structures (1). CONCLUSION: To date, OTOPLAN® is the only DICOM viewer with CE marking in the CI field that can process pre-, intra-, and postoperative images in the abovementioned applications.

4.
Environ Sci Technol ; 56(4): 2487-2496, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35080176

RESUMO

Bisphenols and phthalates, chemicals frequently used in plastic products, promote obesity in cell and animal models. However, these well-known metabolism-disrupting chemicals (MDCs) represent only a minute fraction of all compounds found in plastics. To gain a comprehensive understanding of plastics as a source of exposure to MDCs, we characterized the chemicals present in 34 everyday products using nontarget high-resolution mass spectrometry and analyzed their joint adipogenic activities by high-content imaging. We detected 55,300 chemical features and tentatively identified 629 unique compounds, including 11 known MDCs. Importantly, the chemicals extracted from one-third of the products caused murine 3T3-L1 preadipocytes to proliferate, and differentiate into adipocytes, which were larger and contained more triglycerides than those treated with the reference compound rosiglitazone. Because the majority of plastic extracts did not activate the peroxisome proliferator-activated receptor γ and the glucocorticoid receptor, the adipogenic effects are mediated via other mechanisms and, thus, likely to be caused by unknown MDCs. Our study demonstrates that daily-use plastics contain potent mixtures of MDCs and can, therefore, be a relevant yet underestimated environmental factor contributing to obesity.


Assuntos
Adipogenia , Plásticos , Células 3T3-L1 , Adipócitos , Animais , Camundongos , Obesidade , PPAR gama , Plásticos/farmacologia
5.
Environ Sci Technol ; 53(13): 7215-7233, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31120742

RESUMO

Upgrading wastewater treatment plants (WWTPs) with advanced technologies is one key strategy to reduce micropollutant emissions. Given the complex chemical composition of wastewater, toxicity removal is an integral parameter to assess the performance of WWTPs. Thus, the goal of this systematic review is to evaluate how effectively ozonation and activated carbon remove in vitro and in vivo toxicity. Out of 2464 publications, we extracted 46 relevant studies conducted at 22 pilot or full-scale WWTPs. We performed a quantitative and qualitative evaluation of in vitro (100 assays) and in vivo data (20 species), respectively. Data is more abundant on ozonation (573 data points) than on an activated carbon treatment (162 data points), and certain in vitro end points (especially estrogenicity) and in vivo models (e.g., daphnids) dominate. The literature shows that while a conventional treatment effectively reduces toxicity, residual effects in the effluents may represent a risk to the receiving ecosystem on the basis of effect-based trigger values. In general, an upgrade to ozonation or activated carbon treatment will significantly increase toxicity removal with similar performance. Nevertheless, ozonation generates toxic transformation products that can be removed by a post-treatment. By assessing the growing body of effect-based studies, we identify sensitive and underrepresented end points and species and provide guidance for future research.


Assuntos
Ozônio , Poluentes Químicos da Água , Ecossistema , Eliminação de Resíduos Líquidos , Águas Residuárias
6.
Ecotoxicol Environ Saf ; 183: 109481, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31442800

RESUMO

The toxicity and environmental risk of chemicals, such as the antiepileptic drug carbamazepine (CBZ), is commonly assessed using standardized laboratory tests and laboratory-to-field extrapolation. To investigate the toxicity of CBZ to aquatic key organisms in a more complex and environmentally relevant scenario, we conducted a 32-day multiple-stress experiment in artificial indoor streams. We exposed the non-biting midge Chironomus riparius, the blackworm Lumbriculus variegatus, and the New Zealand mud snail Potamopyrgus antipodarum to 80 and 400 µg CBZ/L in six artificial indoor streams. In addition to hydraulic stress, species' interaction, and low organic content in the sediment, organisms were co-exposed to the herbicide terbutryn (TBY) as a second chemical stressor at a concentration of 6 µg/L. The exposure to CBZ under multiple stress conditions resulted in a 10- to more than 25-fold higher toxicity in C. riparius and P. antipodarum when compared to a previous, standardized laboratory experiment. The co-exposure to TBY enhanced the adverse effects of CBZ on snails (reduced production of embryos). This effect was additive as the single exposure to TBY also reduced the reproduction of snails, most likely through the reduction of biofilm biomass. The emergence of C. riparius declined at a CBZ concentration of 400 µg/L (without the co-exposure to TBY) and at 80 µg/L in combination with TBY. The difference in sensitivity between laboratory and indoor stream experiments is indicative of a potential underestimation of risk when toxicity data are extrapolated to field conditions. The present results suggest the inclusion of non-chemical and chemical stressors in environmental hazard and risk assessments.


Assuntos
Anticonvulsivantes/toxicidade , Carbamazepina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Chironomidae/efeitos dos fármacos , Interações Medicamentosas , Gastrópodes/efeitos dos fármacos , Herbicidas/toxicidade , Oligoquetos/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Medição de Risco , Rios , Estresse Fisiológico , Triazinas/toxicidade
7.
Eur Arch Otorhinolaryngol ; 276(3): 679-683, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30617425

RESUMO

PURPOSE: Bilateral cochlear implant (CI) provision is now widely regarded as the most beneficial hearing intervention for acceptable candidates. This study sought to determine if a number of well-regarded hearing professionals at highly reputable clinics shared similar practices and beliefs regarding bilateral CI provision, use, and rehabilitation in children and adults. METHODS: An 11-question online questionnaire was created and distributed to all 27 clinics in the HEARRING group. Questions 1-5 asked for facts; questions 6-11 asked for opinions. RESULTS: 20 completed questionnaires were returned. All 20 respondents reported that their clinics perform bilateral cochlear implantation in children; 18 do so in adults. Regarding the fact-based questions, bilateral CI provision is more commonly performed and more likely to be reimbursed in children than in adults. Children are also much more likely to be implanted simultaneously than are adults. Regarding the opinion-based questions, respondents gave broadly similar answers. Communication between the CIs and speech coding strategies specifically developed for bilateral CI users were regarded as the two future technologies that would most enhance the benefit of bilateral CI use. CONCLUSIONS: Most clinics in the HEARRING group are very familiar with bilateral CI provision and hold similar opinions on its results and benefits. Hopefully the results described herein will lead to a greater acceptance and regular reimbursement of bilateral CI provision, especially in adults.


Assuntos
Atitude do Pessoal de Saúde , Implante Coclear/métodos , Implantes Cocleares , Pesquisas sobre Atenção à Saúde , Adulto , Criança , Implante Coclear/estatística & dados numéricos , Feminino , Pesquisas sobre Atenção à Saúde/métodos , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Humanos , Masculino , Resultado do Tratamento
8.
Laryngorhinootologie ; 98(S 01): S253-S289, 2019 Mar.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-31096301

RESUMO

The implementation of mobile information and communication technology in the field of health services, e. g. in the form of apps, is becoming increasingly important. Unfortunately, the necessary quality criteria are often mising. Thus, it seems important, that in addition to an app controlling authority highly qualified health care professionals participate in the development of these applications. For reasons of liability, however, the physician must exercise great caution in the selection and recommendation of medical apps, especially considering, that only a few apps are certified as medical devices. There are a large number of medical apps on the market, with only a small proportion being assigned to the field of otorhinolaryngology. The areas of audiology, sleep medicine and allergology are most frequently represented. Althouhgh there is increasing scientific work on this topic in the field of otorhinolaryngology, there is a lack of scientific evidence of contents and results, as is generally the case of medical apps. However, there are other possibilities for users to rate medical apps regarding defined qualitiy criteria such as functionality, scientific integrity, but also data privacy. None of the apps assessed by such a evaluation tool met all the required quality criteria, but the applied instrument helped to better assess the application. However, it was possible to consider the quality criteria in the developmental process of an medical app for the field of otorhinolaryngoglogy. In summary, the present work provide a comprehensive insight into the topic "Apps in Otorhinolaryngology" with the aim to use these modern aids in a beneficial way.


Assuntos
Aplicativos Móveis , Otolaringologia
9.
Environ Sci Technol ; 50(19): 10606-10615, 2016 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-26848848

RESUMO

Conventional activated sludge treatment of wastewater does not completely remove micropollutants. Here, extending anaerobic conditions may enhance biodegradation. To explore this, we combined iron-reducing or substrate-limiting and aerobic pilot-scale reactors directly at a wastewater treatment plant. To assess the removal of endocrine disrupting chemicals (EDCs) as group of micropollutants that adversely affects wildlife, we applied a bioanalytical approach. We used in vitro bioassays covering seven receptor-mediated mechanisms of action, including (anti)androgenicity, (anti)estrogenicity, retinoid-like, and dioxin-like activity. Untreated wastewater induced antiandrogenic, estrogenic, antiestrogenic, and retinoid-like activity. Full-scale as well as reactor-scale activated sludge treatment effectively removes the observed effects. Nevertheless, high antiandrogenic and minor dioxin-like and estrogenic effects persisted in the treated effluent that may still be environmentally relevant. The anaerobic post-treatment under substrate-limiting conditions resulted in an additional removal of endocrine activities by 17-40%. The anaerobic pre-treatment under iron-reducing conditions significantly enhanced the removal of the residual effects by 40-75%. In conclusion, this study demonstrates that a further optimization of biological wastewater treatment is possible. Here, implementing iron-reducing anaerobic conditions preceding aerobic treatment appears promising to improve the removal of receptor-mediated toxicity.


Assuntos
Dioxinas , Águas Residuárias , Esgotos , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água
11.
Anal Bioanal Chem ; 406(11): 2495-502, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24604322

RESUMO

As nanoscale materials have gained in economic importance over recent years, concerns about accumulation in the environment and, consequently, analysis of nanoparticles in biological material have increasingly become the focus of scientific research. A nanomaterial used in a wide range of food, consumer and household products is titanium dioxide (nTiO2). Monitoring of nTiO2 via determination of elemental titanium (Ti) can be very challenging because of a variety of possible interferences. This work describes problems during the development of a quantification method for titanium dioxide (TiO2) using inductively coupled plasma-quadrupole mass spectrometry (ICP-qMS). To evaluate the analytical method, certified vegetable reference material NCS DC 73349 was used. Interestingly, measurements of NCS DC 73349 seemed to result in acceptable recovery values-however, this was without considering interferences or conceivable differences in the natural isotopic abundance of the certified titanium calibration solution and NCS DC 73349. Actually, recoveries were lower than initially assumed. The potential interferences causing augmented recovery could be attributed to the presence of the elements sulfur (S) and phosphorus (P), which were able to form oxide ions and nitrogen-interfering species. The effect of such interfering cluster ions could be prevented by dry ashing as a sample preparation step, to evaporate S and P, before digestion with aqua regia in a high-pressure asher (HPA). Final practicability of the analysis method was proved by monitoring the uptake of nTiO2 by the microalgae Scenedesmus acutus in an environmental exposure study.


Assuntos
Clorófitas/química , Espectrometria de Massas/métodos , Microalgas/química , Nanopartículas/análise , Titânio/análise , Verduras/química , Clorófitas/metabolismo , Espectrometria de Massas/normas , Microalgas/metabolismo , Nanopartículas/metabolismo , Padrões de Referência , Titânio/metabolismo , Verduras/metabolismo
12.
Environ Int ; 189: 108791, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38838488

RESUMO

Plastics constitute a vast array of substances, with over 16000 known plastic chemicals, including intentionally and non-intentionally added substances. Thousands of chemicals, including toxic ones, are extractable from plastics, however, the extent to which these compounds migrate from everyday products into food or water remains poorly understood. This study aims to characterize the endocrine and metabolism disrupting activity, as well as the chemical composition of migrates from plastic food contact articles (FCAs) from four countries as significant sources of human exposure. Fourteen plastic FCAs covering seven polymer types with high global market shares were migrated into water and a water-ethanol mixture as food simulants according to European regulations. The migrates were analyzed using reporter gene assays for nuclear receptors relevant to human health and non-target chemical analysis to characterize the chemical composition. Chemicals migrating from each FCA interfered with at least two nuclear receptors, predominantly targeting pregnane X receptor (24/28 migrates). Moreover, peroxisome proliferator receptor gamma was activated by 19 out of 28 migrates, though mostly with lower potencies. Estrogenic and antiandrogenic activity was detected in eight and seven migrates, respectively. Fewer chemicals and less toxicity migrated into water compared to the water-ethanol mixture. However, 73 % of the 15 430 extractable chemical features also transferred into food simulants, and the water-ethanol migrates exhibited a similar toxicity prevalence compared to methanol extracts. The chemical complexity differed largely between FCAs, with 8 to 10631 chemical features migrating into food simulants. Using stepwise partial least squares regressions, we successfully narrowed down the list of potential active chemicals, identified known endocrine disrupting chemicals, such as triphenyl phosphate, and prioritized chemical features for further identification. This study demonstrates the migration of endocrine and metabolism disrupting chemicals from plastic FCAs into food simulants, rendering a migration of these compounds into food and beverages probable.


Assuntos
Disruptores Endócrinos , Embalagem de Alimentos , Plásticos , Disruptores Endócrinos/análise , Humanos , Contaminação de Alimentos
13.
Exp Brain Res ; 226(3): 393-406, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23455726

RESUMO

Neuronal stem cells have been described in the post-natal cochlear nucleus recently. The aim of the study was to analyse the neurogenic potential in the cochlear nucleus from the early post-natal days until adulthood. Cochlear nuclei from Sprague-Dawley rats from post-natal day P3 up to P40 were examined. Neurosphere assays showed persistent neurosphere formation from the early post-natal days until adulthood. The numbers of generated neurospheres were fewer in older ages. Neurospheres were smaller, but displayed the same pattern of neuronal stem cell markers. The markers GFAP, MBP and ß-III Tubulin showed differentiation of dissociated cells from the neurospheres in all cells of the neuronal lineage. BrdU incorporation could be detected, in an age-dependent decrease, in whole-mount experiments of the cochlear nucleus on all examined days. BrdU co-labelled with Atoh1 and ß-III Tubulin. In addition, gene expression and cellular distribution studies of the neuronal stem cell markers displayed an age-dependent reduction in both quantity and numbers. The presented results display a possible neurogenic potential until adulthood in the cochlear nucleus by in vitro and in vivo experiments. The fact that this potential is highest at a critical period of development reveals possible functional importance for the development of the cochlear nucleus and the auditory function. The persistent neurogenic potential displayed until adulthood could be a neurogenic niche in the adult cochlear nucleus, which might be used for potential therapeutic strategies.


Assuntos
Núcleo Coclear/fisiologia , Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Neurônios/fisiologia , Animais , Núcleo Coclear/citologia , Núcleo Coclear/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Proteína Básica da Mielina/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley
14.
J Med Entomol ; 50(3): 668-73, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23802465

RESUMO

The Asian tiger mosquito Aedes albopictus (Skuse, 1894) is a globally invasive prominent vector of viral and parasitic pathogens. To soundly guide insecticide use in control programs it is crucial to use standardized test systems under rigorously controlled environmental conditions that allow for comparisons across laboratories. An acute standard test procedure (24 h) for insecticide resistance monitoring of mosquitoes has been published by the World Health Organization in 1998, but a standardized chronic test to monitor sublethal insecticide effects on the life cycle of mosquitoes does not yet exist. As a first step toward a standardized chronic bioassay (half-life-cycle-test), the exclusion of qualitative and quantitative food effects by means of standardized, optimal larval feeding would greatly facilitate inter-laboratory comparisons. Against this background we evaluated food qualities and quantities for the aquatic part of the A. albopictus life cycle under different thermal conditions. Five mg TetraMin (Tetra, Melle, Germany) larva(-1) at 25 degrees C rendered the lowest mortality and large pupae. Our fundamental data on A. albopictus feeding provide an opportunity to standardize experiments and thus support interlaboratory comparisons of studies on the ecotoxicology of this dangerous vector mosquito.


Assuntos
Aedes/fisiologia , Ração Animal/análise , Testes de Toxicidade/métodos , Aedes/crescimento & desenvolvimento , Animais , Dieta/veterinária , Feminino , Qualidade dos Alimentos , Larva/crescimento & desenvolvimento , Larva/fisiologia , Masculino , Pupa/crescimento & desenvolvimento , Pupa/fisiologia , Temperatura , Testes de Toxicidade/veterinária
15.
Cochlear Implants Int ; 23(1): 32-42, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34519256

RESUMO

OBJECTIVE: There is still a lack in precise postoperative evaluation of the cochlea because of strong artifacts. This study aimed to improve accuracy of postoperative two-turn (2TL) and cochlear duct length (CDL) measurements by applying flat-panel volume computed tomography (fpVCT), secondary reconstruction (fpVCTSECO) and three-dimensional curved multiplanar reconstruction. METHODS: First, 10 temporal bone specimens with or without electrode were measured in multi-slice computed tomography (MSCT), fpVCT and fpVCTSECO and compared to high-resolution micro-CT scans. Later, pre- and postoperative scans of 10 patients were analyzed in a clinical setting. RESULTS: Concerning 2TL, no statistically significant difference was observed between implanted fpVCTSECO and nonimplanted micro-CT in 10 temporal bone specimens. In contrast, there was a significant discrepancy for CDL (difference: -0.7 mm, P = 0.004). Nevertheless, there were no clinically unacceptable errors (±1.5 mm). These results could be confirmed in a clinical setting. Using fpVCTSECO, CDL was slightly underestimated postoperatively (difference: -0.5 mm, P = 0.002) but without any clinically unacceptable errors. CONCLUSION: fpVCTSECO can be successfully applied for a precise measurement of the cochlear lengths pre- and postoperatively. However, users must be aware of a slight systematic underestimation of CDL postoperatively. These results may help to refine electrode selection and frequency mapping.


Assuntos
Implante Coclear , Implantes Cocleares , Cóclea/diagnóstico por imagem , Cóclea/cirurgia , Ducto Coclear/cirurgia , Implante Coclear/métodos , Tomografia Computadorizada de Feixe Cônico , Humanos , Osso Temporal/diagnóstico por imagem , Osso Temporal/cirurgia
16.
Otol Neurotol ; 42(3): e294-e303, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33555750

RESUMO

HYPOTHESIS: Flat-panel volume computed tomography (fpVCT) and secondary reconstruction allow for more accurate measurements of two-turn length (2TL), cochlear duct length (CDL), and angular length (AL). BACKGROUND: Cochlear geometry is a controversially debated topic. In the meantime, there are many different studies partly reporting highly divergent values. Our aim is to discuss the differences and to propose a radiological possibility to improve cochlear measurements using 3D-curved multiplanar reconstruction and fpVCT. METHODS: Performing different image modalities and settings, we tried to find a clinically usable option that allows for a high degree of accuracy. Therefore, we tested them against reference values of high-definition micro-computed tomography. RESULTS: Comparison of 99 µm slice thickness secondary reconstruction of fpVCT and reference showed no significant differences for 2TL and CDL (p ≥ 0.05). Accordingly, ICC (intraclass correlation) values were excellent (ICC ≥ 0.75; lower limit of confidence interval [CI] ≥ 0.75; Cronbach's alpha [α] ≥ 0.9). Evaluating AL, there was a significant difference (difference: -17.27°; p = 0.002). The lower limit of the CI of the ICC was unacceptable (ICC = 0.944; lower limit of CI = 0.248; α = 0.990). Regarding the Bland-Altman plots, there were no clinically unacceptable errors, but a systematic underestimation of AL. CONCLUSION: Secondary reconstruction is a suitable tool for producing reliable data that allow the accurate measurement of 2TL and CDL. The option of generating these reconstructions from raw data limits the need for higher radiation doses. Nevertheless, there is an underestimation of AL using secondary reconstructions.


Assuntos
Cóclea , Ducto Coclear , Cóclea/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Humanos , Microtomografia por Raio-X
17.
Toxicology ; 461: 152900, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34411659

RESUMO

The 3T3-L1 murine pre-adipocyte line is an established cell culture model for screening Metabolism Disrupting Chemicals (MDCs). Despite a need to accurately identify MDCs for further evaluation, relatively little research has been performed to comprehensively evaluate reproducibility across laboratories, assess factors that might contribute to varying degrees of differentiation between laboratories (media additives, plastics, cell source, etc.), or to standardize protocols. As such, the goals of this study were to assess interlaboratory variability of efficacy and potency outcomes for triglyceride accumulation and pre-adipocyte proliferation using the mouse 3T3-L1 pre-adipocyte cell assay to test chemicals. Ten laboratories from five different countries participated. Each laboratory evaluated one reference chemical (rosiglitazone) and three blinded test chemicals (tributyltin chloride, pyraclostrobin, and bisphenol A) using: 1) their Laboratory-specific 3T3-L1 Cells (LC) and their Laboratory-specific differentiation Protocol (LP), 2) Shared 3T3-L1 Cells (SC) with LP, 3) LC with a Shared differentiation Protocol (SP), and 4) SC with SP. Blinded test chemical responses were analyzed by the coordinating laboratory. The magnitude and range of bioactivities reported varied considerably across laboratories and test conditions, though the presence or absence of activity for each tested chemical was more consistent. Triglyceride accumulation activity determinations for rosiglitazone ranged from 90 to 100% across test conditions, but 30-70 % for pre-adipocyte proliferation; this was 40-80 % for triglyceride accumulation induced by pyraclostrobin, 80-100 % for tributyltin, and 80-100 % for bisphenol A. Consistency was much lower for pre-adipocyte proliferation, with 30-70 % active determinations for pyraclostrobin, 30-50 % for tributyltin, and 20-40 % for bisphenol A. Greater consistency was observed for the SC/SP assessment. As such, working to develop a standardized adipogenic differentiation protocol represents the best strategy for improving consistency of adipogenic responses using the 3T3-L1 model to reproducibly identify MDCs and increase confidence in reported outcomes.


Assuntos
Adipogenia/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Estrobilurinas/toxicidade , Compostos de Trialquitina/toxicidade , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Animais , Diferenciação Celular , Proliferação de Células/efeitos dos fármacos , Camundongos , Reprodutibilidade dos Testes , Rosiglitazona/farmacologia , Triglicerídeos/metabolismo
18.
Sci Total Environ ; 711: 134604, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31818558

RESUMO

Microplastics (MP) are contaminants of emerging concern in aquatic ecosystems. While the number of studies is rapidly increasing, a comparison of the toxicity of MP and natural particulate matter is largely missing. In addition, research focusses on the impacts of hydrophobic chemicals sorbed to plastics. However, the interactive effects of MP and hydrophilic, dissolved chemicals remain largely unknown. Therefore, we conducted chronic toxicity studies with larvae of the freshwater dipteran Chironomus riparius exposed to unplasticised polyvinyl chloride MP (PVC-MP) as well as kaolin and diatomite as reference materials for 28 days. In addition, we investigated the effects of particles in combination with the neonicotinoid imidacloprid in a multiple-stressor experiment. High concentrations of kaolin positively affected the chironomids. In contrast, exposure to diatomite and PVC-MP reduced the emergence and mass of C. riparius. Likewise, the toxicity of imidacloprid was enhanced in the presence of PVC-MP and slightly decreased in the co-exposure with kaolin. Overall, parallel experiments and chemical analysis indicate that the toxicity of PVC-MP was not caused by leached or sorbed chemicals. Our study demonstrates that PVC-MP induce more severe effects than both natural particulate materials. However, the latter are not benign per se, as the case of diatomite highlights. Considering the high, environmentally irrelevant concentrations needed to induce adverse effects, C. riparius is insensitive to exposures to PVC-MP.


Assuntos
Chironomidae , Microplásticos , Animais , Ecossistema , Água Doce , Poluentes Químicos da Água
19.
Int J Pediatr Otorhinolaryngol ; 132: 109917, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32032915

RESUMO

OBJECTIVES: Button battery (BB) ingestion can cause life-threatening complications such as esophageal perforation, and mediastinitis. Chest radiography is the method of choice to diagnose BB ingestion. Therefore, an adequate interpretation of X-ray imaging by physicians is mandatory. The study aimed to analyze relevant diagnostic aspects of BB X-ray imaging, and retrospective analysis of the imaging of radiopaque foreign bodies. METHODS: All commercially available BBs and different foreign bodies such as euro coins (EC) and disk magnets (DM) were listed according to their sizes and compositions. Furthermore, an X-ray analysis of a test set of BBs, ECs and DMs was performed at angles of 0°, 45°, and 90°. Retrospective assessment of radiological characteristics was performed for patients with a round and radiopaque foreign body in the esophagus RESULTS: Only BBs with a diameter of at least 20 mm had a reliable positive double rim sign at scan angles of 90°, and 45°. The step-off effect was visible in all BBs regardless of the diameter. DMs and ECs presented a homogeneous X-ray weakening at all investigated scan angles. In the retrospective analysis all five cases of BB ingestion showed a double rim sign, all fifteen cases of coin ingestion a homogeneous X-ray weakening. A corrugated margin was detected for 10 cent, 20 cent and 50 cent coins. CONCLUSIONS: BBs with a diameter of at least 20 mm showed, depending on the battery model, a more or less pronounced double rim sign and step-off effect in conventional X-ray imaging. However the double rim sign can be simulated by for example a pot magnet.


Assuntos
Fontes de Energia Elétrica , Esôfago/diagnóstico por imagem , Corpos Estranhos/diagnóstico por imagem , Imãs , Numismática , Radiografia , Pré-Escolar , Diagnóstico Diferencial , Humanos , Estudos Retrospectivos
20.
Stem Cells Int ; 2019: 5831240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781242

RESUMO

The inferior colliculus (IC) is a nucleus of the auditory pathway and its fourth relay station. It integrates afferent information from the superior olivary complex and the cochlear nucleus. To date, no causal therapeutic options are known for damaged neuronal structures in this area. Regenerative medicine offers a potential approach to causally treating hearing impairment. After neural stem cells had been identified in certain areas of the auditory pathway, the question arouses, whether the IC also has a neurogenic potential. Cells from the IC of postnatal day 6 rats were extracted and cultured as neurospheres. Cells in the neurospheres showed mitotic activity and positive stain of neural stem cell markers (Nestin, DCX, Atoh1, and Sox-2). In addition, single cells were differentiated into neuronal and glial cells shown by the markers ß-III-tubulin, GFAP, and MBP. In summary, basic stem cell criteria could be detected and characterized in cells isolated from the IC of the rat. These findings will lead to a better understanding of the development of the auditory pathway and may also be relevant for identifying causal therapeutic approaches in the future.

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